Research design considerations for chronic pain prevention clinical trials: IMMPACT recommendations.

Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. Specific design considerations included subject identification, timing and duration of treatment, outcomes, timing of assessment, and adjusting for risk factors in the analyses. We provide a detailed examination of 4 models of chronic pain prevention (ie, chronic postsurgical pain, postherpetic neuralgia, chronic low back pain, and painful chemotherapy-induced peripheral neuropathy). The issues discussed can, in many instances, be extrapolated to other chronic pain conditions. These examples were selected because they are representative models of primary and secondary prevention, reflect persistent pain resulting from multiple insults (ie, surgery, viral infection, injury, and toxic or noxious element exposure), and are chronically painful conditions that are treated with a range of interventions. Improvements in the design of chronic pain prevention trials could improve assay sensitivity and thus accelerate the identification of efficacious interventions. Such interventions would have the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials.

Research design considerations for chronic pain prevention clinical trials: IMMPACT recommendations.

Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. Specific design considerations included subject identification, timing and duration of treatment, outcomes, timing of assessment, and adjusting for risk factors in the analyses. We provide a detailed examination of 4 models of chronic pain prevention (ie, chronic postsurgical pain, postherpetic neuralgia, chronic low back pain, and painful chemotherapy-induced peripheral neuropathy). The issues discussed can, in many instances, be extrapolated to other chronic pain conditions. These examples were selected because they are representative models of primary and secondary prevention, reflect persistent pain resulting from multiple insults (ie, surgery, viral infection, injury, and toxic or noxious element exposure), and are chronically painful conditions that are treated with a range of interventions. Improvements in the design of chronic pain prevention trials could improve assay sensitivity and thus accelerate the identification of efficacious interventions. Such interventions would have the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials.

Driving Ability in Patients with Severe Chronic Low Back or Osteoarthritis Knee Pain on Stable Treatment with Tapentadol Prolonged Release: A Multicenter, Open-label, Phase 3b Trial.

INTRODUCTION: Strong centrally acting analgesics, including tapentadol prolonged release (PR), have demonstrated efficacy for the management of non-malignant, chronic pain. Maintaining patient independence, including the ability to drive safely, is a key goal of long-term analgesic therapy. This multicenter, open-label, phase 3b trial evaluated the effects of tapentadol PR on driving ability. METHODS: This study included patients who had completed previous tapentadol PR trials for severe low back or osteoarthritis pain. After at least 6 weeks of dose stability, patients continued taking tapentadol PR (50-250 mg twice daily) and could take supplemental immediate-release tapentadol 50 mg, except on the day before or day of the driving test (before the test). Pain intensity was assessed using an 11-point numerical rating scale. The Vienna Test System-Traffic Plus was used to assess cognitive and psychomotor function. The key surrogate parameter for driving ability was a global judgment based on 6 battery tests. RESULTS: Thirty-eight patients enrolled and completed the trial, and 35 patients completed all 6 tests. Pain scores remained unchanged from enrollment to final visit [mean (standard deviation) change, -0.2 (1.0)]. Approximately two-thirds [65.7% (23/35)] of patients were classified as fit to drive based on the global judgment of driving-specific ability [34.3% (12/35) not fit to drive]. Total daily tapentadol PR dose (>200 vs. ≤200 mg/day) did not affect global judgment of driving ability (P = 0.4885). Two adverse events (considered unrelated to study drug) were reported. CONCLUSION: Results suggest that most patients receiving a stable dose of tapentadol PR for severe, chronic pain would be able to drive, consistent with earlier studies evaluating stable treatment with strong opioids. Study design limitations and needs for individual patient assessment must be considered in clinical practice.