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From the CTN Special Issue of American Journal of Drug and Alcohol Abuse: Read the other articles here.




Baseline Matters: The Importance of Covariation for Baseline Severity in the Analysis of Clinical Trials.

American Journal of Drug and Alcohol Abuse 2011;37(5):446-452. [doi: 10.3109/00952990.2011.596980]

Edward V. Nunes, MD (New York State Psychiatric Institute, GNY Node), Martina Pavlicova, PhD (Columbia University, GNY Node), Mei-Chen Hu, PhD (Columbia University, GNY Node), Aimee N. C. Campbell, MSW, PhD (New York State Psychiatric Institute, GNY Node), Gloria M. Miele, PhD (New York State Psychiatric Institute, GNY Node), Denise A. Hien, PhD (New York State Psychiatric Institute, GNY Node), Donald F. Klein, MD (New York State Psychiatric Institute, GNY Node).

Clinical trials testing the effectiveness of interventions for addictions, HIV transmission risk, and other behavioral health problems are important to advancing evidence-based treatment. Such trials are expensive and time-consuming to conduct, but the underlying effect sizes tend to be modest, and often findings are disappointing, failing to show evidence of treatment effects. This study aimed to demonstrate how appropriate covariation for baseline severity can enhance detection of treatment effects, using an example from the National Drug Abuse Treatment Clinical Trials Network (protocol CTN-0015, "Women and Trauma"). Baseline severity, the score of the outcome measure at baseline, prior to randomization, is often strongly associated with outcome in such studies. Covariation for baseline score may enhance detection of treatment effects, because the variance explained by the baseline score is removed from the error variance in the estimate of the difference in outcome between treatments. Alternatively, the effect of treatment may manifest in the form of a baseline-by-treatment interaction. Common interaction patterns include that treatment may be more effective among patients with higher levels of baseline severity, or treatment may be more effective among patients with low severity at baseline ("relapse prevention" effect). Such effects may be important to developing treatment guidelines and offer clues toward understanding the mechanisms of action of treatments and of the disorders.

Conclusions: This article illustrates principles of covariation for baseline and the baseline-by-treatment interaction in nontechnical graphical terms, and discusses examples from clinical trials, including the CTN. Implications for the design and analysis of clinical trials are discussed, and it is argued that covariation for baseline severity of the outcome measure and testing of the baseline-by-treatment interaction should be considered for inclusion in the primary outcome analyses of treatment effectiveness trials of substantial size. (Article (Peer-Reviewed), PDF, English, 2011)

Keywords: Baseline data | CTN protocol development | Outcomes evaluation | Research design | Statistical analysis | Statistical models | American Journal of Drug and Alcohol Abuse (journal)

Document No: 735, PMID: 21854288, PMCID: PMC3260520.

Submitted by CTN Dissemination Librarians, 8/23/2011.


Campbell, Aimee N. C. mail
Hien, Denise A. mail
Hu, Mei-Chen
Klein, Donald F.
Miele, Gloria M. mail
Nunes, Edward V. mail
Pavlicova, Martina
NIDA-CTN-0015 www

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Supported by a grant from the National Institute on Drug Abuse to the University of Washington Alcohol and Drug Abuse Institute.
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