The DOI matches its Crossref record; 640 of the 645 references it cites were found in a registry or an index.
Interventions for enhancing medication adherence
Open accessAbstract
BACKGROUND: People who are prescribed self administered medications typically take only about half their prescribed doses. Efforts to assist patients with adherence to medications might improve the benefits of prescribed medications. OBJECTIVES: The primary objective of this review is to assess the effects of interventions intended to enhance patient adherence to prescribed medications for medical conditions, on both medication adherence and clinical outcomes. SEARCH METHODS: We updated searches of The Cochrane Library, including CENTRAL (via http://onlinelibrary.wiley.com/cochranelibrary/search/), MEDLINE, EMBASE, PsycINFO (all via Ovid), CINAHL (via EBSCO), and Sociological Abstracts (via ProQuest) on 11 January 2013 with no language restriction. We also reviewed bibliographies in articles on patient adherence, and contacted authors of relevant original and review articles. SELECTION CRITERIA: We included unconfounded RCTs of interventions to improve adherence with prescribed medications, measuring both medication adherence and clinical outcome, with at least 80% follow-up of each group studied and, for long-term treatments, at least six months follow-up for studies with positive findings at earlier time points. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted all data and a third author resolved disagreements. The studies differed widely according to medical condition, patient population, intervention, measures of adherence, and clinical outcomes. Pooling results according to one of these characteristics still leaves highly heterogeneous groups, and we could not justify meta-analysis. Instead, we conducted a qualitative analysis with a focus on the RCTs with the lowest risk of bias for study design and the primary clinical outcome. MAIN RESULTS: The present update included 109 new RCTs published since the previous update in January 2007, bringing the total number of RCTs to 182; we found five RCTs from the previous update to be ineligible and excluded them. Studies were heterogeneous for patients, medical problems, treatment regimens, adherence interventions, and adherence and clinical outcome measurements, and most had high risk of bias. The main changes in comparison with the previous update include that we now: 1) report a lack of convincing evidence also specifically among the studies with the lowest risk of bias; 2) do not try to classify studies according to intervention type any more, due to the large heterogeneity; 3) make our database available for collaboration on sub-analyses, in acknowledgement of the need to make collective advancement in this difficult field of research. Of all 182 RCTs, 17 had the lowest risk of bias for study design features and their primary clinical outcome, 11 from the present update and six from the previous update. The RCTs at lowest risk of bias generally involved complex interventions with multiple components, trying to overcome barriers to adherence by means of tailored ongoing support from allied health professionals such as pharmacists, who often delivered intense education, counseling (including motivational interviewing or cognitive behavioral therapy by professionals) or daily treatment support (or both), and sometimes additional support from family or peers. Only five of these RCTs reported improvements in both adherence and clinical outcomes, and no common intervention characteristics were apparent. Even the most effective interventions did not lead to large improvements in adherence or clinical outcomes. AUTHORS' CONCLUSIONS: Across the body of evidence, effects were inconsistent from study to study, and only a minority of lowest risk of bias RCTs improved both adherence and clinical outcomes. Current methods of improving medication adherence for chronic health problems are mostly complex and not very effective, so that the full benefits of treatment cannot be realized. The research in this field needs advances, including improved design of feasible long-term interventions, objective adherence measures, and sufficient study power to detect improvements in patient-important clinical outcomes. By making our comprehensive database available for sharing we hope to contribute to achieving these advances.
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“Although there is a wealth of controlled trials on interventions to improve adherence, current methods of improving medication adherence for chronic health problems are mostly complex and not effective [2,3,4].”
From Factors Contributing to Medication Adherence in Patients with a Chronic Condition: A Scoping Review of Qualitative Research (2021) · cites this paper as [3]
In the citing paper
“This review is in agreement with other, CF-related reviews and general adherence reviews, which have highlighted the limitations of many included trials in terms of having small sample sizes and being underpowered to detect a meaningful difference in adherence (Goldbeck 2014; Nieuwlaat 2014).”
