After receiving approval from the US Food and Drug Administration (FDA) for a novel therapeutic, pharmaceutical companies frequently conducted voluntarily postapproval clinical trials, most commonly for new or expanded drug indications, according to a study published in JAMA Network Open.1
“While most therapeutics had at least 1 postapproval trial evaluating safety or efficacy, only 12% of trials exclusively studied first FDA-approved indications, and more than 60% of trials instead focused on unapproved or supplemental indications,” researchers wrote.
The analysis looked at postapproval clinical trials conducted with at least 1 site in the United States sponsored by pharmaceutical companies of therapies approved from 2009 to 2012.
During that time, the FDA approved 110 novel therapeutics for 120 indication; 37 (representing 39 indications) were novel and did not have postmarketing requirements or commitments.
For the majority (83.8%) of approvals, there were postapproval clinical trials sponsored by pharmaceutical companies. Of those, most investigated therapeutics for new indications (60%) or for expanded populations (20.3%). Only 12% exclusively studied the first FDA-approved indication.
“Most trials were nonrandomized, unblinded, and uncontrolled, and more than one-third focused on a surrogate marker of efficacy rather than a clinical end point,” the researchers wrote.
As of July 2018, only about one-third of the trials were classified as complete on ClinicalTrials.gov, with 13.7% listed as terminated and 23% listed as active but not recruiting. Of the 300 terminated or completed trials, 68% had reported results to ClinicalTrials.gov a median of 16 months after primary completion date.
“To ensure that patients and physicians have access to comprehensive clinical trial data informing treatment and prescribing decisions, robust communication between the FDA and pharmaceutical companies, including the effective use of postmarketing requirements and commitments, is essential to the investigation of therapeutic safety and efficacy after market approval,” researchers concluded.
In an accompanying editorial,2 Joel Lexchin, MSc, MD, of York University, Toronto, Canada, wrote that the study’s findings raise many “troubling” questions.
“Postapproval studies need to advance clinical care by answering unresolved questions,” Dr Lexchin wrote. “The findings by Skydel et al demonstrate that, at least when trials were undertaken at the initiative of pharmaceutical companies, they were unlikely to do so. Clinicians and patients deserve better.”
- Skydel JJ, Luxkaranayagam AT, Dhruva SS, Ross JS, Wallach JD. Analysis of postapproval clinical trials of therapeutics approved by the US Food and Drug Administration without clinical postmarketing requirements or commitments. JAMA Netw Open. 2019;2(5):e193410.
- Lexchin J. Pharmaceutical industry-initiated postapproval studies – not requested by the US FDA, little value, and many questions. JAMA Netw Open. 2019;2(5):e193392.