Research design considerations for chronic pain prevention clinical trials

Abstract

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 (i.e., chronic post-surgical 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 (i.e., surgery, viral infection, injury, and toxic/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.

Local anaesthetics and regional anaesthesia versus conventional analgesia for preventing persistent postoperative pain in adults and children

“…One did record pain as a dichotomous out-come but did not report it in the manuscript, and provided the review authors with the data via email (Kurmann 2015). Nine studies (Brown 2004; Burney 2004; Gupta 2006; Karanikolas 2006; Karmakar 2014; Katz 2004;; McKeen 2014; Sprung 2006; Wodlin 2011), reported continuous complex outcome instruments, like the McGill questionnaire (Dworkin 2009b), or the Short Form Health Survey (SF-36) (Ware 1992), which are recommended in consensus statements for the assessment of chronic pain (Gewandter 2015; Turk 2006). …”

Adverse Effects of Antidepressants for Chronic Pain: A Systematic Review and Meta-analysis

“…In fact, specific guidelines exist for the conduction of prevention clinical trials in this population that pose a useful guide to researchers (94). …”

Neuropathic pain

“…Secondary prevention involves administering preventive interventions to individuals who are experiencing an illness, injury or treatment that can cause chronic neuropathic pain. Examples of this approach include the perioperative treatment of surgical patients to prevent chronic postsurgical pain 92 and the use of antiviral or analgesic treatment in patients with herpes zoster infection 93 . Furthermore, proper management of health conditions, such as diabetes mellitus, may prevent neuropathic pain before it even presents 94 .…”