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Meta-Analysis
. 2014 Nov 20;2014(11):CD000011.
doi: 10.1002/14651858.CD000011.pub4.

Interventions for enhancing medication adherence

Robby Nieuwlaat  1 , Nancy Wilczynski, Tamara Navarro, Nicholas Hobson, Rebecca Jeffery, Arun Keepanasseril, Thomas Agoritsas, Niraj Mistry, Alfonso Iorio, Susan Jack, Bhairavi Sivaramalingam, Emma Iserman, Reem A Mustafa, Dawn Jedraszewski, Chris Cotoi, R Brian Haynes
Affiliations
Meta-Analysis

Interventions for enhancing medication adherence

Robby Nieuwlaat et al. Cochrane Database Syst Rev. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

  1. RN ‐ RN received a research grant to assess barriers in hypertension management and a congress travel/accommodation reimbursement from Boehringer Ingelheim, and is co‐investigator on research teams that received Canadian Institutes of Health Research grants for testing a hypertension implementation program in low‐ and middle‐income countries as well as building a Canadian research network to reduce stroke in atrial fibrillation.

  2. NW ‐ none known.

  3. TN ‐ the update of this review was partly supported by a Knowledge Synthesis grant, KRS 262115, from the Canadian Institutes of Health Research.

  4. NH – none known.

  5. RJ ‐ none known.

  6. AK ‐ none known.

  7. TA ‐ none known.

  8. NM ‐ none known.

  9. AI ‐ none known.

  10. SJ ‐ none known.

  11. BS ‐ none known.

  12. EI ‐ none known.

  13. RM ‐ none known.

  14. DJ ‐ none known.

  15. CC – none known.

  16. RBH ‐ the update of this review was partly supported by a Knowledge Synthesis grant, KRS 262115, from the Canadian Institutes of Health Research.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' summary: review authors' judgments about each risk of bias item for each included study.
See this image and copyright information in PMC

