Patient phenotyping in clinical trials of chronic pain treatments: IMMPACT recommendations

Robert R Edwards¹, Robert H Dworkin², Dennis C Turk³, Martin S Angst⁴, Raymond Dionne⁵, Roy Freeman¹, Per Hansson⁶, Simon Haroutounian⁷, Lars Arendt-Nielsen⁸, Nadine Attal⁹, Ralf Baron¹⁰, Joanna Brell¹¹, Shay Bujanover¹², Laurie B Burke^{13

14}, Daniel Carr¹⁵, Amy S Chappell¹⁶, Penney Cowan¹⁷, Mila Etropolski¹⁸, Roger B Fillingim¹⁹, Jennifer S Gewandter², Nathaniel P Katz^{15

20}, Ernest A Kopecky²¹, John D Markman², George Nomikos²², Linda Porter²³, Bob A Rappaport²⁴, Andrew S C Rice²⁵, Joseph M Scavone²⁶, Joachim Scholz²⁷, Lee S Simon²⁸, Shannon M Smith², Jeffrey Tobias²⁹, Tina Tockarshewsky³⁰, Christine Veasley³¹, Mark Versavel³², Ajay D Wasan³³, Warren Wen³⁴, David Yarnitsky³⁵

Affiliations

¹ Harvard Medical School, Boston, MA, USA.
² University of Rochester, Rochester, NY, USA.
³ University of Washington, Seattle, WA, USA.
⁴ Stanford University, Palo Alto, CA, USA.
⁵ East Carolina University, Greenville, NC, USA.
⁶ Oslo University Hospital, Oslo, Norway and Karolinska Institute, Stockholm, Sweden.
⁷ Washington University, St. Louis, MO, USA.
⁸ Aalborg University, Aalborg, Denmark.
⁹ Hôpital Ambroise Paré, APHP and INSERM U 987, Boulogne-Billancourt, France and University Versailles Saint Quentin, Versailles, France.
¹⁰ University of Kiel, Kiel, Germany.
¹¹ MetroHealth Medical Center, Cleveland, OH, USA.
¹² Depomed, Newark, CA, USA.
¹³ LORA Group, LLC, Royal Oak, MD, USA.
¹⁴ University of Maryland, Baltimore, MD, USA.
¹⁵ Tufts University, Boston, MA, USA.
¹⁶ Eli Lilly, Indianapolis IN, USA.
¹⁷ American Chronic Pain Association, Rocklin, CA, USA.
¹⁸ Johnson and Johnson, Titusville, NJ, USA.
¹⁹ University of Florida, Gainesville, FL, USA.
²⁰ Analgesic Solutions, Natick, MA, USA.
²¹ Collegium Pharmaceutical, Inc., Canton, MA, USA.
²² Astellas Pharma, Northbrook, IL, USA.
²³ National Institutes of Health, Bethesda, MD, USA.
²⁴ Arlington, VA, USA.
²⁵ Imperial College, London, United Kingdom.
²⁶ Pfizer, Groton, CT, USA.
²⁷ Columbia University, New York, NY, USA.
²⁸ SDG LLC, Cambridge, MA, USA.
²⁹ Jazz Pharmaceuticals, Palo Alto, CA, USA.
³⁰ Ceres Consulting, Fort Montgomery, NY, USA.
³¹ Chronic Pain Research Alliance, North Kingstown, RI, USA.
³² Zalicus, Cambridge, MA, USA.
³³ University of Pittsburgh, Pittsburgh, PA, USA.
³⁴ Purdue Pharma, Stamford, CT, USA.
³⁵ Rambam Health Care Campus and Technion Faculty of Medicine, Haifa, Israel.

PMID: 27152687
PMCID: PMC5965275
DOI: 10.1097/j.pain.0000000000000602

Review

Patient phenotyping in clinical trials of chronic pain treatments: IMMPACT recommendations

Robert R Edwards et al. Pain. 2016 Sep.

. 2016 Sep;157(9):1851-1871.

doi: 10.1097/j.pain.0000000000000602.

