Clinical Trial Evidence Supporting FDA Approval of Novel Therapeutic Agents, 2005-2012

Pharmacogenomic biomarkers as inclusion criteria in clinical trials of oncology-targeted drugs: a mapping of ClinicalTrials.gov

“…We did not specifically assess the characteristics of pivotal trials in this study, but for the 55 oncology novel therapeutic agents approved by the FDA between 2005 and 2012, only half of the pivotal trials were randomized, 27% were double-blind, and only 16% had a clinical outcome as a primary end point, reflecting a lower level of evidence of studies for FDA approval in oncology compared with nononcology areas. 37 This finding could be explained in part by the high frequency of orphan drugs in oncology and the lower level of evidence for such drugs compared with nonorphan oncology drugs. 38 This relatively low level of evidence of trials could also be explained by the high number of indications (either the first or subsequent ones) approved under the accelerated approval process; pivotal studies supporting accelerated approvals are often early-phase, nonrandomized trials using surrogate end points.…”

La reproducibilidad de las investigaciones biomédicas: Quo vadis?

“…Pues bien, el 35% de re-análisis publicados de ensayos clínicos dieron lugar a diferencias en los resultados respecto de los originalmente publicados, que afectaban a los tipos y número de pacientes que deberían ser tratados 13 . Hay que destacar que, habitualmente, las agencias de regulación exigen -excepto para oncología-la realización de dos (o más) ensayos confirmatorios de eficacia (fase 3) para la autorización de nuevos medicamentos 14 ; estos 2 ensayos, en la mayoría de los casos son prácticamente idénticos (en criterios de selección, posología y variables de evaluación), lo que viene a ser una replicación simultánea.…”

How Medical Practice Has Gone Wrong: Causes of the Lack-of-Reproducibility Crisis in Medical Research

“…The three major points made and documented in these sources (22)(23)(24)(25) and elsewhere (1,(26)(27)(28) are listed below.…”