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Meta-Analysis
. 2020 May 8;5(5):CD012419.
doi: 10.1002/14651858.CD012419.pub2.

Interventions for improving medication-taking ability and adherence in older adults prescribed multiple medications

Amanda J Cross  1 , Rohan A Elliott  1   2 , Kate Petrie  1 , Lisha Kuruvilla  1   3 , Johnson George  1
Affiliations
Meta-Analysis

Interventions for improving medication-taking ability and adherence in older adults prescribed multiple medications

Amanda J Cross et al. Cochrane Database Syst Rev. .

Abstract

Background: Older people taking multiple medications represent a large and growing proportion of the population. Managing multiple medications can be challenging, and this is especially the case for older people, who have higher rates of comorbidity and physical and cognitive impairment than younger adults. Good medication-taking ability and medication adherence are necessary to ensure safe and effective use of medications.

Objectives: To evaluate the effectiveness of interventions designed to improve medication-taking ability and/or medication adherence in older community-dwelling adults prescribed multiple long-term medications.

Search methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, CINAHL Plus, and International Pharmaceutical Abstracts from inception until June 2019. We also searched grey literature, online trial registries, and reference lists of included studies.

Selection criteria: We included randomised controlled trials (RCTs), quasi-RCTs, and cluster-RCTs. Eligible studies tested interventions aimed at improving medication-taking ability and/or medication adherence among people aged ≥ 65 years (or of mean/median age > 65 years), living in the community or being discharged from hospital back into the community, and taking four or more regular prescription medications (or with group mean/median of more than four medications). Interventions targeting carers of older people who met these criteria were also included.

Data collection and analysis: Two review authors independently reviewed abstracts and full texts of eligible studies, extracted data, and assessed risk of bias of included studies. We conducted meta-analyses when possible and used a random-effects model to yield summary estimates of effect, risk ratios (RRs) for dichotomous outcomes, and mean differences (MDs) or standardised mean differences (SMDs) for continuous outcomes, along with 95% confidence intervals (CIs). Narrative synthesis was performed when meta-analysis was not possible. We assessed overall certainty of evidence for each outcome using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). Primary outcomes were medication-taking ability and medication adherence. Secondary outcomes included health-related quality of life (HRQoL), emergency department (ED)/hospital admissions, and mortality.

Main results: We identified 50 studies (14,269 participants) comprising 40 RCTs, six cluster-RCTs, and four quasi-RCTs. All included studies evaluated interventions versus usual care; six studies also reported a comparison between two interventions as part of a three-arm RCT design. Interventions were grouped on the basis of their educational and/or behavioural components: 14 involved educational components only, 7 used behavioural strategies only, and 29 provided mixed educational and behavioural interventions. Overall, our confidence in results regarding the effectiveness of interventions was low to very low due to a high degree of heterogeneity of included studies and high or unclear risk of bias across multiple domains in most studies. Five studies evaluated interventions for improving medication-taking ability, and 48 evaluated interventions for improving medication adherence (three studies evaluated both outcomes). No studies involved educational or behavioural interventions alone for improving medication-taking ability. Low-quality evidence from five studies, each using a different measure of medication-taking ability, meant that we were unable to determine the effects of mixed interventions on medication-taking ability. Low-quality evidence suggests that behavioural only interventions (RR 1.22, 95% CI 1.07 to 1.38; 4 studies) and mixed interventions (RR 1.22, 95% CI 1.08 to 1.37; 12 studies) may increase the proportions of people who are adherent compared with usual care. We could not include in the meta-analysis results from two studies involving mixed interventions: one had a positive effect on adherence, and the other had little or no effect. Very low-quality evidence means that we are uncertain of the effects of educational only interventions (5 studies) on the proportions of people who are adherent. Low-quality evidence suggests that educational only interventions (SMD 0.16, 95% CI -0.12 to 0.43; 5 studies) and mixed interventions (SMD 0.47, 95% CI -0.08 to 1.02; 7 studies) may have little or no impact on medication adherence assessed through continuous measures of adherence. We excluded 10 studies (4 educational only and 6 mixed interventions) from the meta-analysis including four studies with unclear or no available results. Very low-quality evidence means that we are uncertain of the effects of behavioural only interventions (3 studies) on medication adherence when assessed through continuous outcomes. Low-quality evidence suggests that mixed interventions may reduce the number of ED/hospital admissions (RR 0.67, 95% CI 0.50 to 0.90; 11 studies) compared with usual care, although results from six further studies that we were unable to include in meta-analyses indicate that the intervention may have a smaller, or even no, effect on these outcomes. Similarly, low-quality evidence suggests that mixed interventions may lead to little or no change in HRQoL (7 studies), and very low-quality evidence means that we are uncertain of the effects on mortality (RR 0.93, 95% CI 0.67 to 1.30; 7 studies). Moderate-quality evidence shows that educational interventions alone probably have little or no effect on HRQoL (6 studies) or on ED/hospital admissions (4 studies) when compared with usual care. Very low-quality evidence means that we are uncertain of the effects of behavioural interventions on HRQoL (1 study) or on ED/hospital admissions (2 studies). We identified no studies evaluating effects of educational or behavioural interventions alone on mortality. Six studies reported a comparison between two interventions; however due to the limited number of studies assessing the same types of interventions and comparisons, we are unable to draw firm conclusions for any outcomes.

