[ps2id id=’research-ethics-approval’ target=”/]
24. RESEARCH ETHICS APPROVAL
Plans for seeking research ethics committee/institutional review board (REC/IRB) approval.
Example
“This protocol and the template informed consent forms contained in Appendix II will be reviewed and approved by the sponsor and the applicable IRBs/ECs [institutional review boards/ethical committees] with respect to scientific content and compliance with applicable research and human subjects regulations . . .
The protocol, site-specific informed consent forms (local language and English versions), participant education and recruitment materials, and other requested documents — and any subsequent modifications — also will be reviewed and approved by the ethical review bodies (IRBs/ECs) . . .
Subsequent to initial review and approval, the responsible local Institutional Review Boards/Ethical Committees (IRBs/ECs) will review the protocol at least annually. The Investigator will make safety and progress reports to the IRBs/ECs at least annually and within three months of study termination or completion at his/her site. These reports will include the total number of participants enrolled . . . and summaries of each DSMB [Data Safety and Monitoring Board] review of safety and/or efficacy.” 287
Explanation
A universal requirement for the ethical conduct of clinical research is the review and approval of the research protocol by qualified individuals who are not associated with the research team and have no disqualifying competing interests as reviewers.1 The review is typically conducted by a formal REC/IRB in accordance with jurisdictional policy. Despite the importance of ethics review, approval by a REC/IRB is not always obtained. Among 767 trials published in leading general medical journals from 1993-95, 37 authors (5%) disclosed that such approval had not been sought for their trials.344 The protocol should document where approval has been obtained, or outline plans to seek such approval.[ps2id id=’protocol-amendments’ target=”/]
25. PROTOCOL AMENDMENTS
Plans for communicating important protocol modifications (e.g., changes to eligibility criteria, outcomes, analyses) to relevant parties (e.g., investigators, REC/IRBs, trial participants, trial registries, journals, regulators).
Example
“13.10 Modification of the Protocol
Any modifications to the protocol which may impact on the conduct of the study, potential benefit of the patient or may affect patient safety, including changes of study objectives, study design, patient population, sample sizes, study procedures, or significant administrative aspects will require a formal amendment to the protocol. Such amendment will be agreed upon by BCIRG [Breast Cancer International Research Group] and Aventis, and approved by the Ethics Committee/IRB [institutional review board] prior to implementation and notified to the health authorities in accordance with local regulations.
Administrative changes of the protocol are minor corrections and/or clarifications that have no effect on the way the study is to be conducted. These administrative changes will be agreed upon by BCIRG and Aventis, and will be documented in a memorandum. The Ethics Committee/IRB may be notified of administrative changes at the discretion of BCIRG.” 345
Explanation
After initial ethics approval, about half of trials have subsequent protocol amendments submitted to the REC/IRB.125;346;347 While some amendments may be unavoidable, a study of pharmaceutical industry trials found that according to the sponsors, a third of amendments could have been prevented with greater attention to key issues during protocol development.346 Substantive amendments can generate challenges to data analysis and interpretation if they occur part way through the trial (e.g., changes in eligibility criteria),348 and can introduce bias if the changes are made based on the trial data.173;176 The implementation and communication of amendments are also burdensome and potentially costly.346
Numerous studies have revealed substantive changes between prespecified methods (e.g., as stated in approved protocols, registries, or regulatory agency submissions) and those described in trial publications, including changes to primary outcomes,12;172-176 sample size calculations,6 eligibility criteria,125;133; 134 as well as methods of allocation concealment,2 blinding,3 and statistical analysis.6-8;174 These substantive modifications are rarely acknowledged in the final trial reports, providing an inaccurate impression of trial integrity.
