Presently, the only real postmarket surveillance in the pharmaceutical industry comes from passive, generally unreliable adverse
event reports by doctors and pharmacists. But now Congress has instructed FDA to establish an active postmarket safety surveillance
and analysis system. The new Sentinel System, part of the FDA Amendments Act (FDAAA), will expand FDA initiatives to access
health information databases on an estimated 25 million patients by 2010, and 100 million by 2012. This more extensive monitoring
system will detect drug safety signals much faster, and provide a broader picture of drug utilization and related safety problems.
While FDA and industry are busy rolling out implementation plans and launching pilots for more effective postmarket surveillance,
the initiative raises a larger issue: How will improved understanding of drugs' effects in real world settings influence
drug discovery and FDA approval of new products? The agency has been blasted in recent years for approving drugs that later
prove to have safety problems. And even where FDA is not consciously more risk-averse, sponsors have been dropping development
programs, and fewer new drugs are coming to market. A number of high-profile products marketed in Europe have not made it
through the FDA review system, and additional postmarket monitoring requirements are generating considerable uncertainty in
pharma R&D departments. In addition, marketers fear that earlier and broader postmarket data assessment will yield false negatives
that set off alarms on every new drug.
A more proactive, more efficient postmarket surveillance system will give regulators more confidence that safety problems
can be identified quickly and correctly after a drug goes to market. As a result, FDA may be more willing to approve applications
for innovative products despite risks. Agency officials are optimistic about the potential benefits of the Sentinel System,
and believe that the program may even reduce the scope of late-stage clinical trials and Phase IV studies. Expanded postmarket
assessment could dispel safety concerns about a new drug or vaccine raised in pre-licensure studies, observes Jesse Goodman,
director of the Center for Biologics Evaluation and Research (CBER). "The data can cut both ways," says Goodman.
At a Brookings Institution forum in June, former FDA commissioner and Medicare chief Mark McClellan (now with Brookings) predicted
"a new era for determining how drugs should be used on the market." FDA commissioner Andrew von Eschenbach agreed that sophisticated
information-gathering technologies will support new discovery platforms. Johnson & Johnson corporate vice president Garry
Neil anticipates "a true revolution in healthcare," as clinical information supports the discovery of safer, more effective,
less costly medical products.
McClellan further explained at the June annual meeting of the Drug Information Association (DIA) that an active postmarket
surveillance system reflects a move away from distinct pre- and postmarket regulatory processes and toward a life-cycle approach
to drug development and regulation. However, he also noted that rising FDA concerns about drug safety are "not just a pendulum
swing," but reflect higher expectations about long term safety.
To achieve this regulatory revolution, FDA published a five-year drug safety plan and a formal Sentinel Initiative proposal
spelling out the multiple goals and deadlines for establishing an active surveillance system. The initiative requires standards
and methods for more effective analysis of health information, and better strategies for communicating new safety information
to providers and patients. One important project is to improve FDA's existing adverse event reporting program [see sidebar:
Agency officials, however, are not looking to build a giant federal health database based on an expanded AERS system. Instead,
FDA will expand postmarket surveillance by accessing more data—on drug use, patient outcomes, and specific safety issues—held
by private health plans, database operators, government agencies, and manufacturers. By utilizing this distributed network,
all personal medical data will remain behind firewalls, reducing concerns about patient privacy and data security.