Overview

         In this blog, I hope to show that there is no proper way to perform a sham orthopaedic manual therapy (OMT) study in a way that unambiguously allows a comparison between an intervention and therapeutic intent. The idea is good. The execution is likely not possible.

 

A Placebo Trial

It has been said that the “gold standard” for testing the clinical effectiveness in treatment interventions is the “randomized, placebo-controlled” clinical trial [1]. In a placebo-controlled trial design, patients are randomly assigned to receive an active treatment intervention or a control intervention that consists of a placebo-based intervention. A placebo is ‘an inert substance or sham procedure’ provided to patients to make it impossible for them and the clinicians applying the treatment to know who is receiving an active or inactive intervention’ [2]. A placebo-controlled trial is most commonly used during the testing of pharmaceuticals, where the application of a placebo-based pill or injection is easier to manage.

Critical Aspects of a Placebo

In a placebo-controlled randomized trial, the placebo-based intervention should ideally be “bespoke” – tailored to mimic all aspects of a specific intervention, including dosage, expectations, taste (if a pill is used), touch, appearance, and method of administration [3]. The only element missing should be the actionable element that results in the specific effect of the placebo-based intervention. For example, suppose the placebo-based intervention was based on testing a pill that was designed to reduce pain and inflammation. In that case, all aspects of the administration of that pill should be similar to the real pill, except the chemicals and agents in the pill that reduce pain and inflammation. Further, to identify a true placebo response, the approach requires the clinician to be blinded to the intervention provided.

When a true placebo-based approach can’t be used, a sham technique is adopted in its place. In general, the term “placebo” is used in pharmacological studies, whereas “sham treatment” is used for non-pharmacological studies, including those looking at devices and psychological and physical treatments [4].  According to the National Cancer Institute, a sham treatment is an inactive procedure designed to mimic the active procedure being studied in a clinical trial as closely as possible. For example, in sham acupuncture, needles that look and feel similar to the needles used in active acupuncture therapy are used except the needles are not actually inserted into the skin. The placebo effect associated with sham procedures can often be substantial and has been well documented in the scientific literature [5].  Although useful in theory, using a sham manual therapy approach is unlikely to determine whether the treatment has a specific or non-specific effect.

Sham Doesn’t Work for Manual Therapy Interventions

Rarely are manual therapy interventions performed in a single way that is transferable from patient to patient. Most manual therapy interventions involve more than one application during a session and require adjustment based on the feedback from the patient. Most manual therapy interventions are performed over several treatment sessions (not one). They are combined with in-clinic exercise and a home exercise program that is assigned to augment the treatment. This is commonly called a “multi-modal” approach. A clinician cannot be blinded to the sham or manual therapy approach can also alter overall outcomes. Studies have shown that the clinician’s preferences of a treatment approach can influence outcomes [6,7], which could bias a study’s results.  Lastly, patients typically also know they are not receiving the active treatment (it’s difficult to fake a massage or a spine manipulation). Because of this, we lose the ability to test the contextual aspects of a manual therapy treatment.

Not Useful So Far

The use of a sham approach for manual therapy has led to questionable results [8]. In a systematic review by  Lavazzo and colleagues [2], the authors attempted to summarize the results of sham versus manual therapy outcomes. Firstly, the authors included very questionable approaches some of which include Reflexology, Kinesiology, BLR technique, Cranio-sacral therapy, Strain-counterstrain, the Hakata approach to the sacroiliac joint. I would argue that these are not evidence-based manual therapy interventions. When we repeated the meta-analyses with removing these studies, it notably influenced the overall findings. Secondly, the authors included studies in which the treatment was applied only once during one session, which is atypical for manual therapy-related management. It is unlikely this process has any therapeutic fidelity. Thirdly, the long term could not be performed due to substantial levels of heterogeneity found using a random-effects model. Additionally, the study quality was very poor, with a certainty of evidence score (GRADE) of Low (for adverse events) and Very Low (for pain). This means the confidence in the findings is poor. Lastly, nearly all patients in the studies knew they were not receiving a manual therapy procedure and were receiving the sham. 63.5% to 83.5% in spine manipulation studies correctly identified their treatment allocation. Although there is evidence in some studies that knowing one’s group allocation has been less influential in past studies [9], it can undoubtedly influence outcomes and must be considered.

