research ethics protocol example

Write an Error-free Research Protocol As Recommended by WHO: 21 Elements You Shouldn’t Miss!

Principal Investigator: Did you draft the research protocol?

Student: Not yet. I have too many questions about it. Why is it important to write a research protocol? Is it similar to research proposal? What should I include in it? How should I structure it? Is there a specific format?

Researchers at an early stage fall short in understanding the purpose and importance of some supplementary documents, let alone how to write them. Let’s better your understanding of writing an acceptance-worthy research protocol.

Table of Contents

What Is Research Protocol?

The research protocol is a document that describes the background, rationale, objective(s), design, methodology, statistical considerations and organization of a clinical trial. It is a document that outlines the clinical research study plan. Furthermore, the research protocol should be designed to provide a satisfactory answer to the research question. The protocol in effect is the cookbook for conducting your study

Why Is Research Protocol Important?

In clinical research, the research protocol is of paramount importance. It forms the basis of a clinical investigation. It ensures the safety of the clinical trial subjects and integrity of the data collected. Serving as a binding document, the research protocol states what you are—and you are not—allowed to study as part of the trial. Furthermore, it is also considered to be the most important document in your application with your Institution’s Review Board (IRB).

It is written with the contributions and inputs from a medical expert, a statistician, pharmacokinetics expert, the clinical research coordinator, and the project manager to ensure all aspects of the study are covered in the final document.

Is Research Protocol Same As Research Proposal?

Often misinterpreted, research protocol is not similar to research proposal. Here are some significant points of difference between a research protocol and a research proposal:

What Are the Elements/Sections of a Research Protocol?

According to Good Clinical Practice guidelines laid by WHO, a research protocol should include the following:

1. General Information

• Protocol title, protocol identifying number (if any), and date.
• Name and address of the funder.
• Name(s) and contact details of the investigator(s) responsible for conducting the research, the research site(s).
• Responsibilities of each investigator.
• Name(s) and address(es) of the clinical laboratory(ies), other medical and/or technical department(s) and/or institutions involved in the research.

2. Rationale & Background Information

• The rationale and background information provides specific reasons for conducting the research in light of pertinent knowledge about the research topic.
• It is a statement that includes the problem that is the basis of the project, the cause of the research problem, and its possible solutions.
• It should be supported with a brief description of the most relevant literatures published on the research topic.

3. Study Objectives

• The study objectives mentioned in the research proposal states what the investigators hope to accomplish. The research is planned based on this section.
• The research proposal objectives should be simple, clear, specific, and stated prior to conducting the research.
• It could be divided into primary and secondary objectives based on their relativity to the research problem and its solution.

4. Study Design

• The study design justifies the scientific integrity and credibility of the research study.
• The study design should include information on the type of study, the research population or the sampling frame, participation criteria (inclusion, exclusion, and withdrawal), and the expected duration of the study.

5. Methodology

• The methodology section is the most critical section of the research protocol.
• It should include detailed information on the interventions to be made, procedures to be used, measurements to be taken, observations to be made, laboratory investigations to be done, etc.
• The methodology should be standardized and clearly defined if multiple sites are engaged in a specified protocol.

6. Safety Considerations

• The safety of participants is a top-tier priority while conducting clinical research .
• Safety aspects of the research should be scrutinized and provided in the research protocol.

7. Follow-up

• The research protocol clearly indicate of what follow up will be provided to the participating subjects.
• It must also include the duration of the follow-up.

8. Data Management and Statistical Analysis

• The research protocol should include information on how the data will be managed, including data handling and coding for computer analysis, monitoring and verification.
• It should clearly outline the statistical methods proposed to be used for the analysis of data.
• For qualitative approaches, specify in detail how the data will be analysed.

9. Quality Assurance

• The research protocol should clearly describe the quality control and quality assurance system.
• These include GCP, follow up by clinical monitors, DSMB, data management, etc.

10. Expected Outcomes of the Study

• This section indicates how the study will contribute to the advancement of current knowledge, how the results will be utilized beyond publications.
• It must mention how the study will affect health care, health systems, or health policies.

11. Dissemination of Results and Publication Policy

• The research protocol should specify not only how the results will be disseminated in the scientific media, but also to the community and/or the participants, the policy makers, etc.
• The publication policy should be clearly discussed as to who will be mentioned as contributors, who will be acknowledged, etc.

12. Duration of the Project

• The protocol should clearly mention the time likely to be taken for completion of each phase of the project.
• Furthermore a detailed timeline for each activity to be undertaken should also be provided.

13. Anticipated Problems

• The investigators may face some difficulties while conducting the clinical research. This section must include all anticipated problems in successfully completing their projects.
• Furthermore, it should also provide possible solutions to deal with these difficulties.

14. Project Management

• This section includes detailed specifications of the role and responsibility of each investigator of the team.
• Everyone involved in the research project must be mentioned here along with the specific duties they have performed in completing the research.
• The research protocol should also describe the ethical considerations relating to the study.
• It should not only be limited to providing ethics approval, but also the issues that are likely to raise ethical concerns.
• Additionally, the ethics section must also describe how the investigator(s) plan to obtain informed consent from the research participants.
• This section should include a detailed commodity-wise and service-wise breakdown of the requested funds.
• It should also include justification of utilization of each listed item.

17. Supplementary Support for the Project

• This section should include information about the received funding and other anticipated funding for the specific project.

18. Collaboration With Other Researchers or Institutions

• Every researcher or institute that has been a part of the research project must be mentioned in detail in this section of the research protocol.

19. Curriculum Vitae of All Investigators

• The CVs of the principal investigator along with all the co-investigators should be attached with the research protocol.
• Ideally, each CV should be limited to one page only, unless a full-length CV is requested.

20. Other Research Activities of Investigators

• A list of all current research projects being conducted by all investigators must be listed here.

21. References

• All relevant references should be mentioned and cited accurately in this section to avoid plagiarism.

How Do You Write a Research Protocol? (Research Protocol Example)

Main Investigator    

Number of Involved Centers (for multi-centric studies)

Indicate the reference center

Title of the Study

Protocol ID (acronym)

Keywords (up to 7 specific keywords)

Study Design

Mono-centric/multi-centric

Perspective/retrospective

Controlled/uncontrolled

Open-label/single-blinded or double-blinded

Randomized/non-randomized

n parallel branches/n overlapped branches

Experimental/observational

Endpoints (main primary and secondary endpoints to be listed)

Expected Results                                                

Analyzed Criteria

Main variables/endpoints of the primary analysis

Main variables/endpoints of the secondary analysis

Safety variables

Health Economy (if applicable)

Visits and Examinations

Therapeutic plan and goals

Visits/controls schedule (also with graphics)

Comparison to treatment products (if applicable)

Dose and dosage for the study duration (if applicable)

Formulation and power of the studied drugs (if applicable)

Method of administration of the studied drugs (if applicable)

Informed Consent

Study Population

Short description of the main inclusion, exclusion, and withdrawal criteria

Sample Size

Estimated Duration of the Study

Safety Advisory

Classification Needed

Requested Funds

Additional Features (based on study objectives)

Click Here to Download the Research Protocol Example/Template

Be prepared to conduct your clinical research by writing a detailed research protocol. It is as easy as mentioned in this article. Follow the aforementioned path and write an impactful research protocol. All the best!

Clear as template! Please, I need your help to shape me an authentic PROTOCOL RESEARCH on this theme: Using the competency-based approach to foster EFL post beginner learners’ writing ability: the case of Benin context. I’m about to start studies for a master degree. Please help! Thanks for your collaboration. God bless.

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Methodology

• Ethical Considerations in Research | Types & Examples

Ethical Considerations in Research | Types & Examples

Published on October 18, 2021 by Pritha Bhandari . Revised on May 9, 2024.

Ethical considerations in research are a set of principles that guide your research designs and practices. Scientists and researchers must always adhere to a certain code of conduct when collecting data from people.

The goals of human research often include understanding real-life phenomena, studying effective treatments, investigating behaviors, and improving lives in other ways. What you decide to research and how you conduct that research involve key ethical considerations.

These considerations work to

• protect the rights of research participants
• enhance research validity
• maintain scientific or academic integrity

Table of contents

Why do research ethics matter, getting ethical approval for your study, types of ethical issues, voluntary participation, informed consent, confidentiality, potential for harm, results communication, examples of ethical failures, other interesting articles, frequently asked questions about research ethics.

Research ethics matter for scientific integrity, human rights and dignity, and collaboration between science and society. These principles make sure that participation in studies is voluntary, informed, and safe for research subjects.

You’ll balance pursuing important research objectives with using ethical research methods and procedures. It’s always necessary to prevent permanent or excessive harm to participants, whether inadvertent or not.

Defying research ethics will also lower the credibility of your research because it’s hard for others to trust your data if your methods are morally questionable.

Even if a research idea is valuable to society, it doesn’t justify violating the human rights or dignity of your study participants.

Prevent plagiarism. Run a free check.

Before you start any study involving data collection with people, you’ll submit your research proposal to an institutional review board (IRB) .

An IRB is a committee that checks whether your research aims and research design are ethically acceptable and follow your institution’s code of conduct. They check that your research materials and procedures are up to code.

If successful, you’ll receive IRB approval, and you can begin collecting data according to the approved procedures. If you want to make any changes to your procedures or materials, you’ll need to submit a modification application to the IRB for approval.

If unsuccessful, you may be asked to re-submit with modifications or your research proposal may receive a rejection. To get IRB approval, it’s important to explicitly note how you’ll tackle each of the ethical issues that may arise in your study.

There are several ethical issues you should always pay attention to in your research design, and these issues can overlap with each other.

You’ll usually outline ways you’ll deal with each issue in your research proposal if you plan to collect data from participants.

Voluntary participation means that all research subjects are free to choose to participate without any pressure or coercion.

All participants are able to withdraw from, or leave, the study at any point without feeling an obligation to continue. Your participants don’t need to provide a reason for leaving the study.

It’s important to make it clear to participants that there are no negative consequences or repercussions to their refusal to participate. After all, they’re taking the time to help you in the research process , so you should respect their decisions without trying to change their minds.

Voluntary participation is an ethical principle protected by international law and many scientific codes of conduct.

Take special care to ensure there’s no pressure on participants when you’re working with vulnerable groups of people who may find it hard to stop the study even when they want to.

Informed consent refers to a situation in which all potential participants receive and understand all the information they need to decide whether they want to participate. This includes information about the study’s benefits, risks, funding, and institutional approval.

You make sure to provide all potential participants with all the relevant information about

• what the study is about
• the risks and benefits of taking part
• how long the study will take
• your supervisor’s contact information and the institution’s approval number

Usually, you’ll provide participants with a text for them to read and ask them if they have any questions. If they agree to participate, they can sign or initial the consent form. Note that this may not be sufficient for informed consent when you work with particularly vulnerable groups of people.

If you’re collecting data from people with low literacy, make sure to verbally explain the consent form to them before they agree to participate.

For participants with very limited English proficiency, you should always translate the study materials or work with an interpreter so they have all the information in their first language.

In research with children, you’ll often need informed permission for their participation from their parents or guardians. Although children cannot give informed consent, it’s best to also ask for their assent (agreement) to participate, depending on their age and maturity level.

Anonymity means that you don’t know who the participants are and you can’t link any individual participant to their data.

You can only guarantee anonymity by not collecting any personally identifying information—for example, names, phone numbers, email addresses, IP addresses, physical characteristics, photos, and videos.

In many cases, it may be impossible to truly anonymize data collection . For example, data collected in person or by phone cannot be considered fully anonymous because some personal identifiers (demographic information or phone numbers) are impossible to hide.

You’ll also need to collect some identifying information if you give your participants the option to withdraw their data at a later stage.

Data pseudonymization is an alternative method where you replace identifying information about participants with pseudonymous, or fake, identifiers. The data can still be linked to participants but it’s harder to do so because you separate personal information from the study data.

Confidentiality means that you know who the participants are, but you remove all identifying information from your report.

All participants have a right to privacy, so you should protect their personal data for as long as you store or use it. Even when you can’t collect data anonymously, you should secure confidentiality whenever you can.

Some research designs aren’t conducive to confidentiality, but it’s important to make all attempts and inform participants of the risks involved.

As a researcher, you have to consider all possible sources of harm to participants. Harm can come in many different forms.

• Psychological harm: Sensitive questions or tasks may trigger negative emotions such as shame or anxiety.
• Social harm: Participation can involve social risks, public embarrassment, or stigma.
• Physical harm: Pain or injury can result from the study procedures.
• Legal harm: Reporting sensitive data could lead to legal risks or a breach of privacy.

It’s best to consider every possible source of harm in your study as well as concrete ways to mitigate them. Involve your supervisor to discuss steps for harm reduction.

Make sure to disclose all possible risks of harm to participants before the study to get informed consent. If there is a risk of harm, prepare to provide participants with resources or counseling or medical services if needed.

Some of these questions may bring up negative emotions, so you inform participants about the sensitive nature of the survey and assure them that their responses will be confidential.

The way you communicate your research results can sometimes involve ethical issues. Good science communication is honest, reliable, and credible. It’s best to make your results as transparent as possible.

Take steps to actively avoid plagiarism and research misconduct wherever possible.

Plagiarism means submitting others’ works as your own. Although it can be unintentional, copying someone else’s work without proper credit amounts to stealing. It’s an ethical problem in research communication because you may benefit by harming other researchers.

Self-plagiarism is when you republish or re-submit parts of your own papers or reports without properly citing your original work.

This is problematic because you may benefit from presenting your ideas as new and original even though they’ve already been published elsewhere in the past. You may also be infringing on your previous publisher’s copyright, violating an ethical code, or wasting time and resources by doing so.

In extreme cases of self-plagiarism, entire datasets or papers are sometimes duplicated. These are major ethical violations because they can skew research findings if taken as original data.

You notice that two published studies have similar characteristics even though they are from different years. Their sample sizes, locations, treatments, and results are highly similar, and the studies share one author in common.

Research misconduct

Research misconduct means making up or falsifying data, manipulating data analyses, or misrepresenting results in research reports. It’s a form of academic fraud.

These actions are committed intentionally and can have serious consequences; research misconduct is not a simple mistake or a point of disagreement about data analyses.

Research misconduct is a serious ethical issue because it can undermine academic integrity and institutional credibility. It leads to a waste of funding and resources that could have been used for alternative research.

Later investigations revealed that they fabricated and manipulated their data to show a nonexistent link between vaccines and autism. Wakefield also neglected to disclose important conflicts of interest, and his medical license was taken away.

This fraudulent work sparked vaccine hesitancy among parents and caregivers. The rate of MMR vaccinations in children fell sharply, and measles outbreaks became more common due to a lack of herd immunity.

Research scandals with ethical failures are littered throughout history, but some took place not that long ago.

Some scientists in positions of power have historically mistreated or even abused research participants to investigate research problems at any cost. These participants were prisoners, under their care, or otherwise trusted them to treat them with dignity.

To demonstrate the importance of research ethics, we’ll briefly review two research studies that violated human rights in modern history.

These experiments were inhumane and resulted in trauma, permanent disabilities, or death in many cases.

After some Nazi doctors were put on trial for their crimes, the Nuremberg Code of research ethics for human experimentation was developed in 1947 to establish a new standard for human experimentation in medical research.

In reality, the actual goal was to study the effects of the disease when left untreated, and the researchers never informed participants about their diagnoses or the research aims.

Although participants experienced severe health problems, including blindness and other complications, the researchers only pretended to provide medical care.

When treatment became possible in 1943, 11 years after the study began, none of the participants were offered it, despite their health conditions and high risk of death.

Ethical failures like these resulted in severe harm to participants, wasted resources, and lower trust in science and scientists. This is why all research institutions have strict ethical guidelines for performing research.

If you want to know more about statistics , methodology , or research bias , make sure to check out some of our other articles with explanations and examples.

• Normal distribution
• Measures of central tendency
• Chi square tests
• Confidence interval
• Quartiles & Quantiles
• Cluster sampling
• Stratified sampling
• Thematic analysis
• Cohort study
• Peer review
• Ethnography

Research bias

• Implicit bias
• Cognitive bias
• Conformity bias
• Hawthorne effect
• Availability heuristic
• Attrition bias
• Social desirability bias

Ethical considerations in research are a set of principles that guide your research designs and practices. These principles include voluntary participation, informed consent, anonymity, confidentiality, potential for harm, and results communication.

Scientists and researchers must always adhere to a certain code of conduct when collecting data from others .

These considerations protect the rights of research participants, enhance research validity , and maintain scientific integrity.

Research ethics matter for scientific integrity, human rights and dignity, and collaboration between science and society. These principles make sure that participation in studies is voluntary, informed, and safe.

Anonymity means you don’t know who the participants are, while confidentiality means you know who they are but remove identifying information from your research report. Both are important ethical considerations .

You can only guarantee anonymity by not collecting any personally identifying information—for example, names, phone numbers, email addresses, IP addresses, physical characteristics, photos, or videos.

You can keep data confidential by using aggregate information in your research report, so that you only refer to groups of participants rather than individuals.

These actions are committed intentionally and can have serious consequences; research misconduct is not a simple mistake or a point of disagreement but a serious ethical failure.

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Bhandari, P. (2024, May 09). Ethical Considerations in Research | Types & Examples. Scribbr. Retrieved August 5, 2024, from https://www.scribbr.com/methodology/research-ethics/

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Article Contents

Introduction, contents of a research study protocol, conflict of interest statement, how to write a research study protocol.

• Article contents
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Julien Al Shakarchi, How to write a research study protocol, Journal of Surgical Protocols and Research Methodologies , Volume 2022, Issue 1, January 2022, snab008, https://doi.org/10.1093/jsprm/snab008

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A study protocol is an important document that specifies the research plan for a clinical study. Many funders such as the NHS Health Research Authority encourage researchers to publish their study protocols to create a record of the methodology and reduce duplication of research effort. In this paper, we will describe how to write a research study protocol.

A study protocol is an essential part of a research project. It describes the study in detail to allow all members of the team to know and adhere to the steps of the methodology. Most funders, such as the NHS Health Research Authority in the United Kingdom, encourage researchers to publish their study protocols to create a record of the methodology, help with publication of the study and reduce duplication of research effort. In this paper, we will explain how to write a research protocol by describing what should be included.

Introduction

The introduction is vital in setting the need for the planned research and the context of the current evidence. It should be supported by a background to the topic with appropriate references to the literature. A thorough review of the available evidence is expected to document the need for the planned research. This should be followed by a brief description of the study and the target population. A clear explanation for the rationale of the project is also expected to describe the research question and justify the need of the study.

Methods and analysis

A suitable study design and methodology should be chosen to reflect the aims of the research. This section should explain the study design: single centre or multicentre, retrospective or prospective, controlled or uncontrolled, randomised or not, and observational or experimental. Efforts should be made to explain why that particular design has been chosen. The studied population should be clearly defined with inclusion and exclusion criteria. These criteria will define the characteristics of the population the study is proposing to investigate and therefore outline the applicability to the reader. The size of the sample should be calculated with a power calculation if possible.

The protocol should describe the screening process about how, when and where patients will be recruited in the process. In the setting of a multicentre study, each participating unit should adhere to the same recruiting model or the differences should be described in the protocol. Informed consent must be obtained prior to any individual participating in the study. The protocol should fully describe the process of gaining informed consent that should include a patient information sheet and assessment of his or her capacity.

The intervention should be described in sufficient detail to allow an external individual or group to replicate the study. The differences in any changes of routine care should be explained. The primary and secondary outcomes should be clearly defined and an explanation of their clinical relevance is recommended. Data collection methods should be described in detail as well as where the data will be kept secured. Analysis of the data should be explained with clear statistical methods. There should also be plans on how any reported adverse events and other unintended effects of trial interventions or trial conduct will be reported, collected and managed.

Ethics and dissemination

A clear explanation of the risk and benefits to the participants should be included as well as addressing any specific ethical considerations. The protocol should clearly state the approvals the research has gained and the minimum expected would be ethical and local research approvals. For multicentre studies, the protocol should also include a statement of how the protocol is in line with requirements to gain approval to conduct the study at each proposed sites.