It is important that substantive protocol amendments be reviewed by an independent party, such as the REC/IRB, and transparently described in trial reports. The notion of ‘substantive’ is variably defined by authorities, but in general refers to a protocol amendment that can affect the safety of trial participants or the scientific validity, scope, or ethical rigour of the trial.349;350 To reflect the degree of oversight for the trial and adherence to applicable regulation, the protocol should describe the process for making amendments, including who will be responsible for the decision to amend the protocol and how substantive changes will be communicated to relevant stakeholders (e.g., REC/IRBs, trial registries, regulatory agencies). Version control using protocol identifiers and dates (Item 3), as well as a list of amendments, can help to track the history of amendments and identify the most recent protocol version.[ps2id id=’consent-or-assent’ target=”/]
26. CONSENT OR ASSENT
26a. Consent or assent
Who will obtain informed consent or assent from potential trial participants or authorised surrogates, and how (see Item 32).
Example
“. . . Trained Research Nurses will introduce the trial to patients who will be shown a video regarding the main aspects of the trial. Patients will also receive information sheets. Research Nurses will discuss the trial with patients in light of the information provided in the video and information sheets. Patients will then be able to have an informed discussion with the participating consultant. Research Nurses will obtain written consent from patients willing to participate in the trial. Information sheets and consent forms are provided for all parents involved in the trial however these have been amended accordingly in order to provide separate information sheets and consent form which are suitable for children and teenagers [sic]. All information sheets, consent forms and the video transcript have been translated into Bengali, Punjabi, Gujarati, and Urdu. There are also separate information sheets and consent forms for the cohort group.”351
Explanation
The notion of acquiring informed consent involves the presentation of comprehensible information about the research to potential participants, confirmation that they understand the research, and assurance that their agreement to participate is voluntary. The process typically involves discussion between the potential participant and an individual knowledgeable about the research; the presentation of written material (e.g., information leaflet or consent document); and the opportunity for potential participants to ask questions. Surveys of trial investigators reveal that appropriate informed consent is not always obtained.344;352
The content, quantity, and mode of delivery of consent information can affect trial recruitment, participant comprehension, anxiety, retention rates, and recruitment costs.68;114;218;292;353-355 We recommend that a model consent or assent form be provided as a protocol appendix (Item 32). Assent represents a minor’s affirmative agreement to participate in the trial, which typically involves signing a document that provides age-appropriate information about the study.
The protocol should include details of the consent process as well as the status, experience, and training (if applicable) of the research team members who will conduct it. In paediatric research, regulations may stipulate obtaining affirmative assent for participation from children above a certain age.356 The protocol should then describe how pertinent information will be provided to potential participants and how their understanding and assent will be ascertained. When potential participants lack decisional capacity for reasons other than young age (e.g., mental status), and proxy consent can be obtained from a legally-authorised representative, the protocol should describe who will determine an individual’s decisional capacity, whether a formal capacity instrument will be utilised, and how the individual’s informed agreement to continue participation will be secured should they regain decisional capacity. For certain trials, such as cluster randomised trials, it may not be possible to acquire individual informed consent from participants before randomisation, and the consent process may be modified or waived. An explanation should be provided in the protocol in these instances[ps2id id=’ancillary-studies’ target=”/].357
26b. Ancillary studies
Additional consent provisions for collection and use of participant data and biological specimens in ancillary studies, if applicable.
Example
“6.4.1. Samples for Biorepositories
Additional biological samples will be obtained to be stored for use in future studies of the pathobiology of FSGS [focal segmental glomerulosclerosis]. A materials consent will be obtained to specifically address the collection of these . . . urine, serum and plasma specimens . . .
14.3.4. Instructions for Preparation of Requests for an Ancillary Study
. . . A signed consent must be obtained from every participant in the ancillary study, if the data collection/request is not covered in the original informed consent process for the main FSGS Clinical Trial.
. . .
