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There was a consensus that chronic pain clinical trials should assess outcomes representing six core domains: (1) pain, (2) physical functioning, (3) emotional functioning, (4) participant ratings of improvement and satisfaction with treatment, (5) symptoms and adverse events, (6) participant disposition (e.g. adherence to the treatment regimen and reasons for premature withdrawal from the trial). Although consideration should be given to the assessment of each of these domains, there may be exceptions to the general recommendation to include all of these domains in chronic pain trials. When this occurs, the rationale for not including domains should be provided. It is not the intention of these recommendations that assessment of the core domains should be considered a requirement for approval of product applications by regulatory agencies or that a treatment must demonstrate statistically significant effects for all of the relevant core domains to establish evidence of its efficacy.

This article focuses on the necessary psychometric properties of a patient-reported outcomes (PROs) measure. Topics include the importance of reliability and validity, psychometric approaches used to provide reliability and validity estimates, the kinds of evidence needed to indicate that a PRO has a sufficient level of reliability and validity, contexts that may affect psychometric properties, methods available to evaluate PRO instruments when the context varies, and types of reliability and validity testing that are appropriate during different phases of clinical trials. Points discussed include the perspective that the psychometric properties of reliability and validity are on a continuum in which the more evidence one has, the greater confidence there is in the value of the PRO data. Construct validity is the type of validity most frequently used with PRO instruments as few "gold standards" exist to allow the use of criterion validity and content validity by itself only provides beginning evidence of validity. Several guidelines are recommended for establishing sufficient evidence of reliability and validity. For clinical trials, a minimum reliability threshold of 0.70 is recommended. Sample sizes for testing should include at least 200 cases and results should be replicated in at least one additional sample. At least one full report on the development of the instrument and one on the use of the instrument are deemed necessary to evaluate the PRO psychometric properties. Psychometric testing ideally occurs before the initiation of Phase III trials. When testing does not occur prior to a Phase III trial, considerable risk is posed in relation to the ability to substantiate the use of the PRO data. Various qualitative (e.g., focus groups, behavioral coding, cognitive interviews) and quantitative approaches (e.g., differential item functioning testing) are useful in evaluating the reliability and validity of PRO instruments.

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.

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