Bioethics Forum Essay

The Push for Data Transparency and Implications for Research

Some of the most hotly debated questions making the rounds these days include who should interpret, distribute, review, and receive data, and with good reason. From WikiLeaks to National Security Agency whistleblowers, the problems of data privacy, data security, data accuracy, and data availability are making headlines.

Over the summer, The New York Times ran a piece about Peter Doshi, a 32-year-old postdoctoral fellow at Johns Hopkins University, who has been pressing pharmaceutical companies to make their clinical trial data public. Doshi contends that financial conflicts of interest and publication bias in journals necessitate public disclosure so that consumers and patients can make fully informed decisions regarding their own care. It is well-documented, for instance, that only half of all clinical trials are published and that negative results, which are at least as instructive as positive ones, rarely see the light of day.

Although one can hardly imagine a more David-and-Goliath-like match, Doshi and his allies havemade some inroads, most notably in helping to persuade GlaxoSmithKline to commit to sharing detailed data from all global clinical trials conducted by the company over the course of the past 13 years, although nothing has yet been released.

The quest by Doshi and his colleagues for clinical trial transparency began during their work to determine whether or not Tamiflu, manufactured by Roche, was an effective treatment for flu. Their pursuit proved difficult because the bulk of the data on which claims about Tamiflu’s efficacy were based was unavailable. Only two of the ten key Tamiflu trials used to demonstrate the drug’s efficacy had been fully published, and when scientists at the Cochrane Collaboration, a well-respected network of independent researchers working with Doshi, tried to track down the other eight, they hit repeated road blocks. As a result of the missing data, the Cochrane Collaboration determined that they could not endorse Tamiful’s effectiveness, a move that prompted Roche to open its file cabinets and join GlaxoSmithKline in its commitment to share detailed data with outside researchers.

There are other cases fueling the call to require data publication. In June, for example, two independent reports indicated that Medtronic’s spinal surgery product, Infuse,carried with it serious risks, including cancer and male infertility, and that there was no demonstrated improvement over conventional products for the same purpose. The reports, prepared under the auspices of Yale University with funding from Medtronic, examined 17 studies. The news reports surrounding these revelations are rife with allegations that negative data was suppressed, that conflicts of interest abounded, and that Medtronic promoted off-label use.

The demand for transparency of research data is now expanding to include access to individual-level raw data. In June, the European Medicines Agency (EMA) released, to much fanfare, a policy requiring publication of patient-level trial data for all medications at the time that they apply for marketing authorization. The policy is scheduled to go into effect January 1, 2014. The same month that the EMA published its draft policy, the U.S. Food and Drug Administration announced a request for comments on its own proposal to make available de-identified and masked non-summary data derived from medical product applications. The primary goals of these initiatives include not only review and monitoring of completed research, but the possibility of secondary research use of the data collected.

Together, the efforts summarized above have contributed to growing public demand for information that was formerly within the sole province of researchers, clinicians, and journal editors. The Pharmaceutical Research and Manufacturers of America (PhRMA), as well as most drug companies–excluding GlaxoSmithKline and Roche–have opposed this push. Some argue that American consumers already have access to raw data via the federal clearinghouse, but others contend that this is inadequate as there are extensive limitations placed on what kinds of information can be released through that website.

These issues around data transparency and review, among so many others that are rapidly changing the research landscape, could have long-term implications for research and development. One of the concerns being voiced by members of the pharmaceutical industry is how such policy shifts might hamper innovation. John J. Castellani, president and CEO of PhRMA, has been a vocal opponent of the proposed regulatory changes from the EMA and other reforms that he claims are too broad in scope. “Public policies that value intellectual property, a strong regulatory system, and free market access for patients are critical to a robust innovation ecosystem and new progress in the fight against disease,” he argues. The threat at the heart of Castellani’s comment, of course, is that as clinical trial data becomes widely available, so does information that has long been commercially protected.

The development of new drugs is a costly and lengthy endeavor. The high costs associated with developing and bringing new drugs to market have long been tempered by the potential profits that can be achieved when drugs find mass success. In their opposition to the data transparency movement PhRMA raises the question, if data from the drug development process becomes publicly accessible will the incentive structure that has helped fuel the development of new drugs be undermined?

On the other hand, some suggest that data transparency is an ethical imperative, one that demands a paradigm shift. Ben Goldacre, a noted proponent of clinical data transparency, asserts “that the problem of missing trials is one of the greatest ethical and practical problems facing medicine today.” Sharing clinical trial data allows results to be double checked and critically appraised, and means less duplication of effort, greater collaboration, reductions in drug development times, greater public trust in the pharmaceutical industry, and ultimately better protections for patients.

Stuck in the middle are those involved in human research protection programs that oversee the research in question; they face, on the one hand, pressure from funders, desperate patients, and the public at large to foster transparency in the service of accelerating research, and, on the other, pressure from regulators, institutional officials, and other research protections stakeholders to protect subjects’ privacy against the risks of disclosure and data breach.

From the EMA’s proposal to the moves being made by companies such as GlaxoSmithKline and Roche, the tide has shifted toward data transparency. The question that faces research professionals now is exactly what should the sharing of clinical trial data look like. Proposals have emerged from all sides–from PhRMA to EMA and FDA to the AllTrials campaign led by Ben Goldacre–which could shape the future of the clinical research enterprise. For those invested in the conduct of clinical trials, now is a pivotal time to engage in the conversation surrounding data transparency.

Those attending PRIM&R’s 2013 Advancing Ethical Research (AER) Conference or Virtual Meeting on November 7 to 9 in Boston will have an opportunity to participate in this important conversation during a panel on Friday, November 8, titled, Data Sharing on Steroids: Demands for Transparency of Subject-Level Research Data. During this panel, representatives from a patient advocacy group, the pharmaceutical/biotechnology industry, and an institutional oversight body will help attendees wrestle with the potential benefits and concerns around the push to data transparency. For more information about this panel, and the 155 other sessions covering the full range of topics of concern to today’s research ethics professionals, please visit the conference website. For those unable to participate, access to the conference proceedings will be available for purchase after the conference.

Joan Rachlin, JD, MPH, is the executive director; Avery Avrakotos is the education and policy manager; and Elisa Hurley, PhD, is the education director of Public Responsibility in Medicine and Research (PRIM&R)Connect with PRIM&R on Twitter @primrconnect.

Posted by Susan Gilbert at 10/24/2013 11:21:53 AM |

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