A copy of the IRB [Institutional Review Board] letter for the ancillary study should be sent to the DCC [Data Coordinating Center]. If a separate consent form is required for the ancillary study, a copy of the signed ancillary study consent form for each study participant must be included in the FSGS-CT [Focal segmental glomerulosclerosis – Clinical Trial] record. A data file tracking all signed ancillary consent forms must be maintained by the ancillary study and an electronic copy of that file must be delivered to the FSGS-CT DCC.”267
Explanation
Ancillary studies involve the collection or derivation of data for purposes that are separate from the main trial. The acquisition and storage of data and biological specimens for ancillary studies is increasingly common in the context of clinical trials (Item 33). Specimens may be used for a specified subset of studies or for submission to biorepositories for future specified or unspecified research.
Ancillary studies have additional processes and considerations relating to consent, which should be detailed in the protocol. Guidance for the creation of a simplified informed consent document for biobanking is available.358 Participants can be given several options to consider with respect to their participation in ancillary research: consent for the use of their data and specimens in specified protocols; consent for use in future research unrelated to the clinical condition under study; consent for submission to an unrelated biorepository; and consent to be contacted by trial investigators for further informational and consent-related purposes. This is commonly referred to as tiered consent. Participants should also be informed about whether their withdrawal from the ancillary research is possible (e.g., the data and specimens are coded and identifiable); what withdrawal means in this context (e.g., used specimens and data derived from them cannot be withdrawn); and what information derived from the specimen-related research will be provided to them, if any.[ps2id id=’confidentiality’ target=”/]
27.CONFIDENTIALITY
How personal information about potential and enrolled participants will be collected, shared, and maintained in order to protect confidentiality before, during, and after the trial.
Example
“8.5 Confidentiality
All study-related information will be stored securely at the study site. All participant information will be stored in locked file cabinets in areas with limited access. All laboratory specimens, reports, data collection, process, and administrative forms will be identified by a coded ID [identification] number only to maintain participant confidentiality. All records that contain names or other personal identifiers, such as locator forms and informed consent forms, will be stored separately from study records identified by code number. All local databases will be secured with password-protected access systems. Forms, lists, logbooks, appointment books, and any other listings that link participant ID numbers to other identifying information will be stored in a separate, locked file in an area with limited access.
All HIV [human immunodeficiency virus] test results will be kept strictly confidential, all counseling and blood draws will be conducted in private rooms, and study staff will be required to sign agreements to preserve the confidentiality of all participants. Study staff will never inform network members of the serostatus of other members of their group, but counselors will provide general messages about the prevalence of HIV in the study population in the interests of emphasizing harm reduction.
Participants’ study information will not be released outside of the study without the written permission of the participant, except as necessary for monitoring by NIAID [National Institute of Allergy and Infectious Diseases] and/or its contractors . . . representatives of the HPTN CORE [HIV Prevention Trials Network Coordinating and Operations Center] . . . and US or in-country government and regulatory authorities.”359
Explanation
Personal information about participants is acquired during the process of trial recruitment, eligibility screening, and data collection. Much of this information consists of private details over which people customarily wish to maintain control, such as their health status, personal genotype, and social and family history.
The protocol should describe the means whereby personal information is collected, kept secure, and maintained. In general, this involves: 1) the creation of coded, de-personalised data where the participant’s identifying information is replaced by an unrelated sequence of characters; 2) secure maintenance of the data and the linking code in separate locations using encrypted digital files within password-protected folders and storage media; and 3) limiting access to the minimum number of individuals necessary for quality control, audit, and analysis. The protocol should also describe how the confidentiality of data will be preserved when the data are transmitted to sponsors and co-investigators (e.g., Virtual Private Network Internet transmission).[ps2id id=’declaration-of-interests’ target=”/]
28. DECLARATION OF INTERESTS
Financial and other competing interests for principal investigators for the overall trial and each study site.
Example
- Was the Principal Investigator of the second International Stroke Trial (IST-2) to evaluate a neuroprotective compound (619c89) . . .
- Has received lecture fees and travel expenses from Bayer and from Boehringer Ingelheim for lectures given at international conferences.
