Table 1.

Studies of Educational Interventions to Optimize Medication Adherence

Study	Design/ Setting	Sample*	Intervention	Definition of Adherence	Results	Effect Size (Cohen's d)
Begley et al (1997) [32]	RCT/UK	190 men and women, mean age ≥ 75 yr (n's for intervention and controls not reported)	Pharmacist completed 5 home visits over 12 mo for counseling on correct use and storage of drugs vs. Attention Control with 5 home visits but no counseling vs. Usual Care	Taking ≥ 85% of drug doses measured by pill count	At 12 mo, mean percentage adherence was Intervention: 86% (SD = 19) Attention Control: 75% (SD = 21) Usual Care: 69% (SD = 29) P < 0.001	0.58
Bernsten et al (2001) [33]	Cluster RCT/ 7 European countries	190 pharmacies Intervention: n = 104 with 1290 men and women, mean age 74 (8) yr Control: n = 86 with 1164 men and women, mean age 74 (8) yr	Pharmacist assessed patients individually to identify actual and potential drug problems and formulated an intervention and monitoring plan vs. Usual Care	Never experiencing aspects of nonadherence measured on a 4-item, 4-point Likert self-report scale	At 18 mo, proportion who changed from being non- adherent to adherent was Intervention: 15.2% (107/704) Control: 12.2% (77/636) P = 0.028	0.14
Bouvy et al (2003) [34]	RCT/ Netherlands	152 men and women with heart failure Intervention: n = 74, mean age 69.1 (10.2) yr Control: n = 78, mean age, 70.2 (11.2) yr	Pharmacist met with patients monthly over 6 mo for counseling on drug use, reasons for nonadherence, and reinforcement of adherence vs. Usual Care	Days with dosing during scheduled dosing measured by EEM	At 6 mo Intervention: 140/7656 days without diuretic Control: 337/6196 days without diuretic, RR = 0.33 (95% CI, 0.24–0.38)	0.49
Clifford et al (2006) [35]	RCT/UK	492 men and women ≥ 75 yr Intervention: n = 255 Control: n = 237	Pharmacist telephoned patients 2 wk after starting a new medication for a chronic disorder to identify medication- related problems and information needs and provide advice, information, and reassurance vs. Usual Care	Not missing any doses in the last 7 days measured by self-report	At 1 mo, proportion nonadherent was Intervention: 9% (16/185) Control: 16% (31/194) P = 0.032	0.37
Coull et al (2004) [36]	RCT/UK	319 men and women with heart disease Intervention: n = 165, mean age 67.7 yr Control: n = 154, mean age 67.4 yr (SDs not reported)	Monthly small group lay health mentoring on cardiovascular disease including medication adherence vs. Usual Care	Perceived change in taking medication measured by self-report on 5-point Likert scale	At 12 mo, adherence improved more in intervention than control subjects P < 0.01	0.28
Grant et al (2003) [37]	RCT/US	120 men and women with type 2 diabetes Intervention: n = 62, mean age 64 (12) yr Control: n = 58, mean age 69 (10) yr	Pharmacist telephoned patients for tailored education on drug use, help with appointment referrals, and electronic summary to medical record and physician vs. Usual Care	Not missing any doses of any diabetes-related medication in the last 7 days measured by self-report	At 3 mo, mean improvement from baseline was Intervention: n = 61, 0.1 days (SD = 1.0) Control: n = 54, 0.1 days (SD = 0.4) P = 0.80	0.00
Grymonpre et al (2001) [38]	RCT/ Canada	135 men and women Intervention: n = 69, mean age 76.9 (8.4) yr Control: n = 66, mean age 77.2 (8.8) yr	Pharmacist completed a medication history, provided counseling and written information to patients, made recommendations to physician, and followed up as needed vs. medication history and referral to usual pharmacist for Usual Care	Percentage of prescribed doses taken measured by pharmacy refill	At 12 mo, mean adherence by drug was Intervention: n = 309 drugs, 86.7% (SD = 46.0) Control: n = 280 drugs, 85.1% (SD = 41.1) P = 0.895	0.04
Hanlon et al (1996) [39]	RCT/US	208 men and women, mean age ≥ 65 yr Intervention: n = 105 Control: n = 103	Pharmacist met with patients during all scheduled clinic visits to evaluate their drug regimens and make recommendations to them and their physicians vs. Usual Care	Proportion of medications for which the patient's response agreed with the directions for their use on the profile measured by self-report	At 12 mo, mean adherence was Intervention: n = 86, 77.4% Control: n = 83, 76.1% P = 0.88	0.02
