Rare Cancer Trial Design: Lessons from FDA Approvals
Cet article analyse les caractéristiques des essais cliniques ayant servi de base pour l'autorisation de mise sur le marché américain, entre 1987 et 2011, de médicaments prescrits pour des cancers rares
Purpose: A systemic analysis of clinical trials supporting rare cancer drug approvals may identify concepts and terms that can inform the effective design of prospective clinical trials for rare cancers. Experimental Design: Using annual incidence (less than or equal to) 6/100,000 individuals to define rare cancer, we identified clinical trials for rare cancers, supporting FDA drug approvals for rare cancer indications between December 1987 and May 2011. We characterized each selected trial for study design, sample size, primary efficacy endpoints, and statistical comparisons. We also profiled trials with regard to type of submission, review designation, and approval type. Results: Ninety-nine trials were identified that supported the approvals of 45 drugs for 68 rare cancer indications. One-third of these trials were randomized; 69% relied on objective response rate as the primary efficacy endpoint; and 63% were based on a single trial. Drugs granted accelerated approval appeared more likely to be associated with postmarketing safety findings, relative to drugs approved under the regular approval. Data collected across clinical trials were robust: using different lower incidence rates in analyzing these trials did not have effects on trial characteristics. The absolute number of drug approvals for rare cancer indications increased markedly over time. Conclusions: One-third clinical trials supporting drug approvals for rare cancer indications were randomized, affirming the feasibility and value of randomized trial design to evaluate drugs for rare cancers. Postmarketing safety data may relate to trial design and approval type. An operational definition of rare cancer can be useful for the analysis of trial data.
Clinical Cancer Research , résumé, 2012