Justifying the Choice of Endpoints for Clinical Trials
Menées par le groupe d'experts internationaux GASTRIC, ces deux études évaluent l'intérêt d'utiliser la survie sans maladie et la survie sans progression comme critères de substitution à la survie globale dans les essais cliniques de traitements d'un cancer de l'estomac
Survival has been considered traditionally as the gold-standard endpoint for cancer clinical trials. This tradition is congruent with the historical requirement of the US Food and Drug Administration (FDA) that improvement in either survival or meaningful clinical benefit, such as amelioration of major symptoms, is needed to justify marketing approval of a new drug. However, the high failure rate of drugs in the pipeline, notably cancer drugs, led to a perception by many stakeholders that the system of drug approval was too strict, impeding the successful approval of active agents. Urgency in developing drugs to combat the AIDS epidemic provided a strong impetus to consider shorter-term endpoints as surrogates for survival (1,2). This evolving political climate led ultimately to relaxation of the criteria for drug approval by the FDA, notably the initiation of accelerated approval “for drugs that are intended to treat serious or life-threatening conditions … based on an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit” (3). Surrogate endpoints now frequently considered in oncology are disease-free survival (DFS) and progression-free survival (PFS). Likewise, the European Medicines Agency now formally recognizes both DFS and PFS as “acceptable” endpoints, although overall survival (OS) must be reported as a secondary endpoint (4). These trends have led to the design and completion of an increasing number of cancer trials that use actuarial endpoints that occur considerably sooner than death rather than tumor response or OS as endpoints. Such endpoints include DFS, PFS, and a number of other variants. This in turn has led to many studies over …
Journal of the National Cancer Institute , éditorial, 2013