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Shannon M Smith,
Anthony T Wang,
Nathaniel P Katz,
Michael P McDermott,
Laurie B Burke,
Paul Coplan,
Ian Gilron,
Sharon H Hertz,
Allison H Lin, Bob A Rappaport,
Michael C Rowbotham,
Cristina Sampaio,
Michael Sweeney,
Dennis C Turk,
Robert H Dworkin
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ABSTRACT: The development of valid and informative treatment risk-benefit profiles requires consistent and thorough information about adverse event (AE) assessment and participants' AEs during randomized controlled trials (RCTs). Despite a 2004 extension of the Consolidated Standards of Reporting Trials (CONSORT) statement recommending the specific AE information that investigators should report, there is little evidence that analgesic RCTs adequately adhere to these recommendations. This systematic review builds on prior recommendations by describing a comprehensive checklist for AE reporting developed to capture clinically important AE information. Using this checklist, we coded AE assessment methods and reporting in all 80 double-blind RCTs of noninvasive pharmacologic treatments published in the European Journal of Pain, Journal of Pain, and PAIN® from 2006 to 2011. Across all trials, reports of AEs were frequently incomplete, inconsistent across trials, and, in some cases, missing. For example, >40% of trials failed to report any information on serious adverse events. Trials of participants with acute or chronic pain conditions and industry-sponsored trials typically provided more and better-quality AE data than trials involving pain-free volunteers or trials that were not industry sponsored. The results of this review suggest that improved AE reporting is needed in analgesic RCTs. We developed an ACTTION (Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks) AE reporting checklist that is intended to assist investigators in thoroughly and consistently capturing and reporting these critically important data in publications.
Pain 03/2013; · 5.78 Impact Factor
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Robert H Dworkin,
Robert Allen,
Stephen Kopko,
Yun Lu,
Dennis C Turk,
Laurie B Burke,
Paul Desjardins,
Mila Etropolski,
David J Hewitt,
Shyamalie Jayawardena, [......],
Denis Michel,
James Ottinger,
Paul Peloso,
Frank Pucino, Bob A Rappaport,
Vladimir Skljarevski,
David St Peter,
Susan Timinski,
Christine R West,
Hilary D Wilson
Pain 10/2012; · 5.78 Impact Factor
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Shannon M Smith,
R Daniel Chang,
Anthony Pereira,
Nirupa Shah,
Ian Gilron,
Nathaniel P Katz,
Allison H Lin,
Michael P McDermott, Bob A Rappaport,
Michael C Rowbotham,
Cristina Sampaio,
Dennis C Turk,
Robert H Dworkin
[show abstract]
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ABSTRACT: Recommendations for harms (ie, adverse events) reporting in randomized clinical trial publications were presented in a 2004 extension of the Consolidated Standards of Reporting Trials (CONSORT) statement. Our objectives were to assess harms reporting in 3 major pain journals (European Journal of Pain, Journal of Pain, and PAIN®) to determine whether harms reporting improved following publication of the 2004 CONSORT recommendations, and to examine study factors associated with adequacy of harms reporting. A total of 101 randomized, double-blind, noninvasive pharmacologic trials were identified in the 2000-2003 (epoch 1) and 2008-2011 (epoch 2) issues of these journals. Out of 10 reporting recommendations, the mean number fulfilled was 6.08 (SD2.65). Although more harms recommendations were fulfilled in epoch 2 (m(2)=6.49, SD2.66) than in epoch 1 (m(1)=5.39, SD2.52; P=0.04), only the recommendation to report harms per arm was satisfied by >90% of trials in epoch 2, whereas <60% reported withdrawals due to harms. Several trial characteristics (study design, participant type, pain type, frequency of treatment administration, treatment administration method, sponsor, and number of randomized participants) were significantly associated with harms reporting. However, when trial characteristics and epoch were entered into a multiple regression analysis, only trials studying pain patients, those using oral treatments, and industry-sponsored trials were associated with better harms reporting. Despite some improvement in harms reporting, greater improvement is needed to provide informative, consistent reporting of adverse events and safety in analgesic clinical trials.
