Medical Oncology Department, Hospital de la Santa Creu i Sant Pau and Universitat Autònoma de Barcelona, Barcelona, Spain.
Medical Oncology Department and Translational Research Unit, Albacete University Hospital, Albacete, Spain.
JAMA Oncol. 2016 Jun 1;2(6):744-50. doi: 10.1001/jamaoncol.2015.6479.
The US Food and Drug Administration (FDA) advisory committees influence decisions relating to the regulatory approval of drugs in the United States. Outside of the field of oncology, prosponsor voting bias has been observed among members with financial conflicts of interest (FCOIs).
To explore factors associated with Oncologic Drugs Advisory Committee (ODAC) recommendations and the influence ODAC members' FCOIs on the drug approval process.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of 82 ODAC meeting transcripts between January 2000 and December 2014. Analysis was restricted to meetings at which votes were cast relating to oncologic drugs. The influence of methodology of trials supporting approval and frequency and type of self-reported FCOIs of voting members was explored using logistic regression.
ODAC recommendation for drug approval and subsequent FDA approval.
Eighty-two transcripts of ODAC meetings between January 2000 and December 2014 were available for analysis. During the time period analyzed, ODAC members voted on 68 applications in 79 meetings (the remaining 3 meetings included voting questions regarding postmarketing safety or trial design). There was agreement between ODAC recommendations and final FDA approval; FDA approval was received for all 41 drugs that ODAC recommended approval. Additionally, the FDA approved 7 out of 41 agents that were not recommended for approval by ODAC (κ = 0.83). In 51 of 79 meetings, more than 1 trial was available to support the indication of a particular drug, and favorable ODAC recommendations were more likely when this was the case (odds ratio [OR], 1.82; 95% CI, 1.19-2.78; P = .01). Availability of randomized data did not appear to be important with selected single-arm phase 2 trials leading to recommendations for approval, especially in rare diseases. There has been a significant reduction in FCOIs over time (31 of 77 voting members [40%] in 2000 vs 0 of 20 voting members in 2014 [0%]; P < .001). Recommendations for approval were made in 28 of 47 meetings with members reporting FCOIs while among meetings with no reported FCOIs, recommendations for approval were made in 13 of 35 meetings (OR, 1.19; 95% CI, 0.97-1.46; P = .10). No significant association between ODAC recommendations and FDA approval was observed for members with FCOIs with the sponsor (OR, 1.79; 95% CI, 0.97-1.46; P = .19 and OR, 3.48; 95% CI, 0.84-14.35; P = .09, respectively) compared with members with FCOIs with competitors (OR, 1.06; 95% CI, 0.78-1.44; P = .72 and OR, 0.94; 95% CI, 0.69-1.28; P = .69, respectively).
Availability of multiple trials is associated with higher odds of ODAC recommendation and drug approval. Availability of randomized data appears less important. Declaration of FCOIs among ODAC members was frequent during the time period of interest but has decreased significantly over time. There is no apparent association between FCOIs and ODAC recommendations and subsequent FDA approval.
美国食品和药物管理局 (FDA) 顾问委员会会影响到美国药品监管审批的决定。在肿瘤学领域之外，有研究观察到财务利益冲突 (FCOI) 成员在赞成票方面存在偏见。
探索与肿瘤药物咨询委员会 (ODAC) 建议相关的因素，以及 ODAC 成员的 FCOI 对药物审批过程的影响。
设计、地点和参与者：对 2000 年 1 月至 2014 年 12 月期间的 82 次 ODAC 会议记录进行回顾性分析。分析仅限于对与肿瘤药物相关的投票进行的会议。使用逻辑回归探讨支持批准的试验方法、投票成员自我报告的 FCOI 频率和类型对药物批准的影响。
ODAC 对药物批准的建议和随后 FDA 的批准。
在 2000 年 1 月至 2014 年 12 月期间，可分析 82 份 ODAC 会议记录。在分析期间，ODAC 成员在 79 次会议上对 68 项申请进行了投票（其余 3 次会议包含关于上市后安全性或试验设计的投票问题）。ODAC 建议与最终 FDA 批准之间存在一致性；FDA 批准了 ODAC 建议批准的所有 41 种药物。此外，FDA 批准了 41 种药物中的 7 种，而 ODAC 不建议批准（κ=0.83）。在 79 次会议中有 51 次会议中，有超过 1 个试验可支持特定药物的适应证，在这种情况下，ODAC 更有可能给出有利的建议（优势比 [OR]，1.82；95%CI，1.19-2.78；P=0.01）。随机数据的可用性似乎并不重要，因为选定的单臂 2 期试验也可以导致批准建议，尤其是在罕见疾病中。FCOI 的数量随着时间的推移显著减少（2000 年的 77 名投票成员中有 31 名 [40%]，而 2014 年的 20 名投票成员中没有 1 名 [0%]；P<0.001）。在报告有 FCOI 的 47 次会议中有 28 次做出了批准建议，而在没有报告 FCOI 的 35 次会议中有 13 次做出了批准建议（OR，1.19；95%CI，0.97-1.46；P=0.10）。对于与赞助商有 FCOI 的成员，ODAC 建议与 FDA 批准之间没有显著的关联（OR，1.79；95%CI，0.97-1.46；P=0.09 和 OR，3.48；95%CI，0.84-14.35；P=0.09），而与竞争对手有 FCOI 的成员（OR，1.06；95%CI，0.78-1.44；P=0.72 和 OR，0.94；95%CI，0.69-1.28；P=0.69）。
多个试验的可用性与 ODAC 建议和药物批准的可能性增加相关。随机数据的可用性似乎不那么重要。在感兴趣的时间段内，ODAC 成员中 FCOI 的申报很常见，但随着时间的推移已显著减少。FCOI 与 ODAC 建议和随后的 FDA 批准之间没有明显的关联。
