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A meta-analysis of the association between adherence to drug therapy and mortality
Open accessAbstract
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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“In addition, as adherence with placebo also improves survival, 524 physicians should be aware that adherence to medication may reflect generally better health behaviour.”
From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [524]
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ResultAntipsychotic treatment and mortality in schizophrenia.
Torniainen, M., Mittendorfer-Rutz, E., Tanskanen, A., Bjorkenstam, C., Suvisaari, J., Alexanderson, K., & Tiihonen, J. (2015) · Schizophrenia Bulletin · doi:10.1093/schbul/sbu164 · Cited by 208
Foley, L., Larkin, J., Lombard-Vance, R., Murphy, A. W., Hynes, L., Galvin, E., & Molloy, G. J. (2021) · BMJ Open · doi:10.1136/bmjopen-2020-044987 · Cited by 251
General health checks in adults for reducing morbidity and mortality from disease
Krogsbøll, L. T., Jørgensen, K. J., & Gøtzsche, P. C. (2019) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009009.pub3 · Cited by 217
Reminder packaging for improving adherence to self-administered long-term medications
Mahtani, K. R., Heneghan, C. J., Glasziou, P., & Perera, R. (2011) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd005025.pub3 · Cited by 208
Development of an illustrated medication schedule as a low-literacy patient education tool
Kripalani, S. B., Robertson, R., Love-Ghaffari, M. H., Henderson, L. E., Praska, J. L., Strawder, A., Katz, M. G., & Jacobson, T. A. (2007) · Patient Education and Counseling · doi:10.1016/j.pec.2007.01.020 · Cited by 199
“Nonadherence has also been linked to significantly higher health care costs, hospitalization, and patient mortality [7,8].”
BackgroundSussman, J. B., & Hayward, R. A. (2010) · BMJ · doi:10.1136/bmj.c2073 · Cited by 176
“In as treated analyses, participants are analysed entirely on the basis of treatment received (that is, according to their behaviour, not their random assignment). In per protocol analyses, participants who fail to follow the protocol are simply dropped from the study (that is, included or excluded according to their…”
The Association Between Statins and Cancer Incidence in a Veterans Population
Farwell, W. R., Scranton, R. E., Lawler, E. V., Lew, R., Brophy, M. T., Fiore, L. D., & Gaziano, J. M. (2008) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djm286 · Cited by 201
Adherence influencing factors – a systematic review of systematic reviews
Mathes, T., Jaschinski, T., & Pieper, D. (2014) · Archives of Public Health · doi:10.1186/2049-3258-72-37 · Cited by 183
“Adherence is not only a crucial point for the success, but also for the safe and effective use of many therapies [4-6].”
BackgroundGislason, G., Rasmussen, J. N., Abildstrom, S. Z., Schramm, T. K., Hansen, M. L., Buch, P., Sørensen, R., Folke, F., Gadsbøll, N., Rasmussen, S., et al. (2007) · Circulation · doi:10.1161/circulationaha.106.669101 · Cited by 182
Bissonnette, J. M. (2008) · Journal of Advanced Nursing · doi:10.1111/j.1365-2648.2008.04745.x · Cited by 172
“Patient-related consequences include improved morbidity and reduced mortality, conflict resolution, attributional uncertainty, empowerment and possible improvements in quality of life (Buchmann 1997, Wilson et al. 2002, Simpson et al. 2006).”
BackgroundInfluentialVerbrugghe, M., Verhaeghe, S., Lauwaert, K., Beeckman, D., & Van Hecke, A. (2013) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2012.12.014 · Cited by 202
Elliott, R. A., Barber, N., Clifford, S., Horne, R., & Hartley, E. (2007) · Pharmacy World & Science · doi:10.1007/s11096-007-9134-y · Cited by 175
“Potential consequences of nonadherence are health benefits forgone[6] and personal and R.”
An introduction to instrumental variable assumptions, validation and estimation
Lousdal, M. L. (2018) · Emerging Themes in Epidemiology · doi:10.1186/s12982-018-0069-7 · Cited by 173
“This type of confounding has been investigated within the fields of oral contraceptives, postmenopausal hormone therapy, statins and influenza vaccines and termed “compliance bias” [6], “prevention bias” [7], “healthy adherer effect” [8] and “healthy user effect/bias” [9].”
BackgroundBeliefs about medicines and self-reported adherence among pharmacy clients
MÅRDBY, A.-C. M., Åkerlind, I., & Jörgensen, T. (2007) · Patient Education and Counseling · doi:10.1016/j.pec.2007.08.011 · Cited by 173
“Medication-related problems caused by non-adherence can lead to unnecessary suffering, hospitalization [2] and mortality [3], resulting in decreased quality of life and increased costs for both the individual and society as a whole [2].”
BackgroundJohnston, N., Bodegård, J., Jerström, S., Åkesson, J., Brorsson, H., Alfredsson, J., Albertsson, P., Karlsson, J., & Varenhorst, C. (2016) · American Heart Journal · doi:10.1016/j.ahj.2016.05.005 · Cited by 174
Sedjo, R. L., & Devine, S. (2010) · Breast Cancer Research and Treatment · doi:10.1007/s10549-010-0952-6 · Cited by 176
“Adherence to long-term medication therapy for a chronic disease state is pivotal for optimal clinical outcomes [8, 9 ]. As reviewed by Chlebowski and Geller [10], only a few studies have focused on adherence to oral adjuvant endocrine therapy among women with breast cancer in clinical practice.”