Update of

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    1. Sorensen JL, Haug NA, Delucchi KL, Gruber V, Kletter E, Batki SL, et al. Voucher reinforcement improves medication adherence in HIV‐positive methadone patients: a randomized trial. Drug & Alcohol Dependence 2007;88(1):54‐63. [MEDLINE: ] - PMC - PubMed
Staring 2010 {published data only}
    1. Staring AB, Gaag M, Koopmans GT, Selten JP, Beveren JM, Hengeveld MW, et al. Treatment adherence therapy in people with psychotic disorders: randomised controlled trial. British Journal of Psychiatry 2010;197(6):448‐55. [MEDLINE: ] - PubMed
Stevens 2002 {published data only}
    1. Stevens V, Shneidman RJ, Johnson RE, Steele PE, Lee NL. Helicobacter pylori eradication in dyspeptic primary care patients: a randomized controlled trial of a pharmacy intervention. Western Journal of Medicine 2002;176(2):92‐6. [MEDLINE: ] - PMC - PubMed
Strang 1981 {published data only}
    1. Strang JS, Falloon IRH, Moss HB, Razani J, Boyd JL. The effects of family therapy on treatment compliance in schizophrenia. Psychopharmacology Bulletin 1981;17(3):87‐8.
Taiwo 2010 {published data only}
    1. Taiwo BO, Idoko JA, Welty LJ, Otoh I, Job G, Iyaji PG, et al. Assessing the viorologic and adherence benefits of patient‐selected HIV treatment partners in a resource‐limited setting. Journal of Acquired Immune Deficiency Syndromes 2010;54(1):85‐92. [CENTRAL: CN‐00743266] - PubMed
Tuldra 2000 {published data only}
    1. Tuldra A, Fumaz CR, Ferrer MJ, Bayes R, Arno A, Balague M, et al. Prospective randomized two‐arm controlled study to determine the efficacy of a specific intervention to improve long‐term adherence to highly active antiretroviral therapy. Journal of Acquired Immune Deficiency Syndromes 2000;25(3):221‐8. - PubMed
Udelson 2009 {published data only}
    1. Udelson JE, Pressler SJ, Sackner‐Bernstein J, Massaro J, Ordronneau P, Lukas MA, et al. Adherence with once daily versus twice daily carvedilol in patients with heart failure: the Compliance And Quality of Life Study Comparing Once‐Daily Controlled‐Release Carvedilol CR and Twice‐Daily Immediate‐Release Carvedilol IR in Patients with Heart Failure (CASPER) Trial. Journal of Cardiac Failure 2009;15(5):385‐93. [MEDLINE: ] - PubMed
Valencia 2007 {published data only}
    1. Valencia M, Rascon ML, Juarez F, Murow E. A psychosocial skills training approach in Mexican out‐patients with schizophrenia. Psychological Medicine 2007;37(10):1393‐402. [MEDLINE: ] - PubMed
Valenstein 2011 {published data only}
    1. Valenstein M, Kavanagh J, Lee T, Reilly P, Dalack GW, Grabowski J, et al. Using a pharmacy‐based intervention to improve antipsychotic adherence among patients with serious mental illness. Schizophrenia Bulletin 2011;37(4):727‐36. [MEDLINE: ] - PMC - PubMed
van der Meer 2009 {published data only}
    1. Meer V, Bakker MJ, Hout WB, Rabe KF, Sterk PJ, Kievit J, et al. Internet‐based self‐management plus education compared with usual care in asthma: a randomized trial. Annals of Internal Medicine 2009;151(2):110‐20. [2010775594] - PubMed
    1. Meer V, Stel HF, Bakker MJ, Roldaan AC, Assendelft WJ, Sterk PJ, et al. SMASHING (Self‐Management of Asthma Supported by Hospitals, ICT, Nurses and General practitioners) Study Group. Weekly self‐monitoring and treatment adjustment benefit patients with partly controlled and uncontrolled asthma: an analysis of the SMASHING study. Respiratory Research 2010;11(June):74. [MEDLINE: ] - PMC - PubMed
Velligan 2008 {published data only}
    1. Velligan DI, Diamond PM, Mintz J, Maples N, Li X, Zeber J, et al. The use of individually tailored environmental supports to improve medication adherence and outcomes in schizophrenia. Schizophrenia Bulletin 2008;34(3):483‐93. [MEDLINE: ] - PMC - PubMed
Vergouwen 2005 {published data only}
    1. Vergouwen AC, Bakker A, Burger H, Verheij TJ, Koerselman F. A cluster‐randomized trial comparing two interventions to improve treatment of major depression in primary care. Psychological Medicine 2005;35(1):25‐33. - PubMed
Volume 2001 {published data only}
    1. Volume CI, Garris KB, Kassam R, Cox CE, Cave A. Pharmaceutical care research and education project: patient outcomes. Journal of the American Pharmaceutical Association 2001;41(3):411‐20. [MEDLINE: ] - PubMed
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 & E‐Health 2011;17(4):254‐61. [MEDLINE: ] - PubMed
