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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In the citing paper
“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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“A review of 78 randomized trials found relatively few complex interventions and no one simple intervention to improving long-term medication adherence and health outcomes.(70) A variety of approaches are necessary.”
Blaschke, T. F., Osterberg, L. G., Vrijens, B., & Urquhart, J. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011711-113247 · Cited by 420
What are validated self-report adherence scales really measuring?: a systematic review
Nguyen, T., Caze, A. L., & Cottrell, N. (2013) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12194 · Cited by 431
Frost, H., Campbell, P., Maxwell, M., O’Carroll, R. E., Dombrowski, S. U., Williams, B., Cheyne, H., Coles, E., & Pollock, A. (2018) · PLoS ONE · doi:10.1371/journal.pone.0204890 · Cited by 459
Hugtenburg, J. G., Vervloet, M., van Dijk, L., Timmers, L., & Elders, P. J. M. (2013) · Patient Preference and Adherence · doi:10.2147/ppa.s29549 · Cited by 422
Hankey, G. J. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70255-2 · Cited by 399
Improving health outcomes with better patient understanding and education
Adams, R. (2010) · Risk Management and Healthcare Policy · doi:10.2147/rmhp.s7500 · Cited by 384
Wozniak, D. R., Lasserson, T. J., & Smith, I. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007736.pub2 · Cited by 388
Pharmacist services provided in general practice clinics: A systematic review and meta-analysis
Tan, E. C. K., Stewart, K., Elliott, R. A., & George, J. (2013) · Research in Social and Administrative Pharmacy · doi:10.1016/j.sapharm.2013.08.006 · Cited by 383
Medication adherence outcomes of 771 intervention trials: Systematic review and meta-analysis
Conn, V. S., & Ruppar, T. M. (2017) · Preventive Medicine · doi:10.1016/j.ypmed.2017.03.008 · Cited by 367
“Although measuring adherence is challenging, the continued use of self-report measures is unfortunate because their imprecise nature may obscure group differences (Culig and Leppee, 2014; Haynes et al., 2008; Lehmann et al., 2014).”
BackgroundNeugut, A. I., Subar, M., Wilde, E. T., Stratton, S., Brouse, C. H., Hillyer, G. C., Grann, V. R., & Hershman, D. L. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.33.3179 · Cited by 359
Choudhry, N. K., Kronish, I. M., Vongpatanasin, W., Ferdinand, K. C., Pavlik, V. N., Egan, B. M., Schoenthaler, A., Houston Miller, N., Hyman, D. J., & on behalf of the American Heart Association Council on Hypertension; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology (2022) · Hypertension · doi:10.1161/hyp.0000000000000203 · Cited by 349
Reeve, E., Thompson, W., & Farrell, B. (2017) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2016.12.021 · Cited by 331
Effect of outpatient pharmacists' non-dispensing roles on patient outcomes and prescribing patterns
Nkansah, N., Mostovetsky, O., Yu, C., Chheng, T., Beney, J., Bond, C. M., & Bero, L. A. (2010) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd000336.pub2 · Cited by 341
Assessing the value of diagnostic tests: a framework for designing and evaluating trials
di Ruffano, L. F., Hyde, C., McCaffery, K. J., Bossuyt, P. M., & Deeks, J. J. (2012) · BMJ · doi:10.1136/bmj.e686 · Cited by 337
Systematic Review of Migraine Prophylaxis Adherence and Persistence
Hepp, Z., Bloudek, L. M., & Varon, S. F. (2014) · Journal of Managed Care Pharmacy · doi:10.18553/jmcp.2014.20.1.22 · Cited by 334
ESPACOMP Medication Adherence Reporting Guideline (EMERGE)
De Geest, S., Zullig, L. L., Dunbar-Jacob, J., Helmy, R., Hughes, D. A., Wilson, I. B., & Vrijens, B. (2018) · Annals of Internal Medicine · doi:10.7326/m18-0543 · Cited by 360
“EMERGE was developed to help researchers improve the often methodologically weak (8, 35, 36) and suboptimum reporting of medication adherence research (11–13).”
