Clinical Trial Data Sharing: The Time Is Now
Authors: Josephine P. Briggs, Paul M. Palevsky
Journal: Journal of the American Society of Nephrology (2019)

It is not a new concept that pooling data from multiple clinical trials yields more insight than can be gleaned from one study standing alone. Although pooled analyses of clinical trial data date back more than a half-century, a 1987 New England Journal of Medicine article by Sacks et al.1 set out standards for clinical trial meta-analyses. This was an important prod, and clinical medicine changed: changed for the better, most of us think. Nevertheless, uptake in nephrology has lagged. This is changing. Kidney Disease Outcomes Quality Initiative and Kidney Disease Improving Global Outcomes have led the way in sponsoring rigorous evaluation of clinical evidence dependent, when possible, on systematic reviews and meta-analyses. JASN welcomes submission of high-quality, well designed, and rigorous meta-analyses that ask important questions and provide informative answers. The value of a meta-analysis is, of course, dependent on the strength of the underlying data, but the number of high-quality clinical trials in nephrology is increasing, and thus, the value of secondary analyses is growing. This issue of JASN includes a triad of papers2,3 that take on a tough and important goal: development of a surrogate end point to test therapies to slow the progression of CKD. The authors of these analyses make the argument that the rate of decline of eGFR can, under select circumstances, provide a safe substitute for the accepted end points for CKD progression (for example, a composite of fall in eGFR to <15 ml/min, doubling of serum creatinine or fall in eGFR of 40%, or institution of kidney replacement therapy). Critical for the thesis is a powerful meta-analysis that pools individual participant-level data drawn from 47 randomized clinical trials that tested interventions for CKD. This paper illustrates dramatically the value of data sharing.4 In the early days of meta-analyses, studies mostly relied only on the published data. That is no longer the case. Increasingly, secondary analyses of all sorts require a deeper dive into the primary data, including assessment of participant-level data. This has prompted the recognition of the need for stronger rules about data sharing and has resulted in strong statements from the National Academy of Medicine and the World Health Organization about its importance. Data sharing is recognized as part of the ethical commitment to patients who participate in clinical experiments and expect us to make full use of their contribution to new knowledge.5 In 2018, the International Committee of Medical Editors (ICMJE) established new rules for clinical trial data sharing, standards adopted by JASN. The centerpiece of these standards is the requirement for a data-sharing plan (http://www.icmje.org/recommendations/). Data-sharing plans6 compliant with these new rules can, however, include a controversial option: authors can answer the question “will individual participant data be available?” with a simple “no.” JASN editors have decided that this does not go far enough. We will now require that authors submitting a clinical trial for consideration for publication in JASN provide a thoughtfully conceived plan for how they will respond to requests for more information about the primary data that underlie their study. We are prepared to be very flexible about the specifics. We recognize that there are many constraints on the sharing of clinical data about human subjects. Our ultimate standard is that data sharing should be approached with a recognition of the ethical commitment to patients to optimize the value of their participation in clinical research while protecting their privacy. It is also important that the primary purpose of any analyses on the basis of shared data is focused on improving patient outcomes rather than commercial or promotional factors. The ICMJE data-sharing plan asks for answers to a series of questions, and we will continue to ask for answers to these questions. The first question that is asked is “what.” In general, we consider the norm to be sharing the analytic data files of the deidentified individual participant data that underlie the results reported in the manuscript. These files need to be accompanied by the metadata—field definitions, analytic rules, and so on—required to understand and use the files. A number of journals ask for such basic analytic files during review, and their availability is an important aspect of addressing reproducibility concerns. It is worth noting, however, that, in spite of some fears, secondary analyses that challenge the original conclusion of studies seem to be uncommon.7 The next question is “when”; again, we consider flexibility appropriate. In general, of course, prompt sharing is desirable, but we recognize that investigators may need some limited period of time to complete planned secondary analyses and that industry-supported studies may face special issues related to product development. For industry studies, the answer “after completion of regulatory consideration” may be satisfactory. Limits on the duration of data sharing (e.g., “for 5 years after publication”) may be appropriate for studies that rely on local funding or lack resources for assistance in data-sharing requests. Some limitations to access and some vetting of requests are understood to be important. Investigators can turn to a number of resources for help with the answers to the next set of questions: “with whom,” “for what,” and “by what mechanism.” Many data coordinating centers are able to serve as intermediaries in responding to data-sharing requests. National Institutes of Health institutes, particularly the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute, have repository resources available for studies that they have supported. Although some pharmaceutical companies maintain their own data-sharing portals, many pharmaceutical companies and other funders are using common data-sharing portals, such as ClinicalStudyDataRequest.com. In addition, several new initiatives, such as the Vivli Center for Global Clinical Research Data (Vivli.org) and the YODA Project (yoda.yale.edu), are being established to support the vetting processes needed for optimum data sharing, some appropriate for industry-, public sector–, and academic-supported research. We hope that these strengthened data-sharing expectations will serve our discipline well. The editors share the concerns about the shortage of clinical trials in nephrology and the continued under-representation of patients with kidney disease in trials for other conditions. These concerns only add to the sense of urgency to promote full use of the valuable data that emerge from these important studies. So, for the question “will you share your data,” we have decided not to take “no” for an answer. Disclosures Dr. Briggs reports personal fees from Verily, non-financial support from People Centered Research Foundation, outside the submitted work. Dr. Palevsky reports personal fees from Novartis, Baxter, GE Healthcare, HealthSpan Dx, and Durect, and grant support from BioPorto, outside the submitted work.