Routine application of risk-management plans, a public database of clinical trials and closer screening of FDA advisory committee members are among the measures proposed by two US senators in a much-heralded bill to reinforce drug safety in both the pre-and post-approval phase.
While these provisions, and the intention to fund improved oversight of drug safety through higher user fees, are unlikely to find much favour with industry, the Enhancing Drug Safety and Innovation Act (S. 3807) does throw in some crumbs of comfort. It envisages a public-private partnership – the Reagan-Udall Institute for Applied Biomedical Research – to advance the goals of the FDA’s Critical Path initiative and ensure the latest evaluation tools are quickly incorporated into product development and assessment.
The Institute’s remit would include identifying, pursuing and funding research priorities, as well as co-ordinating and expanding existing government R&D programmes. Financial support would come initially from the federal purse and latterly from a mixture of federal funds and contributions from industry and philanthropic organisations. Government officials, industry researchers, academic researchers and patient representatives would sit on the board of directors.
More worryingly for industry, the bipartisan legislation proposed by Senator Mike Enzi, chairman of the Senate Health, Education, Labor and Pensions Committee, and ranking member Senator Edward Kennedy would make all approvals of new drugs/biologics or new indications conditional on an agreed Risk Evaluation and Management Strategy (REMS), to be reviewed by the sponsor and the FDA at least annually for three years.
At a minimum, the REMS would have to include FDA-approved professional labelling; 15-day, quarterly and annual reports of adverse events; a surveillance plan to assess known serious drug risks and identify unexpected serious risks; and a timetable for periodic assessment of the REMS. Where a drug raised particular safety issues, additional requirements might extend to pre-clearance of, or specific disclosures in, advertising and/or a prohibition on direct-to-consumer advertising for no more than two years after approval.
Increased recourse to risk-management plans (RMPs) may not sit too well with the FDA either. Scott Gottlieb, deputy commissioner for medical and scientific affairs, recently expressed concern about growing pressure on the agency to use RMPs, which he feared could impede the supply of medical care by putting up extra barriers to patients and making overburdened clinics reluctant to offer new therapies.
The bill’s provisions for clinical data hinge on the notion of a central clearing house for information on studies and their results, going beyond the limited scope of the National Institutes of Health (NIH) database, ClinicalTrials.gov, or the voluntary registry set up by the industry association PhRMA. The NIH would host a publicly available database of trials to aid patient enrolment and progress-tracking, with all late Phase II, Phase III and Phase IV studies required to register.
This would be supplemented by a public database of clinical trial results, with mandatory submission of all Phase III and Phase IV outcomes. Enzi and Kennedy suggest a variety of enforcement tools, such as making FDA review of a new drug application conditional on trial data being submitted to both databases.
S. 3807 also aims to tighten up FDA screening of advisory committee members for financial conflicts of interest. For example, the categories of financial involvement used to evaluate committee members for service at panel meetings would be streamlined and clarified.
Just last month, the FDA announced its own plan to revamp its advisory committee system in the face of criticism about policies on conflict of interest waivers. While the agency pledged more transparency in granting waivers, it also insisted on being able to tap into the best scientific expertise, even if that might involve conflicts of interest.
The Enzi/Kennedy proposals drew a warm response from the US Association of Clinical Research Organizations (ACRO), which applauded its recognition of the “need to improve the science of clinical trials and the long and costly process of developing new biomedical products."