From Psychological interventions for improving adherence to inhaled therapies in people with cystic fibrosis (2023) · cites this paper as Nieuwlaat 2014
In the citing paper
“Previous Cochrane Reviews on adherence (Nieuwlaat 2014) and CF-specific reviews (Goldbeck 2014; Savage 2014) have not used a coding framework, so this review has improved on existing methodologies.”
From Psychological interventions for improving adherence to inhaled therapies in people with cystic fibrosis (2023) · cites this paper as Nieuwlaat 2014
In the citing paper
“Given the complexity of many adherence interventions tested to date (Nieuwlaat 2014), and the way in which complex interventions are reported or described in the literature, it is o en difficult to determine the content, or the 'active ingredients', of effective interventions that bring about change (Michie 2009).”
From Psychological interventions for improving adherence to inhaled therapies in people with cystic fibrosis (2023) · cites this paper as Nieuwlaat 2014
In the citing paper
“Understanding the 'active ingredients' of promising interventions will make it easier to replicate effective interventions; will reduce the potential waste of time and resources on trials of ineffective techniques (Michie 2009); and will inform adherence research in the future (Nieuwlaat 2014).”
From Psychological interventions for improving adherence to inhaled therapies in people with cystic fibrosis (2023) · cites this paper as Nieuwlaat 2014
In the citing paper
“A previous Cochrane Review highlighted likely inclusion bias in adherence trials, with participants having higher than average adherence at baseline (Nieuwlaat 2014).”
From Psychological interventions for improving adherence to inhaled therapies in people with cystic fibrosis (2023) · cites this paper as Nieuwlaat 2014
In the citing paper
“Underpowered trials are more likely to miss a meaningful difference in adherence, even when improving adherence substantially, and showing an effect on clinical outcomes is likely even harder (Nieuwlaat 2014).”
From Psychological interventions for improving adherence to inhaled therapies in people with cystic fibrosis (2023) · cites this paper as Nieuwlaat 2014
In the citing paper
“Interventions that specifically aim to improve adherence to prescribed medications vary widely (Nieuwlaat 2014).”
From Psychological interventions for improving adherence to inhaled therapies in people with cystic fibrosis (2023) · cites this paper as Nieuwlaat 2014
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“With regard to mediation adherence interventions, primarily it has been health care professionals, and not peers (ie, lay individuals living with the same disease), who have delivered such interventions.(15) Despite concerted efforts and large numbers of medication adherence intervention trials, nonadherence to medica…”
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“3 The implementation of trial-based interventions into routine clinical practice is likely, therefore, to need careful consideration.”
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“Adherence, the extent to which patients’ behaviors follow a recommended treatment path [1], is widely reported as being suboptimal [2].”
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“Nevertheless, compliance has improved only modestly despite decades of work to develop interventions (Haynes et al. 2008; Kripalani, Yao, and Haynes 2007; Molloy and O’Carroll 2017).”
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“Among clients who do remain in treatment, fewer than 50% adhere to their therapists’ recommendations (Nieuwlaat et al., 2014).”
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“These interventions also failed to consider facilitators for real-world implementation [8].”
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“[35‐38] This goal setting approach was used by us and may have facilitated achievement of goals and resultant increased confidence, evident in the intervention group and reported by parents in their close out satisfaction questionnaire.”
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“…were the most common facilitators of adherence, and forgetting, being busy, or away from home, and experiencing a change in routine were the most common adherence barriers; these findings are similar to those reported in the literature in HIV-infected 22,23 and uninfected 17,24,25 populations.”
Martin, L. R., Feig, C., Maksoudian, C. R., Wysong, K. E., & Faasse, K. (2018) · Patient Preference and Adherence · doi:10.2147/ppa.s155971 · Cited by 41
“11,12,108 Interventions should also be appropriately tailored to patient needs.”
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“[42] The study was not 29 powered to determine effects on flare-ups or healthcare seeking.”