    1. Wakefield BJ, Holman JE, Ray A, Scherubel M, Burns TL, Kienzle MG, et al. Outcomes of a home telehealth intervention for patients with heart failure. Journal of Telemedicine & Telecare 2009;15(1):46‐50. [MEDLINE: ] - PubMed
Walley 2001 {published data only}
    1. Walley JD, Khan MA, Newell JN, Khan MH. Effectiveness of the direct observation component of DOTS for tuberculosis: a randomised controlled trial in Pakistan. Lancet 2001;357(9257):664‐9. [MEDLINE: ] - PubMed
Wang 2010 a {published data only}
    1. Wang H, Zhou J, Huang L, Li X, Fennie KP, Williams AB. Effects of nurse‐delivered home visits combined with telephone calls on medication adherence and quality of life in HIV‐infected heroin users in Hunan of China. Journal of Clinical Nursing 2010;19(3‐4):380‐8. [MEDLINE: ] - PubMed
Wang 2010 b {published data only}
    1. Wang KY, Chian CF, Lai HR, Tarn YH, Wu CP. Clinical pharmacist counseling improves outcomes for Taiwanese asthma patients. Pharmacy World & Science 2010;32(6):721‐9. [MEDLINE: ] - PubMed
Weber 2004 {published data only}
    1. Weber R, Christen L, Christen S, Tschopp S, Znoj H, Schneider C, et al. Swiss HIV Cohort Study. Effect of individual cognitive behaviour intervention on adherence to antiretroviral therapy: prospective randomized trial. Antiviral Therapy 2004;9(1):85‐95. [MEDLINE: ] - PubMed
Weinberger 2002 {published data only}
    1. Weinberger M, Murray MD, Marrero DG, Brewer N, Lykens M, Harris LE, et al. Effectiveness of pharmacist care for patients with reactive airways disease: a randomized controlled trial. JAMA 2002;288(13):1594‐602. [MEDLINE: ] - PubMed
Wiggins 2009 {published data only}
    1. Wiggins SA. Family exemplars during implementation of a home pain management intervention. Issues in Comprehensive Pediatric Nursing 2009;32(May):160–79. [CENTRAL: CN‐00728335] - PubMed
Wilson 2010 {published data only}
    1. Wilson SR, Strub P, Buist AS, Knowles SB, Lavori PW, Lapidus J, et al. Better Outcomes of Asthma Treatment (BOAT) Study Group. Shared treatment decision making improves adherence and outcomes in poorly controlled asthma. American Journal of Respiratory & Critical Care Medicine 2010;181(6):566‐77. [MEDLINE: ] - PMC - PubMed
Wolever 2010 {published data only}
    1. Wolever RQ, Dreusicke M, Fikkan J, Hawkins TV, Yeung S, Wakefield J, et al. Integrative health coaching for patients with type 2 diabetes: a randomized clinical trial. Diabetes Educator 2010;36(4):629‐39. [MEDLINE: ] - PubMed
Wu 2006 {published data only}
    1. Wu JY, Leung WY, Chang S, Lee B, Zee B, Tong PC, et al. Effectiveness of telephone counselling by a pharmacist in reducing mortality in patients receiving polypharmacy: randomised controlled trial. BMJ 2006;333(7567):522. [2009294932] - PMC - PubMed
Wu 2012 {published data only}
    1. Wu JR, Corley DJ, Lennie TA, Moser DK. Effect of a medication‐taking behavior feedback theory‐based intervention on outcomes in patients with heart failure. Journal of Cardiac Failure 2012;18(1):1‐9. [5494] - PMC - PubMed
Wysocki 2001 {published data only}
    1. Wysocki T, Greco P, Harris MA, Bubb J, White NH. Behavior therapy for families of adolescents with diabetes: maintenance of treatment effects. Diabetes Care 2001;24(3):441‐6. - PubMed
Xiong 1994 {published data only}
    1. Xiong W, Phillips MR, Hu X, Wang R, Dai Q, Kleinman J, et al. Family‐based intervention for schizophrenic patients in China. A randomised controlled trial. British Journal of Psychiatry 1994;165(2):239‐47. - PubMed
Yopp 2004 {unpublished data only}
    1. Yopp JM. The Impact of Family Functioning on Treatment Adherence and Metabolic Control for Adolescents with Poorly Controlled T1DM [dissertation]. Mount Pleasant, Michigan: Central Michigan University, 2004.
Zhang 1994 {published data only}
    1. Zhang M, Wang M, Li J, Phillips MR. Randomised‐control trial of family intervention for 78 first‐episode male schizophrenic patients. An 18‐month study in Suzhou, Jiangsu. British Journal of Psychiatry 1994;165(Suppl 24):96‐102. - PubMed
Zolfaghari 2012 {published data only}
    1. Zolfaghari M, Mousavifar SA, Pedram S, Haghani H. The impact of nurse short message services and telephone follow‐ups on diabetic adherence: which one is more effective?. Journal of Clinical Nursing 2012;21(13‐4):1922‐31. [MEDLINE: ] - PubMed