Authors

Affiliations

¹ Harvard Medical School, Boston, MA, USA.
² University of Rochester, Rochester, NY, USA.
³ University of Washington, Seattle, WA, USA.
⁴ Stanford University, Palo Alto, CA, USA.
⁵ East Carolina University, Greenville, NC, USA.
⁶ Oslo University Hospital, Oslo, Norway and Karolinska Institute, Stockholm, Sweden.
⁷ Washington University, St. Louis, MO, USA.
⁸ Aalborg University, Aalborg, Denmark.
⁹ Hôpital Ambroise Paré, APHP and INSERM U 987, Boulogne-Billancourt, France and University Versailles Saint Quentin, Versailles, France.
¹⁰ University of Kiel, Kiel, Germany.
¹¹ MetroHealth Medical Center, Cleveland, OH, USA.
¹² Depomed, Newark, CA, USA.
¹³ LORA Group, LLC, Royal Oak, MD, USA.
¹⁴ University of Maryland, Baltimore, MD, USA.
¹⁵ Tufts University, Boston, MA, USA.
¹⁶ Eli Lilly, Indianapolis IN, USA.
¹⁷ American Chronic Pain Association, Rocklin, CA, USA.
¹⁸ Johnson and Johnson, Titusville, NJ, USA.
¹⁹ University of Florida, Gainesville, FL, USA.
²⁰ Analgesic Solutions, Natick, MA, USA.
²¹ Collegium Pharmaceutical, Inc., Canton, MA, USA.
²² Astellas Pharma, Northbrook, IL, USA.
²³ National Institutes of Health, Bethesda, MD, USA.
²⁴ Arlington, VA, USA.
²⁵ Imperial College, London, United Kingdom.
²⁶ Pfizer, Groton, CT, USA.
²⁷ Columbia University, New York, NY, USA.
²⁸ SDG LLC, Cambridge, MA, USA.
²⁹ Jazz Pharmaceuticals, Palo Alto, CA, USA.
³⁰ Ceres Consulting, Fort Montgomery, NY, USA.
³¹ Chronic Pain Research Alliance, North Kingstown, RI, USA.
³² Zalicus, Cambridge, MA, USA.
³³ University of Pittsburgh, Pittsburgh, PA, USA.
³⁴ Purdue Pharma, Stamford, CT, USA.
³⁵ Rambam Health Care Campus and Technion Faculty of Medicine, Haifa, Israel.

PMID: 27152687
PMCID: PMC5965275
DOI: 10.1097/j.pain.0000000000000602

Abstract

There is tremendous interpatient variability in the response to analgesic therapy (even for efficacious treatments), which can be the source of great frustration in clinical practice. This has led to calls for "precision medicine" or personalized pain therapeutics (ie, empirically based algorithms that determine the optimal treatments, or treatment combinations, for individual patients) that would presumably improve both the clinical care of patients with pain and the success rates for putative analgesic drugs in phase 2 and 3 clinical trials. However, before implementing this approach, the characteristics of individual patients or subgroups of patients that increase or decrease the response to a specific treatment need to be identified. The challenge is to identify the measurable phenotypic characteristics of patients that are most predictive of individual variation in analgesic treatment outcomes, and the measurement tools that are best suited to evaluate these characteristics. In this article, we present evidence on the most promising of these phenotypic characteristics for use in future research, including psychosocial factors, symptom characteristics, sleep patterns, responses to noxious stimulation, endogenous pain-modulatory processes, and response to pharmacologic challenge. We provide evidence-based recommendations for core phenotyping domains and recommend measures of each domain.

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Conflict of interest statement

Conflict of interest statement: The views expressed in this article are those of the authors, none of whom have financial conflicts of interest specifically related to the issues discussed in this article.

References

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Patient phenotyping in clinical trials of chronic pain treatments: IMMPACT recommendations

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Patient phenotyping in clinical trials of chronic pain treatments: IMMPACT recommendations

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Conflict of interest statement

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