Pain 09/2012; · 5.78 Impact Factor
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Dennis C Turk,
Alec B O'Connor,
Robert H Dworkin,
Amina Chaudhry,
Nathaniel P Katz,
Edgar H Adams,
John S Brownstein,
Sandra D Comer,
Richard Dart,
Nabarun Dasgupta, [......],
Edward Michna,
Pamela Palmer,
Sarah Peirce-Sandner,
Jennifer S Potter,
Srinivasa N Raja,
Christine Rauschkolb,
Carl L Roland,
Lynn R Webster,
Roger D Weiss,
Kerry Wolf
[show abstract]
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ABSTRACT: Opioids are essential to the management of pain in many patients, but they also are associated with potential risks for abuse, overdose, and diversion. A number of efforts have been devoted to the development of abuse-deterrent formulations of opioids to reduce these risks. This article summarizes a consensus meeting that was organized to propose recommendations for the types of clinical studies that can be used to assess the abuse deterrence of different opioid formulations. Because of the many types of individuals who may be exposed to opioids, an opioid formulation will need to be studied in several populations using various study designs to determine its abuse-deterrent capabilities. It is recommended that the research conducted to evaluate abuse deterrence should include studies assessing: (1) abuse liability, (2) the likelihood that opioid abusers will find methods to circumvent the deterrent properties of the formulation, (3) measures of misuse and abuse in randomized clinical trials involving pain patients with both low risk and high risk of abuse, and (4) postmarketing epidemiological studies.
Pain 07/2012; 153(10):1997-2008. · 5.78 Impact Factor
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CNS Neuroscience & Therapeutics 05/2012; 18(5):367-8. · 4.44 Impact Factor
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Robert H Dworkin,
Dennis C Turk,
Sarah Peirce-Sandner,
Laurie B Burke,
John T Farrar,
Ian Gilron,
Mark P Jensen,
Nathaniel P Katz,
Srinivasa N Raja, Bob A Rappaport, [......],
Kenneth Sommerville,
Brett R Stacey,
Ilona Steigerwald,
Jeffrey Tobias,
Ann Marie Trentacosti,
Ajay D Wasan,
George A Wells,
Jim Williams,
James Witter,
Dan Ziegler
[show abstract]
[hide abstract]
ABSTRACT: A number of pharmacologic treatments examined in recent randomized clinical trials (RCTs) have failed to show statistically significant superiority to placebo in conditions in which their efficacy had previously been demonstrated. Assuming the validity of previous evidence of efficacy and the comparability of the patients and outcome measures in these studies, such results may be a consequence of limitations in the ability of these RCTs to demonstrate the benefits of efficacious analgesic treatments vs placebo ("assay sensitivity"). Efforts to improve the assay sensitivity of analgesic trials could reduce the rate of falsely negative trials of efficacious medications and improve the efficiency of analgesic drug development. Therefore, an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials consensus meeting was convened in which the assay sensitivity of chronic pain trials was reviewed and discussed. On the basis of this meeting and subsequent discussions, the authors recommend consideration of a number of patient, study design, study site, and outcome measurement factors that have the potential to affect the assay sensitivity of RCTs of chronic pain treatments. Increased attention to and research on methodological aspects of clinical trials and their relationships with assay sensitivity have the potential to provide the foundation for an evidence-based approach to the design of analgesic clinical trials and expedite the identification of analgesic treatments with improved efficacy and safety.
