Once upon a time, the very existence of a clinical trial was considered confidential, and sponsors would disclose new findings only after they had passed the rigors of the traditional biomedical peer review publication process. In recent years, however, there has been a groundswell of public criticism—and several highly publicized lawsuits—surrounding industry practices related to information from clinical trials. That has translated into a complex web of regulations and guidance that govern the registration of clinical trials and disclosure of results—and that ultimately have the potential to affect how data are published.
As wave after wave of deadlines send companies scrambling to meet these new rules, the industry is taking a crash course in compliance. And with the next deadline at the end of this month (requiring trial sponsors to post basic results information on ClinicalTrials.gov/), pharmas are realizing that this is just the beginning. A gathering storm of international regulations has appeared on the horizon, with different countries setting out different, and often conflicting, requirements for trial registration and results disclosure.
What are the implications of these regulatory changes? Here we outline the emergence of new regulations in the US and beyond, examine the industry's response to date, and suggest how companies might best future-proof their compliance strategy to stay up-to-date with these rapidly emerging requirements in a cost-effective manner.Clinical Data Disclosure: How Did We Get Here?
Starting in the late 1990s, patients and their advocates led the charge for more information about clinical trials, mostly because they wanted to participate in actively recruiting trials that could offer the potential for life-saving drugs. This was a perfectly reasonable goal, but the drive for more information may have touched off the firestorm of compliance challenges.
Opening round: Drug trials to treat life-threatening conditions The first step toward regulating the disclosure of clinical trial protocols came in November 1997, when the US government signed the Food and Drug Administration Modernization Act (FDAMA) into law. FDAMA covered a wide range of provisions, including the extension of the Prescription Drug User Fees. But Section 113 (which remains in full force today) required the establishment of a "clinical trials databank" that would serve as a centralized information repository on clinical trials for drugs intended to treat serious or life-threatening conditions. Patients were the anticipated audience, but it was also thought that it could be of use to researchers and healthcare providers. The databank eventually emerged in February 2000 as the National Library of Medicine (NLM) Web site, ClinicalTrials.gov/.
Medical journals step in In September 2004, the International Committee of Medical Journal Editors (better known as ICMJE, and previously known as the Vancouver Group) weighed in. This working group of editors from 11 highly influential medical journals (including the British Medical Journal and the New England Journal of Medicine) announced that if sponsors wanted to publish results in their journals, they had to register all Phase II through Phase IV studies before enrolling their first patient.
In particular, ICMJE wanted more transparency on clinical trials that "reflect unfavorably on a research sponsor's product." They were concerned about under-reporting of "negative" results—a longtime problem in clinical research, as it tends to distort the body of scientific evidence. For the first time, there were material consequences should sponsors fail to register trials; companies that wanted their study results to remain eligible for publication had to comply. In the months preceding the ICMJE-imposed September 2005 deadline for trial registration, the number of studies registered on ClinicalTrials.gov/ jumped from 13,153 to 22,714, as companies scrambled to meet the requirements.