BackgroundBrieger, D. B., Amerena, J. V., Attia, J., Bajorek, B. V., Chan, K. H., Connell, C., Freedman, B., Ferguson, C., Hall, T. L., Haqqani, H. M., et al. (2018) · Heart Lung and Circulation · doi:10.1016/j.hlc.2018.06.1043 · Cited by 335
“Unfortunately, the most effective interventions are usually complex (comprising tailored ongoing support, cognitive behavioural therapy, motivational interviewing, education, or daily treatment support; which are delivered face-to-face, often via pharmacists) and may be difficult to implement in real-world practice [4…”
Mobile phone messaging for preventive health care
Vodopivec‐Jamšek, V., de Jongh, T. E., Gurol‐Urganci, I., Atun, R. A., & Car, J. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007457.pub2 · Cited by 316
Assessing medication adherence: options to consider
Lehmann, A., Aslani, P., Ahmed, R. A., Dotta-Celio, J., Gauchet, A., Bedouch, P., Bugnon, O., Allenet, B., & Schneider, M. P. (2013) · International Journal of Clinical Pharmacy · doi:10.1007/s11096-013-9865-x · Cited by 320
Ravn-Nielsen, L. V., Duckert, M.-L., Lund, M. L., Henriksen, J. P., Nielsen, M. L., Eriksen, C. S., Buck, T. C., Pottegård, A., Hansen, M. R., & Hallas, J. (2018) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2017.8274 · Cited by 310
Beinart, N. A., Goodchild, C. E., Weinman, J. A., Ayis, S., & Godfrey, E. L. (2013) · The Spine Journal · doi:10.1016/j.spinee.2013.08.027 · Cited by 294
for the ABC project team, Demonceau, J., Ruppar, T. M., Kristanto, P., Hughes, D. A., Fargher, E., Kardas, P., Geest, S. D., Dobbels, F., Lewek, P., et al. (2013) · Drugs · doi:10.1007/s40265-013-0041-3 · Cited by 321
Dobbels, F., Ruppar, T. M., Geest, S. D., Decorte, A., Damme‐Lombaerts, R. V., & Fine, R. Ν. (2009) · Pediatric Transplantation · doi:10.1111/j.1399-3046.2010.01299.x · Cited by 306
Bhattacharya, D., Aronsohn, A. I., Price, J. C., Re, V. L., Heald, J., Demisashi, G., Durzy, E., Davis-Owino, A., & Tynes, S. A. (2023) · Clinical Infectious Diseases · doi:10.1093/cid/ciad319 · Cited by 345
“Incomplete medication adherence is well known, even in the highly structured clinical trial setting [26, 27].”
BackgroundInterventional tools to improve medication adherence: review of literature
Costa, E. M., Pecorelli, S. L., Giardini, A., Savin, M., Menditto, E., Lehane, E. A., Laosa, O., Monaco, A., & Marengoni, A. (2015) · Patient Preference and Adherence · doi:10.2147/ppa.s87551 · Cited by 307
“This ambiguity mirrors the conclusions made in numerous systematic reviews 23,80–82 in relation to the effectiveness of the majority of adherence enhancing interventions.”
BackgroundNonadherence Consensus Conference Summary Report
Fine, R. Ν., Becker, Y. T., Geest, S. D., Eisen, H. J., Ettenger, R. B., Evans, R., Rudow, D. L., McKay, D. B., Neu, A. M., Nevins, T. E., et al. (2008) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2008.02495.x · Cited by 297
Dew, M. A., DiMartini, A. F., Steel, J. L., Dabbs, A. D. V., Myaskovsky, L., Unruh, M. L., & Greenhouse, J. B. (2008) · Liver Transplantation · doi:10.1002/lt.21278 · Cited by 295
Garfield, S., Clifford, S., Eliasson, L., Barber, N., & Willson, A. (2011) · BMC Medical Research Methodology · doi:10.1186/1471-2288-11-149 · Cited by 305
Jackson, C., Clatworthy, J., Robinson, A., & Horne, R. (2009) · The American Journal of Gastroenterology · doi:10.1038/ajg.2009.685 · Cited by 287
Theory of planned behavior and adherence in chronic illness: a meta-analysis
Rich, A., Brandes, K., Mullan, B., & Hagger, M. S. (2015) · Journal of Behavioral Medicine · doi:10.1007/s10865-015-9644-3 · Cited by 272
Global burden of CVD: focus on secondary prevention of cardiovascular disease
Bansilal, S., Castellano, J. M., & Fuster, V. (2015) · International Journal of Cardiology · doi:10.1016/s0167-5273(15)31026-3 · Cited by 297
“Moreover, complex multifactorial strategies, addressing different barriers have been mostly assessed without previous evaluation of their individual components [59].”
