Table 1.

The US Food and Drug Administration’s Postmarketing Requirement Authorities

Authority (year implemented)	Purpose and requirement	Drug/indication(s)	Postmarketing requirement example	Uncertainties addressed by postmarketing requirement
Accelerated Approval pathway (1992)	To expedite the approval of certain drugs that treat serious diseases and that fill an unmet medical need, FDA approval can be made on the basis of trials with surrogate endpoints “reasonably likely” to predict clinical benefit. FDA then has the authority to require postmarket studies or confirmatory clinical trials.[4]	Bedaquiline Fumarate/MDR-TB	“Conduct a confirmatory randomized double blind placebo controlled multicenter Phase 3 trial in subjects with sputum smear-positive pulmonary multidrug-resistant tuberculosis (MDR-TB). This trial should assess long-term outcomes of failure or relapse or death at least 6 months after all MDR-TB treatment is completed”	FDA approval was based on two small randomized-controlled trials evaluating surrogate microbiological markers of treatment response. A confirmatory clinical trial evaluating a clinical outcome is necessary.
Pediatric Research Equity Act (PREA) (2003)	To provide pediatric use information in product labeling for drugs developed for indications that occur in both adult and pediatric patients, FDA can approve drugs for use in adults without corresponding studies for the same indication in the relevant pediatric population.[4] However, FDA can include deferred pediatric studies or clinical trials as postmarketing requirements.	Ceftaroline Fosamil/ABSSSI and Community Acquired Bacterial Pneumonia	“Perform a randomized comparison of Teflaro (ceftaroline fosamil) and comparator in pediatric subjects with ABSSSI including patients with infection suspected or demonstrated to be caused by MRSA. Pediatric patients under 17 years of age with ABSSSI must be enrolled, with a minimum of 150 patients receiving Teflaro (ceftaroline fosamil)”	FDA approval was granted for use in adults. Under PREA, all application for new indications, dosage forms, dosing regimens, routes of administration, and indications are required to contain effectiveness and safety assessments of the product for claimed indication in pediatric populations, unless they are inapplicable, deferred, or waived. Ceftaroline Fosamil was approved with a deferred submission.
Food and Drug Administration Amendments Act (FDAAA) (2007)	To provide additional information for novel drugs, FDA can require postmarket studies that assess know serious risks, signs of serious risks, or unexpected serious risked related to the use of a novel drug.	Tocilizumab/Rheumatoid arthritis	“A randomized, controlled trial to rule out a moderate increase in the risk of serious cardiovascular events with tocilizumab, e.g., stroke, non-fatal MI, cardiovascular death”	FDA approval was based on 5 multinational phase 3 clinical trials with > 4000 patients. However, safety concerns were reported in tocilizumab-treated patients.

FDA, Food and Drug Administration; MDR-TB, multidrug-resistant tuberculosis; ABSSSI, acute bacterial skin and structure infection; MRSA, methicillin-resistant Staphylococcus aureus; MI, myocardial infarction; PREA, Pediatric Research Equity Act. Our sample did not contain any clinical trials issued under the Animal Efficacy Rule (AER) (2002). Under AER, postmarketing requirements may be issued for certain drugs approved without human efficacy studies and field trials when they are not ethical and feasible