Improving Study Conduct and Data Quality in Clinical Trials of Chronic Pain Treatments: IMMPACT Recommendations - 06/11/20
Doi : 10.1016/j.jpain.2019.12.003
Jennifer S. Gewandter *, ⁎ 
, Robert H. Dworkin *, Dennis C. Turk †, Eric G. Devine ‡, David Hewitt §, Mark P. Jensen †, Nathaniel P. Katz ¶, ‖, Amy A. Kirkwood ⁎⁎, Richard Malamut ††, John D. Markman *, Bernard Vrijens ‡‡, Laurie Burke §§, James N. Campbell ¶¶, Daniel B. Carr ‖‖, Philip G. Conaghan ⁎⁎⁎, Penney Cowan †††, Mittie K. Doyle ‡‡‡, Robert R. Edwards §§§, Scott R. Evans ¶¶¶, John T. Farrar ‖‖‖, Roy Freeman §§§, Ian Gilron ⁎⁎⁎⁎, Dean Juge ††††, Robert D. Kerns ‡‡‡‡, Ernest A. Kopecky ††, #, Michael P. McDermott *, Gwendolyn Niebler §§§§, Kushang V. Patel †, Richard Rauck ¶¶¶¶, Andrew S.C. Rice ‖‖‖‖, Michael Rowbotham ⁎⁎⁎⁎⁎, Nelson E. Sessler †††††, Lee S. Simon ‡‡‡‡‡, Neil Singla §§§§§, Vladimir Skljarevski ¶¶¶¶¶, Tina Tockarshewsky ‖‖‖‖‖, Geertrui F. Vanhove ⁎⁎⁎⁎⁎⁎, Ajay D. Wasan ††††††, James Witter ‡‡‡‡‡‡
, Robert H. Dworkin *, Dennis C. Turk †, Eric G. Devine ‡, David Hewitt §, Mark P. Jensen †, Nathaniel P. Katz ¶, ‖, Amy A. Kirkwood ⁎⁎, Richard Malamut ††, John D. Markman *, Bernard Vrijens ‡‡, Laurie Burke §§, James N. Campbell ¶¶, Daniel B. Carr ‖‖, Philip G. Conaghan ⁎⁎⁎, Penney Cowan †††, Mittie K. Doyle ‡‡‡, Robert R. Edwards §§§, Scott R. Evans ¶¶¶, John T. Farrar ‖‖‖, Roy Freeman §§§, Ian Gilron ⁎⁎⁎⁎, Dean Juge ††††, Robert D. Kerns ‡‡‡‡, Ernest A. Kopecky ††, #, Michael P. McDermott *, Gwendolyn Niebler §§§§, Kushang V. Patel †, Richard Rauck ¶¶¶¶, Andrew S.C. Rice ‖‖‖‖, Michael Rowbotham ⁎⁎⁎⁎⁎, Nelson E. Sessler †††††, Lee S. Simon ‡‡‡‡‡, Neil Singla §§§§§, Vladimir Skljarevski ¶¶¶¶¶, Tina Tockarshewsky ‖‖‖‖‖, Geertrui F. Vanhove ⁎⁎⁎⁎⁎⁎, Ajay D. Wasan ††††††, James Witter ‡‡‡‡‡‡ ⁎ University of Rochester Medical Center, Rochester, New York
† University of Washington, Seattle, Washington
‡ Boston University, Boston, Massachusetts
§ Syneos Health, Blue Bell, Pennsylvania
¶ Analgesic Solutions, Natick, Massachusetts
‖ Tufts University, Boston, Massachusetts
⁎⁎ CR UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, UK
†† Collegium, Pharmaceutical, Stoughton, Massachusetts
‡‡ AARDEX Group & Liège University, Belgium
§§ The Lora Group, LLC, Maryland
¶¶ Centrexion Corporation, Boston, Massachusetts
‖‖ Tufts University School of Medicine, Boston, Massachusetts
⁎⁎⁎ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, & NIHR Leeds Biomedical Research Centre, Leeds, UK
††† American Chronic Pain Association, Rocklin, California
‡‡‡ CSL Behring, King of Prussia, Pennsylvania
§§§ Brigham & Women's Hospital, Boston, Massachusetts
¶¶¶ George Washington University, Washington, District of Columbia
‖‖‖ University of Pennsylvania, Philadelphia, Pennsylvania
⁎⁎⁎⁎ Queen's University, Kingston, Ontario, Canada
†††† Horizon Pharma, Lake Forest, Illinois
‡‡‡‡ Yale University, New Haven, Connecticut
§§§§ Egalet Corporation, Wayne, Pennsylvania
¶¶¶¶ Wake Forest University School of Medicine, Winston-Salem, North Carolina
‖‖‖‖ Imperial College, London, UK
⁎⁎⁎⁎⁎ CPMC Research Institute (Sutter Health), San Francisco, California
††††† Purdue Pharma, Stamford, Connecticut
‡‡‡‡‡ SDG, LLC, Cambridge, Massachusetts
§§§§§ Lotus Clinical Research, Pasadena, California
¶¶¶¶¶ Eli Lilly, Indianapolis, Indiana
‖‖‖‖‖ Ceres Consulting, West Point, New York
⁎⁎⁎⁎⁎⁎ Jazz Pharmaceuticals, Palo Alto, California
†††††† University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
‡‡‡‡‡‡ National Institutes of Health, Bethesda, Maryland
##Address reprint requests to Jennifer S. Gewandter, PhD, MPH, Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave., Box 604, Rochester, NY 14642.Department of AnesthesiologyUniversity of Rochester School of Medicine and Dentistry601 Elmwood Ave., Box 604RochesterNY14642
Highlights |
• | Optimizing clinical trial conduct and data quality is essential for drug development. |
• | Expert consensus recommendations to improve data quality discussed. |
• | Key elements include: site selection and training, participant selection and training. |
• | Key elements include: treatment adherence, data collection, and study monitoring. |
