John D. Loeser Award Lecture: Size does matter, but it isn't everything: the challenge of modest treatment effects in chronic pain clinical trials

An implantable restorative-neurostimulator for refractory mechanical chronic low back pain: a randomized sham-controlled clinical trial

“…Responses to effective pain treatments are multidimensional, 25 , 83 and across most secondary and supporting endpoints at 120 days, the 95% CIs excluded zero and were consistent with a clinically meaningful treatment effect (Table 2 ). 12 , 24 , 26 , 35 , 41 , 67 , 76 , 78 The prespecified secondary CPRA of the ITT primary outcome data showed a significant separation across the range of possible responder thresholds, illustrating the adverse impact of information loss due to primary outcome dichotomization (Fig. 4 ).…”

If the Doors of Perception Were Cleansed, Would Chronic Pain be Relieved? Evaluating the Benefits and Risks of Psychedelics

“…128 As Table 2 also notes, effect sizes in chronic pain clinical trials over the past several decades have been declining, and this must be considered in sample size determination and in the interpretation of study results. 41,129,130 As emphasized in the section on adverse effects and safety, the risks associated with psychedelics when administered in research settings are relatively rare but can be significant. Because these risks are not well characterized, clinical trials of psychedelics must include careful assessments of adverse events, not only during and immediately following the psychedelic session but also longer-term adverse outcomes (see Table 2).…”

Clinical Trials in Pancreatitis: Opportunities and Challenges in the Design and Conduct of Patient-Focused Clinical Trials in Recurrent Acute and Chronic Pancreatitis

“…To address challenges in the design, conduct, and analysis of pain clinical trials, various factors should be considered. [24][25][26][27][28][29][30] These include increased attention to (1) patient selection and training; (2) adequate blinding of participants, investigators, and outcome assessors; (3) mitigation of treatment nonadherence; (4) prespecification of outcomes, analyses, and accommodation of intercurrent events and missing data; (5) reducing placebo group responses by minimizing placebo effects and participant expectations to the greatest extent possible; (6) distinguishing clinically meaningful within-participant improvements from clinically meaningful group differences in clinical trials; (7) engaging patient partners throughout all stages of developing pain treatments; and (8) analyzing heterogeneity of treatment effects, a crucial basis for the development of precision pain treatments. An evidencebased approach to the design of clinical trials, especially when involving pain treatments, has the potential to increase assay sensitivity (ie, the ability to detect a true benefit when present) and informativeness, thereby accelerating the availability of novel treatments for patients with painful RAP or CP.…”