- Defining Clinical Trial Transparency
- Clinical Trial Spin and Suppression
- Benefits and Costs of Transparency
- Legislative Strategies to Encourage Transparency
- Bottom-Up Strategies for Clinical Trial Transparency
- Conclusions: Towards Greater Transparency
- Clinical Trial Transparency References
Clinical trials are necessary to establish the safety and efficacy of new drugs, biotherapeutics, and medical devices. Trials are typically sponsored by the companies that are developing new products, in order to support a New Drug Appplication (NDA) to the Food and Drug Administration to obtain approval to sell and market a drug or device in the US. The majority of the drug approval process operates behind closed doors. While companies interact closely with the FDA through meetings and correspondence, neither the data that supports an NDA nor the full analysis and reasoning that supports an FDA regulatory decision is made public. In some cases, a subset of information about a drug may be obtained from the FDA by filing a request under the Freedom of Information Act (FOIA). However, submissions to the FDA are typically protected from public disclosure, even under FOIA, because FOIA allows the US government to withold publication of proprietary information such as trade secrets. Therefore, the vast majority of information about clinical trials — until quite recently, even the existence of a clinical trial — has remained a secret shared between the sponsoring company and the FDA. As a result, clinical trials and data are not subject to outside scrutiny until the trial sponsor elects to publish information about the trial in a scientific journal.
The need for increased scrutiny of clinical trials follows from an examination of the conduct of trial sponsors over the last decade. The pharma, biotech, and device companies that sponsor trials have significant economic interests in their success, and negative or ambiguous results from a trial can lead to failure to gain approval, loss of market share, loss of credibility and difficulty raising additional capital. Companies therefore have strong incentives to avoid publication of unsuccessful trials. As a result of the progress in biotechnology over last two decades, many drugs are now developed, at least initially, by small biotechnology companies. Biotechnology companies are particularly susceptible to the tension between managing expectations and publishing clinical trials. Small biotech companies are often under financial pressure and frequently need to raise capital and forge partnerships with larger companies. Small companies also have risk concentrated on a small number of products, and may lack sufficient human and financial resources to full analyze and interpret data, especially after disappointing trial results have been observed.
In this series of posts, I will attempt do the following:
- Review current US law and administrative procedures that govern clinical trials and data publication
- Highlight recent cases in which trial sponsors have attempted to suppress and spin clinical trial results, and which illustrate classes of problems with current trial reporting.
- Look at how increased transparency of clinical trial result data could lead to better trials, more efficient investment decisions, better scientific research, more cost-effective healthcare, and reduced risk to trial participants and patients.
- Evaluate the arguments against clinical trial transparency. Over the last decade, a consensus has emerged both within the US regulatory community and among international health organizations that clinical trial transparency is important. The major arguments against making clinical trial results available involve the risks that:
a) data may be misinterpreted by the medical community or the public
b) proprietary business information could be made public, hurting the business prospects of a drug or company
c) the costs of disseminating trial information would be burdensome
d) companies generating and publishing additional information could expose themselves to significant tort liabilities, and transparency could therefore have a paradoxical chilling effect on clinical research.
- I’ll argue that that the claims that publication results would damage companies by revealing trade secrets and proprietary information are not valid, and that the risks of misinterpretation of results are outweighed by the benefits of increased scrutiny, especially when the cost and difficulty of publishing data is decreasing due to the adoption of better information technology.
Having established that increased clinical trial transparency is both desirable and economically feasible, I will evaluate potential legislative and policy approaches that could encourage greater transparency. Clinical trials are complex activities that depend on the cooperation of numerous stakeholders: sponsoring companies, regulatory agencies (FDA and NIH), clinical physicians, healthcare institutions, patients, and publishers. In addition to the disclosure rules dictated by legislation and FDA regulations, the physicians who execute clinical trials and the patients who consent to trials are in a position to do much more to encouge the dissemination of trial results.
Trial sponsors ultimately depend on the cooperation of doctors and patients for trial recuritment. Both physicians and patients hold considerable power in the clinical trial process, because clinical trials require explicit, contractual informed consent and because patient information rights are guaranteed by laws such as HIPAA. I will propose that, in addition to the continued implementation and extension of the FDA Amendment Act of 2007 (FDAAA), institutions such as universities and hospitals should adopt policies to require enhanced clinical trial disclosure, and that such institutions are in actually in a strong position to exert pressure to encourage transparency much more quickly than can be accomplished by additional legislation or actions by regulatory agencies.