Background: The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) are responsible for scientific evaluation and approval of medicines. Approval of new drugs is based on the evaluation of individual clinical studies conducted by manufacturers who produce new compounds. Concerns have been raised regarding the rules governing approval of medicines, quality and transparency of evaluations.
Objectives: To critically review regulations for drug approvals in Europe and the U.S. and to ascertain whether the use of meta-analytical approaches may inform regulatory decisions. Mental disorders are used as a paradigmatic example in view of several medicines already available for these conditions.
Methods: We reviewed EMA and FDA regulations for approval of new drugs for mental disorders. Additionally, as case examples, regulatory trials for three recently approved drugs for mental disorders (esketamine, paliperidone 3-months long-acting and cariprazine) will be meta-analyzed to summarize evidence available at the time of approval.
Results: FDA and EMA require at least two “positive” trials showing superiority over placebo, or noninferiority over active comparators, to grant marketing authorization for new psychotropic medicines. The use of meta-analytical techniques is not a requirement. We will present the results of meta-analyses of regulatory trials of esketamine, paliperidone 3-months long-acting and cariprazine and of network meta-analyses including these medicines. Such examples will show that pooling available evidence for efficacy and tolerability outcomes may offer an added dimension to the evaluation of new medicines, especially for comparing new medicines with those already on the market.
Conclusions: Evaluation of new medicines should be complemented by regulatory meta-analyses of all relevant clinical studies performed at the time of approval, including network meta-analysis if feasible, and individual participant data (IPD). This would be especially relevant in areas where several medicines already exist, as it would inform regulatory authorities on comparative efficacy and acceptability of new drugs compared with those already available. Regulatory meta-analyses should ideally be conducted by independent organizations such as Cochrane. Cochrane may work in consultation with regulatory authorities in developing transparent and high-quality overviews of existing evidence to complement data from clinical studies during the regulatory approval process. Patient/public/healthcare-consumer involvement: Results will improve quality of care.