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Proportion attributable to contextual effects in general medicine: a meta-epidemiological study based on Cochrane reviews
  1. Yusuke Tsutsumi1,2,
  2. Yasushi Tsujimoto3,4,
  3. Aran Tajika5,
  4. Kenji Omae3,6,
  5. Tomoko Fujii7,8,
  6. Akira Onishi9,
  7. Yuki Kataoka3,10,
  8. Morihiro Katsura11,
  9. Hisashi Noma12,
  10. Ethan Sahker7,13,
  11. Edoardo Giuseppe Ostinelli14,
  12. Toshi A Furukawa7
  1. 1Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan
  2. 2Department of Emergency Medicine, National Hospital Organization Mito Medical Center, Ibaraki, Japan
  3. 3Department of Healthcare Epidemiology, Kyoto University Graduate School of Medicine/ School of Public Health, Kyoto, Japan
  4. 4Department of Nephrology and Dialysis, Kyoritsu Hospital, Kawanishi, Japan
  5. 5Department of Psychiatry, Kyoto University Hospital, Kyoto, Japan
  6. 6Department of Innovative Research and Education for Clinicians and Trainees (DiRECT), Fukushima Medical University Hospital, Fukushima, Japan
  7. 7Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine / School of Public Health, Kyoto, Japan
  8. 8Intensive Care Unit, Jikei University Hospital, Tokyo, Japan
  9. 9Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Hyogo, Japan
  10. 10Hospital Care Research Unit/ Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, Hyogo, Japan
  11. 11Department of Surgery, Okinawa Chubu Hospital, Okinawa, Japan
  12. 12Department of Data Science, The Institute of Statistical Mathematics, Tokyo, Japan
  13. 13Population Health and Policy Research Unit, Medical Education Center, Kyoto University Graduate School of Medicine, Kyoto, Japan
  14. 14Oxford Health NHS Foundation Trust, Warneford Hospital /Department of Psychiatry, University of Oxford, Oxford, UK
  1. Correspondence to Dr Yusuke Tsutsumi, Kyoto University, Kyoto, Japan; tsutsumi.yusuke.84x{at}


Objectives Our objectives were to examine the magnitude of the proportion attributable to contextual effects (PCE), which shows what proportion of the treatment arm response can be achieved by the placebo arm across various interventions, and to examine PCE variability by outcome type and condition.

Design We conducted a meta-epidemiological study.

Setting We searched the Cochrane Database of Systematic Reviews with the keyword ‘placebo’ in titles, abstracts and keywords on 1 January 2020.

Participants We included reviews that showed statistically significant beneficial effects of the intervention over placebo for the first primary outcome.

Main outcome measures We performed a random-effects meta-analysis to calculate PCEs based on the pooled result of each included review, grouped by outcome type and condition. The PCE quantifies how much of the observed treatment response can be achieved by the contextual effects.

Public and patient involvement statement No patient or member of the public was involved in conducting this research.

Results We included 328 out of 3175 Cochrane systematic reviews. The results of meta-analyses showed that PCEs varied greatly depending on outcome type (I2=98%) or condition (I2=98%), but mostly lie between 0.40 and 0.95. Overall, the PCEs were 0.65 (95% CI 0.59 to 0.72) on average. Subjective outcomes were 0.50 (95% CI 0.41 to 0.59), which was significantly smaller than those of semiobjective (PCE 0.78; 95% CI 0.72 to 0.85) or objective outcomes (PCE 0.94; 95% CI 0.91 to 0.97).

Conclusions The results suggest that much of the observed benefit is not just due to the specific effect of the interventions. The specific effects of interventions may be larger for subjective outcomes than for objective or semiobjective outcomes. However, PCEs were exceptionally variable. When we evaluate the magnitude of PCEs, we should consider each PCE individually, for each condition, intervention and outcome in its context, to assess the importance of an intervention for each specific clinical setting.

  • methods
  • placebos

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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  • Contributors YTsut, YTsuj, AT and TAF developed the conception and design of the research. YTsut and TAF are fully responsible for writing the protocol. YTsut, YTsuj, AT, KO, TF, AO, YK, MK, ES, EGO extracted the data. YTsut analysed the data. HN supervised the statistical analyses. TAF supervised the research. All authors contributed to draft the manuscript and gave final approval of the manuscript before submission. TAF is the guarantor of the study.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.