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Placebo Trials in Orthopaedic Surgery

      The authors of “Sham Surgery Studies in Orthopaedic Surgery May Just Be a Sham: A Systematic Review of Randomized Placebo-Controlled Trials”
      • Sochacki K.R.
      • Mather R.C.
      • Nwachukwu B.U.
      • et al.
      Sham surgery studies in orthopaedic surgery may just be a sham: A systematic review of randomized placebo-controlled trials.
      cast a critical eye on placebo surgical trials. We applaud any attempt to identify the methodologic limitations of scientific research and to ask researchers to aim higher. We do, however, have concerns about the recommendations made and the conduct and conclusions of the study.
      The study hypothesis is that “these studies would have multiple significant limitations that invalidate their conclusions.” This hypothesis was not tested, nor was it accepted or rejected (i.e., were the findings of placebo trials invalidated or not). Instead, the study concludes that there were methodologic limitations that “may” invalidate the conclusions. The same could be said of any published research, as no research is perfect.
      We disagree with the claims that studies performed in certain countries such as Finland and Denmark are not generalizable due to high levels of resilience in these populations. For example, the participants in these studies were not resilient enough to avoid complaining of pain and seeking treatment. We also warn against any reliance on per-protocol analyses, as they do not allow casual inference. Intention-to-treat analysis is a key part of experimental research, as it maintains the randomized treatment assignment to ensure balanced groups
      The scientific principles underlying research can be seen simply as methods of error reduction that reduce bias and improve accuracy. We expect the authors to agree that the best test of any surgical procedure is to compare it with not performing the procedure. Further, the 2 treatment groups should not be systematically different (achieved by randomization) and, preferably, the patients and outcome assessors should not know the treatment allocation (to reduce performance and detection bias). We agree that there are other methods (e.g., the method and timing of randomization, blinding the statisticians, ensuring high rates of follow-up) that would add to the reduction of error, but to “invalidate” such high-level (by the authors own ratings) research implies that we should instead rely on studies that do not include blinding, are not randomized, or do not contain a comparator. To do so is to accept inferior methods of measurement, simply because the best methods are not perfect.
      Fortunately, for the conditions most commonly studied in placebo trials of surgery, the results are entirely in keeping with the results of high-quality, non–placebo-controlled trials, particularly after taking into account the overestimation of benefit inherent in open trials with subjective outcomes.
      • Brignardello-Petersen R.
      • Siemieniuk R.
      • Guyatt G.H.
      • et al.
      Knee arthroscopy versus conservative management in patients with degenerative knee disease: A systematic review.
      • Karjalainen T.V.
      • Jain N.B.
      • Page C.M.
      • et al.
      Subacromial decompression surgery for rotator cuff disease.
      • Buchbinder R.
      • Johnston R.
      • Rischin K.J.
      • et al.
      Percutaneous vertebroplasty for osteoporotic vertebral compression fracture.
      There is also an overemphasis on a “placebo effect,” which is largely due to natural history and regression to the mean; using a placebo control is just a good way of blinding patients, and therefore reducing error.
      Rather than asking us to aim higher, we feel the message of this critique may be interpreted as asking us to aim lower.

      Supplementary Data

      References

        • Sochacki K.R.
        • Mather R.C.
        • Nwachukwu B.U.
        • et al.
        Sham surgery studies in orthopaedic surgery may just be a sham: A systematic review of randomized placebo-controlled trials.
        Arthroscopy. 2020; 36: 2750-2762
        • Brignardello-Petersen R.
        • Siemieniuk R.
        • Guyatt G.H.
        • et al.
        Knee arthroscopy versus conservative management in patients with degenerative knee disease: A systematic review.
        BMJ Open. 2017; 7e016114
        • Karjalainen T.V.
        • Jain N.B.
        • Page C.M.
        • et al.
        Subacromial decompression surgery for rotator cuff disease.
        Cochrane Database Syst Rev. 2019; 1: CD005619
        • Buchbinder R.
        • Johnston R.
        • Rischin K.J.
        • et al.
        Percutaneous vertebroplasty for osteoporotic vertebral compression fracture.
        Cochrane Database Syst Rev. 2018; 4: CD006349