BackgroundAbbott, R. A., Moore, D. A., Rogers, M., Bethel, A. C., Stein, K., & Coon, J. T. (2020) · BMC Health Services Research · doi:10.1186/s12913-019-4728-3 · Cited by 38
Sanders‐Pinheiro, H., Colugnati, F. A. B., Denhaerynck, K., Marsicano, E. O., Medina, J. O. P., Geest, S. D., & ADHERE BRAZIL Study Team (2020) · Transplantation · doi:10.1097/tp.0000000000003214 · Cited by 38
“For the first time, this study identified several multilevel correlates of immunosuppressive nonadherence following heart transplantation and noted their importance for risk assessment and multilevel intervention development.(7,10,11,13-15) In KT, only one study attempted to explore the multilevel factors associated w…”
BackgroundMethodInfluentialRitschl, V., Stamm, T., Aletaha, D., Bijlsma, J. W. J., Böhm, P., Dragoi, R. G., Dures, E. K., Estévez‐López, F., Gossec, L., Iagnocco, A., et al. (2020) · RMD Open · doi:10.1136/rmdopen-2020-001432 · Cited by 39
Six‐month outcomes of customized adherence enhancement (CAE) therapy in bipolar disorder
Sajatovic, M., Levin, J. B., Tatsuoka, C. M., Micula‐Gondek, W., Fuentes‐Casiano, E., Bialko, C. S., & Cassidy, K. A. (2012) · Bipolar Disorders · doi:10.1111/j.1399-5618.2012.01010.x · Cited by 38
La comunicación médico paciente: ¿Cuáles son las habilidades efectivas?
Moore, P., Gómez, G., Kurtz, S. M., & Vargas, A. (2010) · Revista médica de Chile · doi:10.4067/s0034-98872010000800016 · Cited by 38
Compliance with Emergency Department Discharge Instructions
Gignon, M., Ammirati, C., Mercier, R., & Detave, M. (2013) · Journal of Emergency Nursing · doi:10.1016/j.jen.2012.10.004 · Cited by 38
Ownby, R. L., Hertzog, C. K., & Czaja, S. J. (2012) · Clinical Gerontologist · doi:10.1080/07317115.2012.657294 · Cited by 38
Norman, J., Fu, M., Ekman, I., Björck, L., & Falk, K. (2018) · European Journal of Cardiovascular Nursing · doi:10.1177/1474515117715843 · Cited by 36
McCullough, A. R., Ryan, C. A., O'Neill, B. M., Bradley, J. M., Elborn, J. S., & Hughes, C. M. (2015) · BMC Health Services Research · doi:10.1186/s12913-015-1004-z · Cited by 37
“prior to the expert panels taking place based on the strength and breadth of literature supporting this approach [4, 32, 33].”
BackgroundMediFrame: A Tablet Application to Plan, Inform, Remind and Sustain Older Adults' Medication Intake
Dalgaard, L. G., Grönvall, E., & Verdezoto, N. X. (2013) · IEEE International Conference on Healthcare Informatics (ICHI) · doi:10.1109/ichi.2013.12 · Cited by 37
Williams, A. F., & Manias, E. (2013) · Journal of Clinical Nursing · doi:10.1111/jocn.12171 · Cited by 37
Methodological Challenges in Psychiatric Treatment Adherence Research
Velligan, D. I., Sajatovic, M., Valenstein, M. M., Riley, W. T., Safren, S. A., Lewis‐Fernández, R., Weiden, P. J., Ogedegbe, G. G., & Jamison, J. (2010) · Clinical Schizophrenia & Related Psychoses · doi:10.3371/csrp.4.1.6 · Cited by 37
Non-adherence in difficult asthma and advances in detection
Lindsay, J. T., & Heaney, L. G. (2013) · Expert Review of Respiratory Medicine · doi:10.1586/17476348.2013.842129 · Cited by 40
Kulik, A., Desai, N. R., Shrank, W. H., Antman, E. M., Glynn, R. J., Levin, R., Reisman, L., Brennan, T. A., & Choudhry, N. K. (2013) · Circulation · doi:10.1161/circulationaha.112.000337 · Cited by 38
Lima, G. R., Silva, E. V., Magalhães, P. O., & Naves, J. O. S. (2016) · Brazilian Journal of Microbiology · doi:10.1016/j.bjm.2016.12.003 · Cited by 37
Haramiova, Z., Stasko, M., Hulín, M., Tesař, T., Kuželová, M., & Morisky, D. (2017) · Trials · doi:10.1186/s13063-017-2063-8 · Cited by 37
“Several interventions to increase patients’ adherence to medication intake have been developed [32].”
