Why a P value<0.05 does not necessarily mean statistical significance:controversy over overall survival results of the ORIENT-11 trial  

作　　者：Fei LIANG 

机构地区：[1]Department of Biostatistics,Zhongshan Hospital,Fudan University,Shanghai 200032,China

出　　处：《Clinical Cancer Bulletin》2022年第1期47-48,共2页临床癌症通报（英文）

摘　　要：On February 10,2022,the U.S.Food and Drug Administration(FDA)’s Oncologic Drugs Advisory Committee voted 14-1 against using data from the ORIENT-11 trial to support a biologics license application for sintilimab injection plus pemetrexed and platinum-based chemotherapy as first-line treatment for patients with nonsquamous non-small cell lung cancer(NSCLC)1.One major reason was that the FDA claimed overall survival(OS)was not statistically tested in ORIENT-11,while previous regular approvals were granted on the basis of statistically significant improvements in OS2.This may be a surprise to some physicians,as the ORIENT-11 trial previously reported improved OS with a hazard ratio(HR)of 0.60(95%confidence interval[CI]:0.45–0.79)and a P value of 0.00033,which is far below the commonly accepted threshold of 0.05 for declaring statistical significance.Some may argue that the OS results of ORIENT-11 were not considered statistically significant by the FDA because OS was only a secondary endpoint.However,in the KEYNOTE-024 trial4,which compared pembrolizumab with chemotherapy in patients with previously untreated advanced NSCLC with PD-L1 expression on at least 50%of tumor cells,OS was also a secondary endpoint.Nevertheless,the OS benefit of the KEYNOTE-024 trial was acknowledged by the FDA and included in the drug label5.The fundamental reason why OS results of ORIENT-11 were not considered statistically significant by the FDA is that the OS endpoint was not included in the multiplicity control strategy.

关 键 词：ORIENT-11 trial P value statistical significance 

分 类 号：R73[医药卫生—肿瘤]