It is essential to comment on how personal information about potential and enrolled participants will be collected, shared and maintained in order to protect confidentiality. This part of the protocol should also state who owns the data arising from the study and for how long the data will be stored. It should explain that on completion of the study, the data will be analysed and a final study report will be written. We would advise to explain if there are any plans to notify the participants of the outcome of the study, either by provision of the publication or via another form of communication.

The authorship of any publication should have transparent and fair criteria, which should be described in this section of the protocol. By doing so, it will resolve any issues arising at the publication stage.

Funding statement

It is important to explain who are the sponsors and funders of the study. It should clarify the involvement and potential influence of any party. The sponsor is defined as the institution or organisation assuming overall responsibility for the study. Identification of the study sponsor provides transparency and accountability. The protocol should explicitly outline the roles and responsibilities of any funder(s) in study design, data analysis and interpretation, manuscript writing and dissemination of results. Any competing interests of the investigators should also be stated in this section.

A study protocol is an important document that specifies the research plan for a clinical study. It should be written in detail and researchers should aim to publish their study protocols as it is encouraged by many funders. The spirit 2013 statement provides a useful checklist on what should be included in a research protocol [ 1 ]. In this paper, we have explained a straightforward approach to writing a research study protocol.

None declared.

Chan   A-W , Tetzlaff   JM , Gøtzsche   PC , Altman   DG , Mann   H , Berlin   J , et al.    SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials . BMJ   2013 ; 346 : e7586 .

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• national health service (uk)

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Submit a Human Ethics Protocol

What do I need before I can begin?

Before submitting a human ethics protocol, you will need access to My Research Human Protocols (MRHP) .  The following information will also help you understand and submit your human ethics protocol.

• Research Ethics Boards
• Who Can Be a Principal Investigator at U of T
• Tips for Writing a Human Ethics Protocol (5 minute video)
• Understanding Human Ethics Principles
• Protocol Submission Deadlines & Who to Submit To

Need to find human ethics guidelines (e.g., informed consent, student participation, data privacy, etc.)?  Please see  Human Ethics Principles & Guidelines .

Submission Process

There are two routes for submitting a human ethics protocol for ethics review.

• My Research Human Protocols (MRHP) : All submissions must be made through MRHP.  Course-based research in departments must also be submitted via MRHP.

Submission Deadlines

Delegate review deadline (for-low risk research): Every Monday or first business day of the week by 4pm .

Full board review deadline (default): These deadlines are determined by the respective Research Ethics Board (REB).

See Protocol Submission Deadlines & Who to Submit To .

Protocols are first approved by the relevant department’s chair or dean before they are reviewed by the REB.

Submission Guidelines

• Submit your protocol well in advance of the expected start date of your research to allow sufficient time for the review process. For delegated review, the review process may take 4-6 weeks from submission to first response.  This first response may be an approval or a request for additional information or changes to your ethics protocol. Full board review may take 2-3 weeks after the meeting to first response.
• Ethics review submissions should normally not include thesis proposals or journal articles.
• Applicants are advised to watch the Tips for Writing a Human Ethics Protocol (5 min. video) and refer to guidelines on various methodological and ethics related topics.
• Other permissions in addition to REB approval may be required to conduct research. It is up to the researcher to determine what these are and obtain them.  Please see Before Engaging in Research for assistance.

Administrative Review

Research to take place at a Toronto Academic Heath Science Network (TAHSN) hospital that involves the University in a peripheral role requires U of T review after REB approval by the hospital’s REB. Such roles include the following.

• Funding administered by U of T
• Involvement of a graduate student on the hospital-based project
• Analysis of data or biospecimens at U of T
• Storage of data or biospecimens at U of T
• Recruitment on campus  

Research that has been approved by an REB from a hospital with full TAHSN membership, or a hospital with TAHSN membership and CTO REB qualification may be reviewed through administrative review. These institutions are:

• Centre for Addiction and Mental Health
• Holland Bloorview Kids Rehabilitation Hospital
• Hospital for Sick Children (SickKids)
• Sinai Health (Includes Mount Sinai Hospital and Bridgepoint Active Healthcare)
• Sunnybrook Health Sciences Centre
• Unity Health Toronto (includes St. Michael’s Hospital, St. Joseph’s Health Centre and Providence Healthcare)
• University Health Network (Includes Toronto General Hospital, Toronto Western Hospital, Princess Margaret Hospital, Toronto Rehabilitation Institute)
• Women’s College Hospital
• TAHSN hospital-based research approved by the Ontario Cancer Research Ethics Board (OCREB)  

To apply for administrative review, use My Research Human Protocols (MRHP) and include the following in your application .

• Approved TAHSN Human Subjects Research Ethics Application form
• Approved research protocol
• All appendices
• REB (of record) approval letter  

There are no deadlines for administrative review. The timeline to first review is 1-2 weeks.

Research to take place at the University or in the community is normally not covered by TAHSN hospital REB approval and therefore U of T REB review and approval is required. This review may be conducted through delegated review in many instances; however full board review is the default process.

Research requiring the use of U of T Institutional Data

U of T Date Use

Scholarly research that requires the use of U of T institutional data as part of a study must also be approved through the Common Review Process (CRP) for non-routine data requests.

The CRP will confirm if the correct data to support the research request are available and whether there are University resources available to support this request. This process will also articulate the conditions of use, while ensuring that data is disclosed with the appropriate protections.

You can submit a request using this CRP submission form . Please submit your CRP request at the same time as your REB proposal.

For questions, please contact [email protected] .

Research involving U of T Students, Faculty, Librarians, Staff & Alumni by U of T Researchers

U of T Community Participants

Research that involves  U of T students, faculty, librarians, staff and/or alumni may require approval through an administrative process in addition to REB review. Please see relevant guidelines below.

• Guideline for U of T-based researchers
• Guideline for external researchers  
• All requests to survey U of T Doctor of Medicine (MD) Program Students should use the Education Research/Scholarly Project Approval, Survey/Participation and Data Requests form developed by the Temerty Faculty of Medicine. Questions regarding the surveying of MD program students can be directed to the MD Program’s Office of Assessment and Evaluation at [email protected] .
• Requests to survey U of T postgraduate medical education fellows (‘medical residents’) should be sent to the Associate Dean, Post-MD Education within the Temerty Faculty of Medicine, at [email protected] .

Review Timelines

The risk matrix, section 12 on MRHP will help determine the risk level. Risk level 1 goes through delegated review, while risk levels 2 and 3 will be reviewed by a panel of the full REB at a monthly scheduled meeting.

While we try to accommodate reasonable requests, ethics review is not a quick process. The REB is responsible for conducting proportionate review (in relation to level of risk) and full board reviews are conducted according to specific deadlines and scheduled meetings. It is the responsibility of the researcher to ensure sufficient time for review, prior to the commencement of the research activity.

Researchers should make every attempt to be fair in their risk matrix assessment. If you are unsure how to correctly fill out the matrix, please consult the Human Research Ethics Program (HREP) staff. If a protocol is deemed to require full board review once it has been submitted for delegated review, you will be notified and the protocol will be reviewed at the respective REB’s next full board meeting.

• Provide guidance on how to submit an application
• Provide consultations to develop an ethics protocol
• Assist with technical questions for using MRHP

VPRI Contact

General inquiries: human research & ethics unit (hreu), raise help desk, mariya gancheva, kristina ognjanovic.

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• Literature Searching Guide
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What is a study protocol?

A protocol is a detailed plan for a research study, outlining the specifics of how the research will be conducted. It is an essential document that helps to ensure research is conducted in a safe and ethical manner, and that the integrity of the research is preserved throughout the life of the study.

Common elements of a protocol

Melbourne Children's Trials Centre. (2017). Developing, amending and complying with research protocols.  https://www.mcri.edu.au/images/research/training-resources/research-process-resources/guideline_developing_research_protocols.pdf

See the Data Management  page in this guide for information on creating a data management plan (DMP), plus online tools and templates.

Literature review

Protocols draw on relevant literature at multiple points, e.g. in background information, when providing a rationale for the study, and when discussing known risks and benefits. If you haven't yet completed a literature search, now is the time to do one!

The Library offers training and guidance on conducting literature reviews, including a webinar on literature searching and a  Literature Searching Guide .

Library research support

The Library offers various forms of research support depending on the purpose of your research. Our research support includes: 

• Research consultations
• Literature search service
• Literature review report service
• Feedback on your literature search strategy
• Co-authorship for systematic reviews and other evidence synthesis projects

Complete  this online form  to request research support and learn more about each service offered.

Request research support

For an overview of Library research support, click the link below.

Library Research Support Services

Additional resources

• Protocol writing in clinical research  (2016) by A. Al-Jundi & S. Sakka
• Write an error-free research protocol as recommended by WHO: 21 elements you shouldn't miss! (2022) by U. Bhosale
• How to Write a Research Protocol: Tips and Tricks  (2018) by M. Cameli
• Guidance: Developing a protocol for a clinical research project  (n.d.) by the Clinical Research Development Office, RCH

Protocol templates

The Murdoch Children's Research Institute (MCRI) provides annotated protocol templates for the following study designs:

• Clinical trial - drug/device intervention
• Clinical trial - intervention is not drug/device
• Observational studies
• Clinical audits / Quality assurance

To access the templates, click the blue button below and scroll down to the section on  Clinical Research Development Office (CRDO) resources.

MCRI protocol templates

Qualitative studies

The NHS Health Research Authority offers a protocol template for qualitative research at the bottom of the page linked below.

NHS Qualitative protocol template

Example protocols

• RCT -  A clinical investigation evaluating efficacy of a full-thickness placental allograft (Revita) in lumbar microdiscectomy outcomes
• Observational study -  Prospective observational long-term safety registry of Multiple Sclerosis patients who have participated in cladribine clinical trials (PREMIERE)
• Systematic review and meta-analysis -  Protocol for a systematic review and meta-analysis on the associations between shift work and sickness absence

Tip:  The results of your literature search may include published protocols relevant to your research question.

Journal requirements

Journals that publish study protocols provide guidelines for the content required in protocol manuscripts. It can be helpful to review these guidelines even if you do not intend to publish your protocol in a peer-reviewed journal.

Search for the manuscript guidelines for your preferred journal(s) or review the examples below.

• BMC Nursing

Registering or publishing your protocol

Researchers are encouraged to submit their protocol for publication in a scholarly journal, and/or register their protocol in a relevant database. Many funding agencies also require grant recipients to register or publish their study protocol.

Where to register your protocol

Your study design generally determines where you register your protocol. See the table below for options on where to register your protocol.

Where to publish your protocol

There are two main options:

• E.g. Journal of Clinical Epidemiology , Journal of Allied Health , Journal of Clinical Nursing
• E.g. BMC Trials , JMIR Research Protocols , Contemporary Clinical Trials

Be aware of predatory publishers - Check our our Writing, Referencing & Publishing Guide or our Predatory Publishing A-Z  for more information.

Relevant Prompt documents include:

• Research Agreements Procedure
• Publication and dissemination of research findings
• Intellectual Property
• Research Ethics and Governance – Protocol and Investigational Brochure Content, Design, Amendments and Compliance
• Privacy and Confidentiality in Research
• Research Ethics and Governance – Authorship for Research

Visit the Forms Library from Research Support Services for links and more information. 

Research - Forms Library

Research agreements

The  Research Agreements Procedure  provides guidance on which agreement to use in which circumstance and the pathway to follow for seeking review and approval. There are preferred templates for various types of studies, such as collaborative or investigator-initiated studies.

For more information, visit the Research Agreements page from Research Support Services.

Research Agreements page  

Protocol amendments

Once your protocol is finalised and ethics approval has been granted, you must notify the Monash Health Research Support Services team regarding protocol amendments . 

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National Institute of Environmental Health Sciences

Your environment. your health., what is ethics in research & why is it important, by david b. resnik, j.d., ph.d..

December 23, 2020

The ideas and opinions expressed in this essay are the author’s own and do not necessarily represent those of the NIH, NIEHS, or US government.

When most people think of ethics (or morals), they think of rules for distinguishing between right and wrong, such as the Golden Rule ("Do unto others as you would have them do unto you"), a code of professional conduct like the Hippocratic Oath ("First of all, do no harm"), a religious creed like the Ten Commandments ("Thou Shalt not kill..."), or a wise aphorisms like the sayings of Confucius. This is the most common way of defining "ethics": norms for conduct that distinguish between acceptable and unacceptable behavior.

Most people learn ethical norms at home, at school, in church, or in other social settings. Although most people acquire their sense of right and wrong during childhood, moral development occurs throughout life and human beings pass through different stages of growth as they mature. Ethical norms are so ubiquitous that one might be tempted to regard them as simple commonsense. On the other hand, if morality were nothing more than commonsense, then why are there so many ethical disputes and issues in our society?

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One plausible explanation of these disagreements is that all people recognize some common ethical norms but interpret, apply, and balance them in different ways in light of their own values and life experiences. For example, two people could agree that murder is wrong but disagree about the morality of abortion because they have different understandings of what it means to be a human being.

Most societies also have legal rules that govern behavior, but ethical norms tend to be broader and more informal than laws. Although most societies use laws to enforce widely accepted moral standards and ethical and legal rules use similar concepts, ethics and law are not the same. An action may be legal but unethical or illegal but ethical. We can also use ethical concepts and principles to criticize, evaluate, propose, or interpret laws. Indeed, in the last century, many social reformers have urged citizens to disobey laws they regarded as immoral or unjust laws. Peaceful civil disobedience is an ethical way of protesting laws or expressing political viewpoints.

Another way of defining 'ethics' focuses on the disciplines that study standards of conduct, such as philosophy, theology, law, psychology, or sociology. For example, a "medical ethicist" is someone who studies ethical standards in medicine. One may also define ethics as a method, procedure, or perspective for deciding how to act and for analyzing complex problems and issues. For instance, in considering a complex issue like global warming , one may take an economic, ecological, political, or ethical perspective on the problem. While an economist might examine the cost and benefits of various policies related to global warming, an environmental ethicist could examine the ethical values and principles at stake.

See ethics in practice at NIEHS

Read latest updates in our monthly  Global Environmental Health Newsletter

Many different disciplines, institutions , and professions have standards for behavior that suit their particular aims and goals. These standards also help members of the discipline to coordinate their actions or activities and to establish the public's trust of the discipline. For instance, ethical standards govern conduct in medicine, law, engineering, and business. Ethical norms also serve the aims or goals of research and apply to people who conduct scientific research or other scholarly or creative activities. There is even a specialized discipline, research ethics, which studies these norms. See Glossary of Commonly Used Terms in Research Ethics and Research Ethics Timeline .

There are several reasons why it is important to adhere to ethical norms in research. First, norms promote the aims of research , such as knowledge, truth, and avoidance of error. For example, prohibitions against fabricating , falsifying, or misrepresenting research data promote the truth and minimize error.

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See how we put research Ethics to practice.

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Second, since research often involves a great deal of cooperation and coordination among many different people in different disciplines and institutions, ethical standards promote the values that are essential to collaborative work , such as trust, accountability, mutual respect, and fairness. For example, many ethical norms in research, such as guidelines for authorship , copyright and patenting policies , data sharing policies, and confidentiality rules in peer review, are designed to protect intellectual property interests while encouraging collaboration. Most researchers want to receive credit for their contributions and do not want to have their ideas stolen or disclosed prematurely.

Third, many of the ethical norms help to ensure that researchers can be held accountable to the public . For instance, federal policies on research misconduct, conflicts of interest, the human subjects protections, and animal care and use are necessary in order to make sure that researchers who are funded by public money can be held accountable to the public.

Fourth, ethical norms in research also help to build public support for research. People are more likely to fund a research project if they can trust the quality and integrity of research.

Finally, many of the norms of research promote a variety of other important moral and social values , such as social responsibility, human rights, animal welfare, compliance with the law, and public health and safety. Ethical lapses in research can significantly harm human and animal subjects, students, and the public. For example, a researcher who fabricates data in a clinical trial may harm or even kill patients, and a researcher who fails to abide by regulations and guidelines relating to radiation or biological safety may jeopardize his health and safety or the health and safety of staff and students.

Codes and Policies for Research Ethics

Given the importance of ethics for the conduct of research, it should come as no surprise that many different professional associations, government agencies, and universities have adopted specific codes, rules, and policies relating to research ethics. Many government agencies have ethics rules for funded researchers.

• National Institutes of Health (NIH)
• National Science Foundation (NSF)
• Food and Drug Administration (FDA)
• Environmental Protection Agency (EPA)
• US Department of Agriculture (USDA)
• Singapore Statement on Research Integrity
• American Chemical Society, The Chemist Professional’s Code of Conduct
• Code of Ethics (American Society for Clinical Laboratory Science)
• American Psychological Association, Ethical Principles of Psychologists and Code of Conduct
• Statement on Professional Ethics (American Association of University Professors)
• Nuremberg Code
• World Medical Association's Declaration of Helsinki

Ethical Principles

The following is a rough and general summary of some ethical principles that various codes address*:

Strive for honesty in all scientific communications. Honestly report data, results, methods and procedures, and publication status. Do not fabricate, falsify, or misrepresent data. Do not deceive colleagues, research sponsors, or the public.

Objectivity

Strive to avoid bias in experimental design, data analysis, data interpretation, peer review, personnel decisions, grant writing, expert testimony, and other aspects of research where objectivity is expected or required. Avoid or minimize bias or self-deception. Disclose personal or financial interests that may affect research.

Keep your promises and agreements; act with sincerity; strive for consistency of thought and action.

Carefulness

Avoid careless errors and negligence; carefully and critically examine your own work and the work of your peers. Keep good records of research activities, such as data collection, research design, and correspondence with agencies or journals.

Share data, results, ideas, tools, resources. Be open to criticism and new ideas.

Transparency

Disclose methods, materials, assumptions, analyses, and other information needed to evaluate your research.

Accountability

Take responsibility for your part in research and be prepared to give an account (i.e. an explanation or justification) of what you did on a research project and why.

Intellectual Property

Honor patents, copyrights, and other forms of intellectual property. Do not use unpublished data, methods, or results without permission. Give proper acknowledgement or credit for all contributions to research. Never plagiarize.

Confidentiality

Protect confidential communications, such as papers or grants submitted for publication, personnel records, trade or military secrets, and patient records.

Responsible Publication

Publish in order to advance research and scholarship, not to advance just your own career. Avoid wasteful and duplicative publication.

Responsible Mentoring

Help to educate, mentor, and advise students. Promote their welfare and allow them to make their own decisions.

Respect for Colleagues

Respect your colleagues and treat them fairly.

Social Responsibility

Strive to promote social good and prevent or mitigate social harms through research, public education, and advocacy.

Non-Discrimination

Avoid discrimination against colleagues or students on the basis of sex, race, ethnicity, or other factors not related to scientific competence and integrity.

Maintain and improve your own professional competence and expertise through lifelong education and learning; take steps to promote competence in science as a whole.

Know and obey relevant laws and institutional and governmental policies.

Animal Care

Show proper respect and care for animals when using them in research. Do not conduct unnecessary or poorly designed animal experiments.

Human Subjects protection

When conducting research on human subjects, minimize harms and risks and maximize benefits; respect human dignity, privacy, and autonomy; take special precautions with vulnerable populations; and strive to distribute the benefits and burdens of research fairly.

* Adapted from Shamoo A and Resnik D. 2015. Responsible Conduct of Research, 3rd ed. (New York: Oxford University Press).

Ethical Decision Making in Research

Although codes, policies, and principles are very important and useful, like any set of rules, they do not cover every situation, they often conflict, and they require interpretation. It is therefore important for researchers to learn how to interpret, assess, and apply various research rules and how to make decisions and act ethically in various situations. The vast majority of decisions involve the straightforward application of ethical rules. For example, consider the following case:

The research protocol for a study of a drug on hypertension requires the administration of the drug at different doses to 50 laboratory mice, with chemical and behavioral tests to determine toxic effects. Tom has almost finished the experiment for Dr. Q. He has only 5 mice left to test. However, he really wants to finish his work in time to go to Florida on spring break with his friends, who are leaving tonight. He has injected the drug in all 50 mice but has not completed all of the tests. He therefore decides to extrapolate from the 45 completed results to produce the 5 additional results.