- He serves on the Independent Data Monitoring and Safety Board of the RELY trial, funded by Boehringer Ingelheim and receives attendance fees and travel expenses for attending board meetings.
- He does not have any paid consultancies with pharmaceutical companies, and is not a member of the Speaker’s Panel of any company.
- Received an honorarium for a lecture from Boehringer Ingelheim and had costs for participating in scientific meetings reimbursed . . .”124
Explanation
Competing interests, or conflicts of interest, exist when there is potential for divergence between an individual’s or institution’s private interests and their responsibilities to scientific and publishing activities.360 More positive outcomes, larger treatment effect sizes, and more favourable interpretation of results have been found in clinical trials with pharmaceutical industry sponsorship (Item 4)27;36-38;42 and investigators who have declared competing interests,57;60 compared to those without such interests. Although competing interests are most often associated with drug and device industries, they may exist with support from or affiliation with government agencies, charities, not for profit organisations, and professional and civic organisations.
Competing interests do not in themselves imply wrongdoing. Their disclosure and regular updating enables appropriate management plans to be developed and implemented, and facilitates transparent assessment of the potential for bias.
Many trials and non-industry sponsors have a conflict of interest policy for their investigators, and checklists are available to guide potential interests that should be disclosed and regularly updated by trial investigators.361;362 Types of financial ties include salary support or grants; ownership of stock or options; honoraria (e.g., for advice, authorship, or public speaking); paid consultancy or service on advisory boards and medical education companies; and receipt of patents or patents pending. Non-financial competing interests include academic commitments; personal or professional relationships; and political, religious, or other affiliations with special interests or advocacy positions.[ps2id id=’access-to-data’ target=”/]
29. ACCESS TO DATA
Statement of who will have access to the final trial dataset, and disclosure of contractual agreements that limit such access for investigators.
Example
“12.10.1 Intra-Study Data Sharing
The Data Management Coordinating Center will oversee the intra-study data sharing process, with input from the Data Management Subcommittee.
All Principal Investigators (both U.S. and host country) will be given access to the cleaned data sets. Project data sets will be housed on the Project Accept Web site and/or the file transfer protocol site created for the study, and all data sets will be password protected. Project Principal Investigators will have direct access to their own site’s data sets, and will have access to other sites data by request. To ensure confidentiality, data dispersed to project team members will be blinded of any identifying participant information.”113
Explanation
The validity of results from interventional trials can only be verified by individuals who have full access to the complete final dataset. For some multicentre trials, only the steering group has access to the full trial dataset in order to ensure that the overall results are not disclosed by an individual study site prior to the main publication. Many of these trials will allow site investigators to access the full dataset if a formal request describing their plans is approved by the steering group. The World Medical Association supports the principle that trial investigators retain the right to access data.363 However, among protocols of industry-initiated randomised trials published in 2008-9 in the Lancet or approved in 2004 by a Danish ethics committee, 30-39% stated that the sponsor owned the data while 0-3% stated that principal investigators had access to all trial data.10;364 Similar constraints were found in Danish trial protocols from 1994-5.10
The protocol should identify the individuals involved in the trial who will have access to the full dataset. Any restrictions in access for trial investigators should also be explicitly described.[ps2id id=’ancillary-and-post-trial-care’ target=”/]
30. ANCILLARY AND POST-TRIAL CARE
Provisions, if any, for ancillary and post-trial care, and for compensation to those who suffer harm from trial participation.
