Cumulative proportion of responders analysis (CPRA) as a tool to assess treatment outcome in alcohol clinical trials

Daniel E. Falk, Raye Z. Litten, Raymond F. Anton, Henry R. Kranzler, Bankole A. Johnson, Earle Bain, Carla Canuso, Marc de Somer, Jay Graham, Thomas Kosten, Karl Mann, David McCann, Didier Meulien, Roger Meyer, Charles O'Brien, Stephanie O'Malley, Joseph Palumbo, Thomas Permutt, Beatrice Rendenbach-Mueller, Rebecca Robinson & 6 others Lars Torup, Bernard Silverman, Susan Van Meter, Celia Winchell, Conrad Wong, Sarah Timm

Research output: Contribution to journalArticle

Abstract

Objective: Several definitions of treatment response have been proposed for alcohol clinical trials (e.g., abstinence and no heavy drinking). However, each of these outcomes allows only one definition of successful response. In contrast, the cumulative proportion of responders analysis (CPRA) includes all of the possible drinking response cutoff points, providing a more complete picture of the therapeutic effects of a treatment. CPRA has been used to examine the efficacy of analgesics but not alcohol pharmacotherapy. To demonstrate its potential utility, we conducted CPRA in two large alcohol treatment trials: the COMBINE (Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence) trial (naltrexone) and a multisite topiramate trial. CPRA was used to demonstrate the efficacy of naltrexone and topiramate on continuous measures of in-treatment drinking-heavy drinking days and drinks per day-and their reductions from pretreatment. Method: All possible cutoff points were portrayed for each measure. We provide graphs to illustrate the effects of the active medications compared with placebo and examined them statistically over a number of salient drinking outcomes to evaluate their efficacy. Results: Treatment group responder curves were not parallel across the entire range of cutoff points; rather, they separated only at lower levels of drinking. In general, effect sizes increased by 0.10-0.15 when going from the lowest drinking level cutoff (i.e., abstinence and no heavy drinking) to the cutoff associated with the maximal treatment effect. Conclusions: CPRA may be useful in designing subsequent trials and helping to illustrate for treatment providers the likelihood of treatment success given various definitions of a positive response.

Original languageEnglish (US)
Pages (from-to)335-346
Number of pages12
JournalJournal of Studies on Alcohol and Drugs
Volume75
Issue number2
StatePublished - 2014
Externally publishedYes

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Drinking
alcohol
Alcohols
Clinical Trials
Drug therapy
Naltrexone
Therapeutics
Analgesics
Drug Therapy
medication
Therapeutic Uses
Alcoholism
Placebos
Group
topiramate

ASJC Scopus subject areas

  • Health(social science)
  • Psychiatry and Mental health
  • Toxicology
  • Medicine(all)

Cite this

Falk, D. E., Litten, R. Z., Anton, R. F., Kranzler, H. R., Johnson, B. A., Bain, E., ... Timm, S. (2014). Cumulative proportion of responders analysis (CPRA) as a tool to assess treatment outcome in alcohol clinical trials. Journal of Studies on Alcohol and Drugs, 75(2), 335-346.

Cumulative proportion of responders analysis (CPRA) as a tool to assess treatment outcome in alcohol clinical trials. / Falk, Daniel E.; Litten, Raye Z.; Anton, Raymond F.; Kranzler, Henry R.; Johnson, Bankole A.; Bain, Earle; Canuso, Carla; de Somer, Marc; Graham, Jay; Kosten, Thomas; Mann, Karl; McCann, David; Meulien, Didier; Meyer, Roger; O'Brien, Charles; O'Malley, Stephanie; Palumbo, Joseph; Permutt, Thomas; Rendenbach-Mueller, Beatrice; Robinson, Rebecca; Torup, Lars; Silverman, Bernard; Van Meter, Susan; Winchell, Celia; Wong, Conrad; Timm, Sarah.

In: Journal of Studies on Alcohol and Drugs, Vol. 75, No. 2, 2014, p. 335-346.