Many different research ethics policies would hold that Tom has acted unethically by fabricating data. If this study were sponsored by a federal agency, such as the NIH, his actions would constitute a form of research misconduct , which the government defines as "fabrication, falsification, or plagiarism" (or FFP). Actions that nearly all researchers classify as unethical are viewed as misconduct. It is important to remember, however, that misconduct occurs only when researchers intend to deceive : honest errors related to sloppiness, poor record keeping, miscalculations, bias, self-deception, and even negligence do not constitute misconduct. Also, reasonable disagreements about research methods, procedures, and interpretations do not constitute research misconduct. Consider the following case:

Dr. T has just discovered a mathematical error in his paper that has been accepted for publication in a journal. The error does not affect the overall results of his research, but it is potentially misleading. The journal has just gone to press, so it is too late to catch the error before it appears in print. In order to avoid embarrassment, Dr. T decides to ignore the error.

Dr. T's error is not misconduct nor is his decision to take no action to correct the error. Most researchers, as well as many different policies and codes would say that Dr. T should tell the journal (and any coauthors) about the error and consider publishing a correction or errata. Failing to publish a correction would be unethical because it would violate norms relating to honesty and objectivity in research.

There are many other activities that the government does not define as "misconduct" but which are still regarded by most researchers as unethical. These are sometimes referred to as " other deviations " from acceptable research practices and include:

• Publishing the same paper in two different journals without telling the editors
• Submitting the same paper to different journals without telling the editors
• Not informing a collaborator of your intent to file a patent in order to make sure that you are the sole inventor
• Including a colleague as an author on a paper in return for a favor even though the colleague did not make a serious contribution to the paper
• Discussing with your colleagues confidential data from a paper that you are reviewing for a journal
• Using data, ideas, or methods you learn about while reviewing a grant or a papers without permission
• Trimming outliers from a data set without discussing your reasons in paper
• Using an inappropriate statistical technique in order to enhance the significance of your research
• Bypassing the peer review process and announcing your results through a press conference without giving peers adequate information to review your work
• Conducting a review of the literature that fails to acknowledge the contributions of other people in the field or relevant prior work
• Stretching the truth on a grant application in order to convince reviewers that your project will make a significant contribution to the field
• Stretching the truth on a job application or curriculum vita
• Giving the same research project to two graduate students in order to see who can do it the fastest
• Overworking, neglecting, or exploiting graduate or post-doctoral students
• Failing to keep good research records
• Failing to maintain research data for a reasonable period of time
• Making derogatory comments and personal attacks in your review of author's submission
• Promising a student a better grade for sexual favors
• Using a racist epithet in the laboratory
• Making significant deviations from the research protocol approved by your institution's Animal Care and Use Committee or Institutional Review Board for Human Subjects Research without telling the committee or the board
• Not reporting an adverse event in a human research experiment
• Wasting animals in research
• Exposing students and staff to biological risks in violation of your institution's biosafety rules
• Sabotaging someone's work
• Stealing supplies, books, or data
• Rigging an experiment so you know how it will turn out
• Making unauthorized copies of data, papers, or computer programs
• Owning over $10,000 in stock in a company that sponsors your research and not disclosing this financial interest
• Deliberately overestimating the clinical significance of a new drug in order to obtain economic benefits

These actions would be regarded as unethical by most scientists and some might even be illegal in some cases. Most of these would also violate different professional ethics codes or institutional policies. However, they do not fall into the narrow category of actions that the government classifies as research misconduct. Indeed, there has been considerable debate about the definition of "research misconduct" and many researchers and policy makers are not satisfied with the government's narrow definition that focuses on FFP. However, given the huge list of potential offenses that might fall into the category "other serious deviations," and the practical problems with defining and policing these other deviations, it is understandable why government officials have chosen to limit their focus.

Finally, situations frequently arise in research in which different people disagree about the proper course of action and there is no broad consensus about what should be done. In these situations, there may be good arguments on both sides of the issue and different ethical principles may conflict. These situations create difficult decisions for research known as ethical or moral dilemmas . Consider the following case:

Dr. Wexford is the principal investigator of a large, epidemiological study on the health of 10,000 agricultural workers. She has an impressive dataset that includes information on demographics, environmental exposures, diet, genetics, and various disease outcomes such as cancer, Parkinson’s disease (PD), and ALS. She has just published a paper on the relationship between pesticide exposure and PD in a prestigious journal. She is planning to publish many other papers from her dataset. She receives a request from another research team that wants access to her complete dataset. They are interested in examining the relationship between pesticide exposures and skin cancer. Dr. Wexford was planning to conduct a study on this topic.

Dr. Wexford faces a difficult choice. On the one hand, the ethical norm of openness obliges her to share data with the other research team. Her funding agency may also have rules that obligate her to share data. On the other hand, if she shares data with the other team, they may publish results that she was planning to publish, thus depriving her (and her team) of recognition and priority. It seems that there are good arguments on both sides of this issue and Dr. Wexford needs to take some time to think about what she should do. One possible option is to share data, provided that the investigators sign a data use agreement. The agreement could define allowable uses of the data, publication plans, authorship, etc. Another option would be to offer to collaborate with the researchers.

The following are some step that researchers, such as Dr. Wexford, can take to deal with ethical dilemmas in research:

What is the problem or issue?

It is always important to get a clear statement of the problem. In this case, the issue is whether to share information with the other research team.

What is the relevant information?

Many bad decisions are made as a result of poor information. To know what to do, Dr. Wexford needs to have more information concerning such matters as university or funding agency or journal policies that may apply to this situation, the team's intellectual property interests, the possibility of negotiating some kind of agreement with the other team, whether the other team also has some information it is willing to share, the impact of the potential publications, etc.

What are the different options?

People may fail to see different options due to a limited imagination, bias, ignorance, or fear. In this case, there may be other choices besides 'share' or 'don't share,' such as 'negotiate an agreement' or 'offer to collaborate with the researchers.'

How do ethical codes or policies as well as legal rules apply to these different options?

The university or funding agency may have policies on data management that apply to this case. Broader ethical rules, such as openness and respect for credit and intellectual property, may also apply to this case. Laws relating to intellectual property may be relevant.

Are there any people who can offer ethical advice?

It may be useful to seek advice from a colleague, a senior researcher, your department chair, an ethics or compliance officer, or anyone else you can trust. In the case, Dr. Wexford might want to talk to her supervisor and research team before making a decision.

After considering these questions, a person facing an ethical dilemma may decide to ask more questions, gather more information, explore different options, or consider other ethical rules. However, at some point he or she will have to make a decision and then take action. Ideally, a person who makes a decision in an ethical dilemma should be able to justify his or her decision to himself or herself, as well as colleagues, administrators, and other people who might be affected by the decision. He or she should be able to articulate reasons for his or her conduct and should consider the following questions in order to explain how he or she arrived at his or her decision:

• Which choice will probably have the best overall consequences for science and society?
• Which choice could stand up to further publicity and scrutiny?
• Which choice could you not live with?
• Think of the wisest person you know. What would he or she do in this situation?
• Which choice would be the most just, fair, or responsible?

After considering all of these questions, one still might find it difficult to decide what to do. If this is the case, then it may be appropriate to consider others ways of making the decision, such as going with a gut feeling or intuition, seeking guidance through prayer or meditation, or even flipping a coin. Endorsing these methods in this context need not imply that ethical decisions are irrational, however. The main point is that human reasoning plays a pivotal role in ethical decision-making but there are limits to its ability to solve all ethical dilemmas in a finite amount of time.

Promoting Ethical Conduct in Science

Do U.S. research institutions meet or exceed federal mandates for instruction in responsible conduct of research? A national survey

 Read about U.S. research instutuins follow federal manadates for ethics in research 

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Most academic institutions in the US require undergraduate, graduate, or postgraduate students to have some education in the responsible conduct of research (RCR) . The NIH and NSF have both mandated training in research ethics for students and trainees. Many academic institutions outside of the US have also developed educational curricula in research ethics

Those of you who are taking or have taken courses in research ethics may be wondering why you are required to have education in research ethics. You may believe that you are highly ethical and know the difference between right and wrong. You would never fabricate or falsify data or plagiarize. Indeed, you also may believe that most of your colleagues are highly ethical and that there is no ethics problem in research..

If you feel this way, relax. No one is accusing you of acting unethically. Indeed, the evidence produced so far shows that misconduct is a very rare occurrence in research, although there is considerable variation among various estimates. The rate of misconduct has been estimated to be as low as 0.01% of researchers per year (based on confirmed cases of misconduct in federally funded research) to as high as 1% of researchers per year (based on self-reports of misconduct on anonymous surveys). See Shamoo and Resnik (2015), cited above.

Clearly, it would be useful to have more data on this topic, but so far there is no evidence that science has become ethically corrupt, despite some highly publicized scandals. Even if misconduct is only a rare occurrence, it can still have a tremendous impact on science and society because it can compromise the integrity of research, erode the public’s trust in science, and waste time and resources. Will education in research ethics help reduce the rate of misconduct in science? It is too early to tell. The answer to this question depends, in part, on how one understands the causes of misconduct. There are two main theories about why researchers commit misconduct. According to the "bad apple" theory, most scientists are highly ethical. Only researchers who are morally corrupt, economically desperate, or psychologically disturbed commit misconduct. Moreover, only a fool would commit misconduct because science's peer review system and self-correcting mechanisms will eventually catch those who try to cheat the system. In any case, a course in research ethics will have little impact on "bad apples," one might argue.

According to the "stressful" or "imperfect" environment theory, misconduct occurs because various institutional pressures, incentives, and constraints encourage people to commit misconduct, such as pressures to publish or obtain grants or contracts, career ambitions, the pursuit of profit or fame, poor supervision of students and trainees, and poor oversight of researchers (see Shamoo and Resnik 2015). Moreover, defenders of the stressful environment theory point out that science's peer review system is far from perfect and that it is relatively easy to cheat the system. Erroneous or fraudulent research often enters the public record without being detected for years. Misconduct probably results from environmental and individual causes, i.e. when people who are morally weak, ignorant, or insensitive are placed in stressful or imperfect environments. In any case, a course in research ethics can be useful in helping to prevent deviations from norms even if it does not prevent misconduct. Education in research ethics is can help people get a better understanding of ethical standards, policies, and issues and improve ethical judgment and decision making. Many of the deviations that occur in research may occur because researchers simply do not know or have never thought seriously about some of the ethical norms of research. For example, some unethical authorship practices probably reflect traditions and practices that have not been questioned seriously until recently. If the director of a lab is named as an author on every paper that comes from his lab, even if he does not make a significant contribution, what could be wrong with that? That's just the way it's done, one might argue. Another example where there may be some ignorance or mistaken traditions is conflicts of interest in research. A researcher may think that a "normal" or "traditional" financial relationship, such as accepting stock or a consulting fee from a drug company that sponsors her research, raises no serious ethical issues. Or perhaps a university administrator sees no ethical problem in taking a large gift with strings attached from a pharmaceutical company. Maybe a physician thinks that it is perfectly appropriate to receive a $300 finder’s fee for referring patients into a clinical trial.

If "deviations" from ethical conduct occur in research as a result of ignorance or a failure to reflect critically on problematic traditions, then a course in research ethics may help reduce the rate of serious deviations by improving the researcher's understanding of ethics and by sensitizing him or her to the issues.

Finally, education in research ethics should be able to help researchers grapple with the ethical dilemmas they are likely to encounter by introducing them to important concepts, tools, principles, and methods that can be useful in resolving these dilemmas. Scientists must deal with a number of different controversial topics, such as human embryonic stem cell research, cloning, genetic engineering, and research involving animal or human subjects, which require ethical reflection and deliberation.

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StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

StatPearls [Internet].

Research ethics.

Jennifer M. Barrow ; Grace D. Brannan ; Paras B. Khandhar .

Affiliations

Last Update: September 18, 2022 .

• Introduction

Multiple examples of unethical research studies conducted in the past throughout the world have cast a significant historical shadow on research involving human subjects. Examples include the Tuskegee Syphilis Study from 1932 to 1972, Nazi medical experimentation in the 1930s and 1940s, and research conducted at the Willowbrook State School in the 1950s and 1960s. [1]  As the aftermath of these practices, wherein uninformed and unaware patients were exposed to disease or subject to other unproven treatments, became known, the need for rules governing the design and implementation of human-subject research protocols became very evident.

The first such ethical code for research was the Nuremberg Code, arising in the aftermath of Nazi research atrocities brought to light in the post-World War II Nuremberg Trials. [1]  This set of international research standards sought to prevent gross research misconduct and abuse of vulnerable and unwitting research subjects by establishing specific human subject protective factors. A direct descendant of this code was drafted in 1978 in the United States, known as the Belmont Report, and this legislation forms the backbone of regulation of clinical research in the USA since its adoption. [2]  The Belmont Report contains 3 basic ethical principles:

• Respect for persons
• Beneficence

Additionally, the Belmont Report details research-based protective applications for informed consent, risk/benefit assessment, and participant selection. [3]

• Issues of Concern

The first protective principle stemming from the 1978 Belmont Report is the principle of Respect for Persons, also known as human dignity. [2]  This dictates researchers must work to protect research participants' autonomy while also ensuring full disclosure of factors surrounding the study, including potential harms and benefits. According to the Belmont Report, "an autonomous person is an individual capable of deliberation about personal goals and acting under the direction of such deliberation."  [1]

To ensure participants have the autonomous right to self-determination, researchers must ensure that potential participants understand that they have the right to decide whether or not to participate in research studies voluntarily and that declining to participate in any research does not affect in any way their access to current or subsequent care. Also, self-determined participants must be able to ask the researcher questions and comprehend the questions asked by the researcher. Researchers must also inform participants that they may stop participating in the study without fear of penalty. [4]  As noted in the Belmont Report definition above, not all individuals can be autonomous concerning research participation. Whether because of the individual's developmental level or because of various illnesses or disabilities, some individuals require special research protections that may involve exclusion from research activities that can cause potential harm or appointing a third-party guardian to oversee the participation of such vulnerable persons. [5]

Researchers must also ensure they do not coerce potential participants into agreeing to participate in studies. Coercion refers to threats of penalty, whether implied or explicit, if participants decline to participate or opt out of a study. Additionally, giving potential participants extreme rewards for agreeing to participate can be a form of coercion. The rewards may provide an enticing enough incentive that the participant feels they need to participate. In contrast, they would otherwise have declined if such a reward were not offered. While researchers often use various rewards and incentives in studies, they must carefully review this possibility of coercion. Some incentives may pressure potential participants into joining a study, thereby stripping participants of complete self-determination. [3]

An additional aspect of respecting potential participants' self-determination is to ensure that researchers have fully disclosed information about the study and explained the voluntary nature of participation (including the right to refuse without repercussion) and possible benefits and risks related to study participation. A potential participant cannot make a truly informed decision without complete information. This aspect of the Belmont Report can be troublesome for some researchers based on their study designs and research questions. Noted biases related to reactivity may occur when study participants know the exact guiding research questions and purposes. Some researchers may avoid reactivity biases using covert data collection methods or masking critical study information. Masking frequently occurs in pharmaceutical trials with placebos because knowledge of placebo receipt can affect study outcomes. However, masking and concealed data collection methods may not fully respect participants' rights to autonomy and the associated informed consent process. Any researcher considering hidden data collection or masking of some research information from participants must present their plans to an Institutional Review Board (IRB) for oversight, as well as explain the potential masking to prospective patients in the consent process (ie, explaining to potential participants in a medication trial that they are randomly assigned either the medication or a placebo). The IRB determines if studies warrant concealed data collection or masking methods in light of the research design, methods, and study-specific protections. [6]

The second Belmont Report principle is the principle of beneficence. Beneficence refers to acting in such a way to benefit others while promoting their welfare and safety. [7]  Although not explicitly mentioned by name, the biomedical ethical principle of nonmaleficence (not harm) also appears within the Belmont Report's section on beneficence. The beneficence principle includes 2 specific research aspects:

• Participants' right to freedom from harm and discomfort
• Participants' rights to protection from exploitation  [8]

Before seeking IRB approval and conducting a study, researchers must analyze potential risks and benefits to research participants. Examples of possible participant risks include physical harm, loss of privacy, unforeseen side effects, emotional distress or embarrassment, monetary costs, physical discomfort, and loss of time. Possible benefits include access to a potentially valuable intervention, increased understanding of a medical condition, and satisfaction with helping others with similar issues. [8]  These potential risks and benefits should explicitly appear in the written informed consent document used in the study. Researchers must implement specific protections to minimize discomfort and harm to align with the principle of beneficence. Under the principle of beneficence, researchers must also protect participants from exploitation. Any information provided by participants through their study involvement must be protected.

The final principle contained in the Belmont Report is the principle of justice, which pertains to participants' right to fair treatment and right to privacy. The selection of the types of participants desired for a research study should be guided by research questions and requirements not to exclude any group and to be as representative of the overall target population as possible. Researchers and IRBs must scrutinize the selection of research participants to determine whether researchers are systematically selecting some groups (eg, participants receiving public financial assistance, specific ethnic and racial minorities, or institutionalized) because of their vulnerability or ease of access. The right to fair treatment also relates to researchers treating those who refuse to participate in a study fairly without prejudice. [3]

The right to privacy also falls under the Belmont Report's principle of justice. Researchers must keep any shared information in their strictest confidence. Upholding the right to privacy often involves procedures for anonymity or confidentiality. For participants' data to be completely anonymous, the researcher cannot have the ability to connect the participants to their data. The study is no longer anonymous if researchers can make participant-data connections, even if they use codes or pseudonyms instead of personal identifiers. Instead, researchers are providing participant confidentiality. Various methods can help researchers assure confidentiality, including locking any participant identifying data and substituting code numbers instead of names, with a correlation key available only to a safety or oversight functionary in an emergency but not readily available to researchers. [3]

• Clinical Significance

One of the most common safeguards for the ethical conduct of research involves using external reviewers, such as an Institutional Review Board (IRB). Researchers seeking to begin a study must submit a full research proposal to the IRB, which includes specific data collection instruments, research advertisements, and informed consent documentation. The IRB may perform a complete or expedited review depending on the nature of the study and the risks involved. Researchers cannot contact potential participants or start collecting data until they obtain full IRB approval. Sometimes, multi-site studies require approvals from several IRBs, which may have different forms and review processes. [3]

A significant study aspect of interest to IRB members is using participants from vulnerable groups. Vulnerable groups may include individuals who cannot give fully informed consent or those individuals who may be at elevated risk of unplanned side effects. Examples of vulnerable participants include pregnant women, children younger than the age of consent, terminally ill individuals, institutionalized individuals, and those with mental or emotional disabilities. In the case of minors, assent is also an element that must be addressed per Subpart D of the Code of Federal Regulations, 45 CFR 46.402, which defines consent as "a child's affirmative agreement to participate in research; mere failure to object should not, absent affirmative agreement, be construed as assent."  [9] There is a lack in the literature on when minors can understand research, although current research suggests that the age by which a minor could assent is around 14. [10]  Anytime researchers include vulnerable groups in their studies, they must have extra safeguards to uphold the Belmont Report's ethical principles, especially beneficence. [3]

• Enhancing Healthcare Team Outcomes

Research ethics is a foundational principle of modern medical research across all disciplines. The overarching body, the IRB, is intentionally comprised of experts across various disciplines, including ethicists, social workers, physicians, nurses, other scientific researchers, counselors, mental health professionals, and advocates for vulnerable subjects. There is also often a legal expert on the panel or available to discuss any questions regarding the legality or ramifications of studies.

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Disclosure: Jennifer Barrow declares no relevant financial relationships with ineligible companies.

Disclosure: Grace Brannan declares no relevant financial relationships with ineligible companies.