Pain 04/2012; 153(6):1148-58. · 5.78 Impact Factor
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Anesthesia and analgesia 11/2011; 113(5):963-4. · 3.08 Impact Factor
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The Lancet 08/2011; 378(9792):665-6; author reply 666. · 38.28 Impact Factor
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Robert H Dworkin,
Dennis C Turk,
Nathaniel P Katz,
Michael C Rowbotham,
Sarah Peirce-Sandner,
Igor Cerny,
Chekesha S Clingman,
Benjamin C Eloff,
John T Farrar,
Cornelia Kamp,
Michael P McDermott, Bob A Rappaport,
Wendy R Sanhai
Pain 03/2011; 152(3 Suppl):S107-15. · 5.78 Impact Factor
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New England Journal of Medicine 08/2010; 363(9):806-7. · 53.30 Impact Factor
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Anesthesiology 03/2010; 112(3):509-10. · 5.36 Impact Factor
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Pain 03/2010; 150(1):12-6. · 5.78 Impact Factor
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Robert H Dworkin,
Dennis C Turk,
Sarah Peirce-Sandner,
Ralf Baron,
Nicholas Bellamy,
Laurie B Burke,
Amy Chappell,
Kevin Chartier,
Charles S Cleeland,
Ann Costello, [......],
Christine Rauschkolb,
Bryce B Reeve,
Thomas Rhodes,
Cristina Sampaio,
David M Simpson,
Joseph W Stauffer,
Gerold Stucki,
Jeffrey Tobias,
Richard E White,
James Witter
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ABSTRACT: There has been an increase in the number of chronic pain clinical trials in which the treatments being evaluated did not differ significantly from placebo in the primary efficacy analyses despite previous research suggesting that efficacy could be expected. These findings could reflect a true lack of efficacy or methodological and other aspects of these trials that compromise the demonstration of efficacy. There is substantial variability among chronic pain clinical trials with respect to important research design considerations, and identifying and addressing any methodological weaknesses would enhance the likelihood of demonstrating the analgesic effects of new interventions. An IMMPACT consensus meeting was therefore convened to identify the critical research design considerations for confirmatory chronic pain trials and to make recommendations for their conduct. We present recommendations for the major components of confirmatory chronic pain clinical trials, including participant selection, trial phases and duration, treatment groups and dosing regimens, and types of trials. Increased attention to and research on the methodological aspects of confirmatory chronic pain clinical trials has the potential to enhance their assay sensitivity and ultimately provide more meaningful evaluations of treatments for chronic pain.
Pain 03/2010; 149(2):177-93. · 5.78 Impact Factor
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Robert H Dworkin,
Dennis C Turk,
Michael P McDermott,
Sarah Peirce-Sandner,
Laurie B Burke,
Penney Cowan,
John T Farrar,
Sharon Hertz,
Srinivasa N Raja, Bob A Rappaport,
Christine Rauschkolb,
Cristina Sampaio
[show abstract]
[hide abstract]
ABSTRACT: An essential component of the interpretation of results of randomized clinical trials of treatments for chronic pain involves the determination of their clinical importance or meaningfulness. This involves two distinct processes--interpreting the clinical importance of individual patient improvements and the clinical importance of group differences--which are frequently misunderstood. In this article, we first describe the essential differences between the interpretation of the clinical importance of patient improvements and of group differences. We then discuss the factors to consider when evaluating the clinical importance of group differences, which include the results of responder analyses of the primary outcome measure, the treatment effect size compared to available therapies, analyses of secondary efficacy endpoints, the safety and tolerability of treatment, the rapidity of onset and durability of the treatment benefit, convenience, cost, limitations of existing treatments, and other factors. The clinical importance of individual patient improvements can be determined by assessing what patients themselves consider meaningful improvement using well-described methods. In contrast, the clinical meaningfulness of group differences must be determined by a multi-factorial evaluation of the benefits and risks of the treatment and of other available treatments for the condition in light of the primary goals of therapy. Such determinations must be conducted on a case-by-case basis, and are ideally informed by patients and their significant others, clinicians, researchers, statisticians, and representatives of society at large.