Abstract |
The estimated probability of progressing from phase 3 analgesic clinical trials to regulatory approval is approximately 57%, suggesting that a considerable number of treatments with phase 2 trial results deemed sufficiently successful to progress to phase 3 do not yield positive phase 3 results. Deficiencies in the quality of clinical trial conduct could account for some of this failure. An Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials meeting was convened to identify potential areas for improvement in trial conduct in order to improve assay sensitivity (ie, ability of trials to detect a true treatment effect). We present recommendations based on presentations and discussions at the meeting, literature reviews, and iterative revisions of this article. The recommendations relate to the following areas: 1) study design (ie, to promote feasibility), 2) site selection and staff training, 3) participant selection and training, 4) treatment adherence, 5) data collection, and 6) data and study monitoring. Implementation of these recommendations may improve the quality of clinical trial data and thus the validity and assay sensitivity of clinical trials. Future research regarding the effects of these strategies will help identify the most efficient use of resources for conducting high quality clinical trials.
Perspective |
Every effort should be made to optimize the quality of clinical trial data. This manuscript discusses considerations to improve conduct of pain clinical trials based on research in multiple medical fields and the expert consensus of pain researchers and stakeholders from academia, regulatory agencies, and industry.
Le texte complet de cet article est disponible en PDF.Key Words : Data quality, clinical trial conduct, Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials
Plan
| Financial Disclosure: The views expressed in this article are those of the authors and no official endorsement by the Food and Drug Administration (FDA) or the pharmaceutical and device companies that provided unrestricted grants to support the activities of the ACTTION public-private partnership should be inferred. Disclosures by individual authors are as follows: |
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| Laurie Burke has received in the past 12 months compensation for consulting on clinical outcome assessment and labeling from AbbVie, Aclaris, Alnylam, Brickell, Dermtreat, Inflexxion, Ipsen, Ironshore, Jazz, Global Blood Therapeutics, and Zynerba. |
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| In the past 5 years, Daniel Carr has received consulting fees from 1 startup company (no longer in business), for advice on potential acquisitions of nonopioid analgesics. To his knowledge, none were subsequently marketed. He has been an officer and member of professional associations that accept contributions from the pharmaceutical and medical device industries and use these and other revenues such as membership dues to cover officers’ expenses connected with their operations (eg, attending board or planning meetings). Dr Carr does not have investments, stock options or other holdings in such contributors. Other than ACTTION, these associations are the American Academy of Pain Medicine; the American Society of Anesthesiologists; the European Pain Federation; and the International Association for the Study of Pain (as a participant or representative at meetings or hearings). As a member of the National Institutes of Health (NIH) Interagency Pain Research Coordinating Committee/National Pain Strategy, he has received travel expenses from NIH to attend their meetings. Additionally, he has received or anticipates potentially receiving personal payments (including travel expenses) for occasional participation as an expert witness; service on an NIH-sponsored data safety monitoring board for a clinical trial; participation in a workshop convened by the National Academies of Science, Engineering and Medicine; and consultant fees from the Federal Trade Commission. He has received modest honoraria for participation in accredited medical education activities. |
