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A Historic Moment for Open Science: The Yale University Open Data Access Project and Medtronic

2013; American College of Physicians; Volume: 158; Issue: 12 Linguagem: Inglês

10.7326/0003-4819-158-12-201306180-00009

1539-3704

Harlan M. Krumholz, Joseph S. Ross, Cary P. Gross, Ezekiel J. Emanuel, Beth Hodshon, Jessica Ritchie, Jeffrey B. Low, Richard Lehman,

Meta-analysis and systematic reviews

Editorials18 June 2013A Historic Moment for Open Science: The Yale University Open Data Access Project and MedtronicFREEHarlan M. Krumholz, MD, SM, Joseph S. Ross, MD, MHS, Cary P. Gross, MD, Ezekiel J. Emanuel, MD, PhD, Beth Hodshon, JD, MPH, RN, Jessica D. Ritchie, MPH, Jeffrey B. Low, AB, and Richard Lehman, MDHarlan M. Krumholz, MD, SMFrom Yale University School of Medicine, New Haven, Connecticut; Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania; and Hightown Surgery, Banbury, United Kingdom., Joseph S. Ross, MD, MHSFrom Yale University School of Medicine, New Haven, Connecticut; Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania; and Hightown Surgery, Banbury, United Kingdom., Cary P. Gross, MDFrom Yale University School of Medicine, New Haven, Connecticut; Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania; and Hightown Surgery, Banbury, United Kingdom., Ezekiel J. Emanuel, MD, PhDFrom Yale University School of Medicine, New Haven, Connecticut; Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania; and Hightown Surgery, Banbury, United Kingdom., Beth Hodshon, JD, MPH, RNFrom Yale University School of Medicine, New Haven, Connecticut; Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania; and Hightown Surgery, Banbury, United Kingdom., Jessica D. Ritchie, MPHFrom Yale University School of Medicine, New Haven, Connecticut; Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania; and Hightown Surgery, Banbury, United Kingdom., Jeffrey B. Low, ABFrom Yale University School of Medicine, New Haven, Connecticut; Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania; and Hightown Surgery, Banbury, United Kingdom., and Richard Lehman, MDFrom Yale University School of Medicine, New Haven, Connecticut; Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania; and Hightown Surgery, Banbury, United Kingdom.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-158-12-201306180-00009 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail This issue of Annals heralds a historic moment in the emerging era of open science. It features 2 systematic reviews on recombinant human bone morphogenetic protein-2 (rhBMP-2) (1, 2), an orthobiologic agent used in certain surgeries to promote bone growth that once achieved close to $1 billion in annual sales for Medtronic (Minneapolis, Minnesota). The reviews are based on patient-level data from all clinical trials conducted by Medtronic, which were shared through the Yale University Open Data Access (YODA) Project (3). With the publication of these reviews and the public release of its comprehensive reports, all of the clinical trial data for this product will now be made available by the YODA Project to other investigators for further analysis and examination.The YODA Project seeks to address the problem of unpublished and selectively published clinical evidence (4, 5). Nearly half of clinical trials are never published, and many that are have long delays in publication. Among those published, the information is often incomplete. Evidence suggests that some data are not missing at random and that the sharing of data, particularly patient-level data, often provides new insights that are consequential to patients.Currently, even the most conscientious physicians—those committed to knowing the latest literature—cannot fully understand the true risks and benefits of many treatments. Patients, therefore, are hampered in their ability to make truly informed decisions. In addition, missing data undermine evidence-based medicine, as recommendations based on the published literature, whether in systematic reviews, guidelines, book chapters, or online resources, are not based on the totality of the evidence. To improve the care of patients, clinical trial data, protocols, and results need to be made more widely available and shared for public benefit (6).Amid the current dialogue about open science in medicine, few imagined that such a prominent company would voluntarily make available all of its internal patient-level clinical research data on one of its major products. At a time when many companies express verbal support of