Proposals for the full disclosure of all clinical trial data, both positive and negative, could have important impacts on the safety of new therapeutics.
By: Joan Rachlin, JD, MPH, Executive Director of Public Responsibility in Medicine and 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 I read a piece in The New York Times about Peter Doshi, PhD, a 32-year-old post-doctoral fellow at Johns Hopkins University, who has been pressing pharmaceutical companies to make their clinical trial data public. Dr. 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, Dr. Doshi and his allies have made 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.
Dr. Doshi and his colleagues’ quest 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 out of 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 Dr. 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 which 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 as well. 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 already-existing 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 Medtronics promoted off-label use.
The efforts of Dr. Doshi and the Medtronic example, especially when combined with the recent European Medicines Agency’s proposal requiring wider access to patient-level trial data, 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 ClinicalTrials.gov, but others contend that this is inadequate as there are extensive limitations placed on what kinds of information can be released through that medium.
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 do 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, perhaps the ethical imperative of data transparency 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 of clinical trial data allows for 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 healthcare consumers.
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 on both side of the debate—from PhRMA 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. Do you think public access to clinical trial data should be provided? And if so, how?
Picture Credit: Bill David Brooks via photopin cc