Disclosure: Paras Khandhar declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

• Cite this Page Barrow JM, Brannan GD, Khandhar PB. Research Ethics. [Updated 2022 Sep 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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• Volume 42, Issue 4
• Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees
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This article has a correction. Please see:

• Correction - July 01, 2016

• Rebecca H Li 1 ,
• Mary C Wacholtz 2 ,
• Mark Barnes 1 , 3 ,
• Liam Boggs 4 ,
• Susan Callery-D'Amico 5 ,
• Amy Davis 6 ,
• Alla Digilova 10 ,
• David Forster 7 ,
• Kate Heffernan 8 ,
• Maeve Luthin 8 ,
• Holly Fernandez Lynch 9 ,
• Lindsay McNair 6 ,
• Jennifer E Miller 11 ,
• Jacquelyn Murphy 12 ,
• Luann Van Campen 13 ,
• Mark Wilenzick 14 ,
• Delia Wolf 15 ,
• Cris Woolston 16 ,
• Carmen Aldinger 1 ,
• Barbara E Bierer 17
• 1 Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard , Boston, Massachusetts , USA
• 2 Janssen R&D , Johnson & Johnson , Raritan, New Jersey , USA
• 3 Ropes & Gray LLP , Boston, Massachusetts , USA
• 4 The Global Health Network/Oxford University , Oxford , UK
• 5 Quality Assurance , AbbVie , Chicago, Illinois , USA
• 6 WCG (WIRB- Copernicus Group) , Olympia, Washington , USA
• 7 Health Care Group , Verrill Dana LLP , Boston, Massachusetts , USA
• 8 Public Responsibility in Medicine and Research , Boston, Massachusetts , USA
• 9 Petrie-Flom Center, Harvard Law School , Cambridge, Massachusetts , USA
• 10 Morgan Lewis , New York, NY , USA
• 11 NYU Langone Medical Center , New York, New York , USA
• 12 Colorado School of Public Health Anschutz Medical Campus Aurora , CO
• 13 Eli Lilly and Company , Indianapolis, Indiana , USA
• 14 International AIDS Vaccine Initiative , New York, New York , USA
• 15 Harvard School of Public Health , Boston, Massachusetts , USA
• 16 Sanofi , New York, New York , USA
• 17 Multi-Regional Clinical Trials Center, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts , USA
• Correspondence to Dr Rebecca Li, Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard, 14 Story Street, 4th Floor, Cambridge, MA 02138, USA; RLi{at}bwh.harvard.edu

A novel Protocol Ethics Tool Kit (‘Ethics Tool Kit’) has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency and transparency between clinical trial protocols and research ethics committee reviews. It may also streamline ethics review and may facilitate and expedite the review process by anticipating the concerns of ethics committee reviewers. Specific attention was given to issues arising in multinational settings. With the use of this Tool Kit, researchers have the opportunity to address critical research ethics issues proactively, potentially speeding the time and easing the process to final protocol approval.

• Clinical Ethics
• Clinical trials
• Ethics Committees/Consultation

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/medethics-2014-102540

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The principal goal of clinical research, even when benefiting individual trial participants, is to advance ‘generalisable knowledge’ to help future patients. While that goal is laudatory, clinical research is fraught with ethical challenges including those that occur when research is conducted across multiple trial sites, in different countries or regions, in low-resource settings, in developing countries and with different, sometimes vulnerable, populations. The written clinical trial protocol is the appropriate instrument to illuminate, acknowledge and address ethical challenges specific to each individual study. However, writers of clinical trial protocols—members of the clinical research team in either industry, non-profit or academic settings—may not have access to satisfactory single-source guidance to identify and address relevant ethical issues. The lack of guidance results in clinical trial protocols that either are silent on the ethical issues and choices made or include non-specific language about compliance with ethical principles without explicitly delineating such principles or challenges. In the absence of explicit description or discussion of ethical questions and choices, ethics committees (institutional review boards (IRBs) and research ethics committees (RECs), depending on the region) must identify the ethical issues implicit in the clinical trial protocol, infer how protocol writers addressed concerns and may assume—without seeing evidence to the contrary—that ethical issues were not considered and appropriately managed. The lack of explicit description of, approach to and mitigation of ethical issues in a clinical trial protocol can result in time-consuming delay, as ethics committees pose questions that the writers must then answer in a later resubmission. Of even greater importance, not anticipating and planning for important ethical issues may potentially lead to problems in the trial itself.

To provide guidance and to raise the overall quality of clinical trial protocols, the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard (MRCT Center) i undertook the initial development of a Protocol Ethics Tool Kit (‘Ethics Tool Kit’), accompanied by a guidance document with points to consider (available in fillable Microsoft Word format at http://mrctcenter.org/resources/2014–11-14-training-material-mrct-ethics-essential-elements-and-points-to-consider-reference-document-toolkit/ ). The intent of these resources is to help protocol writers recognise and address common ethical challenges in clinical trials, with specific attention to issues that arise in multinational settings. The Ethics Tool Kit is also intended to help ethics committees review and analyse clinical trial protocols in a more efficient, explicit and comprehensive manner.

Clinical trial protocols are central to the conduct of clinical trials and facilitate evaluation and review by key stakeholders, including regulators and ethics committees. 1 Despite the importance of sound, well-written and ethical clinical trial protocols, existing guidelines for protocol writers have had limitations such as insufficient stakeholder involvement, lack of systematic development and weak empirical support. 2 Two relatively recent documents provide a structure and define needed components of a clinical trial protocol, although neither focused specifically on the ethical issues raised by a planned study. The CONSORT (Consolidated Standards of Reporting Trials) Statement, updated in 2010, presents systematic evidence-based guidance for organising final study reports based on a checklist, and this can be used to inform protocol writing. 3 CONSORT's checklist highlights 3 of the 11 elements contained in our Ethics Tool Kit, specifically the importance of proper study design, the choice of study population and the criticality of addressing potential harms. Similarly, the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement, generated by an international group of stakeholders, recommends minimum standards for inclusion in clinical trial protocols. 1 SPIRIT includes two topics that might particularly require ethical consideration: the importance of informed consent and trial design, which are both included and broadened in our Ethics Tool Kit. Neither CONSORT nor SPIRIT comprehensively and directly addressed ethical issues in clinical trial protocols. The Ethics Tool Kit complements and expands these two prior documents by offering more focused guidance for identifying and treating ethical issues in clinical trial protocols.

The development of the MRCT Center Ethics Tool Kit involved (1) formation of a working group, (2) literature review and (3) review of a sample of 100 approved clinical trial protocols. Following these initial steps, the multi-stakeholder working group aggregated, aligned and reviewed focused ethical questions that were then formatted as (4) an Ethics Tool Kit and accompanying guidance document to allow dynamic usage by protocol writers and ethics committees alike.

Formation of a working group

A group of 20 experts from academic institutions (6), pharmaceutical companies (4), non-profit organisations (4), law firms (3) and ethics committees (3), with backgrounds in clinical trials, medicine, bioethics and law was formed by the MRCT Center in 2012 to create a list of ethical elements that should be addressed when writing and/or reviewing a clinical trial protocol. Each member introduced potential ethical elements by drawing upon the research ethics literature and existing sponsor protocol templates, areas identified as confusing by ethics committees and domestic and international guidelines. 4–8 Initially, all recommendations from all 20 members were compiled. The ethics elements were then discussed, challenged and categorised to appropriately group similar elements and reduce redundancy. ii The working group met a total of 24 times over a period of approximately 18 months by teleconference. One in-person meeting was also held to reach consensus on issues that could not be reconciled earlier. The ‘Essential Elements’ that comprise the basis of the Ethics Tool Kit were then compiled, annotated, reviewed and refined.

Literature review

PubMed was searched to identify articles in English published from January 1995 to April 2015 that included recommendations for a list of essential ethical issues to consider when reviewing and/or drafting a clinical trial protocol. Search terms included: (1) (‘clinical trial’ [publication type] OR ‘clinical trials as topic’ [MeSH Terms] OR ‘clinical trials’ [All Fields]) AND (‘ethics’ [Subheading] OR ‘ethics’ [All Fields] OR ‘ethics’ [MeSH Terms]) NOT ‘clinical trial’ [Publication Type] and (2) clinical trials as topic {MeSH Terms] AND protocol AND ethics NOT ‘clinical trial’ [Publication Type].

Clinical trial protocol review

The working group undertook a descriptive review of a sample of 100 clinical trial protocols to determine if the Essential Elements drafted through consensus were present in current approved clinical trial protocols and, if they were, whether they were discussed directly from an ethical perspective. To minimise bias in the choice of clinical trial protocols to be evaluated and the review process, the review was conducted using a set of predefined guidelines. Protocols were selected based on the following criteria:

Protocols that had been reviewed and approved by ethics committees

Multi-site trials with at least one site outside of the USA

Interventional trials, including medical, social/behavioural and devices

Trials involving greater than minimal risk, as defined by US research regulations 9

Selection was retrospective and consecutive from the start date, 30 June 2013, proceeding back in time until 100 clinical trial protocols matching the selection criteria were identified. Prior to selection, no protocol was reviewed for content (other than for the selection criteria listed above). Informed consent forms were also reviewed when available, as some of the Essential Elements might be addressed in the informed consent form instead of the protocol. Two authors reviewed each protocol; if there were disagreement on the assessment, a third author arbitrated. However, little disagreement between the two primary reviewers actually occurred; the kappa statistic, which measures inter-rater agreement, was 0.96.

Recommendations of the working group

Although the assembled working group members had extensive involvement with various aspects of study design and protocol assessment, in their experience, clear and specific discussion of primary ethical issues in clinical trial protocols was unusual. This working group recommended that a dedicated ethics section be included in every protocol. Inclusion of such a section would (1) help clinical research teams proactively consider and articulate ethical considerations associated with their protocol and, as a result (2) improve the dialogue between ethics committees and clinical research teams and among clinical research team members themselves. No working group members were aware of a similar prior suggestion or exposition of how such a section should be structured.

Based on their collective expertise, and informed by the literature and protocol reviews, the MRCT Center work group identified 11 items (called Essential Elements; also see table 1 ) that should be considered for discussion in a dedicated ethics section within a clinical research protocol.

Addressing Relevant Question

Choice of Control and Standard of Care

Choice of Study Design

Choice of Subject Population

Potential Benefits and Harms

Informed Consent

Community Engagement

Return of Research Results and Incidental Findings

Post-Trial Access

Payment for Participation

Study Related Injury.

• View inline

Essential Elements and survey results (sample size=100 protocols)

Using the search criteria listed above, the literature review found only one relevant scholarly article that provided guidance for drafting and/or reviewing the ethical elements of a clinical trial protocol. The study was published in the psychiatry literature more than 15 years ago, and referenced the Research Protocol Ethics Assessment Tool (RePEAT), a 24-item checklist that contained some of the items identified in our work. 4 , 10 Thus, we found little available guidance in a single organised format to guide which items should be considered for discussion in a protocol and how these considerations might be organised in a dedicated ethical section.

A total of 100 clinical trial protocols were reviewed to determine if the 11 Essential Elements the working group drafted were present in the current approved clinical trial protocols and, if they were, whether they were discussed explicitly from an ethical perspective . A total of 40 clinical trial protocols were identified from publicly available published trials in the New England Journal of Medicin e, 40 had been approved by independent central IRBs and were available to one of the working group members and 20 had been approved by academic IRBs and were available to one of the working group members. Of the 100 clinical trial protocols reviewed, 57 were funded by industry, 32 by governments, 3 by academic institutions, 3 by different combinations of the above categories and 5 were of indeterminate funding source.

As summarised in table 1 , our list of 11 Essential Elements was variably addressed in these 100 clinical trial protocols. For example, while the first element, ‘Addressing Relevant Question’, was almost always included in a clinical trial protocol (96%), other Essential Elements were mentioned much less frequently. It is not surprising that some Essential Elements such as Community Engagement or Post-Trial Access, for example, were mentioned in only 9% and 22% of protocols, respectively. Community Engagement and Post-Trial Access may not be relevant to some protocols, and the latter is, admittedly, an emerging issue. 11 However, evidence of the thinking around Potential Benefits and Harms was not addressed in 24% of protocols, and Challenges in Informed Consent was not found in 44%. Other Essential Elements that might be expected to be important for almost all protocols (Elements 2, 3, 4, 6, 9, 11) were mentioned in 39%–59% of protocols. This variability may not be surprising as no regulation presently requires explicit discussion of ethical issues in written clinical trial protocols or informed consent forms. Absent regulatory requirements, study sponsors and funders may not dedicate resources to document the background thought processes in protocols.

The significance of these findings should not be overinterpreted. The lack of documentation of ethical considerations does not mean that the study was unethical, only that the thinking behind the choices made (eg, in study design, in study population choice, etc.) was not explicit. In addition, it does not imply that the ethics committee did not consider the ethical issues; the ethics committee meeting minutes were not reviewed nor were the exchanges, written or otherwise, between the ethics committee and the principal investigators. Further, the review itself of the 100 sampled protocols had limitations including the small sample size, the admittedly non-representative nature of the protocols that were available and the use of non-validated review criteria. Some clinical trial protocols were analysed by representative(s) of organisations from which the protocols were obtained. This was necessary to protect confidentiality but may have introduced bias into the assessment process. In addition, no regulation presently requires explicit discussion of ethical issues in written clinical trial protocols or informed consent forms. Nonetheless, these findings suggest that critical ethical issues typically of serious concern to ethics committees are often not addressed explicitly in submitted clinical trial protocols.

The Protocol Ethics Tool Kit: a tool to recognise and address ethical issues

To ensure and reinforce adequate exposition of ethical issues within clinical trial protocols and to ease the burden of distilling and including this information, the MRCT Center working group developed the Protocol Ethics Tool Kit incorporating the Essential Elements. The Ethics Tool Kit was developed to (1) provide protocol writers and study teams with a tool to recognise and address common clinical trial ethical issues and (2) to ensure that ethics committees are able to evaluate clinical trial protocols comprehensively and efficiently. The Ethics Tool Kit is not intended to prescribe requirements, to limit ethical considerations or to impose mandates on how ethical issues must be addressed in a trial protocol. Rather, the Ethics Tool Kit is intended to guide thought and discussion and to ensure that ethical concerns specific to a clinical study are, at a minimum, considered in protocol development and made explicit in the protocol itself.

The Ethics Tool Kit is structured in such a way that it can be adapted to meet an individual user's needs and address specific challenges. Each Essential Element has (1) a short explanation, (2) specific points to consider, (3) background information, (4) practical examples and (5) references. Table 2 provides a brief description of the components of the Ethics Tool Kit and to whom they could be relevant. An online supplementary table S4 presents the short explanation and specific points to consider for each Essential Element. 12–23 The Ethics Tool Kit in its entirety can be accessed at http://mrctcenter.org/resources/2014-11-14-training-material-mrct-ethics-essential-elements-and-points-to-consider-reference-document-toolkit/ .

Components of the MRCT Center's Protocol Ethics Tool Kit

Use of the Ethics Tool Kit may surface ethical issues that would be otherwise unexplored and also encourage rational, clearly articulated responses. For example, see table 3 on Essential Element 8: Return of Research Results and Incidental Findings.

Ethics Tool Kit in action—Essential Element 8: Return of Research Results and Management of Incidental Findings

The Ethics Tool Kit is not intended to serve as an exhaustive list of ethical issues that can occur in clinical research, and not every Essential Element is necessarily relevant to every protocol. However, it is recommended that protocol authors consider all Essential Elements, address those that are pertinent for the particular clinical trial and supplement as needed. Authors may choose to discuss ethics throughout the protocol, but the working group sees value in the practice of detailing ethics approaches in a dedicated ‘Ethics Section’ of the protocol.

Computer-based training of the Ethics Tool Kit

In February 2014, in an effort to disseminate the working group's efforts more widely to researchers in low-income and middle-income countries, the MRCT Center collaborated with colleagues at the Global Health Network at Oxford University, Oxford, England and adapted the Ethics Tool Kit for an innovative digital platform ( https://globalhealthtrainingcentre.tghn.org/essential-elements-ethics/ .) The Essential Elements were first reviewed by our collaborators and then tailored to the electronic format; meaningful visual components were added and assessments at the end of each module were integrated to gauge understanding. A total of 11 course modules corresponding to the 11 Essential Elements have been freely available online through the Global Health Training Centre since 2 December 2014. The uptake of the course has been higher than expected. As of 22 June 2015, the total number of modules taken was 3536 by 1024 users globally. The most commonly accessed modules were (1) Addressing the Relevant Question, (2) Choice of Control and Standard of Care, (4) Choice of Participant Population and (8) Return of Research Results/Incidental Findings. The e-learning course modules were reviewed for content and user-friendliness by the intended end users (investigators in low-income and middle-income countries) and by the leadership of the Global Health Network prior to public release. Furthermore, the Global Health Training Centre e-learning courses are formally recognised for quality and content iii by the Liverpool School of Tropical Medicine ( http://www.lstmed.ac.uk/ ), the Bill and Melinda Gates Foundation ( http://www.gatesfoundation.org/ ) and the Worldwide Antimalarial Resistance Network ( http://www.wwarn.org/ ).

The Ethics Tool Kit has potential uses for individual protocol writers and study teams, study sponsors and ethics committees. For individual protocol writers and study teams, it provides a systematic and methodical approach to address the ethical implications of a planned clinical trial. This will assist protocol writers by alerting them to the important ethical issues in study design, enrolment and conduct of clinical trials, and will encourage articulation of appropriate ethical justification. The framework may be particularly valuable to those with less experience drafting clinical trial protocols. The guidance also may be used beyond the protocol, as it can prompt consideration of context-specific difficulties, pertinent policies and local regulatory requirements. For example, the Ethics Tool Kit may alert investigators in low-resource regions to consider challenges in assessing competencies of local sites, differing local medical standards and potential risks of exploitation of local and/or vulnerable populations.

For study sponsors and funders, the Ethics Tool Kit may be useful for documenting the nature of questions that were considered in protocol design and the analytical approach that formed the basis of the final design. Further, the Ethics Tool Kit may provide sponsors and study teams important insights into the research review process by delineating what research ethics committees are assessing when reviewing studies.

For ethics review committees, the review may be streamlined significantly by altering the protocol model to one in which the ethical reasoning is included in the original submission to the ethics committee. Without an explicit ethics discussion, an ethics committee is left to discern the ethical reasoning behind protocol decisions. When questions arise, the ethics committee engages the principal investigator in dialogue subsequent to the initial review and requests revisions or explanations that can result in significant delay to protocol approval. By altering the model to one in which the ethical reasoning is included in the original submission, dialogue between the sponsor/investigator and the ethics committee can be initiated upfront. The process would therefore become more efficient and ethics issues would be addressed proactively, directly and more completely.

There are limitations of the Ethics Tool Kit. There may be clinical trial questions that do not fit neatly into the framework we have developed, or the Ethics Tool Kit may be of limited utility when certain methodologies are used in clinical trials, particularly as those methodologies develop and change. For instance, adaptive clinical trials introduce the ethical dilemma of whether and when the investigator should disclose the results to date to prospective participants. If results are disclosed, later prospective participants may not wish to be randomised to what appears, with time, to be the inferior arm. Since this is an emerging issue and there is no international guidance on this dilemma, the working group did not address it in the Ethics Tool Kit.

The 11 Essential Elements are considered a starting point for protocol ethics discussion. Emerging concerns (eg, data transparency, publication policy, recruitment feasibility, innovative trial design) may result in future modifications. Feedback is being actively sought by the MRCT Center iv , so that the Ethics Tool Kit can continue to be refined and updated. Based on initial online use metrics, it appears that the Ethics Tool Kit is providing a needed educational resource for those seeking guidance on ethical protocol writing. An update is envisioned in 2017, and in early 2017, a survey will be deployed to uniformly collect user feedback on the value of the Ethics Tool Kit.

Substantive discussion of specific ethical issues is rarely included in clinical trial protocols.

A total of 11 ‘Essential Elements’ have been identified that should be considered and addressed as appropriate in a clinical trial protocol.

The Protocol Ethics Tool Kit has been developed to support protocol writers, study teams, sponsors, ethics committees and reviewers.

Use of this tool could result in more efficient development and review of clinical trial protocols and may result in wider appreciation of the ethical challenges in clinical research.

