Academic Research Organization Consortium for Continuing Evaluation of Scientific Studies--Cardiovascular (ACCESS CV)

Armstrong, PW

Bhatt, DL

Braunwald, E

Camm, AJ

Fox, KA

Gibson, M

Harrington, RA

Hiatt, WR

James, SK

Kirtane, AJ

Leon, MB

Lincoff, AM

Mahaffey, KW

Mauri, L

Mehran, R

Mehta, SR

Montalescot, G

Nicholls, SJ

Patel, MR

Perkovic, V

Peterson, ED

Pocock, SJ

Roe, MT

Sabatine, MS

Sekeres, M

Solomon, SD

Steg, G

Stone, GW

Van de Werf, F

Wallentin, L

White, HD

New England Journal of Medicine

English

Spiral - Imperial College Digital Repository

PERSPECTIVE407Toward Fairness in Data Sharingn engl j med 375;5 nejm.org August 4, 2016portunity to conduct confirma-tory analyses before publication of an article, thereby advancing the ICMJE’s stated goal of in-creasing “confidence and trust in the conclusions drawn from clin-ical trials.” Finally, persons who were not involved in an investiga-tor-initiated trial but want access to the data should financially compensate the original investi-gators for their efforts and invest-ments in the trial and the costs of making the data available.The writing committee of the Internation-al Consortium of Investigators for Fairness in Trial Data Sharing included P.J. Devereaux, M.D., Ph.D., Gordon Guyatt, M.D., Hertzel Gerstein, M.D., Stuart Connolly, M.D., and Salim Yusuf, M.B., B.S., D.Phil. — all from McMaster University, Hamilton, ON, Canada. This article was reviewed and endorsed by 282 investigators in 33 countries, who are listed in the Supplementary Appendix.Disclosure forms provided by the authors are available at NEJM.org.1. Taichman DB, Backus J, Baethge C, et al. Sharing clinical trial data: a proposal from the International Committee of Medical Journal Editors. JAMA 2016; 315: 467-8.2. Bastian H, Glasziou P, Chalmers I.  Seventy-five trials and eleven systematic re-views a day: how will we ever keep up? PLoS Med 2010; 7(9): e1000326.3. Gordon D, Taddei-Peters W, Mascette A, Antman M, Kaufmann PG, Lauer MS. Publi-cation of trials funded by the National Heart, Lung, and Blood Institute. N Engl J Med 2013; 369: 1926-34.DOI: 10.1056/NEJMp1605654Copyright © 2016 Massachusetts Medical Society.Toward Fairness in Data SharingSharing Data from Cardiovascular Clinical TrialsSharing Data from Cardiovascular Clinical Trials — A ProposalThe Academic Research Organization Consortium for Continuing Evaluation of Scientific Studies — Cardiovascular (ACCESS CV) Participants in clinical research volunteer in order to support the development of scientific knowledge and help future pa-tients. Inherent in their commit-ment is the belief that research will lead to new insights that will be disseminated. As clinical re-searchers, we fully support the concept of data sharing as fun-damental to achieving this goal.We formed the Academic Re-search Organization Consortium for Continuing Evaluation of Sci-entific Studies — Cardiovascular (ACCESS CV) to provide avenues for sharing data from cardiovas-cular clinical trials while mini-mizing risks and unintended consequences. The goal of the consortium is to create a strategy to thoughtfully operationalize the recommendations of the Interna-tional Committee of Medical Jour-nal Editors (ICMJE) and the In-stitute of Medicine (IOM) for sharing clinical trial data.1,2 The ACCESS CV partners broadly sup-port the concepts of data trans-parency and open access. The benefits of sharing patient-level data from clinical trials include confirmation of results, opportu-nities for new discoveries from secondary analyses, and eventu-ally the possibility of aggregation of data sets from related studies to facilitate high-quality system-atic meta-analyses.The potential benefits of shar-ing patient-level data need to be balanced against potentially un-intended consequences (see the Supplementary Appendix, avail-able with the full text of this ar-ticle at NEJM.org). We have iden-tified the following challenges: complexity of the data and meta-data, publication bias or selection bias in proposed new analyses, increased risk of type I error (from multiple unplanned second-ary analyses), and patient privacy.Clinical trial databases are commonly large and complex, of-ten containing millions of data points from various sources (e.g., case-report forms, central labora-tory review, safety reporting, and end-point adjudication). Attempts to validate trial findings made by persons who are either unfamil-iar with the data set structure or inexperienced in the analysis tech-niques could create apparent dis-crepancies where none exist, po-tentially alarming the public and hindering rather