BackgroundMethodHealth Literacy, Cognitive Ability, and Functional Health Status among Older Adults
Serper, M., Patzer, R. E., Curtis, L. M., Smith, S. G., O’Conor, R. M., Baker, D. W., & Wolf, M. S. (2014) · Health Services Research · doi:10.1111/1475-6773.12154 · Cited by 186
Wright, D. E., Poon, L. C., Rolnik, D. L., Syngelaki, A., Delgado⋈, J. L., Vojtassakova, D., de Alvarado, M., Kapeti, E., Rehal, A., Pazos, A., et al. (2017) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2017.08.110 · Cited by 172
Supporting Adherence to Medicines for Long-Term Conditions
Horne, R., Cooper, V., Wileman, V., & Chan, A. H. Y. (2019) · European Psychologist · doi:10.1027/1016-9040/a000353 · Cited by 178
“Chronic Illness: The Need for More Effective Interventions The prescription of a medicine is one of the most common interventions in developed health economies (Kantor, Rehm, Haas, Chan, & Giovannucci, 2015) and is essential to the treatment of most chronic illnesses (Simpson et al., 2006).”
BackgroundNew Prescription Medication Gaps: A Comprehensive Measure of Adherence to New Prescriptions
Karter, A. J., Parker, M. M., Moffet, H. H., Ahmed, A. T., Schmittdiel, J. A., & Selby, J. V. (2009) · Health Services Research · doi:10.1111/j.1475-6773.2009.00989.x · Cited by 166
“…been associated with poorer glycemic, blood pressure, and lipid control (Morris et al. 1997; Ho et al. 2006a), higher rates of acute metabolic events (Morris et al. 1997), and increased risk of hospitalization and mortality (Ho et al. 2006a, b; Simpson et al. 2006; Jackevicius, Li, and Tu 2008).”
BackgroundBrundisini, F. K., Vanstone, M. G., Hulan, D., DeJean, D., & Giacomini, M. K. (2015) · BMC Health Services Research · doi:10.1186/s12913-015-1174-8 · Cited by 167
“clinical care of Type 2 diabetes because it directly contributes to the effectiveness of patients’ treatment and wellbeing [1, 2].”
BackgroundF. Piepoli, M. (2017) · International Journal of Behavioral Medicine · doi:10.1007/s12529-016-9583-6 · Cited by 162
“Adherence to medication in individuals at high risk and in pa-tients with CVD is low, resulting in worse outcomes and higher health care costs [487].”
von Seidlein, L., Peto, T. J., Landier, J., Nguyen, T.-N., Tripura, R., Phommasone, K., Pongvongsa, T., Lwin, K. M., Keereecharoen, L., Kajeechiwa, L., et al. (2019) · PLoS Medicine · doi:10.1371/journal.pmed.1002745 · Cited by 157
“Some of the observed higher impact in people who adhered to the complete 3 rounds of MDA compared to people who took part in none or fewer than 3 rounds could be due to the people adhering to the 3 rounds being healthier than the people who did not adhere [66,67].”
BackgroundMedication nonadherence: health impact, prevalence, correlates and interventions
Stewart, S.-J., Moon, Z., & Horne, R. (2022) · Psychology and Health · doi:10.1080/08870446.2022.2144923 · Cited by 204
“…World Health organisation (WHo) estimated that around half of medicines prescribed for long-term conditions were not taken as advised (Sabaté, 2003; Simpson et al., 2006), and a 2018 report from the organisation for economic Co-operation and Development estimated that poor adherence results in…”
BackgroundTommelein, E., Mehuys, E., Hees, T. J. V., Adriaens, E., Bortel, L. M. V., Christiaens, T. C., Tongelen, I. V., Remon, J., Boussery, K., & Brusselle, G. (2013) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12242 · Cited by 167
Wampold, B. E., & Budge, S. L. (2012) · The Counseling Psychologist · doi:10.1177/0011000011432709 · Cited by 157
Parekh, N., Ali, K., Stevenson, J. M., Davies, G., Schiff, R., van der Cammen, T. J. M., Harchowal, J., Raftery, J. P., Rajkumar, C., & on behalf of the PRIME study group (2018) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.13613 · Cited by 154
Why are we failing to implement effective therapies in cardiovascular disease?
Nieuwlaat, R., Schwalm, J.-D., Khatib, R., & Yusuf, S. (2013) · European Heart Journal · doi:10.1093/eurheartj/ehs481 · Cited by 155
Metadata
- Authors
- Simpson, S. H., Eurich, D. T., Majumdar, S. R., Padwal, R. S., Tsuyuki, R. T., Varney, J., & Johnson, J. A.
- Affiliations
- University of Alberta (CA)
- Institute of Health Economics (CA)
- Corresponding author
- Simpson, Scot H
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2006-06-21
- Volume
- 333
- Issue
- 7557
- Pages
- 15
- ISSN
- 0007-1447 (ISSN-L)
- 0959-8138
- 1468-5833
- PMC
- PMC1488752
- OpenAlex
- W2147982456
- Cited by
- 1,353
- References
- 39
- Citations by year
- 2026: 37 · 2025: 40 · 2024: 57 · 2023: 56 · 2022: 55 · 2021: 83 · 2020: 55 · 2019: 74 · 2018: 90 · 2017: 91 · 2016: 69 · 2015: 71 · 2014: 83 · 2013: 77 · 2012: 86
- FWCI
- 8.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- BMJ (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Health Sciences › Medicine › Family Practice › Medication Adherence and Compliance
- Health Sciences › Health Professions › Pharmacy › Pharmacy and Medical Practices
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Keywords
- medication adherence, pharmacotherapy, mortality, adherence measurement methods
- MeSH terms
- Drug Therapy, Epidemiologic Methods, Humans, Patient Compliance, Prognosis, Randomized Controlled Trials as Topic
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