Example 1
“Patients that are enrolled into the study are covered by indemnity for negligent harm through the standard NHS [National Health Service] Indemnity arrangements. The University of Sheffield has insurance to cover for non-negligent harm associated with the protocol . . . This will include cover for additional health care, compensation or damages whether awarded voluntarily by the Sponsor, or by claims pursued through the courts. Incidences judged to arise from negligence (including those due to major protocol violations) will not be covered by study insurance policies. The liability of the manufacturer of IL1RA (Amgen Corporation) is strictly limited to those claims arising from faulty manufacturing of the commercial product and not to any aspects of the conduct of the study.”145
Example 2
“13.6 Access to Effective Products
Should this study provide evidence of the effectiveness of TDF [tenofovir disoproxil fumarate], FTC [emtricitabine]/TDF and/or tenofovir 1% gel in preventing HIV [human immunodeficiency virus] infection, it will be critical to provide access to the effective product(s) to study participants, their communities, and the worldwide population at risk for HIV infection in a timely manner. In preparation for this study, discussions have begun with Gilead Sciences, Inc. and CONRAD [Contraceptive Research and Development Organization] to ensure such access. Considerations under discussion include licensing agreements and preferred pricing arrangements for the study communities and other resource-poor settings.
While this study is ongoing, the MTN [Microbicide Trials Network] will continue these discussions. In addition, discussions will be initiated with other public and private funding sources such as the WHO [World Health Organization], UNAIDS [Joint United Nations Program on HIV/AIDS], Gates Foundation, and appropriate site government agencies that may be able to purchase product supplies in bulk and offer them at low or no cost to the study communities and other resource-poor communities most in need of the product(s). Operations and marketing research also may be conducted to determine how best to package and distribute the products, and maximize their acceptability and use, in at-risk populations.”365
Explanation
The provision of ancillary care refers to the provision of care beyond that immediately required for the proper and safe conduct of the trial, and the treatment of immediate adverse events related to trial procedures. It is generally agreed that trial sponsors and investigators should plan to provide care for participants’ health care needs that arise as a direct consequence of trial participation (e.g., intervention-related harms). It is also important to consider whether care should be provided for certain ancillary needs that may otherwise arise during trial participation. Provision of care for ancillary needs reflects the fact that participants implicitly, but unavoidably, entrust certain aspects of their health to the research team. The scope of entrustment will vary depending on the nature of the trial (e.g., setting, health condition under study, investigations performed).366 Additional factors that influence the strength of the claim to ancillary care include participants’ vulnerabilities; uncompensated burdens and harms; the intensity and duration of the participant-researcher relationship; and the degree to which participants are uniquely dependent on the research team for health care.367
The Declaration of Helsinki states that “the protocol should describe arrangements for post-study access by study participants to interventions identified as beneficial in the study or access to other appropriate care or benefits”.1 This principle is particularly applicable – and controversial – when research enabling the development and regulatory approval of interventions is performed in countries where subsequent access to the interventions is limited by cost or lack of availability.368
The protocol should describe any plans to provide or pay for ancillary care during the trial and identify any interventions, benefits, or other care that the sponsor will continue to provide to participants and host communities after the trial is completed.369 Any plans to compensate participants for trial-related harms should also be outlined.[ps2id id=’dissemination-policy’ target=”/]
31. DISSEMINATION POLICY
31a. Trial results
Plans for investigators and sponsor to communicate trial results to participants, healthcare professionals, the public, and other relevant groups (e.g., via publication, reporting in results databases, or other data sharing arrangements), including any publication restrictions.
Example
“XII. Publication Policy
The Publications subcommittee will review all publications following the guidelines given below and report its recommendations to the Steering Committee.
A. Data analysis and release of results
The scientific integrity of the project requires that the data from all BEST [Beta-Blocker Evaluation of Survival Trial] sites be analyzed study-wide and reported as such. Thus, an individual center is not expected to report the data collected from its center alone . . . all presentations and publications are expected to protect the integrity of the major objective(s) of the study; data that break the blind will not be presented prior to the release of mainline results. Recommendations as to the timing of presentation of such endpoint data and the meetings at which they might be presented will be given by the Steering Committee.
B. Review process
Each paper or abstract, as described below, must be submitted to the appropriate Subcommittee for review of its appropriateness and scientific merit prior to submission. The Subcommittee may recommend changes to the authors and will finally submit its recommendations to the Steering Committee for approval.
