Pain trials

The purpose of this study is to determine the usefulness of combining PET scan activity and MRI image biomarkers for the clinical management of spinal joint low back pain. Spinal cord stimulation SCS has been used for almost 30 years to treat many intractable back pain conditions. Another trial has demonstrated superiority of SCS over repeat surgery in the same patient population.

However, the ability to reliably capture the low back with paresthesia coverage has remained challenging and elusive despite numerous strategies designed to overcome this limitation. Strategies that have been introduced but so far with limited This research study is designed to evaluate the efficacy of Tuina therapy Chinese massage therapy compared to physiotherapy for low back pain. The purpose of this study is to evaluate if subjects who have already experienced tonic spinal cord stimulation would have a better pain relief status with burst spinal cord stimulation.

The purpose of this study is to determine if intra-articular lumbar facet and sacroiliac joint injections, or lumbar radiofrequency ablation RFA are effective in improving 1 patient-reported measures of pain, function and quality of life; 2 capacity; and 3 performance as measured by change in activity counts. Secondarily, the value of measuring capacity and performance following diagnostic medial branch blocks as a predictor of successful outcomes after lumbar RFA will be explored.

The purpose of this pilot phase study is to assess functionality and ease of use of an exercise monitoring system and decide whether any modifications are necessary before beginning a larger study using this system.

This study will assess the effect of incorporating a tonal exercise device into clinical and chiropractic care for lower back pain. The purpose of this study is to assess the effects of lofexidine on opioid tapering in adults undergoing opioid tapering prior to elective lumbar spine surgery.

Patients with active Axial Spondyloarthritis without x-ray evidence of Ankylosing Spondylitis and with signs of inflammation will be randomly assigned to receive certolizumab pegol CZP mg every two weeks or placebo. Additional socially meaningful group statistics include resumption of employment and leaving the disability system, or racial and ethnic differences in short- or long-term outcomes.

Although complex and technically difficult to estimate the effects of specific acute, time-limited interventions on chronic outcomes, such analyses are important 76 and posttrauma studies 97 are likely to increase in the near term.

Many believe that unidimensional verbal, numerical, or visual analogue scales simply cannot capture the complex experience of pain. In this context, it is worth recalling that the McGill-Melzack Pain Questionnaire was derived from the descriptors volunteered by patients during their recounting of personal pain narratives. The tension between clinical trial methods in many cases designed to reduce the effect of outliers on estimates of treatment efficacy, and the growing importance of personalized, precision medicine is a major challenge for biomedicine beyond just pain research.

Current approaches to reducing patient heterogeneity by pretesting so as to exclude placebo responders, or to enrich enrollment with likely treatment responders embody efforts to increase the sensitivity of analgesic trials while identifying target populations likely to benefit. If successful, such strategies will be important for the clinical development of new chemical identities whose marketing for use in clinical practice depends on proving efficacy in commercially meaningful numbers of patients.

Durations of postsurgical hospital stays have been shortened or even eliminated ie, by conversion from inpatient to outpatient procedures after the adoption of minimally invasive surgical techniques, prolonged delivery of postoperative regional anesthesia, and other advances in the standard of care. Thus, postoperative stays during which patient responses to single- or multiple-dose analgesic therapies may be scrutinized are becoming less frequent.

This reality may be dealt with by planning to extend the duration of acute, in-hospital observation but doing so adds expense to the trial the sponsor would be expected to cover the extra per diem costs.

Furthermore, the opportunity to see whether the investigational treatment may shorten the time to discharge during routine care would be lost. Alternatively, such investigations could transition from the inpatient to the outpatient setting as is often performed with chronic pain trials.

At the same time, there is ongoing interest in optimizing perioperative management so as to benefit long-term outcomes by reducing persistent pain or accelerating rehabilitation. Evolving surgical methods and routine, consensus acute analgesic practice impact as well on the selection or de novo development of efficacy assessments most suitable to determine optimal analgesic regimens for specific operations in particular subgroups eg, children vs older persons.

Furthermore, a functional outcome measure appropriate for application in patients undergoing knee replacement using conventional general anesthesia and systemic opioids might simply consist of a measurement of maximal knee flexion.

Yet, if regional anesthesia were combined with an anti-inflammatory agent as the baseline regimen, so many patients may have substantial knee flexion that this outcome may not be sensitive to the addition of an experimental analgesic. In the latter patients, distance walked during timed ambulation is better suited to assess analgesic efficacy. A similar point may be made for other topics related to acute pain control, eg, the application of programs to enhance recovery after surgery. The generic postoperative quality of recovery scales developed by Myles et al.

