Meta-analysis of pain and function placebo responses in pharmacological osteoarthritis trials

Abstract

Objective To evaluate contextual effects in the form of placebo responses (PRs) for patient-reported pain and function and objectively measured function in osteoarthritis (OA) clinical trials. Methods Two authors independently searched major electronic databases from inception to 20 May 2019. Included studies were randomized, placebo-controlled OA trials of pharmacological agents reporting both patient-reported and objectively measured outcomes. PRs for each type of outcome measure were compared by standardized mean differences (SMDs). The placebo response ratio (PRR) assessed the placebo to treatment effect size. The effect sizes of PRs and PRRs were pooled using a random effects model. Results Twenty-one trials met the inclusion criteria; 20 were double-blinded with one not reporting on blinding status. Compared with patients’ self-reported outcome (PRO) pain, PRs were significantly lower for PRO function (SMD − 0.16 [95% CI = − 0.28, − 0.05], p = 0.006), objectively measured muscle strength (SMD − 0.34 [95% CI − 0.58, − 0.10], p = 0.006), and range of motion (SMD = − 0.31 [95% CI = − 0.54, − 0.08], p = 0.008) function. Generally, PRs for function outcomes (patient-reported and objectively measured) were similar. The overall PRR for different measures ranged from the smallest (most favorable) for walking time/distance (0.30, 95% CI 0.16 to 0.43) to the largest for PRO pain (0.44, 95% CI 0.23 to 0.65). Conclusion Function measures both subjective and objective had less contextual effects than pain measures in OA trials. Our results support the OMERACT-OARSI recommendations to include measures of physical function in all clinical trials of hip and knee OA and suggest that a greater use of function measures might enhance the success rates of pharmacological OA trials. Increasing the availability of mobile health apps should facilitate the acquisition of measured function data. Electronic supplementary material The online version of this article (10.1186/s13075-019-1951-6) contains supplementary material, which is available to authorized users.

Pentosan polysulfate sodium for Ross River virus-induced arthralgia: a phase 2a, randomized, double-blind, placebo-controlled study

“…A limitation of our study is the potential impact a placebo effect may have on subjective endpoints such as pain and function. In a meta-analysis of pain and function placebo responses in patients with osteoarthritis, Huang et al [ 38 ] calculated a “placebo response ratio” of 0.44 (where 0 means the placebo effect made no contribution to the response and 100 means all the response is due to placebo effect). Combining this with the subjective nature of evaluating pain may have resulted in our failing to achieve statistical significance in all but one of the patient-reported outcome pain measures used.…”

Clinical Efficacy and Safety of Yellow Oil Formulations 3 and 4 versus Indomethacin Solution in Patients with Symptomatic Osteoarthritis of the Knee: A Randomized Controlled Trial

“…Though VAS is valid and reliable for use in pain assessment, it is subjective and largely dependent on the patient's perception of pain [ 52 , 53 ]. The literature suggests that the favorable effects of treatment interventions in OA knee trials may partly be attributable to contextual effects such as patient beliefs and expectancy as well as to the patient-physician relationship [ 54 , 55 ]. In addition, withholding effective treatment might not be considered ethical in a setting where topical NSAIDs are available and widely prescribed [ 22 ].…”

Evaluation of the efficiency and safety of magnet therapy for osteoarthritis. Results of the multicenter blind placebo-controlled study COSMO (Clinical Evaluation of Current Magnet Therapy for Osteoarthritis)

“…Любопытной особенностью нашего исследования стало достаточно высокое терапевтическое действие ложной МТ. Следует уточнить, что значительный эффект плацебо при лечении ОА был отмечен рядом ведущих экспертов по этому заболеванию [18,19]. Так, по мнению W. Zhang, более 75% снижения боли, скованности и улучшения функции при лечении ОА (при использовании любых методов терапии) определяется плацебо-эффектом [20].…”

“…Так, по мнению W. Zhang, более 75% снижения боли, скованности и улучшения функции при лечении ОА (при использовании любых методов терапии) определяется плацебо-эффектом [20]. Считается, что данный феномен связан с особенностями формирования хронической боли при ОА, патогенез которой в значительной степени связан с центральной сенситизацией и недостаточной эффективностью антиноцицептивной системы [18][19][20]. Тем не менее применение истинной Мт в нашем исследовании оказывало достоверно больший лечебный эффект, чем ложная Мт.…”