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The Unmet Challenge of Medication Nonadherence
Kleinsinger, F. (2018) · The Permanente Journal · doi:10.7812/tpp/18-033 · Cited by 274
Medication Adherence to Multidrug Regimens
Marcum, Z. A., & Gellad, W. F. (2012) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2012.01.008 · Cited by 273
Chan, A. H. Y., Stewart, A. W., Harrison, J., Camargo, C. A., Black, P. N., & Mitchell, E. A. (2015) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(15)00008-9 · Cited by 265
Smith, S. G., Šestak, I., Forster, A. S., Partridge, A. H., Side, L. E., Wolf, M. S., Horne, R., Wardle, J., & Cuzick, J. M. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv590 · Cited by 263
“Attempts to correct such beliefs have had mixed results [87 – 89], but several studies have indicated that necessity beliefs and concerns are amenable to change [90 – 92].”
Beinart, N., Norton, S., Dowling, D., Gavriloff, D., Vari, C., Weinman, J. A., & Godfrey, E. L. (2016) · Physiotherapy · doi:10.1016/j.physio.2016.11.001 · Cited by 262
A Systematic Review of Medication Adherence Thresholds Dependent of Clinical Outcomes
Baumgartner, P. C., Haynes, R. B., Hersberger, K. E., & Arnet, I. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01290 · Cited by 257
“, adherence rate) and varies from 0% to over 100% in literature (DiMatteo, 2004; Briesacher et al., 2008; Fischer et al., 2010; Nieuwlaat et al., 2014; Huurne et al., 2015).”
BackgroundSelf-citationRisk Factors for Nonadherence to Antihypertensive Treatment
Gupta, P., Patel, P., Štrauch, B., Lai, F. Y., Akbarov, A., Marešová, V., White, C. M. J., Petrák, O., Gulsin, G. S., Patel, V., et al. (2017) · Hypertension · doi:10.1161/hypertensionaha.116.08729 · Cited by 256
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“It is known that current interventions provide inconsistent results in improving adherence [5].”
ResultWhat’s in a name? Compliance, adherence and concordance in chronic psychiatric disorders
Chakrabarti, S. (2014) · World Journal of Psychiatry · doi:10.5498/wjp.v4.i2.30 · Cited by 257
Imaz-Iglesia, I., Zegarra, P., González-Enríquez, J., Rubio, B., Alcázar, R. A., & Amate, J. M. (2009) · Osteoporosis International · doi:10.1007/s00198-009-1134-4 · Cited by 252
Tomás Pantoja, C., Opiyo, N., Lewin, S. A., Paulsen, E., Ciapponi, A., Wiysonge, C. S., Herrera, C. A., Gabriel Rada, G., Peñaloza, B., Dudley, L., et al. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011086.pub2 · Cited by 272
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Interventions to improve medication-adherence after transplantation: a systematic review
Bleser, L. D., Matteson, M., Dobbels, F., Russell, C. L., & Geest, S. D. (2009) · Transplant International · doi:10.1111/j.1432-2277.2009.00881.x · Cited by 248
Non-adherence to cardiovascular medications
Kolandaivelu, K., Leiden, B. B., O’Gara, P. T., & Bhatt, D. L. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu364 · Cited by 249
“Treatment-, patient-, and healthcare system-related factors all influence adherence (Table 2).(6,24,52) While prediction remains challenging, new technologies and data repositories promise to yield approaches to better manage the highly individualized nature of nonadherence.”
BackgroundA systematic review of medication non-adherence in persons with dementia or cognitive impairment
Smith, D., Lovell, J., Weller, C., Kennedy, B., Winbolt, M., Young, C., & Ibrahim, J. (2017) · PLOS ONE · doi:10.1371/journal.pone.0170651 · Cited by 242
Interventions to improve adherence to antiretroviral therapy
Chaiyachati, K. H., Ogbuoji, O., Price, M., Suthar, A. B., Negussie, E. K., & Bärnighausen, T. (2014) · AIDS · doi:10.1097/qad.0000000000000252 · Cited by 235
Ogedegbe, G. O. (2012) · Archives of Internal Medicine · doi:10.1001/archinternmed.2011.1307 · Cited by 230
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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