- Ted J Kaptchuk, associate professor of medicine1,
- John M Kelley, assistant professor of psychology and statistics2,
- Lisa A Conboy, instructor of medicine1,
- Roger B Davis, associate professor of medicine and biostatistics3,
- Catherine E Kerr, instructor of medicine1,
- Eric E Jacobson, lecturer4,
- Irving Kirsch, professor of psychology5,
- Rosa N Schyner, research associate1,
- Bong Hyun Nam, research fellow1,
- Long T Nguyen, research fellow1,
- Min Park, research coordinator1,
- Andrea L Rivers, research coordinator1,
- Claire McManus, research coordinator1,
- Efi Kokkotou, assistant professor of medicine3,
- Douglas A Drossman, professor of medicine6,
- Peter Goldman, professor emeritus 7,
- Anthony J Lembo, assistant professor of medicine3
- 1Osher Research Center, Harvard Medical School, 401 Park Drive, Boston, MA 02215, USA
- 2Endicott College, 376 Hale Street, Beverly, MA 01915, USA
- 3Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
- 4Department of Social Medicine, Harvard Medical School, 641 Huntington Avenue, Boston, MA 02215, USA
- 5Department of Psychology, University of Hull, Hull HU6 7RX
- 6Center for Functional GI and Motility Disorders, University of North Carolina School of Medicine, Chapel Hill, NC 27699, USA
- 7Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA
- Correspondence to: T J Kaptchuk
- Accepted 2 March 2008
Objective To investigate whether placebo effects can experimentally be separated into the response to three components—assessment and observation, a therapeutic ritual (placebo treatment), and a supportive patient-practitioner relationship—and then progressively combined to produce incremental clinical improvement in patients with irritable bowel syndrome. To assess the relative magnitude of these components.
Design A six week single blind three arm randomised controlled trial.
Setting Academic medical centre.
Participants 262 adults (76% women), mean (SD) age 39 (14), diagnosed by Rome II criteria for and with a score of ≥150 on the symptom severity scale.
Interventions For three weeks either waiting list (observation), placebo acupuncture alone (“limited”), or placebo acupuncture with a patient-practitioner relationship augmented by warmth, attention, and confidence (“augmented”). At three weeks, half of the patients were randomly assigned to continue in their originally assigned group for an additional three weeks.
Main outcome measures Global improvement scale (range 1-7), adequate relief of symptoms, symptom severity score, and quality of life.
Results At three weeks, scores on the global improvement scale were 3.8 (SD 1.0) v 4.3 (SD 1.4) v 5.0 (SD 1.3) for waiting list versus “limited” versus “augmented,” respectively (P<0.001 for trend). The proportion of patients reporting adequate relief showed a similar pattern: 28% on waiting list, 44% in limited group, and 62% in augmented group (P<0.001 for trend). The same trend in response existed in symptom severity score (30 (63) v 42 (67) v 82 (89), P<0.001) and quality of life (3.6 (8.1) v 4.1 (9.4) v 9.3 (14.0), P<0.001). All pairwise comparisons between augmented and limited patient-practitioner relationship were significant: global improvement scale (P<0.001), adequate relief of symptoms (P<0.001), symptom severity score (P=0.007), quality of life (P=0.01).Results were similar at six week follow-up.
Conclusion Factors contributing to the placebo effect can be progressively combined in a manner resembling a graded dose escalation of component parts. Non-specific effects can produce statistically and clinically significant outcomes and the patient-practitioner relationship is the most robust component.
Trial registration Clinical Trials NCT00065403.
We thank Franklin Miller, Kate Stoney, and Jongbae Park for scientific mentorship; Mary Quilty, Oriana Rodrigues, Gabriel Kaptchuk, Elizabeth Morey, and Patricia Wilkinson for research assistance; and the research nurses at the BIDMC, under the direction of Mary Williams and Jamie Vickers, and acupuncturists Stephanie Prady, Bella Rosner, and Lisa Desrosiers for all their hard work. We also thank J Thomas LaMont for his thoughtful review of the manuscript and the university seminar on effective and affordable health care at Harvard University for input on study design and analysis.
Contributors: TJK is guarantor and led the conception, design, and analysis of the study. AJL, LAC, JMK, PG, RBD, CEK, EEJ, IK, RNS, DAD, and EK contributed to conception, design, and analysis. BHN, MP, ALR, CMcM contributed to design and implementation. JMK, RBD, LAC, BHN, and LTN performed statistical analyses.
Funding: NIH grant No 1R01 AT001414-01 from the National Center for Complementary and Alternative Medicine (NCCAM) and the National Institutes of Digestive, Diabetes and Kidney Disease (NIDDK), grant No 1R21 AT002860-01 from NCCAM and the Office of Behavioral and Social Science Research (OBSSR), and grant No 1 R21 AT002564 and 1K24 AT004095 from NCCAM. This research was also supported in part by grant RR 01032 to the Beth Israel Deaconess Medical Center (BIDMC) General Clinical Research Center from the NIH.
Ethical approval: Institutional review boards at the Beth Israel Deaconess Medical Center and Harvard Medical School.
Competing interests: TJK is a consultant for Kan Herbal Company, Scotts Valley, CA. AL has served on the scientific advisory boards and served as a consultant for Novartis, Takeda, Sucampo, Schwarz, Salix, Microbia, and GSK. PG is a consultant for Tsumura.
Provenance and peer review: Not commissioned; externally peer reviewed.
- Accepted 2 March 2008