Hovland, R., Bremer, S., Frigaard, C., Henjum, S., Faksvåg, P. K., Sæther, E. M., & Kristiansen, I. S. (2019) · International Journal of Pharmacy Practice · doi:10.1111/ijpp.12598 · Cited by 38
“Lastly, studies evaluating the effects of the interventions are often poorly designed, and the outcomes are inconsistent.([10]) Since 2011, accredited community pharmacies in England have been offering patients, who have been prescribed a new medicine for asthma, chronic obstructive pulmonary disease, hypertension, ty…”
BackgroundYeo, S., Toh, M. P. H. S., Lee, S. H., Seet, R. C. S., Wong, L. Y., & Yau, W. (2020) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.4981 · Cited by 43
“In these reported trials, the interventions were complex and unlikely to be cost-effective.(53) Another review identified three interventions (automated short message service reminder,(54) community health worker-based intervention(55) and fixed-dose combination pill(56)) that demonstrated improvements in adherence an…”
BackgroundMethodInfluentialTang, J., James, L. J., Howell, M., Tong, A., & Wong, G. (2020) · Transplantation · doi:10.1097/tp.0000000000003294 · Cited by 44
Merks, P., Cameron, J. D., Bilmin, K., Świeczkowski, D., Chmielewska‐Ignatowicz, T., Harężlak, T., Białoszewska, K., Šola, K. F., Jaguszewski, M. J., & Vaillancourt, R. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.582200 · Cited by 43
Accuracy of measures for antiretroviral adherence in people living with HIV
Smith, R., Villanueva, G., Probyn, K., Sguassero, Y., Ford, N. P., Orrell, C., Cohen, K., Chaplin, M., Leeflang, M., & Hine, P. (2022) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd013080.pub2 · Cited by 39
What is resistant arterial hypertension?
Shalaeva, E. V., & Messerli, F. H. (2023) · Blood Pressure · doi:10.1080/08037051.2023.2185457 · Cited by 45
“Several systematic reviews and meta-analyses have assessed the impact of interventions, including modification of antihypertensive therapy, on adherence to antihypertensive medications [18,19].”
BackgroundReconceptualizing Medication Adherence: Six Phases of Dynamic Adherence
Gearing, R. E., Townsend, L. D., MacKenzie, M. J., & Charach, A. (2011) · Harvard Review of Psychiatry · doi:10.3109/10673229.2011.602560 · Cited by 37
Nunney, J., Raynor, D. K., Knapp, P., & Closs, S. J. (2011) · Drugs & Aging · doi:10.2165/11587180-000000000-00000 · Cited by 36
Working with the Noncompliant Patient
Kleinsinger, F. (2010) · The Permanente Journal · doi:10.7812/tpp/09-064 · Cited by 37
Medication Adherence in People of Culturally and Linguistically Diverse Backgrounds: A Meta-Analysis
Manias, E., & Williams, A. F. (2010) · Annals of Pharmacotherapy · doi:10.1345/aph.1m572 · Cited by 37
Senoo, K., Miki, T., Ohkura, T., Iwakoshi, H., Nishimura, T., Shiraishi, H., Teramukai, S., & Matoba, S. (2022) · JMIR mHealth and uHealth · doi:10.2196/30807 · Cited by 36
“To improve medication adherence, various methods such as reminders, counseling, telephone support, and patient education are effective; however, these long-term interventions impose a considerable burden on health care providers [11,12].”
