Postmarketing studies for novel drugs approved by both the FDA and EMA between 2005 and 2010: a cross-sectional study

Abstract

ObjectivesTo characterise postmarketing studies for drugs that were newly approved by the US Food and Drug Administration and the European Medicines Agency.Design and settingCross-sectional analysis of postmarketing studies registered in ClinicalTrials.gov until September 2014 for all novel drugs approved by both regulators between 2005 and 2010. Regulatory documents from both agencies were used.Primary and secondary outcome measuresAll identified postmarketing studies were classified according to planned enrolment, funding, status and geographical location, and we determined whether studies studied the originally approved indication.ResultsOverall, 69 novel drugs approved between 2005 and 2010 were eligible for inclusion. A total of 6679 relevant postmarketing studies were identified; 5972 were interventional (89.4%). The median number of studies per drug was 55 (IQR 33–119) and median number of patients to be enrolled per study was 60 (IQR 28–183). Industry was the primary sponsor of 2713 studies (40.6%) and was a primary or secondary sponsor in 4176 studies (62.5%). In all, 2901 studies (43.4%) were completed, 487 (7.3%) terminated, 1013 (15.2%) active yet not recruiting, 1895 (28.4%) recruiting and 319 (4.8%) not yet recruiting. A total of 80% of studies were conducted in only one country and 84.4% took place in Europe and/or North America; 2441 (36.5%) studied another indication than the originally approved indication. Studies designed in the originally approved indication were found to be more industry-sponsored than others 68.7%vs53.7%; P<0.0001.ConclusionsPostmarketing pharmaceutical research was highly variable and predominantly located in North America and Europe. Postmarketing studies were frequently designed to study indications other than the originally approved one. Although some findings were reassuring, others question the lack of coordination of postmarketing research.

Patient burden and clinical advances associated with postapproval monotherapy cancer drug trials: a retrospective cohort study

“…There is high variability in the number of trials pursued per trajectory and also in the number of patients enrolled per trajectory. This confirms a result shown in other work conducted on postapproval trials in the same time period 26. This variability may arise from many different sources: lack of coordination, market considerations, regulatory incentives for rare diseases or individual agendas of small research centres.…”

“…Our findings might also inform research policy. Others have reported high levels of postapproval clinical testing and raised concerns about redundancy and the lack of coordination of postapproval trials 26. One study suggested a relationship between high revenue generation for a drug and postapproval testing 27.…”

“…Research funders and policy-makers might consider incentives that would encourage more selective conduct of postapproval trials and greater efforts towards confirming promising findings from exploratory postapproval studies. Regulators might also reconsider policies that grant companies safe harbour from off-label promotion29 when they circulate reprints of clinical trials testing off-label treatments 26 27. There is high variability in the number of trials pursued per trajectory and also in the number of patients enrolled per trajectory.…”

“…However, given the tendency to selectively report positive trials, we suspect our findings would be even less favourable for label-extending research had we been able to capture the results of unpublished studies. Second, we considered only anticancer drug development; anticancer postapproval clinical testing may be more extensive than other disease areas 26. Third, a more recent sample of drugs—one that includes immunotherapies or precision-medicine drugs—might show greater rates of successful translation.…”

US Food and Drug Administration utilization of postmarketing requirements and postmarketing commitments, 2009–2018

“…31 However, nearly one-quarter of clinical postmarketing requirements and commitments focused on modified or unapproved therapeutic indications, including one-half of confirmatory postmarketing requirements for therapeutics receiving accelerated approval designation. This rate is comparable to that observed for postmarket clinical studies overall, which are primarily sponsored by industry, 32 frequently evaluate new therapeutic uses, 33,34 and may play a role in promoting medication use after approval. 35 This has also been observed for therapeutics receiving accelerated approval designation, which are integrated into clinical practice, including new applications, without confirmation of clinical benefit for original indications.…”