1. From a systematic review, intra-articular and topical placebos had greater effects on pain scores than oral placebos.
2. When accounting for differential effects of placebo treatments, intra-articular hyaluronic acid controlled pain best at 3 months.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Placebo treatments are used as inactive treatments to establish a baseline for comparison with the active treatments of interest in clinical trials. However, it is unclear whether different placebos have different levels of baseline efficacy. In this systematic review, placebo treatments for osteoarthritis (OA) pain were compared to each other and to several active treatments for OA. Results of the analysis show that intra-articular (IA) and topical placebo formulations had significantly greater effect sizes for pain control than the oral placebo formulation after 3 months. When comparing all possible treatment pairs with each other, it was found that IA hyaluronic acid had the greatest effect on pain scores at 3 months. On the other hand, when all placebos were compared with each active treatment as a single category, oral nonselective NSAIDs had the greatest effect on pain scores. This study was limited in that it did not account for the additional impact that the patient-doctor relationship may have on placebo efficacy. Overall, this study demonstrates that different modes of placebo administration can have different clinical effects, and this phenomenon should be accounted for when assessing the relative efficacies of different treatments for a particular disease.
In-Depth [systematic review and meta-analysis]: This study included data from 149 randomized, controlled trials that compared at least 2 knee OA treatments and reported on their relative pain control efficacy. Placebo treatments included oral, IA, topical and oral plus topical formulations, while active treatments included acetaminophen, oral nonselective NSAIDs, oral COX-2–selective NSAIDs, topical NSAIDs, IA corticosteroids, and IA hyaluronic acid. IA and topical placebos had significantly greater effect sizes when compared to oral placebo after 3 months (0.29, 95%CI 0.09-0.49; and 0.20, 95%CI 0.02-0.38, respectively). IA hyaluronic acid had the highest mean differences in pain score when compared to oral, oral plus topical, topical and IA placebos at 3 months (0.60, 0.47, 0.40 and 0.31, respectively).
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