C. Primary outcome papers
The primary outcome papers of BEST are papers that present outcome data . . . The determination of whether or not a particular analysis represents a primary outcome will be made by the Steering Committee on the recommendation of the Publications Subcommittee . . .
D. Other study papers, abstracts and presentations
All studies other than those designated as “Primary Outcome” fall within this category . . . All papers and abstracts must be approved by the Publications Committee before they are submitted.
It is possible that in certain instances BEST may be asked to contribute papers to workshops, symposia, volumes, etc. The individuals to work on such requests should be appointed by the Executive Committee, but where time permits, a proposal will be circulated soliciting other participants as in the case of other study papers as described in the Application Review Process.
XIII. Close-out Procedures
BEST may terminate at the planned target of 1.5 years after the last participant has been randomized, or at an earlier or later date if the circumstances warrant . . . Regardless of the timing and circumstances of the end of the study, close-out will proceed in two stages:
· Interim period for analysis and documentation of study results
· Debriefing of participants and dissemination of study results.
A. Interim
Every attempt will be made to reduce to an absolute minimum the interval between the completion of data collection and the release of the study results. We expect to take about 3 to 4 months to compile the final results paper for an appropriate journal.
B. Reporting of study results
The study results will be released to the participating physicians, referring physicians, patients and the general medical community.”370
Explanation
A fundamental ethical principle in clinical trials is that the potential risks incurred by study participants should be balanced by the benefit of contributing to publicly-available knowledge.371 Unfortunately, about half of clinical trials remain unpublished.80,83 Trials with statistically non-significant results or industry funding are more prone to non-publication,36;38;80-83 although government-funded trials are also susceptible.81 When published, trials with non-significant results often have a longer delay to publication.80;83 Overall, the medical literature represents a biased subset of existing data, potentially leading to overestimation of benefits, underestimation of harms, and a detrimental impact on patient care and research.80;372-377
Although peer reviewers can be biased in favour of positive findings,378 lack of publication appears to be primarily due to trial investigators or sponsors failing to submit negative or null results, rather than journals rejecting them.80;379 A plan to disseminate trial results to key stakeholders should be outlined in the protocol, including a process and timeframe for approving and submitting reports for dissemination (e.g., via journal publication, trial registry, trial website), and an explicit statement that the results will be disseminated regardless of the magnitude or direction of effect.
Furthermore, any conditions relating to the investigators’ right to publish or present trial results should be explicitly described. Publication restrictions have been imposed by various groups, including industry sponsors or the trial steering group (e.g., to maintain the integrity of the overall dataset).10;380 These restrictions are sometimes not described in the protocol but rather in separate publication agreements.10 However, as they can interfere with the ethical responsibility of investigators and sponsors to disseminate trial results in an unbiased and timely manner,38;381-384 any restrictions should be disclosed in the protocol for review by REC/IRBs, funders, and other stakeholders. A review of industry-initiated randomised trial protocols approved in Denmark in 1994-95 revealed that 91% had publication restrictions imposed by sponsors; similar constraints were noted for protocols approved in 2004[ps2id id=’authorship’ target=”/].10
31b. Authorship
Authorship eligibility guidelines and any intended use of professional writers.
Example
“17.4. Assignment of Writing Committees
Topics suggested for presentation or publication will be circulated to the PIs [Principal investigators] of the CCCs [Core Coordinating Centers], the DCC [Data Coordinating Center], Core Lab and the NIH [National Institutes of Health]. These groups are requested to suggest and justify names for authors to be reviewed by the PC [Publications Committee] . . . If a topic is suggested by a participant of the FSGS-CT [Focal segmental glomerulosclerosis – clinical trial], the writing committee will be formed as just described except that the person making the suggestion may be considered as the lead author. The PI [Principal Investigator] of an ancillary study should be considered for lead author of material derived from this study. Disputes regarding authorship will be settled by the Study Chair after consultation with the Chair of the PC . . .
