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Overcoming placebo-related challenges in manual therapy trials: The ‘whats and hows’ and the ‘touch equality assumption’ proposals

Published:October 14, 2021DOI:https://doi.org/10.1016/j.ijosm.2021.10.003

      Highlights

      • PhoP/PhoQ system in C. sakazakii affected its biofilm formation.
      • Deletion of the phoPQ gene in C. sakazakii influenced flagellar assembly.
      • PhoP/PhoQ system impacted transcription of genes involved in biofilm formation.

      Abstract

      Due to the significant increase in interest in placebos, biomedical scientists have incorporated placebo innovations into a modern methodological research scenario in order to increase the quality of clinical studies. Indeed, the randomised-controlled trial design has changed dramatically, and these changes have had an impact on manual therapy research as well. The present paper outlines the main difficulties that placebo-controlled trials pose for research in manual therapy, for example, designing ineffective sham protocols, the role of touch in triggering neurobiological responses, or the unique specificity of manual therapies. The paper then offers suggestions on how to overcome such challenges, for example by providing a definition of ‘specificity’ in the context of manual therapies, and specifically osteopathy, suggesting how to design adequate sham procedures, and by introducing the so-called ‘touch equality assumption'.

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      References

        • Enck P.
        • Klosterhalfen S.
        Placebos and the placebo effect in drug trials.
        Handb Exp Pharmacol. 2019; 260: 399-431
        • Ernst E.
        Placebo: new insights into an old enigma.
        Drug Discov Today. 2007; 12: 413-418
        • Grünbaum A.
        The placebo concept in medicine and psychiatry.
        Psychol Med. 1986; 16: 19-38
        • Hernández A.
        • Baños J.-E.
        • Llop C.
        • Farré M.
        The definition of placebo in the informed consent forms of clinical trials.
        PLoS One. 2014; 9e113654
        • Howick J.
        • Friedemann C.
        • Tsakok M.
        • Watson R.
        • Tsakok T.
        • Thomas J.
        • et al.
        Are treatments more effective than placebos? A systematic review and meta-analysis.
        PLoS One. 2013; 8e62599
        • Hróbjartsson A.
        What are the main methodological problems in the estimation of placebo effects?.
        J Clin Epidemiol. 2002; 55: 430-435
        • Moerman D.E.
        • Jonas W.B.
        Deconstructing the placebo effect and finding the meaning response.
        Ann Intern Med. 2002; 136: 471
        • Macedo A.
        • Farrè M.
        • Banos J.-E.
        Placebo effect and placebos: what are we talking about? Some conceptual and historical considerations.
        Eur J Clin Pharmacol. 2003; 59: 337-342
        • Annoni M.
        Better than nothing: a historical account of placebos and placebo effects from modern to contemporary medicine. International Review of Neurobiology.
        Elsevier, 2020: 3-26
        • Benedetti F.
        Placebo effects: from the neurobiological paradigm to translational implications.
        Neuron. 2014; 84: 623-637
        • Rossettini G.
        • Testa M.
        Manual therapy RCTs: should we control placebo in placebo control?.
        Eur J Phys Rehabil Med. 2018; 54: 500-501
        • Clifford V.
        The placebo mystique: implications for clinical trial methodology: placebo use in clinical trials.
        J Paediatr Child Health. 2011; 47: 361-366
        • Kampermann L.
        • Nestoriuc Y.
        • Shedden-Mora M.C.
        Physicians' beliefs about placebo and nocebo effects in antidepressants – an online survey among German practitioners.
        PLoS One. 2017; 12e0178719
        • Leckridge R.W.
        Human effect is important.
        BMJ (Clin Res ed). 2008; 336 (1087.2)
        • Silva M.A.
        • Duarte G.S.
        • Camara R.
        • Rodrigues F.B.
        • Fernandes R.M.
        • Abreu D.
        • et al.
        Placebo and nocebo responses in restless legs syndrome: a systematic review and meta-analysis.
        Neurology. 2017; 88: 2216-2224
        • Hensel K.L.
        • Pacchia C.F.
        • Smith M.L.