• Tetzlaff JM ,
• Gøtzsche PC , et al
• Kitchen J , et al
• ↵ CONSORT . The CONSORT statement . 2010 . http://www.consort-statement.org/consort-statement/overview0/
• Roberts LW ,
• Geppert CMA ,
• Emanuel EJ ,
• Wendler D ,
• ↵ World Medical Association . Declaration of Helsinki: ethical principles for medical research involving human subjects . JAMA 2013 ; 310 : 2191 – 4 . doi:10.1001/jama.2013.281053 OpenUrl CrossRef PubMed Web of Science
• ↵ National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research . The belmont report . Fed Regist 1979 ; 44 : 23192 – 7 . OpenUrl PubMed
• ↵ Council for International Organizations of Medical Sciences . International ethical guidelines for biomedical research involving human subjects, revised draft . Geneva : CIOMS , 2002 . http://www.cioms.ch/frame_guidelines_nov_2002.htm (accessed 2 Apr 2014 )
• ↵ Protection of Human Subjects, 45 C.F.R. § 46.102 . 2009 .
• Van der Graaf R ,
• van Delden JJM
• ↵ International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). Guidance for industry E6 good clinical practice: Consolidated guidance. Department of Health and Human Services . 1996 . See §4.8 .
• Goldsand G ,
• Zawati MH ,
• Knoppers BM
• ↵ Association of the British Pharmaceutical Industry (ABPI) . Clinical trial compensation guidelines . ABPI . 1994 .

Supplementary materials

Supplementary data.

This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

• Data supplement 1 - Online supplement

Contributors The paper originated from the work of a multi-stakeholder group convened by the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard (MRCT Center) to develop ethical principles for writers and reviewers of protocols for clinical trials that involve emerging economies. Participants in the working group were self-selected based on relevant expertise and were self-funded. The MRCT Center is supported by voluntary contributions from a variety of entities as well as grants (see http://mrctcenter.org/about-mrct/funding-and-support/ ). Each of the authors participated in convened meetings that formed the basis of the content, and contributed to writing one or more sections of the toolkit described in the article; each author reviewed a draft of and the final submitted manuscript. The manuscript itself was written and revised by the first two and last two authors listed. The guarantor is Barbara E. Bierer, MD Professor of Medicine, Harvard Medical School and Faculty Co-chair of the MRCT Center; she retains final responsibility for the content.

Competing interests None declared.

Provenance and peer review Not commissioned; externally peer reviewed.

↵ i The MRCT Center was founded in 2009 to improve the design, conduct and oversight of multi-regional clinical trials, focusing on trials conducted in emerging economies and the developing world. The MRCT Center seeks to establish common, explicit, feasible and ethical standards for conduct of transnational clinical research ( http://www.mrctcenter.org ).

↵ ii Nevertheless, not all elements are truly ‘unique’ and many are overlapping. For instance, a number of elements impact ‘risk/benefit’ even though risk/benefit is called out as a separate element.

↵ iii https://globalhealthtrainingcentre.tghn.org/elearning/other-resources/

↵ iv An online feedback discussion forum is available at https://bioethicsresearchreview.tghn.org/community/groups/group/essential_elements/ that captures comments in real time.

Linked Articles

• Correction Correction BMJ Publishing Group Ltd and Institute of Medical Ethics Journal of Medical Ethics 2016; 42 449-449 Published Online First: 11 Apr 2016. doi: 10.1136/medethics-2014-102540corr1

Read the full text or download the PDF:

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University research ethics approval

Approval process and documents.

All research projects at the University are required to secure ethical approval before they are allowed to proceed.

Before you start your application

Before starting to fill in the application form, there are a few preliminary steps that will help you prepare a quality application. You will not be expected to provide proof of these in your EthOS application but completing them will greatly help you in correctly planning your research. Some of the links provided in this section will only be accessible to staff members, and Supervisors are advised to provide support for any students who might need to access them. 

• Make sure you have completed the necessary training. All research active staff and PGR students are asked to complete our Research Integrity Training module and text, which you can find on your Moodle account. You might also be asked to complete Data Protection or Health & Safety training – more info on these can be found on the Intranet pages for  Legal and Health & Safety
• Although the concept of “data” might be significantly different for you depending on your academic discipline, all research projects should have a plan for handling their data. You can find information and help for building a Data Management Plan (DMP) on our Library’s website
• If your project involves any type of personal data that can identify a living individual, you are expected to complete a Data Privacy Impact Assessment (DPIA) Process. Details and help can be found here .

If your project involves any type of increased need for IT security you are expected to complete an Information Security Project form. More info and help with this can be found here .

Where to apply

Ethical applications at Manchester Met are submitted and processed via EthOS. Use your standard university credentials to log in (ID number and password).

Access EthOS and find guidance here .

Documents you may be required to upload to your EthOS application

Protocol Template for Non-Medical Research ‌ A research protocol is the document that outlines the full details of the research plan for a project, something that the EthOS application form can never fully contain. The protocol is the researcher’s main tool in delivering good project management and demonstrating research integrity. It is also the document against which your research will be insured, monitored and audited by the University and other relevant regulatory authorities.  As always in research governance, deviation from protocol requires amendment of ethics approval, which can be applied for at any time during the project.

Participant Information Sheet Template The information sheet is an important part of recruiting research participants. It ensures that the potential participants have sufficient information to make an informed decision about whether to take part in your research or not.

Consent Form Template Clear evidence must be obtained that the participant has given informed consent to take part in the study. The University expects that this will normally be in the form of a signed consent form although other evidence of clear affirmative action will be accepted if approved under review.

MMU Insurance Checklist  Insurance questions are integrated into the EthOS form and the majority of users will not need to use this form or upload it to their application. However, there might be occasions when your reviewers ask you to provide a separate insurance checklist for your research – you should do so by using this template.

Health and Safety Risk Assessment  Depending on the type of research proposed, some applicants might be asked by reviewers to upload a Risk Assessment to their EthOS application. Staff members can find templates and user guides for the Risk Assessment Form on the Health and Safety Intranet page . Students will not be able to access these.

Other helpful resources

Guide for the Ethical Approval of Taught Unit Applications

Prevent Duty in Research

Procedure for Reviewing External Requests for Access to Staff and Students

Guidance Note on Withdrawal from Research

Covid-19 Ethics Guidance

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NeurIPS has asked authors to consider ethics and broader impact when submitting their papers since 2021, and adopted a Code of Ethics in April 2023 . Ethics reviews are a second round of review that take place should the program committee flag any potential concerns during the technical review phase. Ethics reviewers provide feedback to the program committee regarding risks and harms of the work, and recommend potential mitigations prior to acceptance. To minimize exposure risks, ethics reviews are only published at the author’s discretion; unlike the main reviews, which are all public. Please refer below and to the Ethics Review Guidelines for further details.

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You become involved when a paper is flagged for ethics review. This primarily occurs during the initial review process, though some cases may arise later during the discussion period or during reviews by AC and PC chairs.

What is an Ethics Review?

The ethics review differs from the primary review in several ways. Ethics review is limited in scope to evaluating the possibility of ethical risks, specifically those flagged by the primary reviewers. When the primary review flags a paper, it indicates a claim that an ethical concern exists. Your role as an ethics reviewer is to validate or disprove this claim, focusing on the evaluation of the claim and providing a critical discussion supporting your evaluation. For example, if a paper is flagged for potential ethical concerns around safety and security (e.g., misuse of autonomous weapons, misinformation, deepfakes, etc.), you will comment on the validity of these risks and whether the authors have done enough to mitigate them. Note that it is perfectly acceptable to conclude that no ethical concern exists , and we expect this to be true for some of the papers assigned to you. You are also encouraged to recommend reasonable risk mitigation strategies wherever appropriate.

To summarize, the following key aspects are typically addressed in an ethics review:

• Are the flagged ethical concerns valid?
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Write thoughtful and constructive reviews. Ensure your reviews align with the NeurIPS code of conduct. Although the double-blind review process helps reduce discrimination, subtle discrimination can still occur and should be actively avoided.

Example: Instead of saying, "Please have your submission proof-read by a native English speaker,” use a neutral formulation such as "Please have your submission proof-read for English style and grammar issues.”

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If you would like the authors to clarify something during the author response phase, articulate this clearly in your review (e.g., “I would like to see a discussion on risk X”).

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• Study Protocol
• Open access
• Published: 02 August 2024

Understanding the impact of distance and disadvantage on lung cancer care and outcomes: a study protocol

• Daisy McInnerney 1 ,
• Samantha L. Quaife 1 ,
• Samuel Cooke 2 ,
• Lucy Mitchinson 1 ,
• Zara Pogson 3 ,
• William Ricketts 4 ,
• Adam Januszewski 4 ,
• Anna Lerner 4 ,
• Dawn Skinner 5 ,
• Sarah Civello 3 ,
• Ros Kane 6 ,
• Ava Harding-Bell 7 ,
• Lynn Calman 8 ,
• Peter Selby 9 , 10 ,
• Michael D. Peake 11 , 12 &
• David Nelson 2 , 13  

BMC Cancer volume  24 , Article number:  942 ( 2024 ) Cite this article

192 Accesses

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Lung cancer is the third most common cancer in the UK and the leading cause of cancer mortality globally. NHS England guidance for optimum lung cancer care recommends management and treatment by a specialist team, with experts concentrated in one place, providing access to specialised diagnostic and treatment facilities. However, the complex and rapidly evolving diagnostic and treatment pathways for lung cancer, together with workforce limitations, make achieving this challenging. This place-based, behavioural science-informed qualitative study aims to explore how person-related characteristics interact with a person’s location relative to specialist services to impact their engagement with the optimal lung pathway, and to compare and contrast experiences in rural, coastal, and urban communities. This study also aims to generate translatable evidence to inform the evidence-based design of a patient engagement intervention to improve lung cancer patients’ and informal carers’ participation in and experience of the lung cancer care pathway.

A qualitative cross-sectional interview study with people diagnosed with lung cancer < 6 months before recruitment (in receipt of surgery, radical radiotherapy, or living with advanced disease) and their informal carers. Participants will be recruited purposively from Barts Health NHS Trust and United Lincolnshire Hospitals NHS Trusts to ensure a diverse sample across urban and rural settings. Semi-structured interviews will explore factors affecting individuals’ capability, opportunity, and motivation to engage with their recommended diagnostic and treatment pathway. A framework approach, informed by the COM-B model, will be used to thematically analyse facilitators and barriers to patient engagement.

The study aligns with the current policy priority to ensure that people with cancer, no matter where they live, can access the best quality treatments and care. The evidence generated will be used to ensure that lung cancer services are developed to meet the needs of rural, coastal, and urban communities. The findings will inform the development of an intervention to support patient engagement with their recommended lung cancer pathway.

Protocol registration

The study received NHS Research Ethics Committee (Ref: 23/SC/0255) and NHS Health Research Authority (IRAS ID 328531) approval on 04/08/2023. The study was prospectively registered on Open Science Framework (16/10/2023; https://osf.io/njq48 ).

Peer Review reports

Globally, lung cancer is a leading cause of cancer mortality and premature death, particularly within communities experiencing deprivation, and is the third most common cancer in the UK [ 1 , 2 ]. NHS England commissioning guidance for optimum lung cancer care recommends management and treatment by a specialist team, with a concentration of experts in one place, providing access to specialised diagnosis and treatment facilities [ 3 ]. However, the complex and rapidly evolving diagnostic and treatment pathways for lung cancer, along with workforce limitations, make achieving this goal challenging [ 4 ]. There are wide variations and inequalities in lung cancer care and survival outcomes across the UK [ 5 ]. Indeed, the deprivation gap (i.e. the survival difference between individuals from the least deprived compared to the most deprived groups) is highest for smoking related cancers, such as lung cancer, compared to other-cancer types [ 6 ]. Evidence suggests that, in the UK, poorer survival rates for people with lung cancer experiencing deprivation compared to more affluent groups are driven by lower screening and treatment rates [ 7 , 8 ]. Broader, structural inequalities related to tobacco-dependence [ 9 ] also drive higher rates of lung cancer incidence and poorer outcomes for people experiencing socio-economic deprivation [ 10 ]. To close this deprivation gap in lung cancer, it is therefore vital to understand and address the factors underlying these lower treatment rates.

One integral factor to consider is patient engagement. Whilst the term ‘patient engagement’ is widely used and may have different meaning across different contexts [ 11 ], in this study, we define this term as the extent to which an individual patient attends, understands and undergoes each investigation, test and treatment that comprises their personal lung cancer pathway, as was recommended by, and agreed mutually with, their clinical care team. Enhancing and supporting patient engagement can improve patient outcomes and care experiences [ 11 ], and in the context of lung cancer may enable greater adherence to recommended diagnostic and treatment pathways. Most work to date has focused more so on improving lung cancer outcomes [ 12 , 13 ] and the quality of the lung cancer services themselves [ 14 ], whilst neglecting to consider how the individual circumstances of people with lung cancer may impact their engagement with available services and support. For example, factors such as an individual’s location in relation to their lung cancer services; their available resources; their language and culture; their prior experiences of and beliefs about healthcare; and availability of social support, may all influence their engagement with care [ 15 , 16 ].

Such factors can be explored systematically using behaviour change models, like the COM-B framework. This theoretical behaviour system model describes three essential and interacting conditions that determine how likely it is that an individual will perform a behaviour (B): their capability (C), opportunity (O) and motivation (M) [ 17 ]. Understanding these interacting factors in relation to individuals’ engagement with their recommended diagnostic and treatment pathway is crucial to identify how best lung cancer patients can be supported to take part in their recommended pathway. For example, one potentially helpful approach is Pathway Navigation. Cancer Alliances report that appointing Pathway Navigators, who provide tailored, individual support to help patients navigate and thus engage with their complex diagnostic test, appointment, and treatment schedules, can double the number of patients receiving lung cancer treatment within the target of 49 days [ 18 ]. Support with pathway navigation may be particularly crucial for individuals who do not have access to informal support from friend or family carers [ 19 ]. Equally, it is critical to understand the experiences of informal carers who are supporting people with lung cancer, to identify areas where additional support from formal healthcare services may be required.

The location of patients relative to the healthcare services they need to access is a particularly important element to consider in relation to an individual’s engagement in their diagnostic and treatment pathway. For instance, services situated in and serving rural or urban areas, are associated with both distinct and overlapping challenges to engagement. The UK consists of large rural and coastal populations that are often characterised by high levels of economic and social deprivation, limited digital infrastructure, poor mental and physical health, high smoking prevalence, and drug and alcohol misuse [ 20 , 21 ]. The Chief Medical Officer for England has recently recognised the importance of better understanding the impact of place on health as well as the urgent need to address health inequalities in rural and coastal areas [ 22 , 23 ]. The challenges faced by rural and coastal communities are often further exacerbated by poor access to healthcare (i.e. long travel distances, poor transport infrastructure, lack of available services) [ 24 , 25 , 26 , 27 ] and workforce limitations (i.e. poor recruitment and retention of healthcare professionals) [ 28 , 29 ]. Urban areas of the UK also experience high levels of economic and social deprivation but typically in more concentrated areas characterised by diverse ethnic communities [ 30 ]. Urban communities also face significant mental and physical health challenges related to unique health inequalities including high population density and heterogeneity [ 31 ], elevated crimes rates [ 32 ], air pollution [ 33 ], lack of green spaces [ 34 ], and poor and unstable housing [ 35 ]. Whilst healthcare access, infrastructure and workforce are typically more developed in urban areas, highly specialised clinical teams are often situated in different hospital settings, requiring significant patient travel and time commitment. Although distances between centres are often shorter than in more rural settings, urban transport systems can be disparate, expensive, and complex to navigate.

There is a distinct lack of research surrounding lung cancer within UK and European settings compared to other tumour sites [ 36 , 37 ]; especially qualitative inquiries that explore experiences across local settings. Further research is needed to gain an in-depth understanding of the individual-level barriers that urban, rural and coastal people living with and affected by lung cancer in the UK face, and to identify facilitators to support engagement. In this study, we will compare and contrast the challenges faced by people with lung cancer and the friends and family members who support them, in urban North East London, to those of predominantly rural and coastal Lincolnshire. The behavioural-science informed approach, theoretically underpinned by the COM-B model, will enable the identification of modifiable factors amendable to intervention to facilitate equitable engagement with the diagnostic and treatment pathway for lung cancer. The aims of this pragmatic and uniquely translational study are:

To explore how lung cancer patients and their informal carers (close family and friends who support people with lung cancer) characteristics and their location in relation to specialist services impact on their capability, opportunity and motivation to attend and participate in their recommended lung cancer diagnostic and treatment pathway in North East London and Lincolnshire.

To generate translatable evidence from both North East London and Lincolnshire to inform the evidence-based design of a patient engagement intervention to improve lung cancer patients’ and informal carers’ participation and experience of the lung cancer care pathway.

Methods/Design

Study design.

This study will use a cross-sectional qualitative interview study design to explore the experiences of people with lung cancer and their informal carers in urban (North East London) and rural (Lincolnshire) areas of England. Guided by the Medical Research Council’s (MRC) framework for the development and evaluation of complex interventions [ 38 ], this study will be conducted in accordance with the intervention ‘development’ phase of the framework, by generating translatable evidence to inform the evidence-based design of a patient engagement intervention that will aim to better support lung cancer patients in engaging in treatment and care pathways. In this study, we are defining patient engagement as the extent to which an individual patient attends, understands and undergoes each investigation, test and treatment that comprises their personal lung cancer pathway, as was recommended by, and agreed mutually with, their clinical care team. This study will be reported in line with the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist [ 39 ].

Study setting

The study will be conducted in an urban (North East London) and rural and coastal area (Lincolnshire) of England, United Kingdom. It should be noted that the county of Lincolnshire also has urban areas such as the city of Lincoln, although the county as a whole, is predominantly rural in geography, with a significant coastline to the East. People diagnosed with lung cancer and their informal carer’s will be recruited from two NHS trusts: Barts Health NHS Trust and United Lincolnshire Hospitals NHS Trust. Barts Health NHS Trust consists of five hospitals in the City of London and East London (Mile End Hospital, Newham University Hospital, Royal London Hospital, St Bartholomew’s Hospital and Whipps Cross University Hospital) and serves a population of ~ 2.6 million people within an urban area. United Lincolnshire Hospitals NHS Trust consists of four hospitals that cover the county of Lincolnshire (Lincoln County Hospital, Grantham and District Hospital, Pilgrim Hospital Boston, and County Hospital Louth) and serves a population of ~ 700,000 people across a predominately rural area. In the case of Lincolnshire, some people with lung cancer are referred to Nottingham City Hospital as part of Nottingham University Hospitals NHS Trust (NUH) for treatment. Nottingham City Hospital is located in the city of Nottingham within the East Midlands region of England and is located approximately 43 miles from Lincoln city and 80 miles from the East coast of Lincolnshire. Poor road conditions and a lack of accessible public transport can make traveling from the more rural and coastal parts of Lincolnshire to Nottingham, both costly and time consuming [ 40 ]. NUH staff from Nottingham City Hospital will support the identification and recruitment of people with lung cancer and their informal carers who have been referred from United Lincolnshire Hospitals NHS Trust sites for treatment.

Ethical approval and study registration

The protocol for this study was registered on Open Science Framework on October 16th, 2023 ( https://osf.io/njq48 ). Ethical approval was obtained (REC Ref: 23/SC/0255; IRAS ID:328531) from the NHS Oxford B Research Ethics Committee and the NHS Health Research Authority on August 4th, 2023.

Theoretical approach

An exploratory qualitative approach underpinned by the COM-B Model for Behaviour Change [ 17 ] will be applied. This will enable the identification of factors potentially amendable to intervention to initiate health behaviour change (i.e., to facilitate improved engagement with the recommended lung cancer diagnostic and treatment pathway). A person-centred pragmatic epistemological approach will be taken [ 41 ], unpinned by the view that knowledge is based on experience, whilst recognising the unique knowledge of each individual as created by their unique experiences. The pragmatist epistemology supports combining inductive and deductive approaches, and selection of research methods based on their appropriateness for addressing real-world problems [ 41 , 42 ]. Here, qualitative interviews and combined inductive and deductive framework analysis have been selected. This will enable inductive analysis of individual’s unique experiences, challenges and needs; mapped deductively to domains of behaviour change, to generate in-depth, person-centred, translational insights. These in turn will be applied to inform development of a pragmatic intervention to address existing inequities in engagement with the recommended lung cancer pathway. By prioritising a ‘practical understanding’ of these issues, this approach will allow us to understand and address the unique challenges and practical needs of people with lung cancer and their informal carers in urban, rural, and coastal areas.