17.5. Reports of the FSGS-CT: Classes of Reports
There are three classes of reports of the FSGS-CT:
A. Reports of the major outcomes of the Study.
B. Reports addressing in detail one aspect of the FSGS-CT, but in which the data are derived from the entire study.
C. Reports of data derived from a subset of centers by members of the FSGS-CT, (e.g., sub-studies or ancillary studies), or reports of investigations initiated outside of the FSGS-CT, but using data or samples collected by the FSGS-CT . . .
17.6. Authorship Policy
The authors of FSGS publications will be listed as detailed below.
Type A publications:
abstracts: from the FSGS Clinical Trial Groupx, presented by XXXX.
papers: from the FSGS Clinical Trial Groupx, prepared by XXXX.
xThe FSGS participant box, detailed below, must be included in these papers. If a journal’s publication policy does not allow authorship by a group, the authors will be listed first as in Type B publications.
Type B publications:
. . .
17.7. Authorship: Professional Participants Listing in the FSGS Participant Box
The FSGS participant box will list all professionals that have participated in the FSGS-CT for a minimum of one year . . . ”267
Explanation
Substantive contributions to the design, conduct, interpretation, and reporting of a clinical trial are recognised through the granting of authorship on the final trial report. Authorship guidelines in the protocol are intended to help enhance transparency and avoid disputes or misunderstanding after trial completion. These guidelines should define criteria for individually named authors or group authorship.385
Individuals who fulfil authorship criteria should not remain hidden (ghost authorship) and should have final authority over manuscript content.9;386;387 Similarly, those who do not fulfil such criteria should not be granted authorship (guest authorship).386;388 The International Committee of Medical Journal Editors has defined authorship criteria for manuscripts submitted for publication,389 although these criteria have reportedly been open to abuse.390 If some protocol authors are not named authors of subsequent publications, their role in protocol design should at least be acknowledged in the published report. Among 44 protocols of industry-initiated trials, 75% had evidence of ghost authorship when compared with corresponding journal publications.9
Professional medical writers are sometimes hired to improve clarity and structure in a trial report, and guidelines for ethical collaborative writing have been developed.391;392 Because the drafting of text can influence how the study results and conclusions are portrayed, plans for the employment of writers and their funding source should be acknowledged in both protocols and trial reports.[ps2id id=’reproducible-research’ target=”/]
31c. Reproducible research
Plans, if any, for granting public access to the full protocol, participant-level dataset, and statistical code.
Example
“Data sharing statement No later than 3 years after the collection of the 1-year postrandomisation interviews, we will deliver a completely deidentified data set to an appropriate data archive for sharing purposes.”393
Explanation
Given the central role of protocols in enhancing transparency, reproducibility, and interpretation of trial results, there is a strong ethical and scientific imperative to ensure that full protocols are made publicly available.24;394;395 High-quality protocols contain relevant details on study design and conduct that are generally not available in journal publications or trial registries.84;396 It is also important to make available the full study report, such as the “clinical study report” submitted to regulatory agencies by industry sponsors.377;396-400 This detailed report provides the most comprehensive description of trial methods (including the full protocol) and all published and unpublished analyses. In addition, there have increasingly been calls to improve the availability of participant-level datasets and statistical code after journal publication to enable verification and replication of analyses, facilitate pooling with other studies, and accelerate research through open knowledge sharing.372;401-406
Avenues for providing access to full protocols include journals,407;408 trial websites, and trial registries.163 Several journals and funders support the sharing of participant-level data,405;409-411 while others routinely publish a statement regarding sharing of protocols, statistical codes, and datasets for all of their published research articles.412;413
The protocol should indicate whether the trial protocol, full study report, anonymised participant-level dataset, and statistical code for generating the results will be made publicly available; and if so, describe the timeframe and any other conditions for access.