Authors' conclusions: Behavioural only or mixed educational and behavioural interventions may improve the proportion of people who satisfactorily adhere to their prescribed medications, but we are uncertain of the effects of educational only interventions. No type of intervention was found to improve adherence when it was measured as a continuous variable, with educational only and mixed interventions having little or no impact and evidence of insufficient quality to determine the effects of behavioural only interventions. We were unable to determine the impact of interventions on medication-taking ability. The quality of evidence for these findings is low due to heterogeneity and methodological limitations of studies included in the review. Further well-designed RCTs are needed to investigate the effects of interventions for improving medication-taking ability and medication adherence in older adults prescribed multiple medications.

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Conflict of interest statement

Amanda J Cross: none declared.

Rohan A Elliott: none declared.

Kate Petrie: none declared

Lisha Kuruvilla: none declared

Johnson George has received investigator‐initiated research grants from Boehringer Ingelheim (2014), from Pfizer through the Global Research Awards for Nicotine Dependence (2017), and from GSK through Medical Education Grants (2018) for unrelated projects. He has also provided consultancy services to GSK (review of educational materials ‐ 2018) and Pfizer (delivering education sessions as part of CPD – 2019; not for promoting any particular product or molecule). These grants have been largely interdisciplinary and involved multiple investigators. He has not used any part of the funding for his salary or for other personal benefits. He has a tenured academic appointment at Monash University. These funds were paid to his employer (Monash University) and were used to support staff working on those projects or for professional development (e.g. conference attendance).

Rohan Elliott was an author of one study that was potentially eligible for inclusion in this review (Elliott 2012). To avoid bias, two independent members of the review team (AC and JG) screened this study and deemed that it was ineligible for inclusion.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1: Interventions versus usual care, Outcome 1: Primary outcome: adherence, grouped by types of interventions (dichotomous)
1.2
1.2. Analysis
Comparison 1: Interventions versus usual care, Outcome 2: Primary outcome: adherence, grouped by types of interventions (continuous)
1.3
1.3. Analysis
Comparison 1: Interventions versus usual care, Outcome 3: Primary outcome: adherence, mixed interventions, grouped by intervention duration (dichotomous)
1.4
1.4. Analysis
Comparison 1: Interventions versus usual care, Outcome 4: Primary outcome: adherence, mixed interventions, grouped by intervention duration (continuous)
1.5
1.5. Analysis
Comparison 1: Interventions versus usual care, Outcome 5: Primary outcome: adherence, mixed interventions, grouped by subjective or objective outcome measures (dichotomous)
1.6
1.6. Analysis
Comparison 1: Interventions versus usual care, Outcome 6: Primary outcome: adherence, mixed interventions, grouped by subjective or objective outcome measure (continuous)
1.7
1.7. Analysis
Comparison 1: Interventions versus usual care, Outcome 7: Primary outcome: adherence, mixed interventions, grouped by provider (dichotomous)
1.8
1.8. Analysis
Comparison 1: Interventions versus usual care, Outcome 8: Primary outcome: adherence, mixed interventions, grouped by provider (continuous)
1.9
1.9. Analysis
Comparison 1: Interventions versus usual care, Outcome 9: Secondary outcome: ED/Hospital admissions, grouped by type of intervention (dichotomous)
1.10
1.10. Analysis
Comparison 1: Interventions versus usual care, Outcome 10: Secondary outcome: mortality, mixed interventions
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD012419

References

References to studies included in this review

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References to studies excluded from this review

ACTRN12616001411437 {published data only}
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D'Agostino 2006 {published data only}
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    1. Sherrard H, Struthers C, Kearns SA, Wells G, Chen L, Mesana T. Using technology to create a medication safety net for cardiac surgery patients: a nurse-led randomized control trial. Canadian Journal of Cardiovascular Nursing 2009;19(3):9-15. - PubMed
Sherrard 2015 {published data only}
    1. Sherrard H, Duchesne L, Wells G, Kearns SA, Struthers C. Using interactive voice response to improve disease management and compliance with acute coronary syndrome best practice guidelines: a randomized controlled trial. Canadian Journal of Cardiovascular Nursing 2015;25(1):10-5. - PubMed
Shuster 1998 {published data only}
    1. Shuster GF. A home based intervention reduced the frequency of hospital readmissions and out of hospital deaths after discharge [commentary on Stewart S, Pearson S, Luke CG, et al. Effects of home-based intervention on unplanned readmissions and out-of-hospital deaths. J Am Geriatr Soc 1998 Feb;46:174-80]. Evidence Based Nursing 1998;1(4):120. - PubMed
Sidel 1990 {published data only}
    1. Sidel VW, Beizer JL, Lisi-Fazio D, Kleinmann K, Wenston J, Thomas C, et al. Controlled study of the impact of educational home visits by pharmacists to high-risk older patients. Journal of Community Health 1990;15(3):163-74. - PubMed
Simkins 1986 {published data only}
    1. Simkins CV, Wenzloff NJ. Evaluation of a computerized reminder system in the enhancement of patient medication refill compliance. Drug Intelligence & Clinical Pharmacy 1986;20(10):799-802. - PubMed
Simoni 2011 {published data only}
    1. Simoni JM, Chen WT, Huh D, Fredriksen-Goldsen KI, Pearson C, Zhao H, et al. A preliminary randomized controlled trial of a nurse-delivered medication adherence intervention among HIV-positive outpatients initiating antiretroviral therapy in Beijing, China. AIDS and Behavior 2011;15(5):919-29. - PMC - PubMed
Sit 2016 {published data only}
    1. Sit JWH, Chair SY, Choi KC, Chan CWH, Lee DTF, Chan AWK, et al. Do empowered stroke patients perform better at self-management and functional recovery after a stroke? A randomized controlled trial. Clinical Interventions in Aging 2016;11:1441-50. - PMC - PubMed
Sledge 2006 {published data only}
    1. Sledge WH, Brown KE, Levine JM, Fiellin DA, Chawarski M, White WD, et al. A randomized trial of primary intensive care to reduce hospital admissions in patients with high utilization of inpatient services. Disease Management 2006;9(6):328-38. - PubMed
Smith 1997 {published data only}
    1. Smith L, McGowan L, Moss-Barclay C, Wheater J, Knass D, Chrystyn H. An investigation of hospital generated pharmaceutical care when patients are discharged home from hospital. British Journal of Clinical Pharmacology 1997;44(2):163-5. - PMC - PubMed
Smith 2004 {published data only}
    1. Smith SM, Bury G, O'Leary M, Shannon W, Tynan A, Staines A, et al. The North Dublin randomized controlled trial of structural diabetes shared care. Family Practice 2004;21(1):39-45. - PubMed
Smith 2007 {published data only}
    1. Smith GE, Lunde AM, Hathaway JC, Vickers KS. Telehealth home monitoring of solitary persons with mild dementia. American Journal of Alzheimers Disease & Other Dementias 2007;22(1):20-6. - PMC - PubMed
Soloman 1998 {published data only}
    1. Solomon DK, Portner TS, Bass GE, Gourley DR, Gourley GA, Holt JM, et al. Clinical and economic outcomes in the hypertension and COPD arms of a multicenter outcomes study. Journal of the American Pharmacists Association 1998;38(5):574-85. - PubMed
Sookaneknun 2004 {published data only}
    1. Sookaneknun P, Richards RME, Sanguansermsri J, Teerasut C. Pharmacist involvement in primary care improves hypertensive patient clinical outcomes. Annals of Pharmacotherapy 2004;38(12):2023-8. - PubMed
Soong 2014 {published data only}
    1. Soong C, Kurabi B, Wells D, Caines L, Morgan MW, Ramsden R, et al. Do post discharge phone calls improve care transitions? A cluster-randomized trial. PLoS ONE 2014;9(11):e112230. - PMC - PubMed
Souter 2017 {published data only}
    1. Souter C, Kinnear A, Kinnear M, Mead G. A pilot study to assess the practicality, acceptability and feasibility of a randomised controlled trial to evaluate the impact of a pharmacist complex intervention on patients with stroke in their own homes. European Journal of Hospital Pharmacy - Science and Practice 2017;24:101-6. - PMC - PubMed
Stange 2013 {published data only}
    1. Stange D, Kriston L, von-Wolff A, Baehr M, Dartsch DC. Reducing cardiovascular medication complexity in a German university hospital: effects of a structured pharmaceutical management intervention on adherence. Journal of Managed Care Pharmacy 2013;19(5):396-407. - PMC - PubMed
Stanhope 2013 {published data only}
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Strobach 2000 {published data only}
    1. Strobach D, Vetter-Kerkhoff C, Bogner J, Breugst W, Schlondorff D. [Patient medication counseling - patient counseling about discharge medication]. Medizinische Klinik 2000;95(10):548-51. - PubMed
Stromberg 2005 {published data only}
    1. Strömberg A, Dahlström U, Fridlund B. Computer-based education for patients with chronic heart failure. A randomised, controlled, multicentre trial of the effects on knowledge, compliance and quality of life. Patient Educationa and Counseling 2006;64(1-3):128-35. - PubMed
Sweeney 1989 {published data only}
    1. Sweeney SJ, Dixon JS, Sutcliffe I. Impact of the clinical pharmacist on compliance in a geriatric population. Pharmaceutical Journal 1989;242(Feb 18 Suppl):242:R4-6.
Tai 2014 {published data only}
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Touchette, 2012 {published data only}
    1. Touchette D, Masica AL, Dolor RJ, Schumock GT, Smith H. Safety-focused medication therapy management: a randomized controlled trial. Journal of the American Pharmacists Association 2012;52(5):603-12. - PubMed
Towfighi 2017 {published data only}
    1. Towfighi A, Cheng EM, Ayala-Rivera M, et al. Randomized controlled trial of a coordinated care intervention to improve risk factor control after stroke or transient ischemic attack in the safety net: Secondary stroke prevention by Uniting Community and Chronic care model teams Early to End Disparities (SUCCEED). BMC Neurology 2017;17:24. - PMC - PubMed
Tu 1999 {published data only}
    1. Tu MS. The effect of health education on self-care behaviors and hypertension control in elderly hypertensive patients at a veterans home. [Korean]. Chinese Journal of Public Health 1999;18(1):54-65.
Tu 2018 {published data only}
    1. Tu Q, Xiao LD, Ullah S, Fuller J, Du H. Hypertension management for community-dwelling older people with diabetes in Nanchang, China: study protocol for a cluster randomized controlled trial. Trials [Electronic Resource] 2018;19(1):385. - PMC - PubMed
Vaillant‐Roussel 2016 {published data only}
    1. Vaillant-Roussel H, Laporte C, Pereira B, De Rosa M, Eschalier B, Vorilhon C, et al. Impact of patient education on chronic heart failure in primary care (ETIC): a cluster randomised trial. BMC Family Practice 2016;17:1-13. - PMC - PubMed
Valimaki 2017 {published data only}
