Timely postmarketing studies
Periodic REMS assessments also include updated information about postapproval studies or clinical trials undertaken by the
sponsor, including study status, expected completion date, and whether difficulties have been encountered in meeting set goals.
Similarly, this information is provided in annual reports on postapproval studies, as required by FDAAA to address complaints
that pharmaceutical companies have failed to complete agreed-on postmarketing studies in a timely manner. Congress authorized
FDA to mandate postapproval studies that achieve specific objectives and to levy fines on companies that miss agreed-on deadlines.
The result is that FDA reviewers now have to determine the scope and timing of postmarketing studies as part of the complex
application-review process. Instead of merely vetting manufacturers' study proposals, agency staffers must examine what scientific
data can best assess known and unknown serious risks and set appropriate timeframes for the completion of postmarket studies
This scrutiny of postmarketing studies seems to be having a notable effect. FDA's latest annual report on the program showed
considerable industry progress in achieving "on schedule" status for fulfilling postmarketing study obligations. About 20%
of studies are ongoing (i.e., were started on schedule) or submitted to FDA, and most are "pending" (i.e., not yet started,
but not delayed). This category includes many studies involving pediatric populations, which have to wait until all other
safety information is submitted and reviewed.
FDA should improve its ability to track and review postmarketing studies following Booz Allen Hamilton's analysis of these
obligations. The contracted analysts cleaned up FDA's confusing database of about 1531 postmarketing studies, identifying
many that have been submitted to FDA or that the agency no longer considers necessary, and determining that more than 80%
are proceeding according to established timelines.
FDAAA also authorizes FDA to require additional postmarket studies for approved drugs and to require changes in labeling when
new safety information emerges. The agency sent 14 letters requiring additional studies from mid-2008 to mid-2009 and issued
18 safety-labeling notification letters during that period. These additional tasks tap the agency's resources.
Because some postmarketing studies are likely to involve thousands of patients, CDER plans to ask advisory committees to weigh
in on acceptable trial designs, numbers of patients, and endpoints. These committee sessions will address study designs for
classes of drugs—rather than for each individual product, which would only extend approval times even more. And broader public
buy-in for innovative studies may help FDA parry second-guessing later on if research is delayed or changed.
Woodcock hopes that CDER's 21st Century Review initiative will deal with these new challenges by better managing the application-review
process. The aim is to compress review times up front to provide more leeway at the end of the review period to address safety
issues and resolve internal and external disputes. But streamlining reviews is a considerable challenge, Woodcock explained
at the symposium, because the average NDA consists of 10 gigabytes of material. The data may no longer come in truckloads,
but CDER reviewers still have to digest a massive amount of information.
CDER conducted a pilot program last year that reviewed 17 applications for NMEs under the new review process. This approach
now is being extended to most NMEs and new biologics license applications and is slated to affect all applications and supplements
by 2012. The streamlined system involves meeting in advance with manufacturers to identify key issues and ensure that applications
are complete when submitted. Earlier internal deadlines have been set for establishing multidisciplinary review teams, for
identifying application deficiencies, and for reviewing product labeling. FDA will assess up front whether an advisory committee
meeting will be needed, what potential postmarket safety requirements might apply, and other possible "showstoppers" that
could delay the approval process.
The agency and industry are optimistic that these efforts, along with staff expansion and training, will get CDER back on
track with review goals and deadlines. But any changes must support FDA's capability for assessing and preventing drug-safety
problems and ensuring safe drug use throughout the product life cycle.
Jill Wechsler is Pharmaceutical Technology's Washington editor, 7715 Rocton Ave., Chevy Chase, MD 20815, tel. 301.656.4634, firstname.lastname@example.org