References to studies excluded from this review

Adamian 2004 {published data only}
    1. Adamian MS, Golin CE, Shain LS, DeVellis B. Brief motivational interviewing to improve adherence to antiretroviral therapy: development and qualitative pilot assessment of an intervention. AIDS Patient Care and STDs 2004;18(4):229‐38. - PubMed
Adams 2000 {published data only}
    1. Adams J, Scott J. Predicting medication adherence in severe mental disorders. Acta Psychiatrica Scandinavica 2000;101(2):119‐24. - PubMed
Adams 2001 {published data only}
    1. Adams RJ, Boath K, Homan S, Campbell DA, Ruffin RE. A randomized trial of peak‐flow and symptom‐based action plans in adults with moderate‐to‐severe asthma. Respirology 2001;6(4):297‐304. - PubMed
Adler 2004 {published data only}
    1. Adler DA, Bungay KM, Wilson B, Pei Y, Supran S, Peckham E, et al. The impact of a pharmacist intervention on 6‐month outcomes in depressed primary care patients. General Hospital Psychiatry 2004;26(3):199‐209. - PubMed
Alhalaiqa 2012 {published data only}
    1. Alhalaiqa F, Deane KH, Nawafleh AH, Clark A, Gray R. Adherence therapy for medication non‐compliant patients with hypertension: a randomised controlled trial. Journal of Human Hypertension 2012;26(2):117‐26. [MEDLINE: ] - PMC - PubMed
Allen 2002 {published data only}
    1. Allen JK, Blumenthal RS, Margolis S, Rohm YD, Miller ER, et al. Nurse case management of hypercholesterolemia in patients with coronary heart disease: results of a randomized clinical trial. American Heart Journal 2002;144(4):678‐86. - PubMed
Al Rashed 2002 {published data only}
    1. Al Rashed SA, Wright DJ, Roebuck N, Sunter W, Chrystyn H. The value of inpatient pharmaceutical counselling to elderly patients prior to discharge. British Journal of Clinical Pharmacology 2002;54(6):657‐64. - PMC - PubMed
Al‐Saffer 2005 {published data only}
    1. Al‐Saffer N, Deshmekh AA, Carter P, Adib AM. Effect of information leaflets and counselling on antidepressant adherence: open randomized controlled trial in a psychiatric hospital in Kuwait. International Journal of Pharmacy Practice 2005;13(2):123‐31.
Alves da Costa 2005 {published data only}
    1. Alves da Costa F, Guerreiro JP, Nunes de Melo M, Costa Miranda A, Martins AP, Garcao J, et al. Effect of reminder cards on compliance with antihypertensive medication. International Journal of Pharmacy Practice 2005;13(3):205‐11.
Antoni 2006 {published data only}
    1. Antoni MH, Carrico AW, Durán RE, Spitzer S, Penedo F, Ironson G, et al. Randomized clinical trial of cognitive behavioral stress management on human immunodeficiency virus viral load in gay men treated with highly active antiretroviral therapy. Psychosomatic Medicine 2006;68(1):143‐51. - PubMed
Armour 2007 {published data only}
    1. Armour C, Bosnic‐Anticevich S, Brillant M, Burton D, Emmerton L, Krass I, et al. Pharmacy Asthma Care Program (PACP) improves outcomes for patients in the community. Thorax 2007;62(6):496‐502. [CENTRAL: CN‐00586650] - PMC - PubMed
Arthur 2002 {published data only}
    1. Arthur AJ, Jagger C, Lindesay J, Matthews RJ. Evaluating a mental health assessment for older people with depressive symptoms in general practice: a randomised controlled trial. British Journal of General Practice 2002;52(476):202‐7. - PMC - PubMed
Atherton‐Naji 2001 {published data only}
    1. Atherton‐Naji A, Hamilton R, Riddle W, Naji S. Improving adherence to antidepressant drug treatment in primary care: a feasibility study for a randomized controlled trial of education intervention. Primary Care Companion to the Journal of Clinical Psychiatry 2001;7(2):61‐7.
Azrin 1998 {published data only}
    1. Azrin NH, Teichner G. Evaluation of an instructional program for improving medication compliance for chronically mentally ill outpatients. Behavior Research and Therapy 1998;36(9):849‐61. - PubMed
Baker 2001 {published data only}
    1. Baker R, Reddish S, Robertson N, Hearnshaw H, Jones B. Randomised controlled trial of tailored strategies to implement guidelines for the management of patients with depression in general practice. British Journal of General Practice 2001;51(470):737‐41. - PMC - PubMed