    1. Valimaki M, Kannisto KA, Vahlberg T, Hatonen H, Adams CE. Short text messages to encourage adherence to medication and follow-up for people With psychosis (Mobile.Net): randomized controlled trial in Finland. Journal of Medical Internet Research 2017;19(7):e245. - PMC - PubMed
Varleta 2017 {published data only}
    1. Varleta P, Acevedo M, Akel C, Salinas C, Navarrete C, Garcia A, et al. Mobile phone text messaging improves antihypertensive drug adherence in the community. Journal of Clinical Hypertension 2017;19(12):1276-84. - PMC - PubMed
Varma 1999 {published data only}
    1. Varma S, McElnay JC, Hughes CM, Passmore AP, Varma M. Pharmaceutical care of patients with congestive heart failure: interventions and outcomes. Pharmacotherapy 1999;19(7):860-9. - PubMed
Verbeek 2016 {published data only}
    1. Verbeek A, Oonk N, Munster E, Movig K, Ter Huurne K, Nijmeijer H, et al. The effect of a structured medication review on quality of life in patients with Parkinson's disease. An interim analysis. Contempory Clinical Trials Communication 2016;31:S170-1.
Via‐Sosa 2013 {published data only}
    1. Via-Sosa MA, Lopes N, March M. Medication management in a geriatric care practice setting. BMC Family Practice 2013;14(1):96-104. - PMC - PubMed
Villani 2014 {published data only}
    1. Villani A, Malfatto G, Compare A, Della Rosa F, Bellardita L, Branzi G, et al. Clinical and psychological telemonitoring and telecare of high risk heart failure patients. Journal of Telemedicine & Telecare 2014;20(8):468-75. - PubMed
Vinks 2009 {published data only}
    1. Vinks TH, Egberts TC, Lange TM, Koning FH. Pharmacist-based medication review reduces potential drug-related problems in the elderly: the SMOG controlled trial. Drugs & Aging 2009;26(2):123-33. - PubMed
Vivian 2002 {published data only}
    1. Vivian EM. Improving blood pressure control in a pharmacist-managed hypertension clinic. Pharmacotherapy 2002;22(12):1533-40. - PubMed
Vollmer 2014 {published data only}
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Wakefield 2011 {published data only}
    1. Wakefield BJ, Holman JE, Ray A, Scherubel M, Adams MR, Hillis SL, et al. Effectiveness of home telehealth in comorbid diabetes and hypertension: a randomized, controlled trial. Telemedicine Journal and e-Health 2011;17(4):254-61. - PubMed
Wakefield 2012 {published data only}
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Wandless 1981 {published data only}
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Wild 2016 {published data only}
    1. Wild SH, Hanley J, Lewis SC, McKnight JA, McCloughan LB, Padfield PL, et al. Supported telemonitoring and glycemic control in people with type 2 diabetes: the Telescot diabetes pragmatic multicenter randomized controlled trial.. PLOS Medicine 2016;13(7):e1002098. - PMC - PubMed
Williams 2004 {published data only}
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Yatabe 2018 {published data only}
    1. Yatabe MS, Yatabe J, Asayama K, Staessen JA, Mujaj B, Thijs L, et al. The rationale and design of reduction of uncontrolled hypertension by Remote Monitoring and Telemedicine (REMOTE) study. Blood Pressure 2018;27(2):99-105. - PubMed
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    1. Yu M. The effectiveness of a heart failure disease management programme on clinical outcomes, health-related quality of life, and psychological status of patients with heart failure in China. Dissertation Abstracts International: Section B: The Sciences and Engineering 2012;73(6-B):3538.
Zermansky 2002 {published data only}
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    1. 李静, 李荣, 张会敏, 张瑞芹. 感恩干预对社区老年高血压病人自我管理水平的影响...Influence of gratitude intervention of self-management level of elderly patients with community hypertension. Chinese Nursing Research 2017;31(2):163-6.

