title: The role of nonrandomized trials in the evaluation of oncology drugs.
abstract: Although randomized trials provide the most reliable evidence of a drug's safety and efficacy, there are situations where randomized trials are not possible or ethical. In this article we discuss when and how single-arm trials can be used to support full approval of oncology drugs. These include situations in which an unprecedented effect on tumor response is observed in a setting of high unmet medical need, clinical trial patients have been well characterized, enabling a target population to be clearly defined, experience exists in a sufficient number of patients to allow adequate assessment of the risk:benefit relationship, and a proper historical context can be provided for analysis. We also discuss how response rates might be considered predictive of long-term outcomes or clinically meaningful in and of themselves in certain contexts.
authors: National Cancer Institute, Bethesda, Maryland, USA.
authors: R
authors: R
authors: Simon
authors: G M
authors: GM
authors: Blumenthal
authors: M L
authors: ML
authors: Rothenberg
authors: J
authors: J
authors: Sommer
authors: S A
authors: SA
authors: Roberts
authors: D K
authors: DK
authors: Armstrong
authors: L M
authors: LM
authors: LaVange
authors: R
authors: R
authors: Pazdur
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods* / Q000592:standards; D017277:Drug Approval; D023381:Endpoint Determination; D019317:Evidence-Based Medicine / Q000379:methods* / Q000592:standards; D006801:Humans; D008495:Medical Oncology / Q000379:methods* / Q000592:standards; D009369:Neoplasms / Q000188:drug therapy*; D017410:Practice Guidelines as Topic; D012107:Research Design / Q000592:standards; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents