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Determining the clinically important difference in visual analog scale scores in abuse liability studies evaluating novel opioid formulations

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Abstract

Purpose

This study determined how the magnitude of change in positive subjective responses predicts clinical outcome in a treatment setting. Specifically, we attempted to define what constitutes a clinically important difference (CID) in subjective responses.

Methods

A 100-mm visual analog scale (VAS) measured subjective ratings of drug “high,” calculated via an anchor-based method with published data from participants receiving sustained-release naltrexone (NTX) and heroin in a laboratory setting. The data were then compared to clinical outcomes in a treatment trial with sustained-release naltrexone. A distribution-based method subsequently analyzed data from participants who received ALO-01 (extended-release morphine with sequestered NTX) to predict its abuse liability.

Results

Differences in ratings of drug high of approximately 10 mm on a 100-mm line were clinically significant. By extrapolation, CIDs were also found between crushed or intact ALO-01 and immediate-release morphine sulfate (IRMS). No CIDs were found between intact and crushed ALO-01.

Conclusions

From laboratory and treatment trial data involving naltrexone, calculation of CIDs in subjective ratings of high is possible. Consequently, crushing/swallowing or injecting ALO-01 produces clinically significantly less drug high than oral or intravenous morphine alone, suggesting that ALO-01 has lower abuse liability by those routes than morphine formulations.

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Abbreviations

CI:

Confidence interval

CID:

Clinically important difference

DEQ:

Drug effects questionnaire

ER:

Extended-release

H:

hours

FDA:

Food and Drug Administration

IRMS:

Immediate-release morphine sulfate

IV:

Intravenous

MS:

Morphine sulfate

NTX:

Naltrexone

Sp :

Pooled standard deviation

SD:

Standard deviation

SEM:

Standard error of the mean

VAS:

Visual analog scale

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Acknowledgments

The authors thank Kevin Flynn from Analgesic Solutions and Florence Paillard, PhD from Focus BioCom for editorial support. Funding for this project was provided by Alpharma Pharmaceuticals, LLC, a wholly owned subsidiary of King Pharmaceuticals, Inc. No author received compensation for writing this manuscript.

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Authors and Affiliations

  1. Analgesic Solutions, Inc, 232 Pond St, Natick, MA, 01760, USA

    Thomas A. Eaton, Jeremiah J. Trudeau, Richard G. van Inwegen & Nathaniel P. Katz

  2. Department of Psychology, Adjunct Faculty, University of Connecticut, Storrs, CT, USA

    Thomas A. Eaton

  3. Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, NY, USA

    Sandra D. Comer

  4. Center for Health Outcomes Research, United BioSource Corporation, Bethesda, MD, USA

    Dennis A. Revicki

  5. Hampshire College, School of Cognitive Science, Amherst, MA, USA

    Jeremiah J. Trudeau

  6. Alpharma Pharmaceuticals, Piscataway, NJ, USA

    Joseph W. Stauffer

  7. Program on Opioid Risk Management, Department of Anesthesiology, Tufts University School of Medicine, Boston, MA, USA

    Nathaniel P. Katz

Authors
  1. Thomas A. Eaton
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  2. Sandra D. Comer
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  3. Dennis A. Revicki
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  4. Jeremiah J. Trudeau
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  5. Richard G. van Inwegen
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  6. Joseph W. Stauffer
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  7. Nathaniel P. Katz
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Corresponding author

Correspondence to Jeremiah J. Trudeau.

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Eaton, T.A., Comer, S.D., Revicki, D.A. et al. Determining the clinically important difference in visual analog scale scores in abuse liability studies evaluating novel opioid formulations. Qual Life Res 21, 975–981 (2012). https://doi.org/10.1007/s11136-011-0012-7

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  • DOI: https://doi.org/10.1007/s11136-011-0012-7

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