Ball 2006 {published data only}
    1. Ball JR, Mitchell PB, Corry JC, Skillecorn A, Smith M, Malhi GS. A randomized controlled trial of cognitive therapy for bipolar disorder: focus on long‐term change. Journal of Clinical Psychiatry 2006;67(2):277‐86. - PubMed
Banet 1997 {published data only}
    1. Banet GA, Felchlia MA. The potential utility of a shared medical record in a "first‐time" stroke population. Journal of Vascular Nursing 1997;15(1):29‐33. - PubMed
Barbanel 2003 {published data only}
    1. Barbanel D, Eldridge S, Griffiths C. Can a self‐management programme delivered by a community pharmacist improve asthma control? A randomised trial. Thorax 2003;58(10):851‐4. - PMC - PubMed
Barcelo 2001 {published data only}
    1. Barcelo A, Robles S, White F, Jadue L, Vega J. An intervention to improve diabetes control in Chile. Revista Panamericana de Salud Publica/Pan American Journal of Public Health 2001;10(5):328‐33. - PubMed
Bass 1986 {published data only}
    1. Bass MJ, McWhinney IR, Donner A. Do family physicians need medical assistants to detect and manage hypertension?. Canadian Medical Association Journal 1986;134(11):1247‐55. - PMC - PubMed
Begley 1997 {published data only}
    1. Begley S, Livingstone C, Hodges N, Williamson V. Impact of domiciliary pharmacy visits on medication management in an elderly population. International Journal of Pharmacy Practice 1997;5(3):111‐21.
Berg 1997 {published data only}
    1. Berg J, Dunbar‐Jacob J, Sereika SM. An evaluation of a self‐management program for adults with asthma. Clinical Nursing Research 1997;6(3):225‐38. - PubMed
Berg 2011 {published data only}
    1. Berg KM, Litwin A, Li X, Heo M, Arnsten JH. Directly observed antiretroviral therapy improves adherence and viral load in drug users attending methadone maintenance clinics: a randomized controlled trial. Drug & Alcohol Dependence 2011;113(2‐3):192‐9. [MEDLINE: ] - PMC - PubMed
    1. Berg KM, Litwin AH, Li X, Heo M, Arnsten JH. Lack of sustained improvement in adherence or viral load following a directly observed antiretroviral therapy intervention. Clinical Infectious Diseases 2011;53(9):936‐43. [CENTRAL: CN‐00806074] - PMC - PubMed
    1. Berg KM, Mouriz J, Li X, Duggan E, Goldberg U, Arnsten JH. Rationale, design, and sample characteristics of a randomized controlled trial of directly observed antiretroviral therapy delivered in methadone clinics. Contemporary Clinical Trials 2009;30(5):481‐9. [MEDLINE: ] - PMC - PubMed
Bertakis 1986 {published data only}
    1. Bertakis KD. An application of the health belief model to patient education and compliance: acute otitis media. Family Medicine 1986;18(6):347‐50. - PubMed
Binstock 1986 {published data only}
    1. Binstock ML, Franklin KL, Formica EK. Therapeutic adherence programme improves compliance and lowers blood pressure. Journal of Hypertension 1986;4 Suppl:375‐7.
Birrer 1984 {published data only}
    1. Birrer RB, Chille E, Weiner M, Gruber S. Hypertension: a double‐blind study of compliance in an urban community. Family Practice Research Journal 1984;3:251.
Birtwhistle 2004 {published data only}
    1. Birtwhistle RV, Godwin MS, Delva MD, Casson RI, Lam M, MacDonald SE, et al. Randomised equivalence trial comparing three and six months of follow up of patients with hypertension by family practitioners. BMJ 2004;328:204‐6. - PMC - PubMed
Bisserbe 1997 {published data only}
    1. Bisserbe JC, Lane RM, Flament MF, the Franco‐Belgian OCD Study Group. A double‐blind comparison of sertraline and clomipramine in outpatients with obsessive‐compulsive disorder. European Psychiatry 1997;12:82‐93. - PubMed
Bodsworth 1997 {published data only}
    1. Bodsworth NJ, Crooks RJ, Borelli S, Vejlsgaard G, Paavonen J, Worm A‐M, et al. The International Valaciclovir HSV Study Group. Valaciclovir versus aciclovir in patient initiated treatment of recurrent genital herpes ‐ a randomised, double blind clinical trial. Genitourinary Medicine 1997;73:110‐6. - PMC - PubMed
Bogner 2008 {published data only}