BackgroundSommers, R., Miller, K., & Berry, D. L. (2012) · Oncology nursing forum · doi:10.1188/12.onf.e373-e379 · Cited by 35
Integrating Technology Into Health Care
Wang, C.-H. J., & Huang, A. T. (2012) · JAMA · doi:10.1001/jama.2012.102 · Cited by 36
Craig, G., & Zumla, A. I. (2015) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2015.01.007 · Cited by 36
U.S. emergency departments visits resulting from poor medication adherence: 2005–07
Heaton, P. C., Tundia, N. L., & Luder, H. R. (2013) · Journal of the American Pharmacists Association · doi:10.1331/japha.2013.12213 · Cited by 36
Transforming our health care system
Naylor, C., Imison, C., Addicott, R., Buck, D., Goodwin, N., Harrison, T., Ross, S., Sonola, L., Tian, Y., & Curry, N. (2013) · Cited by 37
Blood pressure outcomes of medication adherence interventions: systematic review and meta-analysis
Conn, V. S., Ruppar, T. M., & Chase, J. D. (2016) · Journal of Behavioral Medicine · doi:10.1007/s10865-016-9730-1 · Cited by 37
A Screening Tool for Assessing Alcohol Use Risk among Medically Vulnerable Youth
Levy, S., Dedeoğlu, F., Gaffin, J. M., Garvey, K. C., Harstad, E. B., MacGinnitie, A. J., Rufo, P. A., Huang, Q. E., Ziemnik, R. E., Wisk, L. E., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0156240 · Cited by 36
“Past-year alcohol consumption by YCMC is associated with a nearly 80% increase in risk for regular medication non-adherence [21], an important intermediary marker of poor outcomes for medically vulnerable youth [42].”
BackgroundAli, E. E., Leow, J. L., Chew, L. S. T., & Yap, K. Y. (2017) · Journal of Cancer Education · doi:10.1007/s13187-017-1248-x · Cited by 36
“Despite the evidence of their usefulness in enhancing adherence, multicomponent interventions have limited potential for wide spread implementation due to their resource requirements [4].”
BackgroundMeasures and predictors of varenicline adherence in the treatment of nicotine dependence
Peng, A. R., Morales, M., Wileyto, E. P., Hawk, L. W., Cinciripini, P. M., George, T. P., Benowitz, N. L., Nollen, N. L., Lerman, C. E., Tyndale, R. F., et al. (2017) · Addictive Behaviors · doi:10.1016/j.addbeh.2017.07.006 · Cited by 36
Pereira-Salgado, A., Westwood, J. A., Russell, L., Ugalde, A., Ortlepp, B., Seymour, J., Butow, P., Cavedon, L., Ong, K., Aranda, S., et al. (2017) · JMIR mHealth and uHealth · doi:10.2196/mhealth.8349 · Cited by 36
“Reviews of phone text reminder interventions have demonstrated efficacy in enhancing patients’ compliance to drug therapy [35-39]; however, only one study of cancer patients was identified, which was targeted at adolescents and young adults and phone text messages were not utilized [40].”
Ju, I. E., Banks, E., Calabria, B., Ju, A., Agostino, J., Korda, R., Usherwood, T. P., Manera, K., Hanson, C. S., Craig, J. C., et al. (2018) · BMJ Open · doi:10.1136/bmjopen-2017-021137 · Cited by 36
Clusters of non-adherence to medication in neurological patients.
Prell, T., Grosskreutz, J., Mendorf, S., Franke, G., Witte, O., & Kunze, A. (2019) · Research in Social and Administrative Pharmacy · doi:10.1016/j.sapharm.2019.01.001 · Cited by 33
Félix, I. B., Guerreiro, M. P., Cavaco, A. M. D. N., Cláudio, A. P., Mendes, A., Balsa, J., Carmo, M. B., Pimenta, N. M., & Henriques, M. A. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00680 · Cited by 38
“BCTs could be derived (Nieuwlaat et al., 2014; Williams et al., 2014; Sapkota et al., 2015).”
BackgroundWatanabe, C., Nagahori, M., Fujii, T., Yokoyama, K., Yoshimura, N., Kobayashi, T., Yamagami, H., Kitamura, K., Kagaya, T., Nakamura, S., et al. (2020) · Digestive Diseases and Sciences · doi:10.1007/s10620-020-06221-6 · Cited by 36
“This is in line with a Cochrane review on adherence, which concluded that improving medicine intake may have a far greater impact on clinical outcomes than modifying treatments [25].”
