Sample size slippages in randomised trials: exclusions and the lost and wayward

被引:436
作者
Schulz, KF [1 ]
Grimes, DA [1 ]
机构
[1] Family Hlth Int, Res Triangle Pk, NC 27709 USA
关键词
D O I
10.1016/S0140-6736(02)07882-0
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Proper randomisation means little if Investigators cannot include all randomised participants in the primary analysis. Participants might ignore follow-up, leave town, or take aspartame when instructed to take aspirin. Exclusions before randomisation do not bias the treatment comparison, but they can hurt generalisability. Eligibility criteria for a trial should be clear, specific, and applied before randomisation. Readers should assess whether any of the criteria make the trial sample atypical or unrepresentative of the people in which they are interested. In principle, assessment of exclusions after randomisation is simple: none are allowed. For the primary analysis, all participants enrolled should be included and analysed as part of the original group assigned (an intent-to-treat analysis). In reality, however, losses frequently occur. Investigators should, therefore, commit adequate resources to develop and implement procedures to maximise retention of participants. Moreover, researchers should provide clear, explicit information on the progress of all randomised participants through the trial by use of, for instance, a trial profile. Investigators can also do secondary analyses on, for instance, per-protocol or as-treated participants. Such analyses should be described as secondary and non-randomised comparisons. Mishandling of exclusions causes serious methodological difficulties. Unfortunately, some explanations for mishandling exclusions intuitively appeal to readers, disguising the seriousness of the issues. Creative mismanagement of exclusions can undermine trial validity.
引用
收藏
页码:781 / 785
页数:5
相关论文
共 23 条
[1]   The revised CONSORT statement for reporting randomized trials: Explanation and elaboration [J].
Altman, DG ;
Schulz, KF ;
Moher, D ;
Egger, M ;
Davidoff, F ;
Elbourne, D ;
Gotzsche, PC ;
Lang, T .
ANNALS OF INTERNAL MEDICINE, 2001, 134 (08) :663-694
[2]  
Anturane Reinfarction Trial Research Group, 1978, NEW ENGL J MED, V298 , P289
[3]   REPORTING ON METHODS IN CLINICAL-TRIALS [J].
DERSIMONIAN, R ;
CHARETTE, LJ ;
MCPEEK, B ;
MOSTELLER, F .
NEW ENGLAND JOURNAL OF MEDICINE, 1982, 306 (22) :1332-1337
[4]  
Friedman L.M., 1996, FUNDAMENTALS CLIN TR, V3rd
[5]   An overview of clinical research: the lay of the land [J].
Grimes, DA ;
Schulz, KF .
LANCET, 2002, 359 (9300) :57-61
[6]   What is meant by intention to treat analysis? Survey of published randomised controlled trials [J].
Hollis, S ;
Campbell, F .
BRITISH MEDICAL JOURNAL, 1999, 319 (7211) :670-+
[7]   Statistical considerations in the intent-to-treat principle [J].
Lachin, JM .
CONTROLLED CLINICAL TRIALS, 2000, 21 (03) :167-189
[8]   ANALYSIS OF CLINICAL-TRIALS BY TREATMENT ACTUALLY RECEIVED - IS IT REALLY AN OPTION [J].
LEE, YJ ;
ELLENBERG, JH ;
HIRTZ, DG ;
NELSON, KB .
STATISTICS IN MEDICINE, 1991, 10 (10) :1595-1605
[9]   INTENTION TO TREAT - WHO SHOULD USE ITT [J].
LEWIS, JA ;
MACHIN, D .
BRITISH JOURNAL OF CANCER, 1993, 68 (04) :647-650
[10]  
MEIER P, 1981, NEW ENGL J MED, V304, P730