Managing the Placebo Effect: Enhancing the Signal-to-Noise Ratio
- 107 Downloads
Confirming the absence of the placebo response has been the bane of researchers throughout the ages. Thus, the gold standard of research methodology is the evidence for a treatment modality provided by a prospective randomized controlled trial. The “control” arm of a trial is the arm in which the placebo has been administered. Increasing evidence from basic science and clinical research is pointing to the fact that the placebo response may have some biological basis that can translate into enduring therapeutic benefit. Have our placebo-controlled trials simply compared one treatment effect to the treatment effect of the “placebo”? Thus, the “δ” is relative treatment effect; perhaps this may provide some insight as to why some treatment response is low compared to a relatively strong placebo response. How can we use this knowledge to create more robust clinical designs that help establish true treatment effect? This article aims to provide an overview of the contemporary insight into the placebo response.
KeywordsPlacebo effect Treatment signal Treatment noise
No potential conflicts of interest relevant to this article were reported.
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
- 1.Beecher HK: The powerful placebo. J Am MedAssoc. 1955;159:1602–1606.Google Scholar
- 3.Haygarth J: Of the Imagination, as a Cause and as a Cure of Disorders of the Body; Exemplfied by Fictitious Tractors, and Epidemical Convulsions. Bath:Crutwell, 1801]Google Scholar
- 6.Ambersom JB, McMahon BT, Pinner MA: A clinical trial of sanocrysin in pulmonary tuberculosis. Am Rev Tuberculosis 1931; 24: 401–35Google Scholar
- 7.Diehl HS, Baker AB, Cowan DW: Cold vaccines: an evaluation based on a controlled study. JAMA 1938; 111: 1168–73Google Scholar
- 9.Kefauver-Harris: Kefauver-Harris Amendments of October 10, 1962 to Food and Drug and Cosmetic Act. Code Federal Regulation. Code Federal Regulation 1962; 1Google Scholar
- 10.Federal Register: Federal Register. Federal Register 1970; 35: 7250Google Scholar
- 13.•• Benedetti F: Mechanisms of Placebo and Placebo-Related Effects Across Diseases and Treatments. Annual Review of Pharmacology and Toxicology 2008; 48: 33–60. This is an outstanding review of the scientific basis of the placebo and placebo-related effects in all organ system, clearly set out, with diagrams and tables that enhance the key point. PubMedCrossRefGoogle Scholar
- 18.•• Doherty M, Dieppe P: The “placebo” response in osteoarthritis and its implications for clinical practice. Osteoarthritis and Cartilage 2009; 17: 1255–62. This excellent review of the basis of the placebo response provides important historical perspective, and more importantly, the clinical relevance of the placebo response. PubMedCrossRefGoogle Scholar
- 19.Jurko S, Rozinaj G. High Resolution of the ECG Signal by Polynomial Approximation. Radioengineering 2006; 15(1):32–37Google Scholar
- 22.Chen ALC, Chen TJH, Waite RL, Reinking J, Tung HL, Rhoades P, Downs BW, Braverman E, Braverman D, Kerner M, Blum SH, DiNubile N, Smith D, Oscar-Berman M, Prihoda TJ, Floyd JB, O’Brien D, Liu HH, Blum K: Hypothesizing that brain reward circuitry genes are genetic antecedents of pain sensitivity and critical diagnostic and pharmacogenomic treatment targets for chronic pain conditions. Medical Hypotheses 2009; 72: 14–22PubMedCrossRefGoogle Scholar