IMPORTANCE Many medicines prescribed to children have not been studied or formally approved for pediatric use. The Pediatric Research Equity Act of 2003 authorized the US Food and Drug Administration (FDA) to require pediatric clinical studies.OBJECTIVE To evaluate the characteristics, completion rate, and transparency of study design and results for mandatory pediatric postmarketing studies required under the Pediatric Research Equity Act. DESIGN AND SETTING A retrospective cohort study was conducted of pediatric postmarketing studies required for new drugs and new indications approved by the FDA between January 1, 2007, and December 31, 2014, with follow-up through December 1, 2017. Information on the status, design, and results of pediatric studies was obtained from publicly available FDA databases and ClinicalTrials.gov, direct communication with the FDA, and searches of MEDLINE, EMBASE, and Web of Science for peer-reviewed publications.MAIN OUTCOMES AND MEASURES Characteristics and transparency of pediatric studies, results reporting (in ClinicalTrials.gov, peer-reviewed literature, or FDA documents), and availability of pediatric information in drug labels. Rates and times to study completion were evaluated using Cox proportional hazards regression models.RESULTS Between 2007 and 2014, the FDA approved 114 new drugs and new indications for already approved drugs that were subject to Pediatric Research Equity Act requirements. These drugs were associated with 222 required pediatric postmarketing clinical studies. Overall, 75 pediatric studies (33.8%) were completed as of December 1, 2017. The rates of completion were significantly lower for efficacy studies (38 of 132 [28.8%]) compared with pharmacokinetic studies (19 of 34 [55.9%]; adjusted hazard ratio, 0.31; 95% CI, 0.12-0.82). Information on randomization, blinding, comparator, end point, and study size could not be identified for 74 studies (33.3%), and no reason for discontinuation was provided for 29 of the 42 discontinued studies (69.0%). Among the completed studies, the results were reported for 57 (76.0%). At the time of approval, 18 of 114 drug approvals (15.8%) had any pediatric efficacy, safety, or dosing information in their labels. After a median duration of follow-up of 6.8 years (interquartile range, 4.7-9.1 years), 47 of 114 of drug labels (41.2%) had any pediatric information.CONCLUSIONS AND RELEVANCE Only 33.8% of mandatory pediatric postmarketing studies have been completed after a median follow-up of 6.8 years, and most drug labels do not include information important for pediatric use. To improve evidence-based prescribing of medicines to children, more timely completion of pediatric drug studies is needed.

Background/Objectives Evidence-based and patient-centered care of elderly adults with ischemic heart disease requires clinical trials that study the patient population seen by clinicians in practice. We aimed to measure the exclusion of elderly persons from randomized trials studying drug interventions for ischemic heart disease and describe the characteristics of these trials. Design and setting Interventional clinical trials studying a drug intervention for ischemic heart disease and started 2006 and after were identified in ClinicalTrials.gov. Data were extracted on study features, including age-based inclusion criteria. Data on participants and their age distribution were collected from trial publications, investigator inquiry, and result data in ClinicalTrials.gov. Measurements Proportion of trials excluding patients based on age, mean age of trial participants, and proportion of enrolled participants who were ≥65 years and ≥75 years. Results Of 839 identified trials, 446 (53%) explicitly excluded elderly persons. The most frequent upper age limits were 80 (n=164) and 75 (n=114) with a median upper age limit of 80 (IQR 75, 80). Trials with upper age limit exclusions tended to be smaller (median number of participants 100 vs 201, p<0.001) and were more likely to be funded primarily by non-industry sources (78.3% vs 70.0%, p=0.006). The overall mean age of trial participants was 62.7 years with a mean maximum age of 74 years. The estimated proportion of participants that was ≥65 years was 42.5% and the estimated proportion that was ≥75 years was 12.3%. Conclusion Despite the high burden of ischemic heart disease among elderly patients, the majority of drug trials do not enroll participants reflective of age-related prevalence of the disease.

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The Research to Accelerate Cures and Equity (RACE) for Children Act was enacted in 2017 to authorize the US Food and Drug Administration (FDA) to require pediatric studies for new cancer drugs that have a molecular target relevant to the growth or progression of a pediatric cancer. To assess the possible scope of this new policy, we examined all 78 adult cancer drugs approved by the FDA from 2007 to 2017. Only 17 (21.8%) drugs received any pediatric labeling information. Based on the FDA’s Pediatric Molecular Target List, we found that the RACE Act could have increased the proportion of cancer drugs potentially subject to pediatric study requirements from 0% to 78.2%. However, the actual effect of the legislation will depend on how often regulators require pediatric trials and on timely completion of such trials.

A shared latent space matrix factorisation method was useful for ranking trial registrations to reduce the manual workload associated with finding relevant trials for systematic review updates. The results suggest that the approach could be used as part of a semi-automated pipeline for monitoring potentially new evidence for inclusion in a review update.