Challenges in the development of efficacy outcomes related to behavioral factors are presently among the most intriguing to those developing future acute pain trial designs and interpreting their results. Yet, in the past 2 decades, research and practice on acute pain have increasingly explored social and behavioral dimensions such that the core outcome domains of interest in acute and chronic pain trials may now be converging.

The Beecher group's seminal paper characterizing placebo responders in analgesic trials in acute pain explicitly identified patients' high regard for the hospital staff, as well as presurgical social connectedness as gauged by regular church attendance and interest in church affairs, as predictors of placebo responsivity. As noted above in this guide, current systematic reviews of factors to predict high-pain intensity scores and analgesic consumption after surgery are able to account for only about half of the observed variance.

Thus, both as predictive variables as well as outcomes per se, factors related to social connectedness with health care providers during routine care or analgesic trials, with family, and with society in general, may account for much of the still-uncharacterized half of the variation in pain intensity and analgesic consumption after surgery. Although not a trial in the conventional sense, the capture of effectiveness data during routine clinical care is now possible with unprecedented speed and breadth and is increasingly informing postmarketing appraisals of pharmacological effectiveness and safety.

Instead, patient satisfaction was influenced by whether staff members communicated the importance of pain control, and whether they projected concern for achieving good pain control.

When such findings initially emerged, they were viewed as if patients were reporting satisfaction in a naive and misunderstood fashion because nociception and pain intensity were viewed as paramount to the pain experience. However, given the distress, dysphoria, and in particular, sense of social isolation that we now realize we are hardwired to experience during acute and chronic pain, we would have performed well listening to these patients.

Now, we understand that their ratings of satisfaction were based on a more global construct within which both nociception and distress are included. Going forward, we must partner with patients to guide us because we seek to address still-unmet challenges in the design, measurement, and interpretation of efficacy outcomes in analgesic trials. Despite reports nearly 2 decades ago suggesting the need to improve safety reporting in acute pain trials, 34 recent evidence suggests that progress in this area has been too slow.

Regarding methods of AE assessment, periodic open-ended questions may be useful to detect previously unrecognized AEs in early-phase trials. One example of a treatment-specific AE assessment tool is the opioid-related symptom distress scale SDS developed by Apfelbaum et al. Thus, when designing an acute pain trial, careful attention should be given to using validated AE assessment methods that are sensitive to severity of anticipated AEs and appropriately timed so as to facilitate attribution to the study treatment.

Together with such AE assessment and treatment strategies, acute pain trials should also include a prospective statistical analysis plan specific to treatment harms as statistical considerations for these outcomes may be unique and different from those for efficacy outcomes.

We contend that AE reporting is as important as reporting of efficacy outcomes and should include a description of treatment-specific participant trial withdrawals. Subgroup analyses for harms should be described. Finally, the trial report should include a discussion of the perceived balance of benefits and harms in the context of the trial's limitations. Execution of an acute pain trial starts with finalizing the trial protocol—including a predefined statistical analysis plan, obtaining operational funding a critical prerequisite for trial execution , ethics approval, and registration in an external trial registry.

Unique to acute pain trials is the setting in which they are conducted, eg, perioperative setting for postsurgical pain studies 89 and emergency settings for posttraumatic pain studies. Common challenges to participant recruitment in acute care settings include other competing activities eg, presurgical preparation, urgent diagnostic studies, family interactions, etc. Essential aspects of statistical analysis of pain trials are discussed in detail elsewhere. However, a number of issues related to trial analysis of acute pain trials are worthy of brief discussion here.

In earlier postsurgical single-dose analgesic trials where only patients developing moderate to severe pain were randomized to a relatively short-acting treatment or placebo , common analytical methods involved the estimation of area under the time—analgesic effect curve using either measures of pain intensity SPID4, summed pain intensity difference over 4 hours or of pain relief TOTPAR4, total pain relief over 4 hours —typically over a period of 4 to 6 hours.

Although statistical analyses in most earlier acute pain trials involved comparing treatment group means for SPID and TOTPAR measures, it has been recognized that the distribution of analgesic responses within treatment groups may be nonnormal such that few individual treatment responses are similar to the mean. Although estimates of analgesic efficacy derived from acute pain trials applying methods with high assay sensitivity eg, the dental impaction model do not always generalize to all clinical pain conditions, such methods have demonstrated their merits and will likely continue to be useful in drug development.

Perhaps, the greater challenge will be to further cultivate valid methods to generate evidence in support of best care for patients at highest risk of developing moderate to severe acute pain.

