Comments on the ICMJE’s Proposals for Sharing Clinical Trial Data

Displaying 1 - 5 of 320 comments
  • John Abramson
    Harvard Medical School
    Role(s): Researcher
    Date Submitted: Monday, April 18, 2016 - 20:53

    Requirement To Share Data
    Comments: The ICMJE’s proposal to increase transparency of clinical trial data by requiring access to the data necessary to confirm published findings --but only the data required to confirm published findings--will do little to ensure that journals report accurate and reasonably complete results that allow doctors and the public to derive the full benefit of medical science. Not requiring submission of clinical study reports and patient level data at the time of manuscript submission precludes verification of study details and deprives editors and peer reviewers of both easily navigable tabulated data and the primary data necessary to evaluate the accuracy and reasonable completeness of manuscripts.

    6 Month Time Frame
    Comments: Not requiring the data for up to 6 months after publication means that peer-reviewers and medical journal editors will remain unable to verify findings reported in submitted manuscripts prior to publication, and therefore that peer-review will remain essentially meaningless as a tool to ensure accuracy of results reported. Further, the delay in requiring submission of patient-level data will result in journal readers continuing to formulate opinions and beliefs about the clinical impact of study results prior to the confirmatory primary data being available.

    Require a Data Sharing Plan
    • I agree with this general approach
    Comments: Requiring publication of the plan for data sharing will allow access to the data when it becomes available. This would be far more important in the data were both timely (available at the time of publication) and complete (Clinical Study Report and complete patient level data), not limited to data necessary to reproduce published findings.

    Providing Credit
    • I agree with this general approach

    Other Comments: The current ICMJE proposal to increase data transparency is, in my opinion, too narrowly focused on journals’ parochial interests over and above the public’s right to derive maximum benefit from medical research. A proposal that would better serve journals’ various constituencies and restore the meaning of “evidence-based medicine” would require access to clinical study reports and patient-level data (with relevant code books) at the time of manuscript submission, and then require public access to clinical study reports and complete patient-level data at the time of publication. Only such true transparency will assure that physicians and the public have access to the full benefit of medical research. And only medical journals, acting together, are in a position to facilitate such transparency.

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  • Paul Glasziou
    Bond University
    Role(s):
    • Researcher
    • Clinician
    Date Submitted: Monday, April 18, 2016 - 20:34

    Requirement To Share Data
    Comments: Any study is a bundle of linked Methods, Materials, Analysis Plan, Raw data and coded data, with a usable data dictionary, all of which are needed. However, a MUCH higher priority should be placed on public access to methods (protocol) and materials, and the complete summary data (whether published or not) without which the numerical data are often uninterpretable.

    6 Month Time Frame
    Comments: A general timeframe of 6 months is inappropriate, given the number of exceptions that will be needed. Furthermore, this timeframe should spell out the whole timeline for all steps of the bundle of methods, materials, etc needed, eg., (i) the protocol and materials, (ii) the summary data (including items not published, but in the protocol or registry specification), and (iii) the data.

    Require a Data Sharing Plan
    Comments: This may be counter productive. Posting of summary data on clinicaltrials.gov is already required in the USA, but compliance is very poor, so adding this "plan" is unlikely to help, but will waste researchers time. (See https://clinicaltrials.gov/ct2/resources/trends - graph of Number of Registered Studies With Posted Results Over Time). It would also then be consistent to request that those doing secondary data analysis register and post their plan also.

    Providing Credit
    • I agree with this general approach
    Comments: Agreed. Journals should require a statement in the publication stating that the research has been based on shared data with a link to the source and time of data, and also cite the primary publication.

    Other Comments: Responsible data sharing is certainly a good idea, but the specifics ICJME proposal requires more analysis and discussion with stakeholders before this new burden is imposed on researchers. Journals are, appropriately, making increasing requests of authors for better reporting, but do little to assist and check that reporting. For example, the editorial claims that "this requirement aims, in part, to prevent selective publication and selective reporting of research outcomes ..." But the journals could already cross-check submitted trials against the trial registration entry, but mostly fail to do so. The numerous failures in reporting have been documented recently in the 2014 Lancet series: http://www.thelancet.com/campaigns/efficiency/complete-and-usable-reporting and the current proposal may serve as a distraction rather than a solution to those reporting issues that are much more readily and cheaply fixed, and over which journals have considerable influence.