References to studies awaiting assessment

ACTRN12606000247572 {published data only}
    1. ACTRN12606000247572. A randomised controlled trial to measure the effectiveness of dose administration aids (DAAs) in improving veteran adherence and health outcomes and to characterise which veterans have a beneficial outcome. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=1391 (first received 20 June 2006).
ACTRN12611000452998 {published and unpublished data}
    1. ACTRN12611000452998. Medication Reviews ReDirected (MedReDi): acute coronary syndrome as an indication for home medicine review, a randomised controlled trial. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=1261... (first received 3 May 2011).
    1. Bernal DD, Stafford L, Bereznicki LR, Castelino RL, Davidson PM, Peterson GM. Home medicines reviews following acute coronary syndrome: study protocol for a randomized controlled trial. Trials 2012;13:30. - PMC - PubMed
ACTRN12616000910404 {published data only}
    1. ACTRN12616000910404. The effectiveness of motivational interviewing (MINT) and text message reminders on medication adherence among patients with heart disease. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370973 (first received 8 July 2016).
ACTRN12617000665336 {published data only}
    1. ACTRN12617000665336. Impact of clinical pharmacist medication review on appropriate prescribing in elderly patients: a randomized, controlled trial. http://www.who.int/trialsearch/trial2.aspx?Trialid=actrn12617000665336 (first received 8 May 2017).
Ahmad 2010 {published data only}
    1. Ahmad A, Hugtenburg J, Welschen LM, Dekker JM, Nijpels G. Effect of medication review and cognitive behaviour treatment by community pharmacists of patients discharged from the hospital on drug related problems and compliance: design of a randomized controlled trial. Biomed Central Public Health 2010;10:133. - PMC - PubMed
    1. Ahmad A. Beliefs about prescribed medicine and self-reported adherence among elderly patients discharged from hospital. International Journal of Person Centered Medicine 2013;2:818-82.
    1. Hugtenburg JG. The effectiveness of optimised clinical medication reviews for geriatric patients: a cluster randomized controlled trial. In: Pharmacoepidemiology and Drug Safety. Vol. 26(Suppl 2). 2017:194. - PubMed
Cao 2017 {published data only}
    1. Cao XY, Tian L, Chen L, Jiang XL. Effects of a hospital-community partnership transitional program in patients with coronary heart disease in Chengdu, China: a randomized controlled trial. Japan Journal of Nursing Science 2017;14(4):320-31. - PubMed
Char 2017 {unpublished data only}
    1. Char CWT, Yip AYF, Kee KW, Lee ES, Chua AHL. Effectiveness of pre-consultation medication reconciliation service in reducing medication discrepancies during transition of care from hospital discharge to primary care setting in Singapore - a randomised controlled trial. Unpublished (supplied by author) 2017.
Cheema 2017 {published data only}
    1. Cheema R, Kwolek S, Frias J, Mangin D, Moore A, Masrur M. Measurement of medication discrepancies and use of medication wallet cards to increase patient self-efficacy. In: Canadian Family Physician. Vol. 63. 2017:S108.
ChiCTR‐TRC‐12002106 {published data only}
    1. ChiCTR‐TRC‐12002106. Using the picture album of daily self-questionnaires to improve medication adherence of secondary prevention programs for elderly patients with acute coronary syndrome: a randomised controlled trial. http://www.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR-TRC-12002106 (date received 18 April 2012).
Demers 2014 {published data only}
    1. Demers C, Patterson C, Archer N, Coallier J, Strachan P, Keshavjee K, et al. A simple multi-component intervention improves self management in heart failure. In: Canadian Journal of Cardiology. Vol. 30. 2014:S201.
Flink 2016 {published data only}