open science, Medtronic joined the YODA Project and demonstrated what is possible. It is true that Medtronic was embroiled in a controversy about rhBMP-2 when it decided to share data (7). However, among the other companies that also encountered concerns about their products or the transparency of their research, Medtronic was unique in its response. Will the company's decision to release its data through the YODA Project be a footnote or a headline in the history of open clinical science? We hope that the action will reset expectations about the social contract between scientists and society.The YODA Project evolved as a collaborative endeavor guided by aspirations to promote open science, ensure good stewardship of clinical trial data, serve society and patients, and respect industry concerns. The YODA team approached Medtronic with a proposal to provide us with all of its relevant and de-identified rhBMP-2 patient-level clinical trial data. The agreement included 2 parts. First, the YODA team would contract with 2 independent research groups, selected through a competitive and open process, to perform comprehensive analyses of the data to evaluate the quality of the studies and synthesize evidence about the effectiveness and safety of rhBMP-2. The reviews in this issue are the result of those efforts. Second, after these reviews, the YODA team would make the data available to others to address additional potential scientific questions.Cooperation was the key to addressing the challenges of data sharing. We engaged a steering committee that included representation from academia, government, and industry. We convened an additional group of experts for a consensus meeting to develop appropriate methods and best practices. We also held a public comment period on our proposed approach. Although our contract with Medtronic gave us jurisdiction over the data, we sought a path that would navigate Medtronic's concerns about data misuse, false-positive inferences from data mining, legal ramifications, privacy issues, and commercial advantage for competitors. Among the results of these efforts was the development of a data release policy, available at http://medicine.yale.edu/core/projects/yodap/index.aspx.To be worthy of replication, the YODA Project needs to serve society and patients but should also produce benefits for the companies that fund the vast majority of research on medical products. One premise of the project is that companies can address their declining public perception by committing to data transparency and benefit from a culture of open science. Moreover, the open sharing of these data will ensure that conclusions drawn by any group can be checked by other individuals, mitigating concerns that competitors will seek to misuse the data.Will other companies follow suit? It is too early to say, but a recent announcement from GlaxoSmithKline (London, United Kingdom) about plans to share detailed clinical trial data is promising (8). Will clinicians be willing to show a preference for products from companies that share data? Will patients clamor for companies to be forthcoming with data? Will society reject claims that data are proprietary when they relate directly to decisions that people are making about products that are on the market?Our aspiration is for the YODA Project to provide a framework for the release of patient-level data and for the Medtronic release of data not to be an anomaly but a critical step forward in the rapidly changing culture of science. Ultimately, those of us who practice evidence-based medicine or conduct clinical research are the beneficiaries of the generosity of research participants. Participants expect that we will learn from their contributions and use the knowledge to help others. To do so requires that the data and findings from the research be widely and fully disseminated.The concerns about data sharing are relevant to the entire clinical research enterprise, far beyond industry (9, 10). Academia needs to reflect on and change its own culture, which is similarly reluctant to share data. We need to ensure that the current regulatory environment facilitates sharing of de-identified data while developing the technical solutions and the will to promote open science. We also need to find ways to reward those who share data, providing them a piece of the academic credit from the dividends of their work. Here we have a case in which the actions of industry should inspire academia to follow.The process that produced the reviews in this issue ensured that they were based on the totality of the