Clinical trial data from more than 3,200 studies are available for review through open access platforms; however, only 15.5% of these trials were sought for reanalysis, according to recent findings published in JAMA.
“Concerns over bias in clinical trial reporting have stimulated calls for more open data sharing,” Ann Marie Navar, MD, PhD, of the Duke Clinical Research Institute at Duke University Medical Center, and colleagues wrote. “In response, multiple pharmaceutical companies have created mechanisms for investigators to access patient-level clinical trials data. Reasons for underutilization of clinical trials data may include lack of knowledge about these resources, possibly due to lack of publication of results from proposals, or lack of funding to support analyses.”
During a recent investigation, Navar and colleagues assessed the number of clinical trials that are available in three open access platforms (ClinicalStudyDataRequest.com, the Yale University Open Data Access Project and the Supporting Open Access for Researchers Initiative) and how often data from the trials are utilized. Fourteen pharmaceutical companies contributed to the studies, including Astellas, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Medtronic, Novartis, Roche, Sanofi, Takeda, Union Chimique Belge, and ViiV Healthcare.
The platforms contained 3,255 clinical trials, primarily phase 3 (44.3%), according to the researchers. More than 230 proposals seeking access to one or more trials (median, 2) were submitted.
The proposals were reviewed for scientific merit by a panel of experts or platform members, 154 of which were approved. The remaining proposals either were rejected (n = 12), under review (n = 10) or withdrawn (n = 4). Overall, access to 505 individual trials (15.5%) were requested for various reasons, including secondary analyses of treatment effect (n = 50; 44.3%) and disease state (n = 31; 27.4%).
Researchers have ‘ethical obligation’ to share data
In a related editorial, JAMA’s Howard Bauchner, MD, editor in chief; Robert M. Golub, MD, deputy editor; and Phil B. Fontanarosa, MD, MBA, executive editor; discussed the benefits of data sharing and how it prevents information from being lost to research and patient communities and allows data that may have intentionally or inadvertently been withheld from original reporting to be discovered and reanalyzed. The editors wrote that the most “compelling” reason to support data sharing is because of the “responsibility” that investigators have to study participants.
Bauchner and colleagues quoted a statement from the International Committee of Medical Journal Editors declaring there is an “ethical obligation” to share data because study participants put themselves at risk for harm. Not only are participants at risk for major physical or psychological injuries, but they also may suffer from minor and common harms such as discomfort, inconvenience and time away from work, according to the editors.
“The informed consent process makes clear that participants in trials should not expect benefit to themselves as a result of their participation,” they wrote. “The social contract for taking these risks and experiencing these harms imposes an ethical obligation that the results lead to the greatest possible benefit to society.”
Bauchner and colleagues said the contract is “violated” if there is a lack of useful information due to the trial being underpowered or uninterpretable because of high dropout rates, inaccurate hypotheses or other bias outcomes. However, if the data are still publicly available, other investigators may reanalyze the information and use it to generate new hypotheses.
Controversy over data sharing
Despite the benefits of data sharing, there is controversy over which data should be shared and under what circumstances, the editors wrote. To create an ethical open access platform system, they suggested that the platform members ensure study participants are “deidentified” and aware the data may be shared; that funders offer support to the original investigators to help others analyze the data; and guarantee that appropriate credit is given to the original investigators for their work.
“Effective implementation of data sharing will prove far more difficult than implementation of the requirements to register clinical trials,” Bauchner and colleagues concluded. “Conducting clinical trials is already expensive, so it will be important to create an effective, efficient and fair system for data sharing that is not hugely burdensome and expensive to ensure it is worth the intellectual and financial cost; will achieve the goals of advancing scientific discovery, improving clinical care, and maximizing knowledge from clinical trial data; and above all, will fulfill the ethical obligations to participants in clinical trials.” – by Stephanie Viguers
Disclosure: Navar report receiving research funding from Regeneron and Sanofi. Please see the full study for a list of all other authors’ relevant financial disclosures.