    1. Bogner HR, Vries HF. Integration of depression and hypertension treatment: a pilot, randomized controlled trial. Annals of Family Medicine 2008;6(4):295‐301. [CENTRAL: CN‐00649720] - PMC - PubMed
BonAdASIA 2009 {published data only}
    1. BonAdASIA Study Group, Kung AW, Rachman IA, Adam JM, Roeshadi D, Torralba T, et al. Impact of bone marker feedback on adherence to once monthly ibandronate for osteoporosis among Asian postmenopausal women. International Journal of Rheumatic Diseases 2009;12(3):216‐24. [MEDLINE: ] - PubMed
Bonner 2002 {published data only}
    1. Bonner S, Zimmerman BJ, Evans D, Irigoyen M, Resnick D, Mellins RB. An individualized intervention to improve asthma management among urban Latino and African‐American families. Journal of Asthma 2002;39:167‐79. - PubMed
Bouvy 2003a {published data only}
    1. Bouvy ML, Heerdink ER, Urquhart J, Grobbee DE, Hoe AW, Leufkens HGM. Effect of a pharmacist‐led intervention on diuretic compliance in heart failure patients: a randomized controlled study. Journal of Cardiac Failure 2003;9:404‐11. - PubMed
Bouvy 2003b {published data only}
    1. Bouvy ML, Heerdink ER, Urquhart J, Grobbee DE, Hoe AW, Leufkens HGM. Guidance improves compliance. Pharmacist stimulates proper use of loop diuretics in patient with heart failure. Pharmaceutisch Weekblad 2003;138:1432‐9.
Brodaty 1983 {published data only}
    1. Brodaty H, Andrews G. Brief psychotherapy in family practice: a controlled prospective intervention trial. British Journal of Psychiatry 1983;143:11‐9. - PubMed
Brook 2002 {published data only}
    1. Brook I. Antibacterial therapy for acute group A streptococcal pharyngotonsillitis: short‐course versus traditional 10‐day oral regimens. Paediatric Drugs 2002;4:747‐54. - PubMed
Brook 2003 {published data only}
    1. Brook O. Impact of coaching by community pharmacists on drug attitude of depressive primary care patients and acceptability to patients; a randomized controlled trial. European Neuropsychopharmacology 2003;13:1‐9. - PubMed
Brook 2005 {published data only}
    1. Brook OH, Hout H, Stalman W, Nieuwenhuyse H, Bakker B, Heerdink E, et al. A pharmacy‐based coaching program to improve adherence to antidepressant treatment among primary care patients. Psychiatric Services 2005;56(4):487‐9. - PubMed
Brotons 2005 {published data only}
    1. Brotons C, Martinez M, Rayo E, Morralla C, Ballarin E, Perez E, Investigadores del Estudio IC‐DOM. Randomised clinical trial to evaluate the efficacy of a multi‐factorial intervention to reduce hospitalisation and improve the quality of life of patients with heart failure. Atencion Primaria 2005;36(5):280‐3. - PMC - PubMed
Brown 1987 {published data only}
    1. Brown CS, Wright RG, Christensen DB. Association between type of medication instruction and patients’ knowledge, side effects, and compliance. Hospital & Community Psychiatry 1987;38:55‐60. - PubMed
Brown 1997b {published data only}
    1. Brown SJ, Lieberman DA, Gemeny BA, Fan YC, Wilson DM, Pasta DJ. Educational video game for juvenile diabetes: results of a controlled trial. Medical Informatics 1997;22(1):77‐89. - PubMed
Browne 2002 {published data only}
    1. Browne G, Steiner M, Roberts J, Gafni A, Byrne C, Dunn E, et al. Sertraline and/or interpersonal psychotherapy for patients with dysthymic disorder in primary care: 6‐month comparison with longitudinal 2‐year follow‐up of effectiveness and costs. Journal of Affective Disorders 2002;68:317‐30. - PubMed
Buchanan‐Lee 2002 {published data only}
    1. Buchanan‐Lee B, Levetan BN, Lombard CJ, Commerford PJ. Fixed‐dose versus adjusted‐dose warfarin in patients with prosthetic heart valves in a peri‐urban impoverished population. Journal of Heart Valve Disease 2002;11:583‐93. - PubMed
Bukstein 2003 {published data only}
    1. Bukstein DA, Luskin AT, Bernstein A. "Real‐world" effectiveness of daily controller medicine in children with mild persistent asthma. Annals of Allergy, Asthma, & Immunology 2003;90:543‐9. - PubMed
Bungay 2004 {published data only}