Participants

This study will recruit people with a confirmed diagnosis of lung cancer within the last six months from three patient cohorts who are in receipt of (1) surgery (2) radical radiotherapy or (3) currently with advanced disease, including both those having active anticancer treatment and specialist palliative/best supportive care (provided they were eligible for treatment). The criterion of six months was chosen because the insights will inform a patient engagement intervention to be delivered early in the diagnostic and treatment pathway (i.e. during or close to the first lung cancer clinic appointment). It is therefore important that participants can recall their experiences of the earlier phases of the investigation and treatment pathway, whilst balancing this with their treatment burden and ability to participate. This study will also recruit informal carers of people with lung cancer with a confirmed diagnosis within the last six months. People diagnosed outside of this timeframe, who do not have capacity to provide informed consent or who are not able to understand the recruitment materials (i.e., participant information sheet/video and informed consent form) with assistance of an interpreter are not eligible to participate in this study.

This study will aim to recruit up to 60 patients and 30–60 informal carers (at least 15 at each site) across both NHS trusts, split evenly between United Lincolnshire Hospitals NHS Trust and Barts Health NHS Trust. We will use a purposive sampling approach to achieve representation from patients receiving different types of treatment (surgical, radical radiotherapy, or advanced cancer) and informal carers. Once ten people have been recruited, recruitment will be targeted following a maximum variation purposive sampling framework [ 43 ] to ensure diversity within the sample in relation to: gender, ethnicity, age, socioeconomic position, stage of disease at diagnosis and area of North East London or Lincolnshire; and for informal carers, these factors along with the type of caring relationship they have to the patient (e.g., friend, family member). This type of recruitment will allow us to explore the experiences of a diverse set of participants and ensure the findings and recommendations are applicable to the diverse range of individuals who may be referred on a lung cancer pathway. The chosen sample size is in line with norms for qualitative research [ 44 , 45 ]. This sample size is required due to the multi-site nature of the study and the diversity of the population [ 46 , 47 , 48 ]. The sample size is sufficient to achieve appropriate information power for a study which is well-designed, theoretically-grounded, and addressing specific objectives [ 48 ].

Recruitment

Participant recruitment and data collection will run between November 2023 and May 2024. All participants will give their informed consent (i.e. either written or verbal) to take part prior to the start of each interview. At both sites, participants will give consent to a member of the research team who is experienced in qualitative interview methods.

People with lung cancer

Patient lists will be pre-screened for people who meet the eligibility criteria by a member of the direct care team at routine clinic meetings at both NHS sites. For each person who is eligible for the study, a member of their direct care team will give a brief overview of the study during their appointment and ask for their consent for a member of the research team to contact them directly. They will then be given and/or sent an information pack (an invitation letter, information sheet and reply slip) and invited to express an interest in taking part either by post, email, or telephone. The information pack will also contain a link to a video-version of the invitation letter, information sheet and reply slip that can be accessed online. In the case of North East London, the information pack, video-version, invitation letter, information sheet and reply slip will also be made available in Sylheti owing to the large Bangladeshi population living in the geographic area served by Barts Health NHS Trust. If the clinical team do not introduce the study to eligible participants during their appointment, they will receive an invitation and information pack by post. A note will be made on the clinical record once a person has received an invitation to ensure they are not re-invited, and to confirm whether they take part in the study.

Informal carers

The information packs distributed to eligible patients will also include information for informal carers, explaining that they are also invited to take part in a separate interview. The reply slip will include an option for either the patient, informal carer, or both to take part in the interview. The option for informal carers to take part will also be mentioned by health care professionals when they introduce the study during appointments and will be mentioned by a member of the research team on the phone to potential patient participants. Patients whose informal carers’ do not want to or are not able to take part in an interview themselves can still be recruited to the study, as can informal carers whose patients do not want to or are not able to take part in an interview themselves.

Data collection

Interviews will be carried out by researchers (SC and LM) experienced in conducting qualitative research and audio-recorded on an encrypted recorder. Each interview will last approximately 1-hour and will take place face-to-face or via telephone or Microsoft Teams, depending on participant preference. We intend to only interview participants once, however, if they are tired or not feeling well during the interview, a follow up meeting can be arranged to complete the interview. Where possible, interviews with people with lung cancer and informal carers will be conducted separately to minimise social desirability bias [ 49 ]. However, as the interview explores sensitive subjects during an emotionally and physically challenging time of the person with lung cancer and informal carers’ lives (following a recent lung cancer diagnosis), the participant can request their patient/informal carer is present during the interview. In this case, the option to conduct the interview as a dyadic interview will be offered [ 50 ]. For participants who are not able to communicate clearly in English, an interpreter will be arranged to assist with both the phone calls to arrange the interview and the interviews themselves.

Interviews will follow a semi-structured topic guide (Additional file 1 ) developed by the research team, wider steering group and with patient and public involvement. The interviews will explore people with lung cancer and informal carers’ capability (physical and psychological), opportunity (physical and social) and motivation (reflexive and automatic) to participate in the lung cancer pathway, based on their individual characteristics and location in relation to the specialist lung cancer centres. This will include exploring factors associated with navigation of complex travel systems across multiple sites to attend appointments; attending and engaging with key touch-points along the pathway (including diagnostic processes; referral; systemic, radio-therapeutic and surgical treatments; palliative and allied health services); and digital consultations. The questions will be adapted for patient, informal carer, or dyadic interviews.

Demographic information including age, gender, ethnicity, post code (as proxy for region, rural-urban residence and socioeconomic position via Index of Multiple Deprivation score), stage of disease, and performance status will be extracted from the medical records of consenting participants. Additional questions in relation to participant characteristics and health behaviours (e.g. lifestyle, smoking behaviour) will be asked as part of the pre-determined interview schedule. The sample will be described in terms of; age, gender, ethnicity, disease stage, location (e.g. rurality/urban), area-level deprivation (converted from postcode to Index of Multiple Deprivation quintile), and performance status.

Data analysis

Following completion of the interviews, the audio-recordings will be professionally transcribed, and a subset checked for accuracy. Transcripts will be psesudonymised and stored securely on the University of Lincoln’s One Drive and Queen Mary University of London’s Data Safe Haven. The qualitative data analysis software package NVivo will be used to support the analysis. A framework approach to applied thematic analysis, as described by Ritchie and Spencer (1994) [ 51 ], will be used to analyse qualitative data. Framework analysis is well-suited to analytical approaches involving multi-disciplinary team members and will enable comparison and interpretation of patterns of themes both within and between North East London and Lincolnshire. This approach will allow us to identify similarities and differences between the two sites, comparing factors affecting patient engagement in rural and urban settings. It will also enable systematic identification of potentially modifiable factors related to participants’ capability, opportunity and motivation to engage that can be targeted by a patient engagement intervention, as well as interactions between these factors and implementation considerations.

The framework method is a five-stage qualitative analysis process involving; (1) Familiarisation, (2) Identifying a thematic framework, (3) Indexing, (4) Charting, and (5) Mapping and Interpretation [ 51 ]. The coding of data will be guided by an inductive and deductive approach, allowing for a data-driven and theory informed development of an analytical framework. The analytical framework will be developed collaboratively between the North East London and Lincolnshire research teams, in consultation with the broader steering group and Patient and Public Involvement and Engagement (PPIE) representatives. The COM-B model will be used to guide the structure of the analytical framework, enabling the grouping of facilitators and barriers to participants’ engagement (capability, opportunity and motivation to engage) with the lung cancer pathway. The analysis will result in a set of recommendations for the proposed patient engagement tool, drawn from the analysis of both the Lincolnshire and North East London interviews, addressing both (a) common principles; and (b) region-specific recommendations. The quantitative demographic data will be summarised and presented as ranges and percentages to describe the overall sample.

Study management and oversight

The study conduct is overseen by a national steering committee, who meet bimonthly to monitor progress, ensure alignment between research sites and with overall project aims, and contribute to results interpretation; application to intervention development; and dissemination. The steering committee is made up of funding body representatives from Cancer Research UK; researchers with expertise in qualitative methods, behavioural science and health inequalities from both Lincolnshire and London; clinicians (oncologists, respiratory physicians, and nurses); NHS cancer pathway managers and administrators; and PPIE representatives. The steering committee are also responsible for delivering a parallel quantitative service evaluation project, that the results of this qualitative study will inform. Alongside the national steering committee, two regional study management groups have been established to manage operational processes at both sites and inform data interpretation and PPIE collaboration.

Reflexivity

Qualitative research is contextual and we as a diverse team of clinical and non-clinical researchers, healthcare professionals and people with lived experience, recognise the importance of reflexivity as a crucial strategy in the process of generating knowledge via qualitative research [ 52 , 53 ]. Reflexivity is considered a major foci for quality control and understanding how it may influence a study should be carefully considered [ 52 ]. Where researchers clearly describe the contextual intersectional relationships between the participants and themselves, this can improve the robustness of the study and generate a deeper understanding of the findings [ 53 ]. This study takes place within two distinct geographic settings, the predominantly rural and coastal county of Lincolnshire and urban North East London. The context is the delivery of lung cancer care in both these settings and the experiences of people diagnosed with lung cancer care and their informal carers who reside in both Lincolnshire and North East London. Both areas have unique social and environmental contexts but are linked by inequalities in lung cancer care. North East London is the London region with the highest level of deprivation and an ethnically diverse community, with over two-thirds of the community from a minority ethnic group. These factors are associated with higher lung cancer mortality and challenges navigating complex healthcare pathways [ 5 , 6 ]. Lincolnshire is not as ethnically diverse with the majority of the population being White British although there is a sizeable Central and Eastern European community. Access to lung cancer care or oncology care for people living in rural and coastal areas is hindered by the uneven geographic distribution of workforce and services [ 37 , 54 ]. We therefore have site-specific research teams that possess a wealth of subject-specific and methodological expertise as well as individual and collective experiences of residing and/or working in these two sites. Reflexivity will also be carefully considered throughout the study by maintaining reflexive logs to document evolving thoughts, biases, and personal reflections during data collection. These will be shared with the wider team at regular team meetings to promote wider reflexivity insights and will be used to help frame and contextualise the interpretation of and meaning of data. The teams will meet regularly throughout data analysis and interpretation, with meetings minuted and reflected upon, to inform the iterative analysis approach and provide core contextual reflections that will be reported with study findings.

Patient and public involvement and Engagement (PPIE)

This study was developed in response to a need identified by Cancer Research UK based on foundational PPIE focus groups, and PPIE is embedded throughout the study lifecycle. The protocol was developed and co-authored by a public contributor with lived experience as a lung cancer carer (AH-B). The study documents (invite, information sheet, consent form and draft interview questions) have also been reviewed by two people living with lung cancer and one carer using a PPIE consultation sheet (Additional file 2 ) and facilitated by our NHS colleagues. Two region-specific PPIE groups have been established; members have lived experience of living with lung cancer, or as informal carers providing support to individuals living with lung cancer. These groups will be consulted at key points throughout the study lifecycle and will play a crucial role during the conduct of this research through providing unique perspectives, support, and guidance. We will also work with these groups to report our findings in accessible formats informed by patients and informal carers’ needs. There will also be opportunities for patients and informal carers to support the dissemination of our findings to clinical and non-clinical audiences. Where appropriate, there will be opportunities for interested members to collaborate and co-author both academic and non-academic outputs. The involvement of PPIE members will extend beyond the conclusion of this study and will play an integral role is shaping and refining the patient engagement tool throughout its subsequent development phases.

Dissemination

We will publish the study findings in peer-reviewed scientific journals and present them at appropriate national and international conferences. Accessible summaries will also be produced and disseminated to people with lung cancer, informal carers, and healthcare professionals. A detailed dissemination plan for this study has been created and agreed upon by the study steering committee. PPIE representatives contributed to the dissemination plan development to ensure our findings will be shared in an inclusive and community-focused way.

This qualitative cross-sectional study will address an urgent need to better understand the experiences and difficulties of lung cancer patients and their informal carers who reside in urban, rural and coastal areas of the UK. More specifically, this study will gather important insight into the capability, opportunity, and motivational factors that may influence lung cancer patients’ engagement in optimal care pathways in these settings. Recent systematic mapping of global cancer screening, prevention, and diagnosis research between 2007 and 2020 points towards a clear disparity in the volume of cancer research across tumour site, with 61% of included studies ( n  = 1762) conducted in colorectal, breast and cervical cancer [ 36 ]. Despite being the leading cause of cancer related deaths globally [ 2 ], only 6.4% percent of studies were in relation to lung cancer [ 36 ]. Furthermore, evidence suggests that our understanding surrounding the development of and engagement in optimal care pathways for people with lung cancer remains in its infancy across the broader health systems [ 4 ], highlighting the need to better understand how individuals engage in these pathways across local settings [ 4 ]. Whilst the world’s largest independent cancer research organisation, Cancer Research UK have prioritised lung cancer research over the last decade [ 55 ], our understanding of lung cancer within a UK context predominantly stems from epidemiological and quantitative inquiries. There remains a dearth of evidence that explores the qualitative experiences of people living with lung cancer who reside in both rural and urban areas in the UK. This is particularly evident in rural settings with recent review evidence identifying only a limited number of qualitive studies ( n  = 9 studies) undertaken in rural areas none of which were from a UK or European setting [ 56 ].

Cancer care pathways are becoming increasingly challenging to deliver and engage with due to their rapidly evolving and complex nature [ 57 ], as well as the multi-faceted individual-level barriers faced by patients unique to urban and rural settings. By identifying and understanding these factors, the study findings can inform the development of tailored services to enable more personalised and patient-centred lung cancer care. Indeed, evidence generated by this study will directly inform the development of a patient engagement intervention that will aim to support lung cancer patients to optimally engage with their recommended care pathway. The MRC has published, and recently updated, their guidance surrounding the development and evaluation of complex interventions, presenting a framework of four phases: (1) development, (2) feasibility/piloting, (3) evaluation, and (4) implementation [ 38 , 58 ]. The current study forms an integral element as part of the ‘development’ phase of the MRC framework, with the qualitative interview findings iteratively integrated with insights from a series of region-specific key stakeholder workshops with a range of healthcare professionals; service managers and co-ordinators; and PPIE representatives. This approach will ensure that experiences and perceptions are gathered from stakeholders across the care continuum to inform robust, patient-centred and theory-and-evidence-based intervention development, with core implementation factors considered throughout. Once we have developed the key components of the patient engagement intervention, we plan to then undertake iterative feasibility and acceptability testing in late 2024 / early 2025. This will be followed by intervention evaluation where we will ascertain the impact of the intervention on key quantitative indicators of pathway engagement, as well as qualitative exploration of patient and carer experience.

Data availability

The dataset(s) that will support the conclusions of this article will be included within the article and its additional file(s).

Abbreviations

Capability Opportunity Motivation Behaviour Model

General Data Protection Regulation

National Health Service

Patient and Public Involvement and Engagement

United Kingdom

United Lincolnshire Hospitals NHS Trust

Oliver AL. Lung Cancer: Epidemiology and Screening. Surg Clin North Am. 2022;102(3):335–44.

Article   PubMed   Google Scholar  

Cancer Research UK. Lung Cancer Statistics. https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer . Accessed 19 Nov 2023.

NHS England. National Optimal Lung Cancer Pathway: For suspected and confirmed lung cancer: Referral to treatment. https://www.cancerresearchuk.org/sites/default/files/national_optimal_lung_pathway_aug_2017.pdf . Accessed 20 Nov 2023.

Otty Z, Brown A, Sabesan S, Evans R, Larkins S. Optimal care pathways for people with Lung Cancer- a scoping review of the literature. Int J Integr Care. 2020;20(3):14.

Article   PubMed   PubMed Central   Google Scholar  

Conibear J, Nossiter J, Foster C, West D, Cromwell D, Navani N. The National Lung Cancer audit: the impact of COVID-19. Clin Oncol. 2022;34(11):701–7.

Article   CAS   Google Scholar  

Cancer Research Uk. Deprivation gradient for cancer mortality https://www.cancerresearchuk.org/health-professional/cancer-statistics/mortality/deprivation-gradient#heading-One . Accessed 19 Nov 2023.

Forrest LF, Adams J, Rubin G, White M. The role of receipt and timeliness of treatment in socioeconomic inequalities in lung cancer survival: population-based, data-linkage study. Thorax. 2015;70(2):138–45.

Crosbie PAJ, Gabe R, Simmonds I, Hancock N, Alexandris P, Kennedy M et al. Participation in community-based lung cancer screening: the Yorkshire Lung Screening Trial. Eur Respir J 2022;60(5).

Payne NWS, Brown KF, Delon C, Kotrotsios Y, Soerjomataram I, Shelton J. Socio-economic deprivation and cancer incidence in England: quantifying the role of smoking. PLoS ONE. 2022;17(9):e0272202.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Office for National Statitics. Likelihood of smoking four times higher in England’s most deprived areas then least deprived. https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/drugusealcoholandsmoking/articles/likelihoodofsmokingfourtimeshigherinenglandsmostdeprivedareasthanleastdeprived/2018-03-14 . Accessed 25 Nov 2023.

Higgins T, Larson E, Schnall R. Unraveling the meaning of patient engagement: a concept analysis. Patient Educ Couns. 2017;100(1):30–6.

Petty WJ, Paz-Ares L. Emerging strategies for the treatment of small cell lung Cancer: a review. JAMA Oncol. 2023;9(3):419–29.

Li Y, Yan B, He S. Advances and challenges in the treatment of lung cancer. Biomed Pharmacother. 2023;169:115891.

Article   CAS   PubMed   Google Scholar  

Lynch C, Harrison S, Butler J, Baldwin DR, Dawkins P, van der Horst J, et al. An International Consensus on actions to improve Lung Cancer Survival: a modified Delphi Method among Clinical experts in the International Cancer Benchmarking Partnership. Cancer Control. 2022;29:10732748221119354.

Davis RE, Jacklin R, Sevdalis N, Vincent CA. Patient involvement in patient safety: what factors influence patient participation and engagement? Health Expect. 2007;10(3):259–67.

World Health Organisation. Patient Engagement: Technical Series on Safer Primary Care. https://iris.who.int/bitstream/handle/10665/252269/9789241511629-eng.pdf?sequence=1 Accessed 20 Nov 2023.

Michie S, van Stralen MM, West R. The behaviour change wheel: a new method for characterising and designing behaviour change interventions. Implement Sci. 2011;6:42.

United Kingdom Lung Cancer Coalition. Pathways Matter: A review of the implementation of the national optimal lung cancer pathway. https://www.uklcc.org.uk/sites/default/files/2021-06/UKLCC-Pathways-Matter-Report.pdf . Accessed 20 Nov 2023.

Health Education England. Care Navigation: A Competency Framework. 2016. https://www.hee.nhs.uk/sites/default/files/documents/Care%20Navigation%20Competency%20Framework_Final.pdf . Accessed 27 Dec 2023.

Bird W. Improving health in coastal communities. BMJ. 2021;374:n2214.

Philip L, Williams F. Remote rural home based businesses and digital inequalities: understanding needs and expectations in a digitally underserved community. J Rural Stud. 2019;68:306–18.

Article   Google Scholar  

Witty C. Chief Medical Officer’s annual report 2021: Health in coastal communities. https://assets.publishing.service.gov.uk/media/60f98750e90e0703bbd94a41/cmo-annual_report-2021-health-in-coastal-communities-accessible.pdf . 2021. Accessed 10 Nov 2023.

Witty C. Chief Medical Officer’s annual report 2023: Health in an ageing society. https://assets.publishing.service.gov.uk/media/65562ff2d03a8d000d07faa6/chief-medical-officers-annual-report-2023-web-accessible.pdf . 2023. Accessed 10 Nov 2023.

Department for Environment Food & Rural Affairs: Delivering for rural England - the second report on rural proofing. 2022. https://assets.publishing.service.gov.uk/media/6312001de90e077b73f776d7/Delivering_for_rural_England_-_the_second_rural_proofing_report.pdf . Accessed 27 December 2023.