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  • Alexander Ommaya, DSc
    Association of American Medical Colleges
    Role(s): Other
      • AAMC Acting Chief Scientific Officer
    Date Submitted: Monday, April 18, 2016 - 17:35

    Requirement To Share Data
    • I agree with this general approach
    Comments: Meaningful data sharing can: catalyze further research and maximize results from the nation’s extensive research investment; increase the impact of volunteer human subjects; enable comprehensive meta-analyses and timely re-examination or confirmation of critical findings; and leverage networks of researchers and information technology to solve complex medical and biological problems. Our central concern in implementing the proposal is to ensure protection of privacy and other obligations to patients/human subjects. While standard HIPAA or other identifiers can be removed, the ability to reconstruct patient identities from other information remains a concern, particularly from trials involving small numbers of individuals, sensitive information, or vulnerable populations. It should be recognized that asking certain variables and developing constructs to hide others could interfere with the ability to reproduce a study. Nevertheless, investigators and institutions must be permitted to exercise judgment in posting such information. ICMJE should help researchers and institutions identify and disseminate use cases and best practices for sharing sensitive patient data. The community at large should support promulgation of regulations that would penalize reidentification of individual subjects from anonymized data. Because the proposal may require adjustment of subject consent forms, journals should help disseminate model forms or provisions.

    6 Month Time Frame
    Comments: The AAMC is concerned that requiring sharing of patient level data within 6 months of publication is not always the most feasible or appropriate timeframe. Allowing later posting could help adjust the burden on investigators, and could be particularly helpful for trials of products that may be submitted for regulatory approval (such as FDA in the United States). In fact, the impact of the proposal on regulatory review may create other issues that we are unaware of. We are concerned that the requirements could create disincentives for publishing results from particularly large or complex trials in a timely manner, as investigators assess the burdens and significant costs of complying within the proposed six month deadline. The limitations of currently available platforms for sharing the data create additional logistic challenges which we hope will resolve over time. A timeframe tied to one year after publication would promote compliance by institutions and authors. It would also allow time for other studies to begin. We also urge the creation of a process for creating reasonable exceptions or extensions of this timeframe.

    Require a Data Sharing Plan
    • I agree with this general approach
    Comments: The AAMC supports a requirement to develop and make available a data sharing plan prior to publication. To effectively implement this requirement, authors and institutions will need clear guidance on how journal editors will evaluate the plan in the context of a manuscript submission. The AAMC observes that the proposal does not address the modification of a data sharing plan post registration other than in its level of restrictiveness and urges the ICMJE to articulate how such a revision, especially one that improves the data sharing plan, could be implemented. Since the need for effective data sharing is increasingly encouraged in many contexts, the community including the ICMJE should work to communicate the advantages of this movement, and how it serves patients, investigators, and science.

    Providing Credit
    • I agree with this general approach
    Comments: The AAMC strongly supports providing recognition and credit for use of data, although when investigators make use of several secondary sources, it may be difficult and unproductive to require contact or collaborations with the originating authors. Researchers have noted that papers related to genomics or other highly collaborative fields could generate hundreds of additional names. At a minimum, there should be an expectation of recognizing the originators of a data set; higher levels of contact or collaboration should result from authors’ discretion. Data sharing practices currently vary across disciplines and specialties; the AAMC hopes that community norms for citation would evolve as data sharing practices become established. The AAMC notes that using universal identifiers, such as ORCID ID, can facilitate accurate citation. Journals should help ensure that data are used only by qualified researchers, and that original contributors are notified when further research is published or utilized. True transparency is bi-directional: the AAMC has opposed proposed “data access” regulations that would require researchers to make data underlying their research available to un-named third parties; such tactics have been used to harass or undermine investigators’ work for purposes other than scientific advancement.