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| Philip Conaghan has done consultancies or speakers bureaus for AbbVie, AstraZeneca, Bristol Myers Squibb, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, GlaxoSmithKline, Kolon TissueGene, Medivir, Novartis, Pfizer, Roche, Samumed and Stryker. P. Conaghan is supported in part by the UK National Institute for Health Research (NIHR) Leeds Biomedical Research Centre. |
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| Eric Devine has grant and contract funding from NIAAA and NIDA as part of his salary support at Boston University. This includes reimbursed travel expenses to attend study kick-off meetings. Dr. Devine has received travel reimbursement from NIDA to participate as a speaker at an international conference. He has also received travel reimbursement from NIAAA to serve on a grant review committee. Dr. Devine has received teaching stipends from Adcare Educational Institute for conducting workshops on motivational interviewing and substance use treatment. He does not have individual investments, stocks, intellectual property in any healthcare-related industries. |
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| Robert H. Dworkin has received in the past 36 months research grants and contracts from US Food and Drug Administration and US National Institutes of Health, and compensation for consulting on clinical trial methods from Abide, Adynxx, Analgesic Solutions, Aptinyx, Asahi Kasei, Astellas, AstraZeneca, Biogen, Biohaven, Boston Scientific, Braeburn, Celgene, Centrexion, Chromocell, Clexio, Concert, Dong-A, Eli Lilly, Eupraxia, Glenmark, Grace, Hope, Immune, Neumentum, NeuroBo, Novaremed, Novartis, Pfizer, Phosphagenics, Quark, Reckitt Benckiser, Regenacy, Relmada, Sandoz, Scilex, Semnur, Sollis, Teva, Theranexus, Trevena, and Vertex. |
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| John T. Farrar, in the past 36 months has received: research grants and contracts from US Food and Drug Administration and US National Institutes of Health; compensation for consulting on clinical trial methods from Analgesic Solutions, Aptinyx, Biogen, Campbell Alliance, Daiichi Sankyo, DepoMed, Evadera, Jansen, Lilly, Novartis, and Pfizer; DSMB services from NIH-NIA and Cara Therapeutics; and services as associate editor from Wiley. |
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| Jennifer Gewandter has received consulting income in the past 36 months from MundiPharma, Disarm Therapeutics, Asahi Kasei Pharma, and SK Life Science. |
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| Ian Gilron has received support from Biogen, Adynxx, TARIS Biomedical, Astra-Zeneca, Pfizer, and Johnson & Johnson and has received grants from the Canadian Institutes of Health Research, Physicians’ Services Incorporated Foundation, and Queen's University. |
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| Mark P. Jensen has received in the past 36 months research grants from the National Institutes of Health, the National Multiple Sclerosis Society, the Patient-Centered Outcomes Research Institute, The International Association for the Study of Pain, and the Washington State Spinal Injury Consortium. He has also received compensation for consultation from Goalistics. |
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| Robert Kerns has received research funding from NIH, PCORI, Department of Veterans Affairs, Consortium of MS Centers and Honoraria from the American Academy of Pain Medicine (editorial board of Pain Medicine), American Pain Society (reviewer for APS-Pfizer grant program), American Care Management Association (Speaker), American College of Physicians (Speaker), Health Education Resource Organization (Speaker), and Duke University School of Medicine (Speaker). Amy A Kirkwood is funded by Cancer Research UK. |
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| Michael P. McDermott has been supported in the past 36 months by research grants from NIH, FDA, NYSTEM, SMA Foundation, Cure SMA, and PTC Therapeutics. He has received compensation for consulting from Neuropore Therapies, Inc and Voyager Therapeutics. He has served on Data and Safety Monitoring Boards (DSMBs) for NIH, Novartis Pharmaceuticals Corporation, AstraZeneca, Eli Lilly and Company, aTyr Pharma, Inc, Catabasis Pharmaceuticals, Inc, Vaccinex, Inc, Cynapsus Therapeutics, and Voyager Therapeutics. |
