Pain palliation measurement in cancer clinical trials: The US Food and Drug Administration perspective

Authors

  • Ethan Basch MD, MSc,

    Corresponding author
    1. Cancer Outcomes Research Program, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
    • Corresponding author: Ethan Basch, MD, MSc, Cancer Outcomes Research Program, University of North Carolina, 170 Manning Dr, CB# 7305, Physicians' Office Bldg, Suite 3185, Chapel Hill, NC 27599-7305; Fax: (919) 966-6735; ebasch@med.unc.edu

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  • Ann Marie Trentacosti MD,

    1. Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland
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  • Laurie B. Burke MPH,

    1. Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland
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  • Virginia Kwitkowski MD,

    1. Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland
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  • Robert C. Kane MD,

    1. Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland
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  • Karen A. Autio MD, MPH,

    1. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York
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  • Elektra Papadopoulos MD,

    1. Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland
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  • James P. Stansbury PhD, MPH,

    1. Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland
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  • Paul G. Kluetz MD,

    1. Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland
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  • Harry Smith BA,

    1. Office of Communications, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland
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  • Robert Justice MD, MA,

    1. Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland
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  • Richard Pazdur MD

    1. Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland
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  • Presented at the 2010 Genitourinary Cancers Symposium (American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology); March 5-7, 2010; San Francisco, CA.

  • This work was completed while Dr. Basch was a Guest Worker with the Office of New Drugs within the Center for Drug Evaluation and Research of the US Food and Drug Administration and an Associate Attending Physician at Memorial Sloan-Kettering Cancer Center in New York City before his current affiliation with the University of North Carolina at Chapel Hill.

Abstract

BACKGROUND

Pain palliation resulting from antitumor therapy provides direct evidence of treatment benefit when combined with evidence of antitumor activity. The US Food and Drug Administration (FDA) previously issued guidance regarding the use of patient-reported outcome (PRO) measures to support labeling claims. The purpose of this article is to identify common challenges and key design strategies when measuring pain palliation in antitumor therapy clinical trials that are consistent with PRO Guidance principles.

METHODS

Antitumor clinical protocols submitted to the FDA between 1995 and 2012 that included pain palliation as a primary or secondary endpoint were reviewed. Challenges in critical trial design components were identified. Design strategies consistent with PRO Guidance principles are proposed.

RESULTS

The challenges identified were measurement of pain intensity and analgesic use, enrollment eligibility criteria, data collection methods, responder definitions, missing data, and blinding. Strategies included the use of well-defined, reliable, PRO assessments of pain intensity and analgesics; ensuring that enrollment criteria define patients with clinically significant pain attributable to cancer on an optimal analgesic regimen; defining responders using both pain and analgesic use criteria; incorporating an analysis of tumor response to support evidence of pain response; and minimizing missing data and inadvertent unblinding.

CONCLUSIONS

Improvement in cancer-related pain resulting from antitumor therapy is an important treatment benefit that can support drug approval and labeling claims when adequately measured if study results demonstrate statistically and clinically significant findings. Sponsors are encouraged to discuss pain palliation assessment methods with the FDA early in and throughout product development. Cancer 2014;120:761–767. © 2013 American Cancer Society.

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