Proposal for the use of progression-free survival in unblinded randomized trials

被引:45
作者
Freidlin, Boris
Korn, Edward L.
Hunsberger, Sally
Gray, Robert
Saxman, Scott
Zujewski, Lo Anne
机构
[1] NCI, Biometr Res Branch, Bethesda, MD 20892 USA
[2] NCI, Clin Invest Branch, Div Canc Treatment & Diagnosis, Bethesda, MD 20892 USA
[3] Harvard Univ, Sch Publ Hlth, Eastern Cooperat Oncol Grp, Boston, MA 02115 USA
[4] Peace Corps, Washington, DC USA
关键词
D O I
10.1200/JCO.2006.09.6198
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Progression-free survival is an attractive end point for clinical trials when an overall survival end point may be confounded by additional treatments administered after progression. When a trial is performed in an unblinded manner, however, there is the potential for bias between the treatment arms because of the subjective aspects of the progression end point. We discuss the magnitude of this potential bias and suggest methods for lessening it. We propose the carrying forward of any progression information to two designated time points for the statistical analysis for trials that are not blinded. This proposal, possibly combined with central review of progression scans for these two time points, essentially eliminates any bias, with little risk of major efficiency loss compared with using the reported progression times.
引用
收藏
页码:2122 / 2126
页数:5
相关论文
共 14 条
[1]   THE EFFECT OF GROUPING ON THE POWER OF THE MANTEL-HAENSZEL TEST FOR THE COMPARISON OF SURVIVAL RATES [J].
BERGER, A ;
WALLENSTEIN, S .
STATISTICS & PROBABILITY LETTERS, 1993, 16 (01) :19-25
[2]   Cornerstones of a well-designed phase III trial [J].
Buyse, M .
EJC SUPPLEMENTS, 2003, 1 (06) :67-75
[3]   THE EFFICIENCY OF THE PROPORTIONS TEST AND THE LOGRANK TEST FOR CENSORED SURVIVAL-DATA [J].
CUZICK, J .
BIOMETRICS, 1982, 38 (04) :1033-1039
[4]   Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer [J].
de Gramont, A ;
Figer, A ;
Seymour, M ;
Homerin, M ;
Hmissi, A ;
Cassidy, J ;
Boni, C ;
Cortes-Funes, H ;
Cervantes, A ;
Freyer, G ;
Papamichael, D ;
Le Bail, N ;
Louvet, C ;
Hendler, D ;
de Braud, F ;
Wilson, C ;
Morvan, F ;
Bonetti, A .
JOURNAL OF CLINICAL ONCOLOGY, 2000, 18 (16) :2938-2947
[5]   Overall survival is not a realistic end point for clinical trials of new drugs in advanced solid tumors: A critical assessment based on recently reported phase III trials in colorectal and breast cancer [J].
Di Leo, A ;
Bleiberg, H ;
Buyse, M .
JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (10) :2045-2047
[6]   APPLICABILITY OF SAMPLE-SIZE CALCULATIONS BASED ON A COMPARISON OF PROPORTIONS FOR USE WITH THE LOGRANK TEST [J].
GAIL, MH .
CONTROLLED CLINICAL TRIALS, 1985, 6 (02) :112-119
[7]  
GOLDBERG P, 2006, CANC LETT, V32, P1
[8]   Systematic reviews in health care -: Assessing the quality of controlled clinical trials [J].
Jüni, P ;
Altman, DG ;
Egger, M .
BMJ-BRITISH MEDICAL JOURNAL, 2001, 323 (7303) :42-46
[9]   Intentional ignorance: A history of blind assessment and placebo controls in medicine [J].
Kaptchuk, TJ .
BULLETIN OF THE HISTORY OF MEDICINE, 1998, 72 (03) :389-433
[10]  
MANTEL N, 1959, J NATL CANCER I, V22, P719