Todd A, Copeland A, Husband A, Kasim A, Bambra C. Access all areas? An area-level analysis of accessibility to general practice and community pharmacy services in England by urbanity and social deprivation. BMJ Open. 2015;5(5):e007328.

Feng X, Feng Z, Astell-Burt T. Perceived public transport infrastructure modifies the association between public transport use and mental health: multilevel analyses from the United Kingdom. PLoS ONE. 2017;12(8):e0180081.

McPeake K, Jeanes L, Nelson D, Selby P, Cooke S, Gussy M, et al. Developing a ‘Living with Cancer’ programme in a rural and coastal setting: experiences of collaborative and innovative co-production across an Integrated Health System. J Cancer Policy. 2023;38:100452.

Charter L, Scully R, Laidlaw A. The word that comes to mind is polymath’: medical students’ perceptions of rural postgraduate careers. Rural Remote Health. 2021;21(3):6750.

PubMed   Google Scholar  

Maclaren AS, Locock L, Skea Z. Valuing place in doctors’ decisions to work in remote and rural locations. Future Healthc J. 2022;9(3):248–51.

PubMed   PubMed Central   Google Scholar  

Ministry of Housing Communities & Local Government. The English Indices of Deprivation 2019 (IoD2019). 2019. https://assets.publishing.service.gov.uk/media/5d8e26f6ed915d5570c6cc55/IoD2019_Statistical_Release.pdf . Accessed 11 Nov 2023.

Fecht D, Fortunato L, Morley D, Hansell AL, Gulliver J. Associations between urban metrics and mortality rates in England. Environ Health. 2016;15(Suppl 1Suppl 1):34.

Department for Environment Food & Rural Affairs. Key Findings, Statistical digest of rural England. 2024. https://www.gov.uk/government/statistics/key-findings-statistical-digest-of-rural-england/key-findings-statistical-digest-of-rural-england . Accessed 12 Nov 2023.

Kelly FJ, Fussell JC. Air pollution and public health: emerging hazards and improved understanding of risk. Environ Geochem Health. 2015;37(4):631–49.

Public Health England. Improving access to greenspace: A new review for 2020. 2020. https://assets.publishing.service.gov.uk/media/5f202e0de90e071a5a924316/Improving_access_to_greenspace_2020_review.pdf . Accessed 13 Nov 2023.

Nijman J, Wei YD. Urban inequalities in the 21st century economy. Appl Geogr. 2020;117:102188.

O’Dowd EL, Merriel SWD, Cheng VWT, Khan S, Howells LM, Gopal DP, et al. Clinical trials in cancer screening, prevention and early diagnosis (SPED): a systematic mapping review. BMC Cancer. 2023;23(1):820.

Nelson D, Selby P, Kane R, Harding-Bell A, Kenny A, McPeake K, et al. Implementing the European code of cancer practice in rural settings. J Cancer Policy. 2024;39:100465.

Skivington K, Matthews L, Simpson SA, Craig P, Baird J, Blazeby JM, et al. A new framework for developing and evaluating complex interventions: update of Medical Research Council guidance. BMJ. 2021;374:n2061.

Tong A, Sainsbury P, Craig J. Consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups. Int J Qual Health Care. 2007;19(6):349–57.

Rocque GB, Williams CP, Miller HD, Azuero A, Wheeler SB, Pisu M, et al. Impact of Travel Time on Health Care costs and Resource Use by Phase of Care for older patients with Cancer. J Clin Oncol. 2019;37(22):1935–45.

Kaushik V, Walsh CA. Pragmatism as a Research Paradigm and its implications for Social Work Research. Social Sci. 2019;8(9):255.

Patton M. Qualitative Research and Evaluation Methods, 3rd Edition edn: Thousand Oaks: Sage Publications; 2002.

Benoot C, Hannes K, Bilsen J. The use of purposeful sampling in a qualitative evidence synthesis: a worked example on sexual adjustment to a cancer trajectory. BMC Med Res Methodol. 2016;16:21.

Dworkin SL. Sample size policy for qualitative studies using in-depth interviews. Arch Sex Behav. 2012;41(6):1319–20.

Hennink M, Kaiser BN. Sample sizes for saturation in qualitative research: a systematic review of empirical tests. Soc Sci Med. 2022;292:114523.

Jenkins EK, Slemon A, Haines-Saah RJ, Oliffe J. A guide to multisite qualitative analysis. Qual Health Res. 2018;28(12):1969–77.

Philbin MM, Parish CL, Kinnard EN, Reed SE, Kerrigan D, Alcaide ML, Cohen MH, Sosanya O, Sheth AN, Adimora AA, Cocohoba J. Multisite study of women living with HIV’s perceived barriers to, and interest in, long-acting injectable antiretroviral therapy. JAIDS J Acquir Immune Defic Syndr. 2020;84(3):263–70.

Malterud K, Siersma VD, Guassora AD. Sample size in qualitative interview studies: guided by Information Power. Qual Health Res. 2016;26(13):1753–60.

Bergen N, Labonté R. Everything is perfect, and we have no problems: detecting and limiting Social Desirability Bias in qualitative research. Qual Health Res. 2020;30(5):783–92.

Morgan DL, Ataie J, Carder P, Hoffman K. Introducing dyadic interviews as a method for collecting qualitative data. Qual Health Res. 2013;23(9):1276–84.

Ritchie J, Spencer L, Bryman A, Burgess RG. Analysing qualitative data. In.: Routledge, London; 1994.

Berger R. Now I see it, now I don’t: researcher’s position and reflexivity in qualitative research. Qualitative Res. 2015;15(2):219–34.

Dodgson JE. Reflexivity in qualitative research. J Hum Lactation. 2019;35(2):220–2.

Levit LA, Byatt L, Lyss AP, Paskett ED, Levit K, Kirkwood K, et al. Closing the Rural Cancer Care Gap: three institutional approaches. JCO Oncol Pract. 2020;16(7):422–30.

Cancer Research UK. Making Discoveries. Driving Progress. Bringing Hope. Our Research Strategy. 2022. https://www.cancerresearchuk.org/sites/default/files/cancer_research_uk_-_our_research_strategy.pdf . Accessed 22 Nov 2023.

Ali N, Nelson D, McInnerney D, Quaife SL, Laparidou D, Selby P, et al. A systematic review on the qualitative experiences of people living with lung cancer in rural areas. Support Care Cancer. 2024;32(3):144.

Brice SN, Harper P, Crosby T, Gartner D, Arruda E, England T, et al. Factors influencing the delivery of cancer pathways: a summary of the literature. J Health Organ Manag. 2021;35(9):121–39.

O’Cathain A, Croot L, Duncan E, Rousseau N, Sworn K, Turner KM, et al. Guidance on how to develop complex interventions to improve health and healthcare. BMJ Open. 2019;9(8):e029954.

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Acknowledgements

We would like to acknowledge the people living with lung cancer who supported us with the review of the study documents. We would also like to thank Brian Knowles (Senior Research and Evaluation Manager, Cancer Research UK) for commissioning the research and Cancer Research UK for funding it.

Cancer Research UK is a registered charity in England and Wales (1089464), Scotland (SC041666) and the Isle of Man (1103). This research was funded by the Social and Behavioural Research Team, Cancer Research UK (PICATR-2022/100019; PICTAR-2022/100017). http://www.cancerresearchuk.org/ . The protocol manuscript underwent peer review by the funding body as part of the grant application.

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Daisy McInnerney, Samantha L. Quaife & Lucy Mitchinson

Lincoln Institute for Rural and Coastal Health, College of Health and Science, University of Lincoln, Lincoln, UK

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Contributions

DN and DMcI are Co-Principal Investigators of the study. DN, DMcI and SLQ led on the initial funding applications with support from SC, ZP, WR, AJ, DS, SC, RK, AH-B and PS. DN and DMcI led on the ethics application to the NHS Research Ethics Committee and Health Research Authority with support from SLQ. The study design and methods were developed and modified by all co-authors (DN, DMcI, SC, LM, ZP, WR, AJ, DS, SC, RK, AH-B, LC, AL, PS, SLQ, MP). DN, DMcI, SLQ, LM and SC drafted the first version of the manuscript. All authors critically reviewed the protocol and approved the final manuscript.

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Correspondence to Lucy Mitchinson .

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The study protocol and supporting documents were approved by the NHS Oxford B Research Ethics Committee and the NHS Health Research Authority (REC Ref: 23/SC/0255; IRAS ID: 328531, August 4th, 2023). All participants are required to give their informed consent before they are recruited to the study.

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MP is a Specialist Clinical Advisor to Cancer Research UK who have funded the study.

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McInnerney, D., Quaife, S.L., Cooke, S. et al. Understanding the impact of distance and disadvantage on lung cancer care and outcomes: a study protocol. BMC Cancer 24 , 942 (2024). https://doi.org/10.1186/s12885-024-12705-9

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DOI : https://doi.org/10.1186/s12885-024-12705-9

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• http://orcid.org/0000-0002-8410-2295 Stephanie A Bernard 3 ,
• http://orcid.org/0000-0003-3472-2469 John A Carrino 4 ,
• http://orcid.org/0000-0003-3593-1449 Torsten Diekhoff 5 ,
• http://orcid.org/0000-0002-4655-9606 Iris Eshed 6 ,
• http://orcid.org/0000-0001-6142-3814 Kay Geert A Hermann 5 ,
• http://orcid.org/0000-0003-0244-0168 Nele Herregods 7 ,
• http://orcid.org/0000-0001-5314-2297 Jacob Jaremko 1 ,
• http://orcid.org/0000-0002-7909-2643 Lennart BO Jans 7 ,
• http://orcid.org/0000-0003-2571-0466 Anne Grethe Jurik 8 ,
• http://orcid.org/0000-0001-6593-4400 John M D O'Neill 9 ,
• http://orcid.org/0000-0002-6906-1851 Monique Reijnierse 10 ,
• http://orcid.org/0000-0001-9259-937X Michael J Tuite 11 ,
• http://orcid.org/0000-0002-1291-1755 Walter P Maksymowych 12
• 1 Radiology and Diagnostic Imaging , University of Alberta , Edmonton , Alberta , Canada
• 2 Rheumazentrum Ruhrgebiet , Ruhr University Bochum , Herne , Germany
• 3 Radiology , Brooke Army Medical Center , Fort Sam Houston , Texas , USA
• 4 Radiology and Imaging , Hospital for Special Surgery , New York , New York , USA
• 5 Department of Radiology , Charité Universitätsmedizin Berlin , Berlin , Germany
• 6 Radiology , Sheba Medical Center , Tel Hashomer , Israel
• 7 Radiology , Ghent University Hospital , Ghent , Belgium
• 8 Department of Radiology , Aarhus University Hospital , Aarhus , Denmark
• 9 Radiology , McMaster University Faculty of Health Sciences , Hamilton , Ontario , Canada
• 10 Radiology , Leiden University Medical Center , Leiden , The Netherlands
• 11 Radiology , University of Wisconsin-Madison School of Medicine and Public Health , Madison , Wisconsin , USA
• 12 Medicine , University of Alberta Faculty of Medicine and Dentistry , Edmonton , Alberta , Canada
• Correspondence to Dr Robert G W Lambert; rlambert{at}ualberta.ca

Background A range of sacroiliac joint (SIJ) MRI protocols are used in clinical practice but not all were specifically designed for diagnostic ascertainment. This can be confusing and no standard diagnostic SIJ MRI protocol is currently accepted worldwide.

Objective To develop a standardised MRI image acquisition protocol (IAP) for diagnostic ascertainment of sacroiliitis.

Methods 13 radiologist members of Assessment of SpondyloArthritis International Society (ASAS) and the SpondyloArthritis Research and Treatment Network (SPARTAN) plus two rheumatologists participated in a consensus exercise. A draft IAP was circulated with background information and online examples. Feedback on all issues was tabulated and recirculated. The remaining points of contention were resolved and the revised IAP was presented to the entire ASAS membership.

Results A minimum four-sequence IAP is recommended for diagnostic ascertainment of sacroiliitis and its differential diagnoses meeting the following requirements. Three semicoronal sequences, parallel to the dorsal cortex of the S2 vertebral body, should include sequences sensitive for detection of (1) changes in fat signal and structural damage with T1-weighting; (2) active inflammation, being T2-weighted with fat suppression; (3) bone erosion optimally depicting the bone–cartilage interface of the articular surface and (4) a semiaxial sequence sensitive for detection of inflammation. The IAP was approved at the 2022 ASAS annual meeting with 91% of the membership in favour.

Conclusion A standardised IAP for SIJ MRI for diagnostic ascertainment of sacroiliitis is recommended and should be composed of at least four sequences that include imaging in two planes and optimally visualise inflammation, structural damage and the bone–cartilage interface.

• Magnetic Resonance Imaging
• Axial Spondyloarthritis

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https://doi.org/10.1136/ard-2024-225882

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Introduction

For several decades, MRI has been used to investigate the early diagnosis of inflammatory sacroiliitis. 1 2 However, worldwide agreement has been lacking regarding the essential components of a diagnostic MRI protocol for suspected arthropathy of the sacroiliac joint (SIJ). The Assessment of SpondyloArthritis International Society (ASAS) published a ‘Definition of active sacroiliitis on MRI for classification of axial spondyloarthritis (axSpA)’ in 2009 and updated the definition in 2016. 3 This definition relies on two MRI sequences to make this determination—semicoronal T1 spin echo and short tau inversion recovery (STIR). Although the ASAS definition does not preclude more MRI sequences being performed since its publication, a single-plane, two-sequence approach to the MRI acquisition protocol has sometimes been inadvertently used for diagnostic purposes when a more comprehensive protocol may be preferable for routine clinical practice.

In 2015, the Arthritis Subcommittee of the European Society of Skeletal Radiology published its recommendations for an SIJ MRI ‘image acquisition protocol’ (IAP) for diagnostic purposes that required four MRI sequences. 4 In 2019, a review of the topic was published by the British Society of Spondyloarthritis making seven recommendations for the ‘acquisition and interpretation of MRI of the spine and SIJ in the diagnosis of axSpA in the UK’. 5 However, this publication did not specifically focus on the SIJ MRI acquisition protocol and recommendation #2 stated only that ‘T1-weighted and fat-suppressed, fluid-sensitive sequences are recommended’ with no details provided.

In 2020, an informal survey of 24 academic radiology departments (12 Europe, 12 North America) confirmed that 24/24 sites performed a minimum of 3 MRI sequences, with 19 performing 4–8 sequences because all centres considered the 2-sequence SIJ MRI protocol to be inadequate for diagnostic purposes. Our objective was to develop the minimum requirements for a standardised IAP for diagnostic MRI evaluation of the SIJ for axSpA that could be applied worldwide on all MRI platforms.

13 radiologist members of ASAS and the SpondyloArthritis Research and Treatment Network (SPARTAN), including two members of Young-ASAS specialising in paediatric radiology, along with one European and one North American rheumatologist with extensive MRI experience in SpA clinical practice and research, were invited to participate in a consensus exercise. A draft IAP was circulated to all participants along with background information and justification for the draft proposal. Examples of the proposed IAP performed on new, 10 and 22 years’ old MRI scanners were made available online for participants to review ( https://www.carearthritis.com/service/mri-spa-imaging-acquisition-protocols/ ). The principles applied to the development of the protocol were as follows:

The proposed protocol should:

Adhere to basic principles of multiplanar cross-sectional imaging.

Be possible to perform on all MRI platforms in routine clinical use regardless of the age of the scanner.

Be practical to perform on all MRI platforms within a reasonable acquisition time.

Consider the complexity and variability of SIJ anatomy and adjacent ligamentous and vascular structures.

Be capable of detecting all common and most uncommon MRI findings that may be found in sacroiliitis and its differential diagnoses. 6

Common in SpA—bone marrow oedema (BME), erosion, fat lesion, sclerosis, ankylosis, inflammation/fluid in the joint space

Less common in SpA—capsulitis, enthesitis, inflammation in an erosion cavity, backfill, bone budding.

Not usually a feature of SpA—osteophyte, extra-articular bone bridge, intra-articular gas, subchondral cyst.

Consider the inevitability of MRI artefacts and, where possible, allow crucial observations to be made even in the presence of significant artefact.

Consider future MRI developments being not overly prescriptive.

Be based on available evidence but not constrained by the lack of published evidence when expert opinion is strongly in favour of a specific approach.

Initially, the four-sequence IAP that was recommended for SIJ MRI as part of the Classification of Axial Spondyloarthritis Inception Cohort Study study was circulated for discussion. This protocol specifies which sequences should be acquired with advice regarding the acquisition parameters. Feedback on all issues was received by email, tabulated and recirculated. Participants were unanimously in favour of several components of the protocol including imaging in at least two planes and consistent orientation of the semicoronal sequences. It was also agreed that recommendations regarding lumbar spine or whole spine imaging were beyond the scope of this exercise. Other matters under discussion included whether to (a) include imaging of the whole pelvis, (b) recommend a different protocol for children and (c) allow elimination of the T1-weighted sequence in favour of T2-weighted Dixon imaging.

Two months later, a videoconference meeting took place and most remaining points of contention were resolved. Next the revised draft of the IAP was presented at the ASAS annual meeting to the entire membership on 14 January 2022, discussed and voted on.

A four-sequence IAP, three semicoronal and one semiaxial, was recommended as a minimum standard for diagnostic ascertainment of sacroiliitis and its differential diagnoses ( table 1 ).

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A standardised MRI acquisition protocol for diagnostic evaluation of the sacroiliac joints for axial spondyloarthritis

The requirements for the four-sequence protocol are as follows:

(A) Consistent orientation of the sequences necessitates that they be performed orthogonal to a consistently present and clearly identifiable part of the sacrum. It is recommended that semicoronal sequences be performed parallel to the dorsal cortex of the S2 vertebral body ( figure 1 ). This recommendation was adopted because it was unanimously agreed that consistent orientation of the semicoronal sequences is essential. SIJ anatomy is highly variable and the interpretation of the variable anatomy is facilitated by consistent orientation of the images. The dorsal cortex of the S2 vertebra was the selected reference line because it is (1) the most consistently available straight line on a sagittal image of the sacrum, (2) not affected by variation in lumbosacral transitional vertebrae, (3) clearly visible on all types of MRI sequence and (4) unaffected by SIJ arthropathy or lumbosacral spondylosis.

(B) Four sequences are required—three-semicoronal sequences and one-semiaxial sequence ( figure 2 ) and should be composed of (1) a semicoronal sequence sensitive for the detection of fat signal changes due to structural damage in bone and bone marrow with T1-weighted imaging recommended. A ‘fat-bright’ sequence with low or absent water signal is considered essential to accurately detect fat lesions in bone marrow and fat metaplasia in an erosion cavity (also called ‘backfill’). Bright water signal would interfere with these observations, and therefore, the sequence must either have low water signal through T1-weighting and/or absent water signal achieved by deconvolution of signal by the Dixon method producing ‘fat-only’ images. (2) A semicoronal sequence sensitive for the detection of active inflammation, being T2-weighted with suppression of fat signal. It is essential that fat signal in bone marrow is markedly reduced or eliminated to allow accurate detection of the increased water signal that occurs when bone marrow is actively inflamed, otherwise known as BME. It is also essential that signal from erythropoietic marrow be reduced as much as possible through proper T2-weighting. Proton density (PD) and intermediate-weighted (IW) sequences are not suitable for detection of BME in the SIJ or spine (discussed further below). (3) A semicoronal sequence that is designed to optimally depict the bone-cartilage interface of the articular surface and to be sensitive for detection of bone erosion. Although all sequences may sometimes demonstrate articular surface erosion, visualisation of an erosion is affected by multiple factors that include its size and surrounding tissue reaction. This may include sclerosis (low signal on all pulse sequences), BME (bright on T2FS, low on T1), fat lesion (bright on T1, low on T2FS) plus the internal signal of the erosion, which may vary according to the degree of activity and/or tissue repair. As a consequence of all these variables, it was recommended that the sequence should have thin slices to reduce partial volume averaging. This will improve sensitivity for small erosion defects even if the thin slice sequence has slightly lower in-plane resolution compared with the standard 3–4 mm thick spin echo sequences. It should be T1-weighted with fat signal suppression to permit more consistent contrast between the bone surface and the erosion cavity/articular surface/joint space. (4) A semiaxial sequence, perpendicular to the semicoronal sequences, sensitive for detection of active inflammation/BME. At least one additional sequence in a second plane was considered an absolute requirement because the detection of BME is pivotal in early axSpA diagnosis. The identification of the size, shape and distribution of the BME lesion is important for distinguishing BME due to axSpA from BME due to biomechanical or degenerative causes. The availability of a second sequence in the semiaxial plane allows the observer to more confidently see the exact anatomical distribution of a lesion and also to exclude false positive findings on one T2-weighted sequence due to phase encoding artefacts that commonly mimic BME but are rarely replicated on a second sequence perpendicular to the first. Therefore, it is recommended that the minimum requirement should include a semiaxial sequence that is T2-weighted with fat suppression sensitive for BME detection.