    1. Bungay KM, Adler DA, Rogers WH, McCoy C, Kaszuba M, Supran S, et al. Description of a clinical pharmacist intervention administered to primary care patients with depression. General Hospital Psychiatry 2004;26:210‐8. - PubMed
Burkhart 2002 {published data only}
    1. Burkhart PV, Dunbar‐Jacob JM, Fireman P, Rohay J. Children's adherence to recommended asthma self‐management. Pediatric Nursing 2002;28:409‐14. - PubMed
Burnand 2002 {published data only}
    1. Burnand Y, Andreoli A, Kolatte E, Venturini A, Rosset N. Psychodynamic psychotherapy and clomipramine in the treatment of major depression. Psychiatric Services 2002;53:585‐90. - PubMed
Bussmann 2009 {published data only}
    1. Bussmann H, Wester CW, Thomas A, Novitsky V, Okezie R, Muzenda T, et al. Response to zidovudine/didanosine‐containing combination antiretroviral therapy among HIV‐1 subtype C‐infected adults in Botswana: two‐year outcomes from a randomized clinical trial. Journal of Acquired Immune Deficiency Syndromes 2009;51(1):37‐46. [MEDLINE: ] - PMC - PubMed
Caine 2002 {published data only}
    1. Caine N, Sharples W, Hollingworth J, French J, Leogan A, Exley D, et al. A randomised controlled crossover trial of nurse practitioner versus doctor‐led outpatient care in a bronchiectasis clinic. Health Technology Assessment 2002;6:1‐71. - PubMed
Canto De Cetina 2001 {published data only}
    1. Canto De Cetina TE, Canto P, Ordonez Luna M. Effect of counseling to improve compliance in Mexican women receiving depot‐medroxyprogesterone acetate. Contraception 2001;63(3):143‐6. - PubMed
Cantor 1985 {published data only}
    1. Cantor JC, Morisky DE, Green LW, Levine DM, Salkever DS. Cost‐effectiveness of educational interventions to improve patient outcomes in blood pressure control. Preventive Medicine 1985;14:782‐800. - PubMed
Capoccia 2004 {published data only}
    1. Capoccia KL, Boudreau DM, Blough DK, Ellsworth AJ, Clark DR, Stevens NG, et al. Randomized trial of pharmacist interventions to improve depression care and outcomes in primary care. American Journal of Health‐System Pharmacy 2004;61:364‐72. - PubMed
Cargill 1992 {published data only}
    1. Cargill JM. Medication compliance in elderly people: influencing variables and interventions. Journal of Advanced Nursing 1992;17:422‐6. - PubMed
Carroll 2004 {published data only}
    1. Carroll CL, Feldman SR, Camacho FT, Balkrishnan R. Better medication adherence results in greater improvement in severity of psoriasis. British Journal of Dermatology 2004;151(4):895‐7. - PubMed
Celik 1997 {published data only}
    1. Celik O, Gok U, Yalcin S, Karlidag T, Susaman N, Cetinkaya T. Comparison of the clinical efficacy of azithromycin and cerufoxime axetile in the treatment of patients with acute otitis media. Mikrobiyoloji Bulteni 1997;31:253‐61.
Chaisson 2001 {published data only}
    1. Chaisson RE, Barnes GL, Hackman J, Watkinson L, Kimbrough L, Metha S, et al. A randomized, controlled trial of interventions to improve adherence to isoniazid therapy to prevent tuberculosis in injection drug users. American Journal of Medicine 2001;110:610‐5. - PubMed
Chang 2010 {published data only}
    1. Chang LW, Kagaayi J, Nakigozi G, Ssempijja V, Packer AH, Serwadda D, et al. Effect of peer health workers on AIDS care in Rakai, Uganda: a cluster‐randomized trial. PloS One 2010;5(6):e10923. [MEDLINE: ] - PMC - PubMed
Chang 2011 {published data only}
    1. Chang LW, Kagaayi J, Arem H, Nakigozi G, Ssempijja V, Serwadda D, et al. Impact of a mHealth intervention for peer health workers on AIDS care in rural Uganda: a mixed methods evaluation of a cluster‐randomized trial. AIDS and Behavior 2011;15(8):1776‐84. [3740] - PMC - PubMed
Cheng 2001 {published data only}
    1. Cheng CL, Chee SP, Tan DT. Patient reliability in the administration of topical ocular medication. Singapore Medical Journal 2001;42:252‐4. - PubMed
Cheung 1988 {published data only}
    1. Cheung R, Sullens CM, Seal D, Dickins J, Nicholson PW, Deshmukh AA, et al. The paradox of using a 7 day antibacterial course to treat urinary tract infections in the community. British Journal of Clinical Pharmacology 1988;26:391‐8. - PMC - PubMed