        Acute improvement in hemodynamic control after osteopathic manipulative treatment in the third trimester of pregnancy.
        Compl Ther Med. 2013; 21: 618-626
        • Wynne M.M.
        • Burns J.M.
        • Eland D.C.
        • Conatser R.R.
        • Howell J.N.
        Effect of counterstrain on stretch reflexes, hoffmann reflexes, and clinical outcomes in subjects with plantar fasciitis.
        J Am Osteopath Assoc. 2006; 106: 547-556
        • Cardoso-de-Mello-E-Mello-Ribeiro A.P.
        • Rodríguez-Blanco C.
        • Riquelme-Agulló I.
        • Heredia-Rizo A.M.
        • Ricard F.
        • Oliva-Pascual-Vaca Á.
        Effects of the fourth ventricle compression in the Regulation of the autonomic Nervous system: a randomized control trial. Evidence-based complementary and alternative Medicine. vol. 2015. eCAM, 2015: 148285
        • 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. 2016; 95e4728
        • Barral P.
        • Klouche S.
        • Barral N.
        • Lemoulec Y.-P.
        • Thés A.
        • Bauer T.
        Preoperative osteopathic manipulative therapy improves postoperative pain and reduces opioid consumption after total knee arthroplasty: a prospective comparative study.
        J Am Osteopath Assoc. 2020; 120: 436
        • Henley C.
        • Wilson T.
        Use of beat-to-beat cardiovascular variability data to determine the validity of sham therapy as the placebo control in osteopathic manipulative medicine research.
        J Am Osteopath Assoc. 2014; 114: 860-866
        • Lougee H.
        • Johnston R.G.
        • Thomson O.P.
        The suitability of sham treatments for use as placebo controls in trials of spinal manipulative therapy: a pilot study.
        J Bodyw Mov Ther. 2013; 17: 59-68
        • Hawk C.
        • Long C.R.
        • Rowell R.M.
        • Gudavalli M.R.
        • Jedlicka J.
        A randomized trial investigating a chiropractic manual placebo: a novel design using standardized forces in the delivery of active and control treatments.
        J Alternative Compl Med. 2005; 11: 109-117
        • Manzotti A.
        • Viganoni C.
        • Lauritano D.
        • Bernasconi S.
        • Paparo A.
        • Risso R.
        • et al.
        Evaluation of the stomatognathic system before and after osteopathic manipulative treatment in 120 healthy people by using surface electromyography.
        Int J Environ Res Publ Health. 2020; 17
        • Hancock M.J.
        • Maher C.G.
        • Latimer J.
        • McAuley J.H.
        Selecting an appropriate placebo for a trial of spinal manipulative therapy.
        Aust J Physiother. 2006; 52: 135-138
        • Vernon H.
        • MacAdam K.
        • Marshall V.
        • Pion M.
        • Sadowska M.
        Validation of a sham manipulative procedure for the cervical spine for use in clinical trials.
        J Manipulat Physiol Therapeut. 2005; 28: 662-666
        • Vernon H.T.
        • Triano J.J.
        • Ross J.K.
        • Tran S.K.
        • Soave D.M.
        • Dinulos M.D.
        Validation of a novel sham cervical manipulation procedure.
        Spine J. 2012; 12: 1021-1028
        • Jamison J.R.
        Nonspecific intervention in chiropractic care.
        J Manipulat Physiol Therapeut. 1998; 21: 423-425
        • Licciardone J.C.
        • Buchanan S.
        • Hensel K.L.
        • King H.H.
        • Fulda K.G.
        • Stoll S.T.
        Osteopathic manipulative treatment of back pain and related symptoms during pregnancy: a randomized controlled trial.
        Am J Obstet Gynecol. 2010; 202 (43): e1-e8
        • Hawk C.
        • Long C.R.
        • Reiter R.
        • Davis C.S.
        • Cambron J.A.
        • Evans R.
        Issues in planning a placebo-controlled trial of manual methods: results of a pilot study.
        J Alternative Compl Med. 2002; 8: 21-32
        • Benedetti F.
        Nascita e sviluppo della medicina scientifica. Il cervello del paziente Le neuroscienze della relazione medico-paziente.
        Giovanni Fioriti Editore, 2012: 36
        • Licciardone J.C.
        • Russo D.P.
        Blinding protocols, treatment credibility, and expectancy: methodologic issues in clinical trials of osteopathic manipulative treatment.
        J Am Osteopath Assoc. 2006; 106: 457-463
        • Abrosimoff M.
        • Rajendran D.