Research output: Contribution to journalArticle

Falk, DE, Litten, RZ, Anton, RF, Kranzler, HR, Johnson, BA, Bain, E, Canuso, C, de Somer, M, Graham, J, Kosten, T, Mann, K, McCann, D, Meulien, D, Meyer, R, O'Brien, C, O'Malley, S, Palumbo, J, Permutt, T, Rendenbach-Mueller, B, Robinson, R, Torup, L, Silverman, B, Van Meter, S, Winchell, C, Wong, C & Timm, S 2014, 'Cumulative proportion of responders analysis (CPRA) as a tool to assess treatment outcome in alcohol clinical trials', Journal of Studies on Alcohol and Drugs, vol. 75, no. 2, pp. 335-346.
Falk, Daniel E. ; Litten, Raye Z. ; Anton, Raymond F. ; Kranzler, Henry R. ; Johnson, Bankole A. ; Bain, Earle ; Canuso, Carla ; de Somer, Marc ; Graham, Jay ; Kosten, Thomas ; Mann, Karl ; McCann, David ; Meulien, Didier ; Meyer, Roger ; O'Brien, Charles ; O'Malley, Stephanie ; Palumbo, Joseph ; Permutt, Thomas ; Rendenbach-Mueller, Beatrice ; Robinson, Rebecca ; Torup, Lars ; Silverman, Bernard ; Van Meter, Susan ; Winchell, Celia ; Wong, Conrad ; Timm, Sarah. / Cumulative proportion of responders analysis (CPRA) as a tool to assess treatment outcome in alcohol clinical trials. In: Journal of Studies on Alcohol and Drugs. 2014 ; Vol. 75, No. 2. pp. 335-346.
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T1 - Cumulative proportion of responders analysis (CPRA) as a tool to assess treatment outcome in alcohol clinical trials

AU - Falk, Daniel E.

AU - Litten, Raye Z.

AU - Anton, Raymond F.

AU - Kranzler, Henry R.

AU - Johnson, Bankole A.

AU - Bain, Earle

AU - Canuso, Carla

AU - de Somer, Marc

AU - Graham, Jay

AU - Kosten, Thomas

AU - Mann, Karl

AU - McCann, David

AU - Meulien, Didier

AU - Meyer, Roger

AU - O'Brien, Charles

AU - O'Malley, Stephanie

AU - Palumbo, Joseph

AU - Permutt, Thomas

AU - Rendenbach-Mueller, Beatrice

AU - Robinson, Rebecca

AU - Torup, Lars

AU - Silverman, Bernard

AU - Van Meter, Susan

AU - Winchell, Celia

AU - Wong, Conrad

AU - Timm, Sarah

PY - 2014

Y1 - 2014

N2 - Objective: Several definitions of treatment response have been proposed for alcohol clinical trials (e.g., abstinence and no heavy drinking). However, each of these outcomes allows only one definition of successful response. In contrast, the cumulative proportion of responders analysis (CPRA) includes all of the possible drinking response cutoff points, providing a more complete picture of the therapeutic effects of a treatment. CPRA has been used to examine the efficacy of analgesics but not alcohol pharmacotherapy. To demonstrate its potential utility, we conducted CPRA in two large alcohol treatment trials: the COMBINE (Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence) trial (naltrexone) and a multisite topiramate trial. CPRA was used to demonstrate the efficacy of naltrexone and topiramate on continuous measures of in-treatment drinking-heavy drinking days and drinks per day-and their reductions from pretreatment. Method: All possible cutoff points were portrayed for each measure. We provide graphs to illustrate the effects of the active medications compared with placebo and examined them statistically over a number of salient drinking outcomes to evaluate their efficacy. Results: Treatment group responder curves were not parallel across the entire range of cutoff points; rather, they separated only at lower levels of drinking. In general, effect sizes increased by 0.10-0.15 when going from the lowest drinking level cutoff (i.e., abstinence and no heavy drinking) to the cutoff associated with the maximal treatment effect. Conclusions: CPRA may be useful in designing subsequent trials and helping to illustrate for treatment providers the likelihood of treatment success given various definitions of a positive response.

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