Chien 2006 {published data only}
    1. Chien WT, Chan SW, Thompson DR. Effects of a mutual support group for families of Chinese people with schizophrenia: 18‐month follow‐up. British Journal of Psychiatry 2006;189:41‐9. - PubMed
Chiou‐Tan 2003 {published data only}
    1. Chiou‐Tan FY, Garza H, Chan KT, Parsons KC, Donovan WH, Robertson CS, et al. Comparison of dalteparin and enoxaparin for deep venous thrombosis prophylaxis in patients with spinal cord injury. American Journal of Physical Medicine & Rehabilitation 2003;82:678‐85. - PubMed
Chisholm 2001 {published data only}
    1. Chisholm MA, Mulloy LL, Jagadeesan M, DiPiro JT. Impact of clinical pharmacy services on renal transplant patients' compliance with immunosuppressive medications. Clinical Transplantation 2001;15:330‐6. - PubMed
Choi 2002 {published data only}
    1. Choi IJ, Jung HC, Choi KW, Kim JH, Ahn DS, Yang US, et al. Efficacy of low‐dose clarithromycin triple therapy and tinidazole‐containing triple therapy for Helicobacter pylori eradication. Alimentary Pharmacology & Therapeutics 2002;16:145‐51. - PubMed
Clancy 2003 {published data only}
    1. Clancy DE, Brown SB, Magruder KM, Huang P. Group visits in medically and economically disadvantaged patients with type 2 diabetes and their relationships to clinical outcomes. Topics in Health Information Management 2003;24:8‐14. - PubMed
Clarkin 1998 {published data only}
    1. Clarkin JF, Carpenter D, Hull J, Wilner P, Glick I. Effects of psychoeducational intervention of married patients with bipolar disorder and their spouses. Psychiatric Services 1998;49(4):531‐3. - PubMed
Clifford 2002 {published data only}
    1. Clifford RM, Batty KT, Davis TME, Davis W, Stein G, Stewart G, et al. A randomised controlled trial of a pharmaceutical care programme in high‐risk diabetic patients in an outpatient clinic. International Journal of Pharmacy Practice 2002;10:85‐9.
Cochran 1984 {published data only}
    1. Cochran SD. Preventing medical noncompliance in the outpatient treatment of bipolar affective disorders. Journal of Consulting and Clinical Psychology 1984;52:873‐8. - PubMed
Cockburn 1997 {published data only}
    1. Cockburn J, Thompson SC, Marks R, Jolley D, Schofield P, Hill D. Behavioural dynamics of a clinical trial of sunscreens for reducing solar keratoses in Victoria, Australia. Journal of Epidemiology and Community Health 1997;51(6):716‐21. - PMC - PubMed
Cohn 2002 {published data only}
    1. Cohn SE, Kammann E, Williams P, Currier JS, Chesney MA. Association of adherence to Mycobacterium avium complex prophylaxis and antiretroviral therapy with clinical outcomes in acquired immunodeficiency syndrome. Clinical Infectious Diseases 2002;34:1129‐36. - PubMed
Colom 2003 {published data only}
    1. Colom F, Vieta E, Reinares M, Martinez‐Aran A, Torrent C, Goikolea JM, et al. Psychoeducation efficacy in bipolar disorders: beyond compliance enhancement. Journal of Clinical Psychiatry 2003;64:1101‐5. - PubMed
Cooper 2004 {published data only}
    1. Cooper C. Efficacy and safety of oral weekly ibandronate in the treatment of postmenopausal osteoporosis. Journal of Clinical Endocrinology & Metabolism 2004;88:4609‐15. - PubMed
Cordina 2001 {published data only}
    1. Cordina M, McElnay JC, Hughes CM. Assessment of a community pharmacy‐based program for patients with asthma. Pharmacotherapy 2001;21:1196‐203. - PubMed
Couturaud 2002 {published data only}
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Cramer 2003 {published data only}
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References to studies awaiting assessment

Andres 2007 {published data only}
    1. Andres Rodriguez NF, Fornos Perez JA, Andres Iglesias JC. Assessment of knowledge/compliance in a drug therapy follow‐up program involving type 2 diabetic patients in community pharmacy: a randomized study. Pharmaceutical Care Espana 2007;9(1):2‐9. [CENTRAL: CN‐00754602]
Clowes 2004 {published data only}
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Additional references

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