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A Word From Our Moderator

A Word From Our Moderator To the Editor: In their Commentary, Dr Kraemer and colleagues1 draw attention to the importance of moderators of treatment outcomes, the often unsatisfactory way these are dealt with (if at all) in randomized clinical trials (RCTs), and the potentially serious consequences of this neglect on patient care. They propose that every RCT should include a search for putative moderators of treatment outcome. Although acknowledging that positive results of such analyses rarely provide proof of the existence of these moderators, they stress that the importance resides in the hypotheses that the analyses generate. These hypotheses can then be tested in subsequent adequately powered and populated RCTs. However, it may take years to design, acquire adequate funding for, and execute such an RCT. As an alternative, conducting N-of-1 trials2 can be valuable to further investigate information on moderators of treatment outcome. As a hypothetical example, suppose an RCT had been conducted to test the efficacy of drug treatment of primary Raynaud phenomenon, that no overall benefit of the drug had been found, but analysis of putative moderators of treatment outcome had suggested that women might respond favorably, although this result was not statistically significant. Women with Raynaud phenomenon could then be included in N-of-1 trials, in which they would be treated in a double-blind crossover design with multiple treatment pairs with either the drug or a placebo in random order.2 The presence or absence of differences in symptom scores during treatment would then prove or disprove the effectiveness of this drug for the patient. Pooling the results of all of these N-of-1 trials may substantiate that sex is a moderator of treatment outcome.3 Moreover, comparison of responders and nonresponders in these N-of-1 trials may be used to identify additional moderators of treatment outcome. This approach may obviate the need for RCTs, which would be a great boon in the case of rare chronic diseases. It has an additional advantage in that daily patient care can be integrated with clinical research. N-of-1 trials have their own limitations. They are not applicable to surgical or acute medical conditions. However, for chronic medical conditions, they may be invaluable in the quest for “tailored therapy,” one of the holy grails of clinical medicine. Back to top Article Information Financial Disclosures: None reported. References 1. Kraemer HC, Frank E, Kupfer DJ. Moderators of treatment outcomes: clinical, research, and policy importance. JAMA. 2006;296:1286-128916968853Google ScholarCrossref 2. Guyatt G, Sackett D, Adachi J. et al. A clinician's guide for conducting randomized trials in individual patients. CMAJ. 1988;139:497-5033409138Google Scholar 3. Zucker DR, Schmid CH, McIntosh MW, D'Agostino RB, Selker HP, Lau J. Combining single patient (N-of-1) trials to estimate population treatment effects and to evaluate individual patient responses to treatment. J Clin Epidemiol. 1997;50:401-4109179098Google ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

A Word From Our Moderator

Deinum, Japp; van der Wilt, Gert Jan
JAMA , Volume 297 (2) – Jan 10, 2007
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References (6)

Publisher
American Medical Association
Copyright
Copyright © 2007 American Medical Association. All Rights Reserved.
ISSN
0098-7484
eISSN
1538-3598
DOI
10.1001/jama.297.2.156-a
Publisher site
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Abstract

To the Editor: In their Commentary, Dr Kraemer and colleagues1 draw attention to the importance of moderators of treatment outcomes, the often unsatisfactory way these are dealt with (if at all) in randomized clinical trials (RCTs), and the potentially serious consequences of this neglect on patient care. They propose that every RCT should include a search for putative moderators of treatment outcome. Although acknowledging that positive results of such analyses rarely provide proof of the existence of these moderators, they stress that the importance resides in the hypotheses that the analyses generate. These hypotheses can then be tested in subsequent adequately powered and populated RCTs. However, it may take years to design, acquire adequate funding for, and execute such an RCT. As an alternative, conducting N-of-1 trials2 can be valuable to further investigate information on moderators of treatment outcome. As a hypothetical example, suppose an RCT had been conducted to test the efficacy of drug treatment of primary Raynaud phenomenon, that no overall benefit of the drug had been found, but analysis of putative moderators of treatment outcome had suggested that women might respond favorably, although this result was not statistically significant. Women with Raynaud phenomenon could then be included in N-of-1 trials, in which they would be treated in a double-blind crossover design with multiple treatment pairs with either the drug or a placebo in random order.2 The presence or absence of differences in symptom scores during treatment would then prove or disprove the effectiveness of this drug for the patient. Pooling the results of all of these N-of-1 trials may substantiate that sex is a moderator of treatment outcome.3 Moreover, comparison of responders and nonresponders in these N-of-1 trials may be used to identify additional moderators of treatment outcome. This approach may obviate the need for RCTs, which would be a great boon in the case of rare chronic diseases. It has an additional advantage in that daily patient care can be integrated with clinical research. N-of-1 trials have their own limitations. They are not applicable to surgical or acute medical conditions. However, for chronic medical conditions, they may be invaluable in the quest for “tailored therapy,” one of the holy grails of clinical medicine. Back to top Article Information Financial Disclosures: None reported. References 1. Kraemer HC, Frank E, Kupfer DJ. Moderators of treatment outcomes: clinical, research, and policy importance. JAMA. 2006;296:1286-128916968853Google ScholarCrossref 2. Guyatt G, Sackett D, Adachi J. et al. A clinician's guide for conducting randomized trials in individual patients. CMAJ. 1988;139:497-5033409138Google Scholar 3. Zucker DR, Schmid CH, McIntosh MW, D'Agostino RB, Selker HP, Lau J. Combining single patient (N-of-1) trials to estimate population treatment effects and to evaluate individual patient responses to treatment. J Clin Epidemiol. 1997;50:401-4109179098Google ScholarCrossref

Journal

JAMA – American Medical Association

Published: Jan 10, 2007

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