ResultZhao, X., Villagran, M. M., Kreps, G. L., & McHorney, C. A. (2011) · Health Communication · doi:10.1080/10410236.2011.569002 · Cited by 37
Improving Post-Discharge Medication Adherence in Patients with CVD: A Pilot Randomized Trial
de Oliveira‐Filho, A. D., Morisky, D. E., Costa, F. A., Pacheco, S. T., Neves, S. J. F., & de Lyra, D. P. (2014) · Arquivos Brasileiros de Cardiologia · doi:10.5935/abc.20140151 · Cited by 37
Liu, T., Congdon, N. G., Yan, X., Jin, L., Wu, Y., Friedman, D. S., & He, M. (2012) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.12-9798 · Cited by 36
Kuosmanen, L., Jakobsson, T., Hyttinen, J., Koivunen, M. H., & Valimaki, M. A. (2010) · Journal of Advanced Nursing · doi:10.1111/j.1365-2648.2010.05411.x · Cited by 35
Wilke, T., Groth, A., Pfannkuche, M., Harks, O., Fuchs, A., Maywald, U., & Krabbe, B. (2014) · Journal of Thrombosis and Thrombolysis · doi:10.1007/s11239-014-1136-8 · Cited by 35
“This grace period is in general accordance with practice documented in the literature [16, 25, 26].”
ResultSecondary prevention program for osteoporotic fractures and long-term adherence to bisphosphonates
Ojeda-Bruno, S., Naranjo, A., Francisco-Hernández, F., Erausquin, C., Rúa‐Figueroa, Í., Quevedo-Abeledo, J. C., & Rodríguez‐Lozano, C. (2010) · Osteoporosis International · doi:10.1007/s00198-010-1414-z · Cited by 35
Drug treatment in an ageing population: Practical implications
Wynne, H., & Blagburn, J. (2010) · Maturitas · doi:10.1016/j.maturitas.2010.03.004 · Cited by 35
Treatment Nonadherence in Inflammatory Bowel Disease
Herman, M. L., & Kane, S. V. (2015) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000581 · Cited by 35
“It has been well established that adherence to long-term therapy for chronic illnesses is extremely poor, averaging around 50% in developed countries.(4,5) In IBD, adherence data vary greatly and can depend on the type and distribution of disease and treatment modality—oral versus infusion versus injection.”
Background
Metadata
- Authors
- Nieuwlaat, R., Wilczynski, N., Navarro, T., Hobson, N., Jeffery, R., Keepanasseril, A., Agoritsas, T., Mistry, N., Iorio, A., Jack, S., Sivaramalingam, B., Iserman, E., Mustafa, R. A., Jedraszewski, D., Cotoi, C., & Haynes, R. B.
- Affiliations
- Hamilton General Hospital (CA)
- McMaster University (CA)
- St. Michael's Hospital (CA)
- University of Guelph (CA)
- ORCID
- Venue
- Cochrane Database of Systematic Reviews
- Publisher
- Wiley
- Published
- 2014-11-20
- Volume
- 2014
- Issue
- 11
- Pages
- CD000011-CD000011
- ISSN
- 1361-6137 (ISSN-L)
- 1465-1858
- PMC
- PMC7263418
- OpenAlex
- W1594567624
- Cited by
- 2,945
- References
- 645
- Citations by year
- 2026: 64 · 2025: 119 · 2024: 108 · 2023: 147 · 2022: 157 · 2021: 177 · 2020: 200 · 2019: 190 · 2018: 209 · 2017: 244 · 2016: 224 · 2015: 191 · 2014: 214
- FWCI
- 37.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cochrane Database of Systematic Reviews (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Canadian Institutes of Health Research
- 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 › Patient Safety and Medication Errors
- Keywords
- medication adherence, adherence interventions, self-administered medication, clinical outcomes, risk of bias, quality of evidence, pill organizers, pharmacists
- MeSH terms
- Drug Therapy, Humans, Patient Education as Topic, Self Administration, Randomized Controlled Trials as Topic, Publication Bias, Medication Adherence
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