Doing so will require well-powered, likely multicenter, trials that focus on a specific surgical procedure or injury and, further, on a specific subpopulation eg, chronic pain patients experiencing acute pain with careful consideration given to multiple outcomes of interest and possibly more sophisticated analytical methods.

Also, more attention needs to be paid to AEs, especially in trials including multimodal analgesia, where little information is available on potential undesirable interactions of different analgesics. Therefore, it is worth noting here the need to further improve trial designs to evaluate interventions for the prevention of the transition from acute to chronic pain. Over the past 50 years, clinical trial methods for the evaluation of treatments for acute pain have dramatically evolved and improved.

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. National Center for Biotechnology Information , U. Journal List Pain Rep v. Pain Rep. Published online Apr 2. Carr , c Paul J. Desjardins , d and Henrik Kehlet e. Daniel B. Paul J. Author information Article notes Copyright and License information Disclaimer.

Departments of a Anesthesiology and Perioperative Medicine and. E-mail address: ac. Published by Wolters Kluwer Health, Inc. This article has been cited by other articles in PMC. Abstract Introduction: The clinical setting of acute pain has provided some of the first approaches for the development of analgesic clinical trial methods.

Objectives: This article reviews current methods and challenges and provides recommendations for future design and conduct of clinical trials of interventions to treat acute pain. Conclusion: Growing knowledge about important diverse patient factors as well as varying pain responses to different acute pain conditions and surgical procedures has highlighted several emerging needs for acute pain trials.

Keywords: Clinical trial, Acute pain, Analgesic trial. Introduction Analgesic trials for acute pain are typically investigated in the context of traumatic injury or surgical procedures. Historical perspective on acute pain trial design Before the initial development of clinical trial designs for the evaluation of pain treatment interventions, much research was first done to better understand the nature of subjective responses to analgesic interventions in the setting of acute pain.

Trial design features 3. Patient stratification Although acute pain occurs in many nonsurgical clinical situations, the vast majority of acute pain research has been conducted in the setting of treating acute pain after surgery. Open in a separate window. Table 2 Recommendations for selecting treatment comparators in acute pain randomized controlled trials. Table 3 Cochrane collaboration's tool for assessing risk of bias.

The primary outcome: pain intensity Measures of pain intensity will always be integral to acute pain efficacy trials and, for the foreseeable future, will continue to be the primary outcome in acute pain trials.

Figure 1. Secondary outcomes Secondary outcomes are expected to be favorably impacted if pain intensity is diminished meaningfully by the experimental intervention. Tertiary outcomes The outcome of interest just cited, namely, opioid use or misuse long after discharge postoperatively, is a population-based outcome that would not ordinarily be assessed in the confines of a registration trial designed to capture data on safety and efficacy.

Qualitative and narrative-based outcomes Many believe that unidimensional verbal, numerical, or visual analogue scales simply cannot capture the complex experience of pain. Trial execution Execution of an acute pain trial starts with finalizing the trial protocol—including a predefined statistical analysis plan, obtaining operational funding a critical prerequisite for trial execution , ethics approval, and registration in an external trial registry.

Trial analysis and interpretation Essential aspects of statistical analysis of pain trials are discussed in detail elsewhere. Conclusion Over the past 50 years, clinical trial methods for the evaluation of treatments for acute pain have dramatically evolved and improved. Disclosures The authors have no conflict of interest to declare. Footnotes Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

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Improving individual measurement of postoperative pain: the pain trajectory. The purpose of this study is to examine patient reported outcomes including pain, quality of life, depression and impact on kidney blood flow before and after procedure to destroy the pain sensory nerves of the kidneys in patients with untreatable one or two sided kidney pain.

The primary purpose of this study is to identify patient characteristics that are associated with unintended prolonged opioid use UPUO. The purpose of this study is to determine if intra-articular lumbar facet and sacroiliac joint injections, or lumbar radiofrequency ablation RFA are effective in improving 1 patient-reported measures of pain, function and quality of life; 2 capacity; and 3 performance as measured by change in activity counts.

Secondarily, the value of measuring capacity and performance following diagnostic medial branch blocks as a predictor of successful outcomes after lumbar RFA will be explored. The purpose of this study is to develop a patient-centered pain plan and standardized preoperative pain education for patients undergoing lumbar procedures to increase postoperative pain control and patient satisfaction.

This study aims to investigate whether administration of vancomycin intravenously via a Bier block, typically a method for providing regional anesthesia in the upper extremity, leads to higher soft tissue and bone antibiotic concentrations compared to routine intravenous administration.

Higher tissue concentrations could be desirable for prophylaxis in complex upper extremity reconstruction, or for treatment of difficult infections.