After the 2011 Institute of Medicine report on chronic pain, the Interagency Pain Research Coordinating Committee (IPRCC) was created to enhance research efforts among federal agencies. The IPRCC and Office of Pain Policy at the National Institutes of Health collaborated to identify gaps in knowledge and address them via a Federal Pain Research Strategy (FPRS). Interdisciplinary work groups (WGs) were established to make research recommendations in 5 areas: prevention of acute and chronic pain, acute pain and acute pain management, transition from acute to chronic pain, chronic pain and chronic pain management, and disparities in pain and pain care; cross-cutting issues were also considered. The objective was to provide guidance on current research and to make recommendations about addressing identified gaps. Findings from the Prevention of Acute and Chronic Pain WG are summarized in this article. The WG created subgroups to develop recommendations on specific aspects of prevention of acute and chronic pain, including: public education, primary prevention, secondary prevention, tertiary prevention, transition from acute to chronic pain, and cross-cutting mediators. No formal literature review was conducted; however, external advisors were available and consulted as needed. Seven key research priorities were identified. The one deemed "greatest near-term value" was to optimize public health strategies to educate patients on managing pain; that deemed "most impactful" was to determine an association between patient and intervention factors. Other recommendations were related to the epidemiology of acute pain from health care procedures, the epidemiology of acute pain from work-related injuries, safety and effectiveness of management of pain associated with health care procedures, optimizing approaches to acute postsurgical pain, and safety and effectiveness of early interventions for tertiary prevention. Stakeholders, including federally sponsored research programs, researchers, health care providers, policy makers, patients, and others should work together to implement recommendations and address important gaps. PERSPECTIVE:The FPRS Steering Committee created 5 WGs to identify research needs and make recommendations in key areas of research. This article reports the results of one-the Prevention of Acute and Chronic Pain group. Several research priorities emerged, and recommendations made to fill existing knowledge gaps.

Objective

Our objective was to identify patient, study, and site factors associated with assay sensitivity in placebo-controlled neuropathic pain trials.

Methods

We examined the associations between study characteristics and standardized effect size (SES) in a database of 200 publicly available randomized clinical trials of pharmacologic treatments for neuropathic pain.

Results

There was considerable heterogeneity in the SESs among the examined trials. Univariate meta-regression analyses indicated that larger SESs were significantly associated with trials that had 1) greater minimum baseline pain inclusion criteria, 2) greater mean subject age, 3) a larger percentage of Caucasian subjects, and 4) a smaller total number of subjects. In a multiple meta-regression analysis, the associations between SES and minimum baseline pain inclusion criterion and age remained significant.

Conclusions

Our analyses have examined potentially modifiable correlates of study SES and shown that a minimum pain inclusion criterion of 40 or above on a 0 to 100 scale is associated with a larger SES. These data provide a foundation for investigating strategies to improve assay sensitivity and thereby decrease the likelihood of falsely negative outcomes in clinical trials of efficacious treatments for neuropathic pain.

Proof-of-concept (POC) clinical trials play an important role in developing novel treatments and determining whether existing treatments may be efficacious in broader populations of patients. The goal of most POC trials is to determine whether a treatment is likely to be efficacious for a given indication and thus whether it is worth investing the financial resources and participant exposure necessary for a confirmatory trial of that intervention. A challenge in designing POC trials is obtaining sufficient information to make this important go/no-go decision in a cost-effective manner. An IMMPACT consensus meeting was convened to discuss design considerations for POC trials in analgesia, with a focus on maximizing power with limited resources and participants. We present general design aspects to consider including patient population, active comparators and placebos, study power, pharmacokinetic-pharmacodynamic relationships, and minimization of missing data. Efficiency of single-dose studies for treatments with rapid onset is discussed. The trade-off between parallel-group and crossover designs with respect to overall sample sizes, trial duration, and applicability is summarized. The advantages and disadvantages of more recent trial designs, including N-of-1 designs, enriched designs, adaptive designs, and sequential parallel comparison designs, are summarized, and recommendations for consideration are provided. More attention to identifying efficient yet powerful designs for POC clinical trials of chronic pain treatments may increase the percentage of truly efficacious pain treatments that are advanced to confirmatory trials while decreasing the percentage of ineffective treatments that continue to be evaluated rather than abandoned.

There is growing concern about lack of scientific rigor and transparent reporting across many preclinical fields of biological research. Poor experimental design and lack of transparent reporting can result in conscious or unconscious experimental bias, producing results that are not replicable. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the U.S. Food and Drug Administration sponsored a consensus meeting of the Preclinical Pain Research Consortium for Investigating Safety and Efficacy (PPRECISE) Working Group. International participants from universities, funding agencies, government agencies, industry, and a patient advocacy organization attended. Reduction of publication bias, increasing the ability of others to faithfully repeat experimental methods, and increased transparency of data reporting were specifically discussed. Parameters deemed essential to increase confidence in the published literature were clear, specific reporting of an a priori hypothesis and definition of primary outcome measure. Power calculations and whether measurement of minimal meaningful effect size to determine these should be a core component of the preclinical research effort provoked considerable discussion, with many but not all agreeing. Greater transparency of reporting should be driven by scientists, journal editors, reviewers, and grant funders. The conduct of high-quality science that is fully reported should not preclude novelty and innovation in preclinical pain research, and indeed, any efforts that curtail such innovation would be misguided. We believe that to achieve the goal of finding effective new treatments for patients with pain, the pain field needs to deal with these challenging issues.

A critical component in development of opioid analgesics is assessment of their abuse liability (AL). Standardization of approaches and measures used in assessing AL have the potential to facilitate comparisons across studies, research laboratories, and drugs. The goal of this report is to provide consensus recommendations regarding core outcome measures for assessing the abuse potential of opioid medications in humans in a controlled laboratory setting. Although many of the recommended measures are appropriate for assessing the AL of medications from other drug classes, the focus here is on opioid medications because they present unique risks from both physiological (e.g., respiratory depression, physical dependence) and public health (e.g., individuals in pain) perspectives. A brief historical perspective on AL testing is provided, and those measures that can be considered primary and secondary outcomes and possible additional outcomes in AL assessment are then discussed. These outcome measures include the following: subjective effects (some of which comprise the primary outcome measures, including drug liking; physiological responses; drug self-administration behavior; and cognitive and psychomotor performance. Before presenting recommendations for standardized approaches and measures to be used in AL assessments, the appropriateness of using these measures in clinical trials with patients in pain is discussed.