    Other Comments: The AAMC envisions an environment where comprehensive medical records and other individual health-related data resources are also available to investigators, with appropriate approval and oversight, in a learning health system. Our support for sharing research data is an extension of this vision, where both anonymized patient records as well as data from clinical studies are available for research. Finally, the ICMJE must recognize that, like many socially beneficial activities undertaken by our community, implementation of this proposal will require significant effort and expense, and may generate risks to individual researchers, their institutions, and their patients. Although we believe the efficiency and effectiveness of research will be improved through data sharing, medical research leaders, sponsors, and members of the public who support data sharing proposals should also encourage increased public funding to cover its costs and resources. The AAMC is grateful to the ICMJE for its leadership on this important public health topic, and for the opportunity to comment. Please contact Dr. Alex Ommaya with questions or for clarification on these comments.

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  • William W. Chin, MD
    Pharmaceutical Research and Manufacturers of America and European Federation of Pharmaceutical Industries and Associations
    Role(s): Other
      • Industry Association
    Date Submitted: Monday, April 18, 2016 - 15:47

    Requirement To Share Data
    • I agree with this general approach
    Comments: PhRMA and EFPIA are strongly committed to enhancing the biomedical research ecosystem through responsible sharing of clinical trial data that protects the privacy and autonomy of research participants, respects the integrity of national regulatory systems, and maintains incentives for investments in biomedical research. Biopharmaceutical companies are already advancing ICMJE’s goals through their clinical trial data-sharing programs adopted pursuant to the PhRMA-EFPIA Principles for Responsible Clinical Trial Data Sharing. We applaud ICMJE’s efforts to develop the proposal, which we understand to be largely aligned with our Principles. We generally support an ICMJE policy that entails sharing of anonymized IPD underlying an article’s results through controlled access arrangements with qualified researchers who are conducting legitimate scientific and medical research in full compliance with all applicable privacy, informed consent, and other laws, including the EU’s privacy laws.

    6 Month Time Frame
    • I agree with this general approach
    Comments: PhRMA and EFPIA understand the six-month timeframe to refer to the time after publication in a print ICMJE journal when a sponsor should be prepared to accept data-sharing requests from external researchers. Based on this understanding, we agree with this approach for data other than those IPD that are intended for submission to and review by a regulatory authority in connection with an unapproved regulatory marketing application. IPD that are or will be under regulatory review are highly sensitive, and sharing these IPD has the potential to undermine the role of national regulatory authorities. For such IPD, requests for sharing should be accepted no later than six months after US and EU regulatory approval of the application. While some sponsors may elect to share data from studies of medicines pre-approval, we are concerned that if ICMJE does not recognize an exception for release of IPD that are or will be in the regulatory process, then sponsors may consider delayed publishing or publish in non-ICMJE journals—perverse results we hope to avoid. With respect to the timeframe for actual sharing of IPD, flexibility is warranted given the need for sponsors to review requests and properly anonymize IPD to protect patient privacy.

    Require a Data Sharing Plan
    • I agree with this general approach
    Comments: PhRMA and EFPIA support this approach, and it appears to be aligned with our Principles. Our members already publicly post information about their data request and review processes on company websites and/or other internet sites. We understand that providing a link to a website where a sponsor’s general data-sharing policy appears and where data-sharing requests can be made would accord with the ICMJE proposal. We support the proposal based on this understanding. Additionally, the proposal states that data-sharing plans should address “where the researchers will house the data.” Pursuant to the Principles, companies may house their own data. We understand that this practice is consistent with the ICMJE proposal, and thus, we also support this aspect of the proposal.

