Considerations for improving assay sensitivity in chronic pain clinical trials: IMMPACT recommendations

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.

Prediction of response to tapentadol in chronic low back pain

“…The finding is explained by the phenomenon of regression to the mean. This response parameter is regarded as a “general predictive effect”, it is found in all clinical trials and is independent of a specific treatment (Dworkin et al., 2012). If future trials are designed with alternative primary outcome parameters like functionality or quality‐of‐life, a low baseline value should be used as an inclusion criterion.…”

Chronic Pain and DepressionAmong Primary Care Patients Treated with Buprenorphine

“…We chose this cutoff based on its use as a threshold for inclusion in clinical trials of analgesics. 46 We asked participants to self-report on the primary bodily location of pain. We used the Brief Pain Inventory interference scale (BPI-I) 47 to assess the degree to which pain interfered with important aspects of life, including general activity, mood, walking ability, normal work (including home and housework), relations with others, sleep, and enjoyment of life; internal consistency reliability was 0.95.…”

Quantitative sensory testing somatosensory profiles in patients with cervical radiculopathy are distinct from those in patients with nonspecific neck–arm pain

“…In order to better interpret our data, the establishment of the clinical profiles included multidimensional aspects of pain as proposed by the IMMPACT guidelines [23]. The following questionnaires were used to characterise the patient groups.…”