Study Finds Few Voluntary Postapproval Trials for First Approved Indication
A study published in JAMA Network Open last week finds that in absence of postmarketing requirements or postmarketing commitments for novel therapeutics approved by the US Food and Drug Administration (FDA), drugmakers rarely conduct voluntary postapproval studies of the drug in the same indication it was initially approved for.“Over the last decade, the FDA has increasingly shifted toward life-cycle evaluation of drugs and biologics, placing greater emphasis on postmarket evidence generation as part of therapeutic evaluation,” the authors write, noting that a growing number of drugs are being approved under expedited approval pathways.
According to the authors, 90% of new drugs and biologics have some form of postmarketing requirement, though less than one-third (31%) of those requirements involve new clinical trials, prospective cohort studies or registries.
The authors also point out that just under half (45%) of new drugs and biologics are approved without postmarketing commitments, which are agreed upon by FDA and the sponsor as a condition of approval.
For the study, the authors looked at 37 new drugs approved by FDA from 2009 to 2012, roughly one-third of the novel therapeutics approved during that period, that did not have postmarketing requirements or commitments to conduct new clinical trials at the time of approval.
Of those 37 products, 14 were granted a priority review, 15 were approved for orphan indications and three received accelerated approval. The authors note that the three products that received accelerated approval had postmarketing requirements to complete ongoing studies.
Of those, the authors identified 31 products that were the subject of 600 postapproval clinical trials conducted in the US.
“Although most therapeutics had at least one postapproval trial generating new safety or efficacy evidence, only 12% of trials were exclusively for the first FDA-approved indication. Instead, most trials investigated new indications or expanded patient populations,” the authors write.
The authors also note that, when reported, results from two-thirds (68%) of the completed or terminated postmarketing trials were published more than a year after the studies were completed. The remaining completed or terminated postmarketing studies “remained without results reported for a median 35 months after completion or termination.”
While the authors say it is difficult to pinpoint why these results are delayed, they point out that “regardless of the cause, such delays lead to clinical and regulatory questions remaining unanswered for years after approval.”
To address these issues, the authors suggest that FDA apply more postmarketing requirements at the time of approval and more judiciously as new questions regarding a product’s safety and efficacy arise.
On the other hand, the authors also say that drugmakers could improve their reporting of voluntary postapproval studies.
JAMA