than advancing science. The problem may be com-pounded by publication bias, which may lead to undue focus on find-ings that seem to differ from those of the original analysis.In addition, data sharing could lead to a large number of un-restricted and non–hypothesis-driven supplementary data analy-ses, which would increase the risk of finding false associations (type I errors). Unplanned explor-atory analyses from a publicly shared database may be numer-ous and redundant. The lack of adjustment for multiple testing and the absence of prespecified hypotheses and transparent ana-lytic plans could result in spuri-ous findings, which might ob-scure the real evidence.Another potential hazard of The New England Journal of Medicine Downloaded from nejm.org at IMPERIAL COLLEGE LONDON on October 6, 2016. For personal use only. No other uses without permission.  Copyright © 2016 Massachusetts Medical Society. All rights reserved. PERSPECTIVE408Sharing Data from Cardiovascular Clinical Trialsn engl j med 375;5 nejm.org August 4, 2016sharing individual-patient–level data is loss of patient privacy. Most patients in a deidentified database can be identified on the basis of their birth date, sex, and ZIP Code.3 Those with rare dis-eases and the very elderly are at an even higher risk of identifica-tion and privacy violation.We propose a secure method of sharing sensitive patient data that balances the legitimate de-sire of the scientific community for data access with the respon-sibility to ensure high-quality analyses and protection of pa-tients’ expectation of privacy.First, with regard to gover-nance of access to trial data, we propose that after publication of the primary results of a trial, re-searchers who were not involved with the trial design or conduct may send requests for analyses to the trial’s publications com-mittee. Beginning 24 months af-ter publication, analysis requests should be considered by a learned review group comprising ACCESS CV members who were not in-volved in the trial, along with the trial’s principal investigator, a trial statistician, and a member of the data and safety monitor-ing board. The 24-month period was chosen to allow time to build secure access to the data-base and to allow trial investiga-tors to perform their own pre-planned secondary analyses. The group’s responsibility would be to review all proposals and ap-prove those that are feasible, hypothesis-based, nonduplicative, and guided by investigators with technical capability and a plan for publication. All requests and subsequent decisions would be posted on an ACCESS CV Web portal, ideally within 60 days.Second, we contend that it is critical to facilitate access in an orderly manner to support the best science and minimize pa-tient risk. We envision the fol-lowing elements of a mechanism of access to ensure a systematic approach: standardized requests on a Web portal, disclosure of conflicts of interest and publica-tion plans, adherence to data-use agreements for planned analyses, provision of appropriate ethics ap-proval, performance of all analy-ses using a secure Web link with an accompanying audit trail, and notification about submission for publication.Such a process would avert the problem of multiple groups pro-posing the same analysis and would require investigators to have prespecified analysis plans. The ICMJE and the IOM3 have stated that data-sharing plans should be provided at the time of trial registration and that the re-sults from a clinical trial should be published in a timely fashion, with individual patient data avail-able 6 months after publication. The IOM recommends full data-base access for secondary analy-ses beginning 18 months after trial completion. (For our specific responses to these recommen-dations, see the Supplementary Appendix, available at NEJM.org.)We propose the following: ACCESS CV members would post data-sharing plans, following the ACCESS CV proposal, on Clinical-Trials.gov. Briefly, starting at the time of publication of primary trial results, secondary-analysis requests from researchers not involved in the trial would be submitted to the trial publica-tions committee. When needed, ACCESS CV would provide a mechanism for validating the pri-mary results using the individual patient data underlying the pri-mary publication of a clinical trial, no later than 12 months after publication. Starting 24 months after the publication of primary results, requests for data access for secondary analyses would be promptly reviewed by a learned review group, as described above. ACCESS CV plans to build a Web-based portal that allows for the