        ‘Tell me your story’ - how osteopaths apply the BPS model when managing low back pain - a qualitative study.
        Int J Osteopath Med. 2020; 35: 13-21
        • Zegarra-Parodi R.
        • Draper-Rodi J.
        • Cerritelli F.
        Refining the biopsychosocial model for musculoskeletal practice by introducing religion and spirituality dimensions into the clinical scenario.
        Int J Osteopath Med. 2019; 32: 44-48
        • Bialosky J.E.
        • Bishop M.D.
        • Penza C.W.
        Placebo mechanisms of manual therapy: a sheep in Wolf's clothing?.
        J Orthop Sports Phys Ther. 2017; 47: 301-304
        • Baroni F.
        • Ruffini N.
        • D'Alessandro G.
        • Consorti G.
        • Lunghi C.
        The role of touch in osteopathic practice: a narrative review and integrative hypothesis.
        Compl Ther Clin Pract. 2021; 42: 101277
        • Benedetti F.
        Placebo and the new physiology of the doctor-patient relationship.
        Physiol Rev. 2013; 93: 1207-1246
        • Frisaldi E.
        • Piedimonte A.
        • Benedetti F.
        Placebo and nocebo effects: a complex interplay between psychological factors and neurochemical networks.
        Am J Clin Hypn. 2015; 57: 267-284
        • Testa M.
        • Rossettini G.
        Enhance placebo, avoid nocebo: how contextual factors affect physiotherapy outcomes.
        Man Ther. 2016; 24: 65-74
        • Abenavoli A.
        • Badi F.
        • Barbieri M.
        • Bianchi M.
        • Biglione G.
        • Dealessi C.
        • et al.
        Cranial osteopathic treatment and stress-related effects on autonomic nervous system measured by salivary markers: a pilot study.
        J Bodyw Mov Ther. 2020; 24 (Epub 2020/11/22): 215-221
        • Cerritelli F.
        • Chiacchiaretta P.
        • Gambi F.
        • Saggini R.
        • Perrucci M.G.
        • Ferretti A.
        Osteopathy modulates brain-heart interaction in chronic pain patients: an ASL study.
        Sci Rep. 2021; 11 (Epub 2021/02/27): 4556
        • Annoni M.
        • Boniolo G.
        Learning by difference: placebo effects and specific efficacy in pharmacological RCTs.
        in: LaCaze A. Osimani B. Uncertainty in pharmacology: Epistemology, methods, and decisions. Springer International Publishing, Cham2020: 211-230
        • Rief W.
        • Bingel U.
        • Schedlowski M.
        • Enck P.
        Mechanisms involved in placebo and nocebo responses and implications for drug trials.
        Clin Pharmacol Ther. 2011; 90: 722-726
        • Feldman R.
        • Singer M.
        • Zagoory O.
        Touch attenuates infants' physiological reactivity to stress.
        Dev Sci. 2010; 13: 271-278
        • Gentsch A.
        • Panagiotopoulou E.
        • Fotopoulou A.
        Active interpersonal touch gives rise to the social softness illusion.
        Curr Biol. 2015; 25: 2392-2397
        • Korosi A.
        • Baram T.Z.
        Plasticity of the stress response early in life: mechanisms and significance.
        Dev Psychobiol. 2010; 52: 661-670
        • Mancini F.
        • Beaumont A.-L.
        • Hu L.
        • Haggard P.
        • Iannetti G.D.D.
        Touch inhibits subcortical and cortical nociceptive responses.
        Pain. 2015; 156: 1936-1944
        • Paloyelis Y.
        • Krahé C.
        • Maltezos S.
        • Williams S.C.
        • Howard M.A.
        • Fotopoulou A.
        The analgesic effect of oxytocin in humans: a double‐blind, placebo‐controlled cross‐over study using laser‐evoked potentials.
        J Neuroendocrinol. 2016; 28
        • Uvnäs-Moberg K.
        • Handlin L.
        • Petersson M.
        Self-soothing behaviors with particular reference to oxytocin release induced by non-noxious sensory stimulation.
        Front Psychol. 2015; 5
        • Chaibi A.
        • Šaltytė Benth J.
        • Bjørn Russell M.
        Validation of placebo in a manual therapy randomized controlled trial.
        Sci Rep. 2015; 511774
        • McGlone F.
        • Wessberg J.
        • Olausson H.
        Discriminative and affective touch: sensing and feeling.
        Neuron. 2014; 82: 737-755
        • D'Alessandro G.
        • Cerritelli F.
        • Cortelli P.
        Sensitization and interoception as key neurological concepts in osteopathy and other manual medicines.
        Front Neurosci. 2016; 10: 100
