By Joe Archer, associate director of data sciences and disclosure services, MMS Holdings Inc.
or those of us in the business of managing clinical trials, it has been quite a journey keeping up with the requirements for clinical trial disclosures. Although the road to transparency was paved with good intentions, for many it has been a bumpy one, and we are not there yet.
From the very beginning, there have been proponents of and opponents to transparency, each representing its own interests. There is reason for these opposing views. The public is demanding information that private industry considers proprietary. Consistent pressure from the general public, healthcare professionals, journal editors, media, and legislators has brought about the passing of two laws, (1) Food and Drug Administration Modernization Act of 1997 (FDAMA), and (2) Food and Drug Administration Amendment Act of 2007 (FDAAA). Proponents of trial disclosure emphasize the importance of this information for patients and their caregivers interested in trials of investigational drugs. This is especially important when available (marketed) treatment options are very limited or no drug is available. Another argument in support of trial disclosure is the desire to share the full context of the research study results in order to prevent a “publication bias” (i.e. cherry picking). If protocol and results summary information for all studies in a given drug program are shared, this curbs “publication bias” in which only studies with positive results are published, a practice that can be especially harmful to physicians practicing evidence-based medicine. Disclosure of full-trial results may also benefit research as a whole. An organization about to conduct a trial may build on the information already available for a comparable chemical or molecular entity, trial design, or targetstudy population. With this in mind, researchers could learn about safety issues before putting patients at risk.
This is where the journey reaches a split in the road. The public benefits from full-trial disclosure as do researchers because they can learn from other trials and possibly spare themselves redundant testing. However, from a competitive standpoint, if you funded a clinical trial that yielded important scientific information, would you want to share these findings with those also in the race? Only 1 in 5,000 compounds in the development pipeline will make it to market, with an average cost of $1 billion. With an 8- to 10-year patent protection period you have limited time to recoup your costs, justify your spend and record a profit to shareholders, and invest in future research. For this reason you may want to prevent your competition from viewing your intellectual property.
The wheels of change continue to turn with two new (i.e. late last year) developments that could more than double the current reporting requirements and begin fining sponsor companies that are out of compliance.
On Aug. 2, 2012, a group of House Democrats introduced the Trial and Experimental Studies Transparency (TEST) Act of 2012, legislation that would update and expand the clinical trial registry data bank ClinicalTrials. gov. TEST mandates the addition of Phase 1 studies, postings of informed consent forms and full protocol documents, disclosure of results for investigational drugs, and reporting compliance and enforcement activities to Congress. This last item identifies enforcement activities. Current U.S. law requires the registration of applicable clinical trials on a public registry and results reporting within one year of study completion for marketed products. However, an audit published in 2012 has shown that 80% of trials failed to comply with this law. Despite this fact, no fines have ever been issued for noncompliance. But that may be about to change.
In September 2012, the U.S. Department of Health & Human Services surrendered to the FDA its authority to oversee information filed to ClinicalsTrials.gov, and to seek out those who fail to file or file misleading or false data. This authority will finally give the current FDA law some teeth to enforce compliance. Potential fines of up to $10,000 per day would be a bitter pill for pharma companies to swallow.
The journey to meet current requirements has already seen many twists and turns in the road, and by all indications the next leg of the trip may be uphill. Pharma companies will need to take caution and prepare accordingly, or potentially face the long arm of the law.