public posting of all data requests and the subsequent de-cisions of the independent review panel.An unresolved issue is the ques-tion of how to provide meaning-ful academic credit (typically authorship) to the team that de-signed and conducted the trial, given that trials are usually enor-mous undertakings requiring sev-eral years of work. During the review of proposals for second-ary analyses, we would expect trial leaders and people request-ing access to data to consider and discuss this important issue and to reach consensus on a path forward for each analysis.ACCESS CV recognizes that to achieve these goals, adequate re-sources and funding are required. Since that significant matter has not been addressed, we plan to work with sponsors of clinical trials, the IOM, the ICMJE, gov-ernmental bodies, and regulatory authorities to develop the infra-structure for the data-sharing proposal we describe.ACCESS CV fully supports transparency and open data shar-ing. We propose these mecha-nisms for structured data access in an effort to provide ready ac-cess to trial data in a timely manner while minimizing risks The New England Journal of Medicine Downloaded from nejm.org at IMPERIAL COLLEGE LONDON on October 6, 2016. For personal use only. No other uses without permission.  Copyright © 2016 Massachusetts Medical Society. All rights reserved. PERSPECTIVE409Sharing Data from Cardiovascular Clinical Trialsn engl j med 375;5 nejm.org August 4, 2016and barriers. We believe that  ACCESS CV is well positioned to generate and share clinical trial data and, eventually, to develop aggregate data sets in cardio-vascular medicine (see the Sup-plementary Appendix). The cur-rent proposal, though specific to cardiovascular clinical trials, may apply equally to other dis-ciplines in which groups may consider building consortia and similar strategies. We aim to in-crease the utilization of shared data as compared with ongoing open-access efforts.4,5 We be-lieve our plans are aligned with the IOM’s recommendations and with the ICMJE proposal and that they will ultimately max-imize the impact of clinical  trials on human health around the world.The authors, who are initial partners in ACCESS CV, are Manesh R. Patel, M.D., Paul W. Armstrong, M.D., Deepak L. Bhatt, M.D., M.P.H., Eugene Braunwald, M.D., A. John Camm, M.D., Keith A.A. Fox, M.B., Ch.B., Robert A. Harrington, M.D., William R. Hiatt, M.D., Stefan K. James, M.D., Ph.D., Ajay J. Kirtane, M.D., Martin B. Leon, M.D., A. Michael Lincoff, M.D., Kenneth W. Ma-haffey, M.D., Laura Mauri, M.D., Roxana Mehran, M.D., Shamir R. Mehta, M.D., Gilles Montalescot, M.D., Stephen J. Nicholls, M.B., B.S., Ph.D., Vlado Perkovic, M.B., B.S., Ph.D., Eric D. Peterson, M.D., M.P.H., Stuart J. Pocock, Ph.D., Matthew T. Roe, M.D., M.H.S., Marc S. Sabatine, M.D., M.P.H., Mikkael Sekeres, M.D., Scott D. Solomon, M.D., Ph.D., Gabriel Steg, M.D., Gregg W. Stone, M.D., Frans Van de Werf, M.D., Ph.D., Lars Wallentin, M.D., Ph.D., Harvey D. White, D.Sc., and C. Michael Gibson, M.D. The institutional affiliations of the part-ners and the full list of ACCESS CV partici-pants are provided in the Supplementary Appendix, available at NEJM.org.Disclosure forms provided by the authors are available at NEJM.org.1. Taichman DB, Backus J, Baethge C, et al. Sharing clinical trial data — a proposal from the International Committee of Medi-cal Journal Editors. N Engl J Med 2016; 374: 384-6.2. Institute of Medicine. Sharing clinical trial data: maximizing benefits, minimizing risk. Washington, DC: National Academies Press, 2015.3. Sweeney L, Abu A, Winn J. Identifying participants in the Personal Genome Project by name. Social Science Research Network. April 29, 2013 (http://ssrn .com/ abstract= 2257732).4. Strom BL, Buyse M, Hughes J, Knoppers BM. Data sharing, year 1 — access to data from industry-sponsored clinical trials. N Engl J Med 2014; 371: 2052-4.5. Navar AM, Pencina MJ, Rymer JA, Lou-zao DM, Peterson ED. Use of open access platforms for clinical trial data. JAMA 2016; 315: 1283-4.DOI: 10.1056/NEJMp1605260Copyright © 2016 Massachusetts Medical Society.Sharing Data from Cardiovascular Clinical TrialsThe New England Journal of Medicine Downloaded from nejm.org at IMPERIAL COLLEGE LONDON on October 6, 2016. For personal use only. No other uses without permission.  Copyright © 2016 Massachusetts Medical Society. All rights reserved. 

Sharing Data from Cardiovascular Clinical Trials--A Proposal.

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Sharing Data from Cardiovascular Clinical Trials--A Proposal.

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