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| Kushang Patel has received in the past 36 months research grants and contracts from US Food and Drug Administration and US National Institutes of Health. |
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| Andrew SC Rice reports the following conflicts of interest occurring in last 24 months 1) consultancy and advisory board work for Imperial College Consultants including remunerated work for: Pharmanovo, Galapagos, Toray, Quartet, Lateral, Novartis, Pharmaleads, Orion, Asahi Kasei & Theranexis; 2) owner of share options in Spinifex Pharmaceuticals from which personal benefit accrued upon the acquisition of Spinifex by Novartis in July 2015 and from which future milestone payments may occur; 3) inventor on patents (a) Rice A.S.C., Vandevoorde S. and Lambert D.M Methods using N-(2-propenyl)hexadecanamide and related amides to relieve pain. WO 2005/079771 (b) Okuse K. et al Methods of treating pain by inhibition of vgf activity EP13702262.0/ WO2013 110945. |
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| Michael Rowbotham has received consulting income in the past 36 months from CODA, Amygdala Neurosciences, Nektar, Adynxx, Toray, and SiteOne Therapeutics. |
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| Lee Simon has received consulting income from the following companies: Affinergy, Astrazeneca, Abraxxis, Alpha Rx, NuvoResearch, Roche, Pfizer, Novartis, PLx Pharma, Hisamatsu, Dr Reddys, Avanir, Cerimon, Leerink Swann, Alimera, Nomura, Luxor, Paraexel, Antares, Bayer, Rigel, JP Morgan, Regeneron, XTL, Inmedix, Eupraxia, Fidelity, Extera, Wyeth, Asahi, Sammuded, Metabolex, Shire, Anthera, Antares, Vical, Daiichi Sankyo, Flexion, AcelRx, Inotek, Gilead, Sandoz, Knopp, Abbott, Omeros, Jazz, Takeda, Teva, Zydus, Proprius, Alder, Cephalon, Purdue, EMDSerono, Alte, Talagen, Tigenix, Agenus, Forest, Genzyme, CaloSyn, pSivida, Horizon, Pozen, Eicos Sciences, Analgesic Solutions, Bayer, Kowa, Array, JRX Biopharm, Imprimis, Dara, Genco, Neos, Durect, Sanofi, Lilly, Idera, Medac, Remedy, Kiniksa. |
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| Neil Singla is the Chief Executive Officer of Lotus Clinical Research, LLC and has received compensation for consulting from AcelRx Pharmaceuticals, AMAG Pharmaceuticals, Antibe Therapautics Inc, Aponia Laboratories, Inc, Arch Therapeutics, Astellas Pharma, Avenue Therapeutics, Biom¹Up, Bonti, Inc, Braeburn Pharmaceuticals, Inc, CerSci Therapeutics, Charleston Laboratories, Inc, Concentric Analgesics, Coronado Biosciences, Davol, a Bard Company, Durect Corporation, Grace Therapeutics, Inc, Grifols, Inc, Heron Therapeutics, Inc, INC Research/ Syneos Health, Innocoll Pharmaceuticals, Insys Therapeutics, Inc, iX Biopharma Ltd., KemPharm, Inc, KLSMC Stem Cells, Inc, Kowa Research Institute, Inc, Mallinckrodt Inc, a Covidien company, MedRx USA, Inc, Merck Sharp & Dohme Corp., Mira Pharma, Inc, Myoscience, Naurex, Inc, Neumentum, Inc, Novartis Consumer Health, Inc, Pacira Pharmaceuticals, Inc, Pfizer Inc, Recro Pharma, Inc, Regenacy Pharmaceuticals, Regeneron Pharmaceuticals, Serina Therapeutics, Shionogi Inc, Sollis Therapeutics, Teva Pharmaceuticals USA, TLC Biopharmaceuticals, Toyama Chemical Co., LTD, Trevena, Inc, Vertex Pharmaceuticals, Inc, Vizuri, Inc, Wex Pharmaceuticals. |
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| Ajay D. Wasan has received in the past 36 months research grants and contracts from US National Institutes of Health, the Patient Centered Outcomes Research Institute, and Collegium Pharmaceuticals. He has received compensation for consulting from Pfizer and Analgesic Solutions. |
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| All other authors report no conflicts. |
© 2020
Publié par Elsevier Masson SAS.
Vol 21 - N° 9-10
P. 931-942 - septembre 2020 Retour au numéro
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