evidence. That we have established a new standard should be a headline. Let us resolve to have this effort be the first step in the next era of cooperation among industry, academia, clinicians, and the public—one that rewards data sharing, promotes open science, and ultimately makes it untenable to obscure data relevant to the risks and benefits of approved medical products.Harlan M. Krumholz, MD, SMJoseph S. Ross, MD, MHSCary P. Gross, MDYale University School of MedicineNew Haven, ConnecticutEzekiel J. Emanuel, MD, PhDPerelman School of Medicine, University of PennsylvaniaPhiladelphia, PennsylvaniaBeth Hodshon, JD, MPH, RNJessica D. Ritchie, MPHJeffrey B. Low, ABYale University School of MedicineNew Haven, ConnecticutRichard Lehman, MDHightown SurgeryBanbury, United KingdomReferences1. Simmonds MC, Brown JV, Heirs MK, Higgins JP, Mannion RJ, Rodgers MA, et al. Safety and effectiveness of recombinant human bone morphogenetic protein-2 for spinal fusion. A meta-analysis of individual-participant data. Ann Intern Med. 2013;158:877-89. LinkGoogle Scholar2. Fu R, Selph S, McDonagh M, Peterson K, Tiwari A, Chou R, et al. Effectiveness and harms of recombinant human bone morphogenetic protein-2 in spine fusion. A systematic review and meta-analysis. Ann Intern Med. 2013;158:890-902. LinkGoogle Scholar3. Krumholz HM, Ross JS. A model for dissemination and independent analysis of industry data. JAMA. 2011;306:1593-4. [PMID: 21990302] CrossrefMedlineGoogle Scholar4. Krumholz HM. Open science and data sharing in clinical research: basing informed decisions on the totality of the evidence. Circ Cardiovasc Qual Outcomes. 2012;5:141-2. [PMID: 22438459] CrossrefMedlineGoogle Scholar5. Ross JS, Lehman R, Gross CP. The importance of clinical trial data sharing: toward more open science. Circ Cardiovasc Qual Outcomes. 2012;5:238-40. [PMID: 22438465] CrossrefMedlineGoogle Scholar6. Gøtzsche PC. Strengthening and opening up health research by sharing our raw data. Circ Cardiovasc Qual Outcomes. 2012;5:236-7. [PMID: 22438464] CrossrefMedlineGoogle Scholar7. Carragee EJ, Hurwitz EL, Weiner BK. A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J. 2011;11:471-91. [PMID: 21729796] CrossrefMedlineGoogle Scholar8. GlaxoSmithKline. GSK gives update on plans to share detailed clinical trial data as part of its commitment to transparency [news release]. London: GlaxoSmithKline; 7 May 2013. Accessed at www.gsk.com/media/press-releases/2013/gsk-gives-update-on-plans-to-share-detailed-clinical-trial-data-.html on 15 May 2013. Google Scholar9. Ross JS, Tse T, Zarin DA, Xu H, Zhou L, Krumholz HM. Publication of NIH funded trials registered in ClinicalTrials.gov: cross sectional analysis. BMJ. 2012;344:d7292. [PMID: 22214755] CrossrefMedlineGoogle Scholar10. Rathi V, Dzara K, Gross CP, Hrynaszkiewicz I, Joffe S, Krumholz HM, et al. Sharing of clinical trial data among trialists: a cross sectional survey. BMJ. 2012;345:7570. [PMID: 23169870] CrossrefMedlineGoogle Scholar Comments 0 Comments Sign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Harlan M. Krumholz, MD, SM; Joseph S. Ross, MD, MHS; Cary P. Gross, MD; Ezekiel J. Emanuel, MD, PhD; Beth Hodshon, JD, MPH, RN; Jessica D. Ritchie, MPH; Jeffrey B. Low, AB; Richard Lehman, MDAffiliations: From Yale University School of Medicine, New Haven, Connecticut; Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania; and Hightown Surgery, Banbury, United Kingdom.Financial Support: Drs. Krumholz and Ross receive support from the U.S. Food and Drug Administration (FDA) to develop methods for postmarket surveillance of medical devices. Dr. Ross receives support from the National Institute on Aging (K08 AG032886) and the American Federation for Aging Research through the Paul B. Beeson Career Development Award Program and from the Pew Charitable Trusts to examine FDA regulatory issues. Dr. Krumholz receives support from a National Heart, Lung and Blood Institute Cardiovascular Outcomes Center Award (1U01HL105270-03).Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-1142.Corresponding Author: Harlan M. Krumholz, MD, SM, Yale University School of Medicine, 1 Church Street, Suite 200, New Haven, CT 06510.Current Author Addresses: Dr. Krumholz, Ms.Hodshon, Ms. Ritchie, and Mr. Low: Yale University School of Medicine, 1 Church Street, Suite 200, New Haven, CT 06510.Dr. Ross: Yale University School of Medicine, Section of General Medicine, PO Box 208093, New Haven, CT 06520.Dr. Gross: Yale University School of Medicine, General Internal Medicine, PO Box 208025, New Haven, CT 06510.Dr. Emanuel: 122 College Hall, University of Pennsylvania, Philadelphia, PA 19104.Dr. Lehman: University of Oxford, Stonebank, Manor Orchard, Horley, Banbury OX15 6DZ, United Kingdom. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoMeta-analysis of Trials of Recombinant Human Bone Morphogenetic Protein-2: What Should Spine Surgeons and Their Patients Do With This Information? Daniel Resnick and Kevin J. 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Steyerberg, PhDSharing of clinical trial data and results reporting practices among large pharmaceutical companies: cross sectional descriptive study and pilot of a tool to improve company practicesOverview and experience of the YODA Project with clinical trial data sharing after 5 yearsPersonalized evidence based medicine: predictive approaches to heterogeneous treatment effectsData Sharing—The Time Has (Not Yet?) ComeCollaborative Approaches to Advance Chemical SafetyData Sharing and Embedded ResearchGregory E. Simon, MD, MPH, Gloria Coronado, PhD, Lynn L. DeBar, PhD, MPH, Laura M. Dember, MD, Beverly B. Green, MD, MPH, Susan S. Huang, MD, MPH, Jeffrey G. Jarvik, MD, MPH, Vincent Mor, PhD, Joakim Ramsberg, PhD, Edward J. Septimus, MD, Karen L. Staman, MS, Miguel A. Vazquez, MD, William M. Vollmer, PhD, Douglas Zatzick, MD, Adrian F. Hernandez, MD, MHS, and Richard Platt, MD, MSUse of recombinant human bone morphogenetic protein-2 in spine surgeryIntrathecal Drug Delivery Systems (IDDS): The Implantable Systems Performance Registry (ISPR)Meta-analysis of the Impact of Patient Characteristics on Estimates of Effectiveness and Harms of Recombinant Human Bone Morphogenetic Protein-2 in Lumbar Spinal FusionResearch and ResponsibilityState of the art review: the data revolution in critical carePublicly Available DataMethylprednisolone for the Treatment of Patients with Acute Spinal Cord Injuries: A Propensity Score-Matched Cohort Study from a Canadian Multi-Center Spinal Cord Injury RegistryTimely publication and sharing of trial data: opportunities and challenges for comparative effectiveness research in cardiovascular diseaseMaking personalized medicine more affordableBig Data and Health Care: Challenges and Opportunities for Coordinated Policy Development in the EULetter to the Editor: Off-label rhBMP-2 use in pediatric spine deformity surgeryEnzyme replacement and substrate reduction therapy for Gaucher diseaseHow Do You Know It Is True? Integrity in Research and PublicationsState of the Art Review: The Data Revolution in Critical CareReferencesData Sharing, Year 1 — Access to Data from Industry-Sponsored Clinical TrialsCost-effective studies in spine surgeries: a narrative reviewThe right to know and the right not to know in the era of neoliberal biopolitics and bioeconomySea Change in Open Science and Data SharingBig Data And New Knowledge In Medicine: The Thinking, Training, And Tools Needed For A Learning Health SystemWho Has Used Internal Company Documents for Biomedical and Public Health Research and Where Did They Find Them?Moving Forward From rhBMP-2Rediscovering the 50% of Medical Research That Doesn't See the Light of DayIncreasing value and reducing waste: addressing inaccessible researchBlack, white, or gray: how different (or similar) are YODA and the The Spine Journal reviews of BMP-2?YODA analyses question rhBMP-2 use in spinal surgeryClosing in on the Truth About Recombinant Human Bone Morphogenetic Protein-2: Evidence Synthesis, Data Sharing, Peer Review, and Reproducible ResearchChristine Laine, MD, MPH, Editor in Chief, Eliseo Guallar, MD, PhD, Associate Editor, Statistics, Cynthia Mulrow, MD, MSc, Senior Deputy Editor, Darren B. Taichman, MD, PhD, Executive Deputy Editor, John E. Cornell, PhD, Associate Editor, Statistics, Deborah Cotton, MD, MPH, Deputy Editor, Michael E. Griswold, PhD, Associate Editor, Statistics, A. Russell Localio, JD, MPH, MS, Associate Editor, Statistics, Anne R. Meibohm, PhD, Associate Editor, Statistics, Catharine B. Stack, PhD, MS, Deputy Editor, Statistics, Sankey V. Williams, MD, Deputy Editor, and Steven N. Goodman, MD, PhD, MHS, Associate Editor, StatisticsClinical Trial Transparency and Orphan Drug Development: Recent Trends in Data Sharing by the Pharmaceutical Industry 18 June 2013Volume 158, Issue 12 Page: 910-911 Keywords Aging Clinical trial reporting Clinical trials Computed axial tomography Evidence based medicine Food and Drug Administration Osteocalcin Scientists Surgery Systematic reviews ePublished: 18 June 2013 Issue Published: 18 June 2013 Copyright & PermissionsCopyright © 2013 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...