        • Cerritelli F.
        • Ginevri L.
        • Messi G.
        • Caprari E.
        • Di Vincenzo M.
        • Renzetti C.
        • et al.
        Clinical effectiveness of osteopathic treatment in chronic migraine: 3-Armed randomized controlled trial.
        Compl Ther Med. 2015; 23: 149-156
        • Hawk C.
        • Azad A.
        • Phongphua C.
        • Long C.R.
        Preliminary study of the effects of a placebo chiropractic treatment with sham adjustments.
        J Manipulat Physiol Therapeut. 1999; 22: 436-443
        • Antolinos-Campillo P.J.
        • Oliva-Pascual-Vaca A.
        • Rodríguez-Blanco C.
        • Heredia-Rizo A.M.
        • Espí-López G.V.
        • Ricard F.
        Short-term changes in median nerve neural tension after a suboccipital muscle inhibition technique in subjects with cervical whiplash: a randomised controlled trial.
        Physiotherapy. 2014; 100: 249-255
        • Hubert D.
        • Soubeiran L.
        • Gourmelon F.
        • Grenet D.
        • Serreau R.
        • Perrodeau E.
        • et al.
        Impact of osteopathic treatment on pain in adult patients with cystic fibrosis--a pilot randomized controlled study.
        PLoS One. 2014; 9: e102465-e
        • Florance B.M.
        • Frin G.
        • Dainese R.
        • Nébot-Vivinus M.H.
        • Marine Barjoan E.
        • Marjoux S.
        • et al.
        Osteopathy improves the severity of irritable bowel syndrome: a pilot randomized sham-controlled study.
        Eur J Gastroenterol Hepatol. 2012; 24 (Epub 2012/05/02): 944-949
        • Rolle G.
        • Tremolizzo L.
        • Somalvico F.
        • Ferrarese C.
        • Bressan L.C.
        Pilot trial of osteopathic manipulative therapy for patients with frequent episodic tension-type headache.
        J Am Osteopath Assoc. 2014; 114: 678-685
        • Giles P.D.
        • Hensel K.L.
        • Pacchia C.F.
        • Smith M.L.
        Suboccipital decompression enhances heart rate variability indices of cardiac control in healthy subjects.
        J Alternative Compl Med. 2013; 19 (Epub 2012/09/22): 92-96
        • Ponzo V.
        • Cinnera A.M.
        • Mommo F.
        • Caltagirone C.
        • Koch G.
        • Tramontano M.
        Osteopathic manipulative therapy potentiates motor cortical plasticity.
        J Am Osteopath Assoc. 2018; 118: 396-402
        • Ruffini N.
        • D'Alessandro G.
        • Mariani N.
        • Pollastrelli A.
        • Cardinali L.
        • Cerritelli F.
        Variations of high frequency parameter of heart rate variability following osteopathic manipulative treatment in healthy subjects compared to control group and sham therapy: randomized controlled trial.
        Front Neurosci. 2015; 9: 272
        • Castro-Sánchez A.M.
        • Matarán-Peñarrocha G.A.
        • Sánchez-Labraca N.
        • Quesada-Rubio J.M.
        • Granero-Molina J.
        • Moreno-Lorenzo C.
        A randomized controlled trial investigating the effects of craniosacral therapy on pain and heart rate variability in fibromyalgia patients.
        Clin Rehabil. 2011; 25: 25-35
        • Haller H.
        • Lauche R.
        • Cramer H.
        • Rampp T.
        • Saha F.J.
        • Ostermann T.
        • et al.
        Craniosacral therapy for the treatment of chronic neck pain: a randomized sham-controlled trial.
        Clin J Pain. 2016; 32: 441-449
        • Başoğlu M.
        • Marks I.
        • Livanou M.
        • Swinson R.
        Double-blindness procedures, rater blindness, and ratings of outcome. Observations from a controlled trial.
        Arch Gen Psychiatr. 1997; 54: 744-748
        • Koes B.W.
        How to evaluate manual therapy: value and pitfalls of randomized clinical trials.
        Man Ther. 2004; 9: 183-184
        • Tramontano M.
        • Cerritelli F.
        • Piras F.
        • Spanò B.
        • Tamburella F.
        • Piras F.
        • et al.
        Brain connectivity changes after osteopathic manipulative treatment: a randomized manual placebo-controlled trial.
        Brain Sci. 2020; 10: 969
        • Howick J.
        • Webster R.K.
        • Rees J.L.
        • Turner R.
        • Macdonald H.
        • Price A.
        • et al.
        TIDieR-Placebo: a guide and checklist for reporting placebo and sham controls.
        PLoS Med. 2020; 17e1003294