Research design| Volume 48, ISSUE 6, P605-614, September 15, 2000

Flexible treatment strategies in chronic disease: clinical and research implications

  • Philip W Lavori
    Address reprint requests to Philip W. Lavori, Ph.D., Stanford University School of Medicine, Department of Health Research and Policy, M/C 5405, Stanford CA 94305
    Department of Veterans Affairs Cooperative Studies Program, Palo Alto, California USA(PWL)

    Department of Health Research and Policy, Stanford University, Stanford (PWL), California USA
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  • Ree Dawson
    Frontier Science Research Foundation, Boston, Massachusetts USA(RD)
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  • A.John Rush
    Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas USA (AJR)
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      Multiple treatments are available for nearly all the mood disorders. This range of treatment options adds a new dimension of choice to clinical decision making. In addition to prescribing the best initial treatment, clinicians should have an algorithm for deciding if and when to make subsequent changes in treatment to take advantage of second-line treatment options when necessary. This article aims to 1) show that a wide variety of clinical decisions can be framed as choices among adaptive (within-patient) threshold-based strategies or algorithms, illustrating the generality of the concept; 2) illustrate two ways to design randomized clinical trials to compare treatment strategies with each other to decide which strategy is best; and 3) discuss some of the advantages offered by these designs, in terms of both patient acceptability and adherence to experimental protocols.


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        • Boden W.E.
        • O’Rourke R.A.
        • Crawford M.H.
        • Blaustein A.S.
        • Deedwania P.C.
        • Zoble R.G.
        • et al.
        Outcomes in patients with acute non-q-wave myocardial infarction randomly assigned to an invasive as compared with a conservative strategy.
        N Engl J Med. 1998; 338: 1785-1792
      1. Dawson R, Lavori PW (in submission): Comparison of designs for adaptive treatment strategies: Classical vs. adaptive randomization.

        • Ferry D.
        • O’Rourke R.
        • Blaustein A.
        • Crawford M.
        • Deedwania P.
        • Carson P.
        • et al.
        Design and baseline characteristics of the veterans affairs non-q-wave infarction strategies in-hospital (VANQWISH) trial.
        J Am Coll Cardiol. 1998; 31: 312-320
        • Keller M.B.
        • Lavori P.W.
        • Kane J.M.
        • Gelenberg A.J.
        • Rosenbaum J.F.
        • Walzer E.A.
        • Baker L.A.
        Subsyndromal symptoms in bipolar disorder.
        Arch Gen Psychiatry. 1992; 49: 371-376
        • Lavori P.W.
        • Dawson R.
        A design for testing clinical strategies.
        J R Stat Soc A. 2000; 163: 29-38
        • Little R.
        • Rubin D.
        Statistical Analysis with Missing Data. Wiley, New York1987
        • Rubin D.
        Estimating causal effects of treatments in randomized and non-randomized studies.
        J Educ Psychol. 1974; 66: 688-701