Pain 12/2009; 146(3):238-44. · 5.78 Impact Factor
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Anesthesia and analgesia 09/2009; 109(2):299-300. · 3.08 Impact Factor
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Robert H Dworkin,
Dennis C Turk,
Dennis A Revicki,
Gale Harding,
Karin S Coyne,
Sarah Peirce-Sandner,
Dileep Bhagwat,
Dennis Everton,
Laurie B Burke,
Penney Cowan,
John T Farrar,
Sharon Hertz,
Mitchell B Max, Bob A Rappaport,
Ronald Melzack
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ABSTRACT: The objective of the present research was to develop a single measure of the major symptoms of both neuropathic and non-neuropathic pain that can be used in studies of epidemiology, natural history, pathophysiologic mechanisms, and treatment response. We expanded and revised the Short-form McGill Pain Questionnaire (SF-MPQ) pain descriptors by adding symptoms relevant to neuropathic pain and by modifying the response format to a 0-10 numerical rating scale to provide increased responsiveness in longitudinal studies and clinical trials. The reliability, validity, and subscale structure of the revised SF-MPQ (SF-MPQ-2) were examined in responses from 882 individuals with diverse chronic pain syndromes and in 226 patients with painful diabetic peripheral neuropathy who participated in a randomized clinical trial. The data suggest that the SF-MPQ-2 has excellent reliability and validity, and the results of both exploratory and confirmatory factor analyses provided support for four readily interpretable subscales-continuous pain, intermittent pain, predominantly neuropathic pain, and affective descriptors. These results provide a basis for use of the SF-MPQ-2 in future clinical research, including clinical trials of treatments for neuropathic and non-neuropathic pain conditions.
Pain 05/2009; 144(1-2):35-42. · 5.78 Impact Factor
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Dennis C Turk,
Robert H Dworkin,
Michael P McDermott,
Nicholas Bellamy,
Laurie B Burke,
Julie M Chandler,
Charles S Cleeland,
Penney Cowan,
Rozalina Dimitrova,
John T Farrar, [......],
Patrick McGrath,
Henry J McQuay,
Steve Quessy, Bob A Rappaport,
Dennis A Revicki,
Margaret Rothman,
Joseph W Stauffer,
Ola Svensson,
Richard E White,
James Witter
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ABSTRACT: The increasing complexity of randomized clinical trials and the practice of obtaining a wide variety of measurements from study participants have made the consideration of multiple endpoints a critically important issue in the design, analysis, and interpretation of clinical trials. Failure to consider important outcomes can limit the validity and utility of clinical trials; specifying multiple endpoints for the evaluation of treatment efficacy, however, can increase the rate of false positive conclusions about the efficacy of a treatment. We describe the use of multiple endpoints in the design, analysis, and interpretation of pain clinical trials, and review available strategies and methods for addressing multiplicity. To decrease the probability of a Type I error (i.e., the likelihood of obtaining statistically significant results by chance) in pain clinical trials, the use of gatekeeping procedures and other methods that correct for multiple analyses is recommended when a single primary endpoint does not adequately reflect the overall benefits of treatment. We emphasize the importance of specifying in advance the outcomes and clinical decision rule that will serve as the basis for determining that a treatment is efficacious and the methods that will be used to control the overall Type I error rate.
Pain 09/2008; 139(3):485-93. · 5.78 Impact Factor
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Dennis C Turk,
Robert H Dworkin,
Dennis Revicki,
Gale Harding,
Laurie B Burke,
David Cella,
Charles S Cleeland,
Penney Cowan,
John T Farrar,
Sharon Hertz,
Mitchell B Max, Bob A Rappaport
[show abstract]
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ABSTRACT: This two-phase study was conducted to identify relevant domains of patient-reported outcomes from the perspective of people who experience chronic pain. In Phase 1, focus groups were conducted to generate a pool of patient outcome-related domains and their components. The results of the focus groups identified 19 aspects of their lives that were significantly impacted by the presence of their symptoms and for which improvements were important criteria they would use in evaluating the effectiveness of any treatment. Phase 2 was conducted to examine the importance and relevance of domains identified from a much larger and diverse sample of people with chronic pain. A survey was developed and posted on the American Chronic Pain Association website. Participants were asked to rate the importance of each item or domain identified by the focus groups on a scale of 0 to10 (i.e., 0="not at all important" and 10="extremely important"). The survey was completed by 959 individuals. The results indicate that all 19 aspects of daily life derived from the focus groups were considered important with a majority of respondents indicating a score of 8 or greater. In addition to pain reduction, the most important aspects were enjoyment of life, emotional well-being, fatigue, weakness, and sleep-related problems. Chronic pain clearly impacts health-related quality of life. The results of the two phases of the study indicate that people with chronic pain consider functioning and well-being as important areas affected by the presence of symptoms and as appropriate targets of treatment. These multiple outcomes should be considered when evaluating the efficacy and effectiveness of chronic pain treatments.
