Research Article| Volume 56, ISSUE 7, P610-617, July 2003

Early stopping in clinical trials and epidemiologic studies for “futility”: Conditional power versus sequential analysis


      Early stopping of a clinical trial is well accepted when there is enough evidence for a significant effect. However, during the course of a trial, there can be reasons to consider early termination for “futility.” In epidemiologic studies, costly or destructive laboratory tests or slow case accrual can make it desirable to stop a study early for reasons of efficiency. Estimation of the conditional power (CP) is proposed as a decision tool to stop a study early or to continue it. We consider the disadvantages of this method. We propose (group) sequential continuation of the trial or study as a less arbitrary strategy. We re-analyzed two data sets from the literature to illustrate the advantages of a sequential approach. We conclude that (group) sequential analyses have several advantages over CP. More studies should consider a sequential design and analysis to enable early stopping when enough evidence has accumulated to conclude a lack of the expected effect. Such a strategy can save valuable resources for more promising hypotheses.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Clinical Epidemiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Pocock S.J.
        • Hughes M.D.
        Practical problems in interim analyses, with particular regard to estimation.
        Control Clin Trials. 1989; 10: 209S-221S
        • Lachin J.M.
        • Lan S.-P.
        • The Lupus Nephritis Collaborative Study Group
        Termination of a clinical trial with no treatment group difference: the Lupus Nephritis Collaborative study.
        Control Clin Trials. 1992; 13: 62-79
        • Hunsberger S.
        • Sorlie P.
        • Geller N.L.
        Stochastic curtailing and conditional power in matched case-control studies.
        Stat Med. 1994; 13: 663-670
        • Jennison C.
        • Turnbull B.W.
        Group sequential methods with applications to clinical trials.
        Chapman & Hall/CRC, Boca Raton2000
        • Pepe M.S.
        • Anderson G.L.
        Two-stage experimental designs: early stopping with a negative result.
        Appl Stat. 1992; 41: 181-190
        • Strömberg U.
        A method for deciding early stopping of inconclusive case-control studies in settings where data are stratified.
        Stat Med. 1997; 16: 2327-2337
        • Betensky R.A.
        Early stopping to accept H0 based on conditional power: approximations and comparisons.
        Biometrics. 1997; 53: 794-806
        • Van der Tweel I.
        • Van Noord P.A.H.
        ‘A method for deciding early stopping of inconclusive case-control studies in settings where data are stratified’ by Strömberg U.
        Stat Med. 1999; 18 ([letter]): 361-363
        • Whitehead J.
        The design and analysis of sequential clinical trials.
        2nd edition. John Wiley & Sons, Chichester1997
        • MPS Research Unit
        PEST4: Operating manual.
        Reading University, Reading (UK)2000
        • Van der Tweel I.
        • Van Noord P.A.H.
        Sequential analysis of matched dichotomous data from prospective case-control studies.
        Stat Med. 2000; 19: 3449-3464
        • Haidich A.-B.
        • Ioannidis J.P.A.
        Patterns of patient enrollment in randomized controlled trials.
        J Clin Epidemiol. 2001; 54: 877-883
        • Lan K.K.G.
        • Simon R.
        • Halperin M.
        Stochastically curtailed tests in long-term clinical trials.
        Comm Statistics-Sequential Analysis. 1982; 1: 207-219
        • Ware J.H.
        • Muller J.E.
        • Braunwald E.
        The futility index: an approach to the cost-effective termination of randomized clinical trials.
        Am J Med. 1985; 78: 635-643
        • Betensky R.A.
        Conditional power calculations for early acceptance of H0 embedded in sequential tests.
        Stat Med. 1997; 16: 465-477
        • Van der Tweel I.
        • Kaaks R.
        • Van Noord P.A.H.
        Comparison of one-sample two-sided sequential t-tests for application in epidemiological studies.
        Stat Med. 1996; 15: 2781-2795
        • Simon R.
        Some practical aspects of the interim monitoring of clinical trials.
        Stat Med. 1994; 13: 1401-1409