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A meta-analysis of the association between adherence to drug therapy and mortality

BMJ 2006; 333 doi: (Published 29 June 2006) Cite this as: BMJ 2006;333:15
  1. Scot H Simpson, assistant professor (ssimpson{at},
  2. Dean T Eurich, research associate2,
  3. Sumit R Majumdar, associate professor3,
  4. Rajdeep S Padwal, assistant professor3,
  5. Ross T Tsuyuki, professor4,
  6. Janice Varney, librarian2,
  7. Jeffrey A Johnson, professor5
  1. 1 Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada T6G 2N8,
  2. 2 Institute of Health Economics, Edmonton, AB,
  3. 3 Division of Internal Medicine, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta,
  4. 4 Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta,
  5. 5 Department of Public Health Sciences, Faculty of Medicine and Dentistry, University of Alberta
  1. Correspondence to: S H Simpson
  • Accepted 21 April 2006


Objective To evaluate the relation between adherence to drug therapy, including placebo, and mortality.

Design Meta-analysis of observational studies.

Data sources Electronic databases, contact with investigators, and textbooks and reviews on adherence.

Review methods Predefined criteria were used to select studies reporting mortality among participants with good and poor adherence to drug therapy. Data were extracted for disease, drug therapy groups, methods for measurement of adherence rate, definition for good adherence, and mortality.

Results Data were available from 21 studies (46 847 participants), including eight studies with placebo arms (19 633 participants). Compared with poor adherence, good adherence was associated with lower mortality (odds ratio 0.56, 95% confidence interval 0.50 to 0.63). Good adherence to placebo was associated with lower mortality (0.56, 0.43 to 0.74), as was good adherence to beneficial drug therapy (0.55, 0.49 to 0.62). Good adherence to harmful drug therapy was associated with increased mortality (2.90, 1.04 to 8.11).

Conclusion Good adherence to drug therapy is associated with positive health outcomes. Moreover, the observed association between good adherence to placebo and mortality supports the existence of the “healthy adherer” effect, whereby adherence to drug therapy may be a surrogate marker for overall healthy behaviour.


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  • We thank the individual trialists for providing information from their study databases and Maria Santana, who translated three Spanish papers. Contributors: SHS had the idea for the article. All authors took part in the planning and design of the study. SHS, DTE, RSP, and JV did the data collection. MS (listed in the acknowledgements) assisted in data collection from articles printed in Spanish. SHS carried out the statistical analyses. SHS,DTE, SRM, RSP, RTT, and JAJ had access to the data and participated in the interpretation of the data. SHS wrote the first draft of the paper. SHS provided leadership for the study and is guarantor.

  • Funding None.

  • Competing interests None declared.

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