    1. Flink M, Lindblad M, Frykholm O, Kneck A, Nilsen P, Årestedt K, et al. The Supporting Patient Activation in Transition to Home (sPATH) intervention: a study protocol of a randomised controlled trial using motivational interviewing to decrease re-hospitalisation for patients with COPD or heart failure. BMJ Open 2017;7:e014178. - PMC - PubMed
Madarshahian 2018 {published data only}
    1. Madarshahian F, Safaie YN, Safaie YA, Roohbakhsh FO, Madarshahian MR. Impact of family support on medication adherence and cognition in stroke patients. In: European Stroke Journal. Vol. 3. 2018:296.
Marusic 2018 {published data only}
    1. Marusic S, Melis P, Lucijanic M, Grgurevic I, Turcic P, Neto PRO, et al. Impact of pharmacotherapeutic education on medication adherence and adverse outcomes in patients with type 2 diabetes mellitus: a prospective, randomized study. Croatian Medical Journal 2018;59(6):290-7. - PMC - PubMed
Muth 2018 {published data only}
    1. Muth C, Uhlmann L, Haefeli WE, Rochon J, den Akker M, Perera R, et al. Effectiveness of a complex intervention on Prioritising Multimedication in Multimorbidity (PRIMUM) in primary care: results of a pragmatic cluster randomised controlled trial. BMJ Open 2018;8(2):e017740. - PMC - PubMed
NCT00560001 {published data only}
    1. NCT00560001. MD.2 medication dispenser medication adherence study. https://clinicaltrials.gov/show/nct00560001 (first received November 19, 2007).
NCT00916214 {published data only}
    1. NCT00916214. Improving compliance among elderly polypharmacy users through community pharmacy based pharmaceutical care program. https://clinicaltrials.gov/show/nct00916214 (first received June 9, 2009).
NCT01105104 {published data only}
    1. NCT01105104. An enhanced medication monitoring program. https://clinicaltrials.gov/show/nct01105104 (first received April 16, 2010).
NCT01534559 {published data only}
    1. NCT01534559. Pharmacist-led medicines management outpatient service (MMC). https://clinicaltrials.gov/ct2/show/NCT01534559 (first received February 16, 2012).
NCT02047448 {published data only}
    1. NCT02047448. Improving medication adherence through a transitional care pharmacy practice model. https://clinicaltrials.gov/ct2/show/NCT02047448 (first received Janurary 28, 2014).
NCT02424786 {published data only}
    1. NCT02424786. Non-adherence and polypharmacy in elderly patients. https://clinicaltrials.gov/ct2/show/NCT02424786 (first received April 23, 2015).
NCT02842840 {published data only}
    1. NCT02842840. The effectiveness of multimodal educational intervention to improve adherence to treatment regimens in older stroke patients. https://clinicaltrials.gov/ct2/show/NCT02842840 (first received July 25, 2016).
NCT03156348 {published data only}
    1. NCT03156348. Impact of clinical pharmacist on adverse drug events in older adults. https://clinicaltrials.gov/show/nct03156348 (first received May 17, 2017).
NCT03162848 {published data only}
    1. NCT03162848. SystemCHANGE™ intervention on medication adherence in older adults with heart failure (ECHO). https://clinicaltrials.gov/ct2/show/NCT03162848 (first received May 22, 2017).
Ostbring 2018 {published data only}
    1. Östbring MJ, Eriksson T, Petersson G, Hellström L. Motivational Interviewing and Medication Review in Coronary heart disease (MIMeRiC): protocol for a randomized controlled trial investigating effects on clinical outcomes, adherence, and quality of life. Journal of Medical Internet Research, Research Protocols 2018;7(2):e57. - PMC - PubMed
Prados‐Torres 2017 {published data only}
    1. Prados-Torres A, Cura-Gonzalez I, Prados-Torres D, López-Rodríguez JA, Leiva-Fernández F, Calderón-Larrañaga A, et al. Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy: study protocol of a cluster randomized clinical trial (Multi-PAP project). Implementation Science 2017;12:54. - PMC - PubMed
Reilly 2016 {published data only}
    1. Reilly K, West E, Jung S, Friedberg JP, Natarajan S. A multicomponent transitional care intervention to improve clinical outcomes among patients being discharged after a heart failure admission: a pilot randomized clinical trial. In: Journal of General Internal Medicine. Vol. 1. 2016:S99.