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The dorsal cortex of the S2 vertebra is an easily identified straight line (A) on a midline T1-weighted sagittal image of the sacrum from which the semicoronal sequences can be orientated. The sacral side of the SIJ primarily arises from the S1 and S2 vertebrae with a smaller component at S3. The shaded area (dashed outline in B) represents the outer perimeter of the cartilage compartments of both SIJ superimposed over the sagittal image. All of the shaded area must be included when planning the semicoronal sequences. The stack of semicoronal images (white box in B) should be orientated parallel to the dorsal cortex of S2 and the centre of the stack should be at the anterior border of the S1/2 vestigial disc. Even when severe deformity is present at L5/S1, such as may occur with spondylolisthesis and/or disc degeneration (C) the straight dorsal cortex of S2 can still be readily identified (arrows in C). SIJ, sacroiliac joint.

Recommended SIJ MRI protocol (3T Magnetom Vida, Simens, Erlangen): Semicoronal T1-weighed spin echo. (A) (TR 530 ms, TE 12 ms, 3 mm thick), Semicoronal T2-weighted spin echo with fat suppression (B) (TR 5940 ms, TE 88 ms, 3 mm thick), Semicoronal T1-weighted three-dimensional gradient echo (VIBE) with fat suppression (C) (TR 4.04 ms, TE 1.57 ms, 1 mm thick) all show normal sacroiliac joints. An axial T2-weighted spin echo Dixon water-only image (TR 4360 ms, TE 93 ms, 4 mm thick) completes the standard protocol. (D) The L5/S1 intervertebral disc is very degenerate with marked decrease in height and decreased signal intensity on T2FS. (B) Note that the 1 mm thick VIBE image (C) defines the bone-cartilage interface of the irregular vertebral endplates better than the spin echo sequences due to superior tissue contrast and a thinner slice. TE, time to echo; TR, repetition time; VIBE, volumetric interpolated breath-hold examination.

The IAP was approved at the 2022 ASAS annual meeting by a vote of the entire membership with 91% in favour.

13 radiologists from Europe and North America and two ASAS/SPARTAN rheumatologists participated in a consensus exercise regarding the development of a standardised IAP for MRI of the SIJ. A four-sequence protocol was recommended and approved by ASAS in 2022.

The first component of the protocol is a requirement that the orientation of the sequences should be orthogonal to the sacrum. The anatomy of the SIJ is highly variable with anatomical variants seen in 40%–80% of subjects. 7 8 This creates challenges for image interpretation and so the articular surfaces of the SIJ need to be imaged in two planes that are perpendicular to the main orientation of the joints and perpendicular to each other. This is currently the case for MRI of all other joints and the SIJ should not be treated differently. Because of the variability of sacroiliac anatomy and the lumbosacral junction, the dorsal surface of the S2 vertebral body is the only consistent straight line available from which the MRI technologist can consistently plan the orientation of the sequences ( figure 1 ). In addition, this part of the sacrum is not affected by SpA.

A range of lesions may be seen in the SIJ related to inflammatory and degenerative disorders. The complexity of the findings in difficult cases necessitates a comprehensive protocol that will be of diagnostic quality in nearly all cases including adults and children. Imaging in more than one plane is a basic principle of cross-sectional radiology because recognition of the patterns of anatomy and pathology is easier when more than one plane is available. For example, MRI positivity for sacroiliitis according to ASAS criteria decreases in healthy populations by 33%–56% when BME in the SIJ is assessed in two perpendicular planes instead of only the semicoronal plane. 9

Sensitive detection of active inflammation is an essential part of the protocol. The required BME-sensitive sequence should be properly T2-weighted. Some prior publications have confirmed that T2-weighted images are superior to PD weighted or IW images for the detection of BME in the SIJ 10 11 and this concurs with the authors’ experience. This is not surprising as sacral bone marrow is composed of a combination of fatty and erythropoietic marrow at most ages. When sequences are fat suppressed, the erythropoietic marrow may appear relatively bright on a dark background but this problem can be ameliorated by proper T2-weighting. The effect of T2-weighting is to reduce signal from bound water (such as in cartilage, muscle or erythropoietic marrow) but signal remains strong in free water (such as in cerebrospinal fluid or BME). Technically, this means the time to echo must be long enough—approximately 80+ms for spin echo sequences and 50+ms for STIR. The water component of T2-weighted Dixon imaging appears to be equally effective for BME detection compared with STIR or T2 with fat saturation. 12 The key requirements of the recommended protocol are strong T2-weighting plus the suppression or elimination of bone marrow fat signal. All authors agreed there is sufficient evidence to confirm that contrast-enhanced sequences are not usually necessary in adults or children and should be reserved for unusual circumstances. 13–17 Contrast enhancement would require additional cost and inconvenience with limited additional benefit. In addition, synovitis, that may be better seen with contrast enhancement, and contrast enhancement of inflammatory tissue in the joint space rarely occurs without associated BME in adults. 17

In children, the clinical situation is slightly different. Interpretation of paediatric SIJ MRI is more difficult because of greater variation in the normal appearances at sites of growth and the differential diagnosis for pain in the SIJ region is different in children. Also, SIJ MRI scans are often supervised in children when a decision regarding contrast enhancement can be made with the aid of real-time expert interpretation. For these reasons, the group chose not to make a specific recommendation regarding a paediatric SIJ MRI protocol.

A T1-weighted spin echo sequence is considered essential for accurate depiction of anatomy, visualisation of certain specific lesions and for the diagnostic assessment of the SIJ for all patients and not just spondyloarthritis cases. T1-weighted spin echo sequences are ‘fat-sensitive’ and fat lesions and backfill in subchondral bone, which are important SpA-related lesions, are best seen on T1-weighted spin echo. The Dixon technique allows any sequence acquisition to be broken down into separate fat-only and water-only images. For example, using the Dixon method, a T2-weighted spin echo sequence can be reconstructed to produce water-only images that appear identical to a T2-weighted sequence with fat saturation, plus fat-only images in which bone marrow fat is bright and the water signal is removed. While there is some evidence that T2-weighted Dixon sequences may be able to provide accurate depiction of structural damage changes in SpA, the literature is limited and contradictory. Özgen showed that a T2-weighted multipoint Dixon sequence can demonstrate the BME, sclerosis and fat lesions of sacroiliitis with better contrast-to-noise than conventional sequences. However, the publication did not assess detection of erosion or diagnostic accuracy. 18 Athira et al suggest that T2 Dixon sequences are superior or comparable to conventional MR sequences, whereas Chien et al concluded that the presence of subchondral oedema in active sacroiliitis decreased the diagnostic accuracy of SIJ erosion detection on T2W Dixon MRI. 19 20 All of these studies were quite limited by their inclusion of only a small number of subjects and only addressing the MRI findings of axSpA. There is no literature available at this time that compares the accuracy of T2-Dixon imaging to conventional sequences for a range of SIJ conditions in broader populations of patients with low back pain. Consequently, an alternative to including a T1-weighted spin echo cannot be recommended at this time.

In the early years, SIJ MRI focused more on the detection of active inflammation that could not be detected by other means. However, BME frequently occurs in other conditions, especially degeneration of the SIJ, and detection of subtle erosion is just as important as BME detection for early diagnosis. 21 It has been shown that structural damage changes can develop early in sacroiliitis and that they occur as frequently as active inflammatory lesions at the time of diagnosis. 22 In addition, there has been a tendency towards overreliance on the importance of BME for diagnosis by some local radiologists compared with central MRI readers. 22 Whereas in fact, the findings with the highest diagnostic value are actually the structural damage changes, in isolation or in combination with BME 23 and it is often only the coexistence of subtle erosion with BME that facilitates discrimination between sacroiliitis and its differential diagnoses. Erosion detection has historically relied on the T1-weighted spin echo sequence but erosions in early disease may be small and are not easy to detect on 3–4 mm thick slices. Furthermore, the subchondral bone plate is extremely thin and is often poorly defined on thick slices so that ‘loss of subchondral cortex’ may be simulated on thick slices in a joint with such frequent anatomical variation, and the majority of children demonstrate absence or blurring of the subchondral cortex on T1-weighted spin echo MRI. 24

Using CT as the gold standard, the reported sensitivity and specificity of T1-weighted spin echo in erosion detection are 61%–79% and 93%–95%, respectively. 25 26 In recent years, numerous publications have confirmed the superiority of thin slice sequences for the detection of SIJ erosion compared with T1-weighted spin echo with sensitivity in the range of 82%–96% and specificity 93%–97%. 25–30 In addition, reader reliability for erosion detection significantly improves using a thin slice 3D sequence (kappa 0.71) compared with standard thickness 2D T1-weighted spin echo (kappa 0.56). 26 It may not matter which 3D gradient echo sequence is employed and the key factors that lead to this superiority include (a) thin slices with good in-plane resolution resulting in a small voxel size and less partial volume averaging that makes small erosions easier to see and (b) gradient echo imaging is superior to spin echo for depicting defects in bone. On gradient echo, healthy bone appears darker due to signal loss related to the presence of calcium in the bone which then makes an erosion cavity appear brighter by comparison because the calcified bone has been destroyed by the erosion ( figure 3 ). This has been known for decades and thicker-slice gradient echo sequences have been used to image the SIJ for over 25 years. 31 Multiple thin slice 3D sequences based on a gradient echo technique have been shown to be superior to T1-weighted spin echo, even if the thicker spin echo sequence has superior in-plane resolution. These include (in alphabetical order): balanced steady-state free precession, Liver Acquisition with Volume Acceleration, sometimes called Black Bone, susceptibility weighted image, ultrashort echo time, volumetric interpolated breath-hold examination, ZTE (zero echo time) to mention but a few, 25–30 with some examples provided in figure 3 . Very little data are available to directly compare these sequences with each other and it is also unclear for several of these sequences if erosion detection is better with or without fat suppression although the majority of publications recommend that the 3D gradient echo sequence be performed with T1-weighting and fat suppression. Also, more recently, it has been shown that a ‘BoneMRI’ reconstruction algorithm can create synthetic CT-like images from a 3D gradient echo MRI sequence that appear similar to CT images. 32 Regardless of exactly which sequence is used, radiologists should recognise the benefit of acquiring a dedicated erosion-sensitive sequence, rather than relying only on STIR and T1-weighted sequences for interpretation. They should include this sequence in their standard SIJ MRI protocol and if only a 2D sequence is available, then a T1-weighted sequence with fat suppression is recommended for erosion detection. Rheumatologists should also encourage this practice by requesting the inclusion of an erosion-sensitive sequence when SIJ MRI is being performed on their patients.

Comparison between 3 mm thick T1-weighted spin echo images (T1 SE) and 1 or 2 mm thick T1-weighted three-dimensional (3D) gradient echo with fat saturation images (T1 3D GE FS) using three different 3D gradient echo techniques (examples taken from the North American cohort of the CLASSIC study). (A, B) T1 SE appears to show probable erosion of the articular surface of the left ilium (arrows in A). However, 2 mm thick 3D FAME confirms that no erosion is present with mild subchondral sclerosis noted (arrowheads in B). (C, D) T1 SE is suggestive for a single erosion in right SIJ (arrowhead in C), however, the image is challenging to interpret. In the 1 mm thick 3D VIBE image, the contrast between bone and cartilage/erosion is much greater and multiple erosions of the right ilium are obvious (arrows in D). (E, F) On the T1 SE, Iliac subchondral bone marrow signal is heterogeneous but no definite erosion is seen and the sacrum appears normal. (E) By comparison, 3D LAVA shows small but definite erosions in the left ilium (arrows in F) and probable erosion in the right ilium. In addition, small but definite right sacral erosions visible on the 3D LAVA (arrowheads in F) are invisible on T1 spin echo (E). FAME, fast acquisition with multiphase elliptical fast gradient echo; LAVA, liver acceleration volume acquisition; VIBE, volumetric interpolated breath-hold examination.

It is suggested that the semiaxial sequence may be performed with a larger field of view and more slices so as to include the pubic symphysis, hip joints and most of the pelvic entheses thereby including one sequence in the protocol which can assess overall pelvic morphology and sites of potential inflammation in the pelvis outside the SIJ. 33 If only one sequence is performed in the semi-axial plane, a T2-weighted spin echo Dixon sequence with all four components reconstructed (in-phase, out-of-phase, water-only and fat-only) may be particularly suitable as it may allow adequate evaluation of most components of sacroiliitis and sacroiliac anatomy.

It should be noted that this protocol has not been designed for screening purposes. It is intended as a diagnostic protocol and not only for axSpA but also for the differential diagnoses of sacroiliitis such as normal variation, joint degeneration, osteitis condensans ilii and other stress/strain reactions and would also detect septic arthritis and focal bone lesions. The recommendations do not include any discussion regarding whether all or part of the spine should or should not be scanned which depends on the population and local factors including cost, availability and the referring physician’s plans for management if the MRI is positive or negative for axSpA. This protocol is designed for adults and all clinical circumstances in which the SIJ are being scanned for possible axSpA regardless of who the requesting healthcare provider may be. Although not specifically designed for use in the paediatric population, the principles and recommended sequences should also be applicable to SIJ MRI in children. However, a comprehensive paediatric protocol needs to be developed that addresses issues which may be specific to that population.

A standardised IAP for MRI of the SIJ for diagnostic evaluation of sacroiliitis due to axSpA is recommended and should be composed of at least four sequences that incorporate imaging of the joints in two planes orthogonal to the sacrum and include an inflammation-sensitive, a fat-sensitive and an erosion-sensitive sequence that will optimally visualise active inflammation, structural damage lesions and the bone-cartilage interface. The protocol can be applied to any MRI scanner and radiologists should follow the principles that underlie the consensus recommendation in the design of their local SIJ MRI protocol.

Ethics statements

Patient consent for publication.

Not applicable.

Acknowledgments

The MRI examples illustrated in figures 1–3 are all provided, with permission, by the North American cohort of the Classification of Axial Spondyloarthritis Inception Cohort Study (CLASSIC) study. This work has been presented in abstract form at two international meetings:EULAR 2022 Congress, Copenhagen, Denmark, 1 June 2022–4 June 2022. Development of international consensus on a standardised image acquisition protocol for diagnostic evaluation of the sacroiliac joints by MRI–an ASAS-SPARTAN collaboration (abstract). R Lambert, X Baraliakos, S Bernard, J Carrino, T Diekhoff, I Eshed et al. Ann Rheum Dis 2022, 81 suppl 1:802—Abstract #3365American College of Rheumatology—ACR Convergence 2022, Philadelphia, Pennsylvania, USA, November 10 November 2022–14 November 2022. Development of International Consensus on a Standardised Image Acquisition Protocol for Diagnostic Evaluation of the Sacroiliac Joints by MRI—an ASAS-SPARTAN Collaboration [abstract]. Lambert R, Baraliakos X, Bernard S, Carrino J, Diekhoff T, Eshed I, Hermann K, Herregods N, Jaremko J, Jans L, Jurik A, O'Neill J, Reijnierse M, Tuite M, Maksymowych W. Arthritis Rheumatol. 2022; 74 (suppl 9). Abstract #1258

• Docherty P ,
• Mitchell MJ ,
• MacMillan L , et al
• François RJ , et al
• Lambert RGW ,
• Bakker PAC ,
• van der Heijde D , et al
• Sudoł-Szopińska I ,
• Eshed I , et al
• Bennett AN , et al
• Maksymowych WP ,
• Lambert RG ,
• Baraliakos X , et al
• Vereecke E ,
• Herregods N , et al
• Ziegeler K ,
• Poddubnyy D , et al
• Zejden A , et al
• Diekhoff T ,
• Sieper J , et al
• Hu X , et al
• Zhang H , et al
• Althoff CE ,
• Burova E , et al
• Madsen KB ,
• de Hooge M ,
• van den Berg R ,
• Navarro-Compán V , et al
• Herregods N ,
• Jaremko JL ,
• Cannane S ,
• Thushara R , et al
• Chien CPY ,
• Chung HY , et al
• Østergaard M , et al
• Pedersen SJ ,
• Weber U , et al
• Baraliakos X ,
• Fruth M , et al
• Schiettecatte E , et al
• Zhang X , et al
• Wolharn L ,
• Guggenberger R ,
• Higashigaito K , et al
• Hermann K-G ,
• Proft F , et al
• Choi EJ , et al
• Hou B , et al
• Kannenberg J , et al
• Elewaut D , et al

Handling editor Josef S Smolen

Contributors All authors meet all four ICMJE criteria for authorship, and all who meet the four criteria are identified as authors. There are no other contributors to the work. No one who fulfils the criteria has been excluded as an author. RGWL: submitting and corresponding author. Responsible for planning, conducting and reporting the work. Guarantor. XB: coauthor involved in conducting and reporting the work. SAB: coauthor involved in conducting and reporting the work. JAC: coauthor involved in conducting and reporting the work TD: coauthor involved in conducting and reporting the work. IE: coauthor involved in conducting and reporting the work. KGH: coauthor involved in conducting and reporting the work. NH: coauthor involved in conducting and reporting the work. JJ: coauthor involved in conducting and reporting the work. LJ: coauthor involved in conducting and reporting the work. AGJ: coauthor involved in conducting and reporting the work. JMDO’N: coauthor involved in conducting and reporting the work. MR: coauthor involved in conducting and reporting the work. MJT: coauthor involved in conducting and reporting the work. WPM: coauthor involved in conducting and reporting the work.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests RGWL: consulting fees from CARE Arthritis and Image Analysis Group. XB: contract with Novartis; Consulting fees from Amgen, Bristol-Myers Squibb, Chugai, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sandoz, Sanofi, and UCB; Payment or honoraria from Amgen, Bristol-Myers Squibb, Chugai, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sandoz, Sanofi, and UCB; Meeting support from Eli Lilly, Janssen, Novartis, Pfizer and UCB; Participation on a Data Safety Monitoring Board or Advisory Board: Amgen, Bristol-Myers Squibb, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB; Leadership role: Editorial Board Member of Annals of Rheumatic Diseases, ASAS President, EULAR President Elect. SAB: Royalties from Elsevier. JAC: Consulting fees from AstraZeneca and Covera Health; Participation on a Data Safety Monitoring Board or Advisory Board: Carestream, Image Analysis Group, Image Biopsy Lab; Leadership role: RSNA, ACR, IAOAI. TD: Grants or contracts from Berlin Institute of Health (BIH); Payment or honoraria from Berlinflame, Canon Medical Systems, Janssen, MSD, Novartis, UCB. IE: Payment or honoraria from Lilly, Novartis. KGH: Payment or honoraria from MSD, AbbVie Novartis; Cofounder of BerlinFlame. NH: None declared. JJ: Stock in Exo. LJ: None declared. AGJ: None declared. JMDO'N:– None declared. MR: ISS Seed Grant; Consultant for ASAS. MJT: Consulting fees from GE HealthCare; Meeting support from International Skeletal Society; Leadership role—President-elect International Skeletal Society. WPM: Grants or contracts from Abbvie, BMS, Eli-Lilly, Pfizer, UCB; Consulting fees from Abbvie, Celgene, BMS, Eli-Lilly, Galapagos, Pfizer, UCB; Payment or honoraria from Abbvie, Janssen, Pfizer, Novartis; Leadership role—SPARTAN Board of Directors; Chief Medical Officer, CARE Arthritis.

Provenance and peer review Not commissioned; externally peer reviewed.

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