What is the Take Home Message?

I think suggesting there is no clinical differences between manual therapy procedures and sham manual therapy approaches is too ambitious and undoubtedly premature. It’s a good idea, but we aren’t there yet.

Chad E Cook PT, PhD, FAPTA

Twitter @chadcookpt

Professor, Department of Orthopaedics, Duke University, Durham, NC. 27516

Competing interests: A portion of Dr. Cook’s salary is funded by the NIH/VA/DoD and the Center of Excellence in Manual and Manipulative Therapy at Duke University.

Author bio(s): Chad Cook is a professor at Duke University, clinical researcher, physical therapist, and professional advocate with a long-term history of clinical care excellence and service. His passions include refining and improving the patient examination process and validating day-to-day physical therapist practice tools. Dr. Cook is a multi-award winner in teaching, research, and service and is a Catherine Worthingham Fellow of the American Physical Therapy Association.

Bibliography

  1. Hariton E, Locascio JJ. Randomised controlled trials – the gold standard for effectiveness research: Study design: randomised controlled trials. BJOG. 2018;125(13):1716. doi:10.1111/1471-0528.15199
  2. Lavazza C, Galli M, Abenavoli A, Maggiani A. Sham treatment effects in manual therapy trials on back pain patients: a systematic review and pairwise meta-analysis. BMJ Open. 2021 May 4;11(5):e045106. doi: 10.1136/bmjopen-2020-045106. PMID: 33947735; PMCID: PMC8098952.
  3. Locher C, Gaab J, Blease C. When a Placebo Is Not a Placebo: Problems and Solutions to the Gold Standard in Psychotherapy Research. Front Psychol. 2018 Nov 26;9:2317. doi: 10.3389/fpsyg.2018.02317. PMID: 30542310; PMCID: PMC6277873.
  4. Sedgwick P, Hooper C. Placebos and sham treatments. BMJ. 2015 Jul 10;351:h3755. doi: 10.1136/bmj.h3755. PMID: 26162858.
  5. Brim RL, Miller FG. The potential benefit of the placebo effect in sham-controlled trials: implications for risk-benefit assessments and informed consent. J Med Ethics. 2013 Nov;39(11):703-7. doi: 10.1136/medethics-2012-101045. Epub 2012 Dec 13. PMID: 23239742; PMCID: PMC3812890.
  6. Cook C, Learman K, Showalter C, Kabbaz V, O’Halloran B. Early use of thrust manipulation versus non-thrust manipulation: a randomized clinical trial. Man Ther. 2013 Jun;18(3):191-8. doi: 10.1016/j.math.2012.08.005. Epub 2012 Oct 2. PMID: 23040656.
  7. Bishop MD, Bialosky JE, Penza CW, Beneciuk JM, Alappattu MJ. The influence of clinical equipoise and patient preferences on outcomes of conservative manual interventions for spinal pain: an experimental study. J Pain Res. 2017 Apr 26;10:965-972. doi: 10.2147/JPR.S130931. PMID: 28490899; PMCID: PMC5414630.
  8. Cerritelli F, Verzella M, Cicchitti L, D’Alessandro G, Vanacore N. The paradox of sham therapy and placebo effect in osteopathy: A systematic review. Medicine (Baltimore). 2016;95(35):e4728. doi:10.1097/MD.0000000000004728
  9. Harvard Health Blog. A placebo can work even when you know it’s a placebo. Available at: https://www.health.harvard.edu/blog/placebo-can-work-even-know-placebo-201607079926