    Providing Credit
    • I agree with this general approach
    Comments: PhRMA and EFPIA agree that authors of secondary analyses should acknowledge in their publications those who generated the primary data sets and attest that their use of the data complied with agreed terms of use. Further, consistent with our Principles, researchers who are provided access to data should be expected to publish the results of their analysis. To promote transparency and avoid misleading impressions, researchers should specify the contribution(s) made by the trial sponsor. In particular, if there is no collaboration between the researcher and sponsor, the publication should: (i) acknowledge that the sponsor provided specified data in accordance with the ICMJE policy and had no involvement in the research or preparation of the secondary publication, and (ii) state that the views and conclusions expressed in the secondary publication are solely those of the author/researcher.

    Other Comments: PhRMA and EFPIA agree that ICMJE’s data-sharing policy should apply only to trials that enroll their first patient at least one year after the final policy is in effect, given the complexities of drafting informed consent forms that address data-sharing practices. Exceptions to the data-sharing policy should be made when adequately justified for legal or public health purposes. In particular, PhRMA and EFPIA urge ICMJE to grant exceptions in circumstances (e.g., trials of rare diseases, single-center studies) where there may be a greater likelihood that patients could be reidentified from the IPD, despite attempts at defensible anonymization. In these situations, it is not possible to attain an acceptably low risk of reidentification while preserving sufficient data integrity to enable the planned analyses. An exception is necessary in these cases so that sponsors can protect the privacy of participants in accordance with legal and ethical principles. Requests for exceptions based on other similarly compelling circumstances also should be granted. We hope that our comments on the proposal are constructive, and we would be happy to discuss them with you as the Committee finalizes its proposal.

    Position:
    Comments:
  • AGO Study Group
    AGO Study Group, Germany
    Role(s):
    • Clinician
    • Clinical trial sponsor / funder
    • Other
      • Academic Study Group
    Date Submitted: Monday, April 18, 2016 - 15:35

    Requirement To Share Data
    • I agree with this general approach
    Comments: The AGO Study group is one of the largest international gynecologic oncology study groups worldwide. The AGO study group generally supports that clinical trial data should be shared with others to enable the validation of the presented/published result to secure transparency and reproducibility of clinical trial results. For us as an academic study group the sharing of clinical trial data with other research groups and investigators, demonstrated by a large number of collaborative publications, is common scientific practice. However, uncontrolled and unrestricted access to clinical trial data for secondary and new analyses, e.g. by parties with limited expertise in a specific area of interest, might lead to misinterpretation of data with a possible negative impact on patient care. Clinical trial protocols require a pre-specified statistical analysis plan including sample size and power calculation and determination of the alpha and beta errors, which are crucial for the interpretation of the primary trial results. Unrestricted reanalysis carries the danger associated with multiple testing including false positive findings which could contribute to the misinterpretation of the overall trial results. New ways to account for these statistical issues have to be defined.

    6 Month Time Frame
    Comments: A general 6 month timeframe does not adequately take into account individual circumstances that may preclude early data sharing. The original investigators should have the opportunity to extensively analyze and publish the data that sometimes took many years to generate. We propose that standards should be developed that take into account individual specificities of clinical trials as well as scientific, ethical, clinical, public health, intellectual property rights or policy implications

    Require a Data Sharing Plan
    • I agree with this general approach

    Providing Credit
    • I agree with this general approach
    Comments: The competing interests including the intellectual properties of study groups and investigators, industry partners, data protection regulations as well as a public interest in the advancement of clinical research have to be respected. Therefore, we firmly believe that such data sharing should always be based on a formal contractual agreement of collaboration between those who have generated the data and scientist interested in using the respective data. This does also include a publishing policy that might account for divergent interpretation of data by the involved parties, e.g. by inclusion of a commentary or an alternative discussion by those who have originally conducted the trial and collected the raw data. Planning and conducting clinical trials and maintaining the underlying data base requires an enormous effort, intellectual input as well as considerable financial resources. Therefor all of these points have to be considered when providing the due credit to those who have originally conducted the trial.

    Other Comments: The AGO Study Group would like to voice that costs are associated with data sharing and that appropriate technologies and infrastructures need to be developed. Therefore, the need for additional resources to implement such measures should also be acknowledged by other funders and institutions.

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    Comments:

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