Pain 08/2008; 137(2):276-85. · 5.78 Impact Factor
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Patrick J McGrath,
Gary A Walco,
Dennis C Turk,
Robert H Dworkin,
Mark T Brown,
Karina Davidson,
Christopher Eccleston,
G Allen Finley,
Kenneth Goldschneider,
Lynne Haverkos, [......],
Jane Scott,
Navil Sethna,
Ola K Svensson,
Jennifer Stinson,
Carl L von Baeyer,
Lynn Walker,
Steven Weisman,
Richard E White,
Anne Zajicek,
Lonnie Zeltzer
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ABSTRACT: Under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), 26 professionals from academia, governmental agencies, and the pharmaceutical industry participated in a 2-stage Delphi poll and a consensus meeting that identified core outcome domains and measures that should be considered in clinical trials of treatments for acute and chronic pain in children and adolescents. Consensus was refined by consultation with the international pediatric pain community through announcement of our recommendations on the Pediatric Pain List and inviting and incorporating comments from external sources. There was consensus that investigators conducting pediatric acute pain clinical trials should consider assessing outcomes in pain intensity; global judgment of satisfaction with treatment; symptoms and adverse events; physical recovery; emotional response; and economic factors. There was also agreement that investigators conducting pediatric clinical trials in chronic and recurrent pain should consider assessing outcomes in pain intensity; physical functioning; emotional functioning; role functioning; symptoms and adverse events; global judgment of satisfaction with treatment; sleep; and economic factors. Specific measures or measurement strategies were recommended for different age groups for each domain. PERSPECTIVE: Based on systematic review and consensus of experts, core domains and measures for clinical trials to treat pain in children and adolescents were defined. This will assist in comparison and pooling of data and promote evidence-based treatment, encourage complete reporting of outcomes, simplify the review of proposals and manuscripts, and facilitate clinicians making informed decisions regarding treatment.
The journal of pain: official journal of the American Pain Society 07/2008; 9(9):771-83. · 3.78 Impact Factor
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Robert H Dworkin,
Dennis C Turk,
Kathleen W Wyrwich,
Dorcas Beaton,
Charles S Cleeland,
John T Farrar,
Jennifer A Haythornthwaite,
Mark P Jensen,
Robert D Kerns,
Deborah N Ader, [......],
Christine Rauschkolb,
Dennis A Revicki,
Margaret Rothman,
Kenneth E Schmader,
Brett R Stacey,
Joseph W Stauffer,
Thorsten von Stein,
Richard E White,
James Witter,
Stojan Zavisic
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[hide abstract]
ABSTRACT: A consensus meeting was convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to provide recommendations for interpreting clinical importance of treatment outcomes in clinical trials of the efficacy and effectiveness of chronic pain treatments. A group of 40 participants from universities, governmental agencies, a patient self-help organization, and the pharmaceutical industry considered methodologic issues and research results relevant to determining the clinical importance of changes in the specific outcome measures previously recommended by IMMPACT for 4 core chronic pain outcome domains: (1) Pain intensity, assessed by a 0 to 10 numerical rating scale; (2) physical functioning, assessed by the Multidimensional Pain Inventory and Brief Pain Inventory interference scales; (3) emotional functioning, assessed by the Beck Depression Inventory and Profile of Mood States; and (4) participant ratings of overall improvement, assessed by the Patient Global Impression of Change scale. It is recommended that 2 or more different methods be used to evaluate the clinical importance of improvement or worsening for chronic pain clinical trial outcome measures. Provisional benchmarks for identifying clinically important changes in specific outcome measures that can be used for outcome studies of treatments for chronic pain are proposed. PERSPECTIVE: Systematically collecting and reporting the recommended information needed to evaluate the clinical importance of treatment outcomes of chronic pain clinical trials will allow additional validation of proposed benchmarks and provide more meaningful comparisons of chronic pain treatments.
Journal of Pain 03/2008; 9(2):105-21. · 4.93 Impact Factor