References to ongoing studies

Adam 2019 {published data only}
    1. Adam L, Moutzouri E, Baumgartner C, Loewe AL, Feller M, M'Rabet-Bensalah K, et al. Rationale and design of OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people (OPERAM): a cluster randomised controlled trial. BMJ Open 2019;9:e026769. - PMC - PubMed
    1. NCT02986425. OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly (OPERAM). https://clinicaltrials.gov/ct2/show/NCT02986425 (date received December 8, 2016).
Bailey 2017 {published data only}
    1. Bailey SC, Wismer GA, Parker RM, Walton SM, Wood AJJ, Wallia A, et al. Development and rationale for a multifactorial, randomized controlled trial to test strategies to promote adherence to complex drug regimens among older adults. Contemporary Clinical Trials 2017;62:21-6. - PMC - PubMed
Dodge 2018 {published data only}
    1. Dodge H, Goodrich E, Lindsley J, Hampstead B, Kaye J. Behavioral RCT using frequent social interaction to enhance cognitive reserve. In: Clinical Trials. Vol. 15. 2018:130-1.
    1. Dodge HH, Hampstead BM, Potempa K, Struble L, Lindsley J, Rooney WD, et al. Behavioral randomized controlled trial (RCT) using internet-based social interactions as a tool to enhance cognitive reserve. In: Alzheimer's & Dementia. Vol. 14. 2018:586.
ISRCTN13355076, 2018 {published data only}
    1. ISRCTN13355076. An educational intervention to promote health-related quality of life after an acute coronary syndrome. http://www.who.int/trialsearch/trial2.aspx?Trialid=isrctn13355076 (first received 8 August 2018).
NCT03511027 {published data only}
    1. NCT03511027. Medication dispenser to improve care at home for the elderly. https://clinicaltrials.gov/show/nct03511027 (first received April 27, 2018).
NCT03722017 {published data only}
    1. NCT03722017. Drug reduction in older patients: the DROP Trial. https://clinicaltrials.gov/show/nct03722017 (first received October 26, 2018).
Vasilevskis 2019 {published data only}
    1. NCT02979353. A randomized controlled trial to deprescribe for older patients with polypharmacy (Shed-Meds). https://clinicaltrials.gov/ct2/show/NCT02979353 (first received December 1, 2016).
    1. Vasilevskis EE, Shah AS, Hollingsworth EK, Shotwell MS, Mixon AS, Bell SP, et al. A patient-centered deprescribing intervention for hospitalized older patients with polypharmacy: rationale and design of the Shed-MEDS randomized controlled trial. BioMed Central Health Services Research 2019;19:165. - PMC - PubMed
Verweij 2018 {published data only}
    1. NTR6316. Cardiac care bridge trial. https://www.trialregister.nl/trial/6169 (first received 4 June 2006).
    1. Verweij L, Jepma P, Buurman BM, Latour CHM, Engelbert RHH, Ter Riet G, et al. The cardiac care bridge program: design of a randomized trial of nurse-coordinated transitional care in older hospitalized cardiac patients at high risk of readmission and mortality. BioMed Central Health Services Research 2018;18:508. - PMC - PubMed

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