Herschorn et al (2004) [40]	RCT/ Canada	84 men and women with overactive bladder Intervention: n = 39, mean age 65.7 (14.5) yr Control: n = 45, mean age 63.1 (15.7) yr	3 information sheets on overactive bladder, behavioral modification, and tolterodine with 3- to 5-min review by physician or study nurse vs. Usual Care	Taking the medication as prescribed measured by self-report	At 4 mo, proportion adherent was Intervention: n = 34, 39% Control: n = 31, 31% P > 0.05	0.22
Higgins et al (2004) [41]	RCT/UK	19 men and women with depression and new prescription for antidepressant, mean age ≥ 65 yr Intervention: n = 10 Control: n = 9	Concordance therapy by a psychiatrist over 3–4 sessions with cognitive behavioral therapy and motivational interviewing, which included medication information vs. Usual Care	Omission and dosage alteration measured on a self-report scale where maximum score of 50 = 100% adherence	At 3 mo, no significant group differences	Unable to compute
Hunt et al (2004) [42]	RCT/US	312 men and women with hypertension Intervention: n = 162, mean age 69.2 (12.4) yr Control: n = 150, mean age 69.3 (12.3) yr	2 mailed educational packets 3 months apart from primary care providers vs. Usual Care	Adherence measured on a 4-item dichotomous self- report scale	At 12 mo, mean adherence was Intervention: 0.35 Control: 0.35 P > 0.05	Unable to compute
Lim et al (2004) [43]	RCT/ Singapore	126 men and women Intervention: n = 64, mean age 79.6 (7.7) yr Control: n = 62, mean age 80.5 (8.1) yr	Pharmacist met with patients to review medical records for existing medication regimens and to counsel patients on medication knowledge and proper administration and use vs. Usual Care	Not forgetting to take medication as prescribed measured by self-report	At 2 mo, no significant group differences Unadjusted OR, 1.50 (90% CI, 0.73–3.08); P = 0.36 Adjusted OR, 2.52 (90% CI, 1.09–5.83); P = 0.07	0.22 0.51
Lowe et al (2000) [44]	RCT/UK	161 men and women Intervention: n = 77, mean age 77.5 yr Control: n = 84, mean age 75.0 yr (SD not reported)	Pharmacist met with patients 3 times for medication review and education vs. Usual Care	Percentage of prescribed doses taken measured by self-report and pill count	At 1 mo, mean adherence was Intervention: n = 73, 91.3% (95% CI, 88.7–93.9) Control: n = 79, 79.5% (95% CI, 74.7–84.3) P < 0.001	0.65
Naunton and Peterson (2003) [45]	RCT/ Australia	121 men and women Intervention: n = 57, mean age 74 yr Control: n = 64, mean age 77 yr	Pharmacist visited patients 5 days after hospital discharge to provide education about medications, encourage adherence, assess for drug-related problems, intervene when appropriate, and communicate findings to health care providers vs. wait list control	Never missing medication measured by single-item self-report	At 3 mo, proportion adherent was Intervention: 87% (47/55) Control: 44% (26/59) P < 0.001	1.28
Oakley and Walley (2006) [46]	RCT/UK	33 women on bisphosphonates, mean age 77 years Intervention: n = 16 Control: n = 17	Osteoporosis workshop; decision aid that included information booklet, audiocassette, and worksheet on personal lifetime risk of hip fracture, family health issues, and personal values; consultation with physician 2 wk later vs. Usual Care	Percentage of prescribed doses taken measured by pharmacy refill	At 4 mo, no significant group differences Intervention: median, 100% Control: median, 100% P = 0.80	0.08
Peterson et al (2004) [47]	RCT/ Australia	81 men and women with hyperlipidemia Intervention: n = 39, mean age 65.5 (11.0) yr Control: n = 42, mean age 63.5 (12.1) yr	Pharmacist assessed patients monthly in their homes regarding lipid therapy and lifestyle modifications vs. Usual Care	Frequency of forgetting to take medications measured by self-report	At 6 mo, no significant group differences	Unable to compute
Roumie et al (2006) [48]	Cluster RCT/US	1341 men and women with hypertension, mean age 65 (12) yr, and 182 health care providers Provider education: n = 324 Provider education and alert: n = 547 Provider education and alert and patient education: n = 470	Provider education about hypertension vs. Provider education and electronic alerts to re-evaluate antihypertensive regimen vs. Provider education and electronic alerts and mailed patient educational material	Adherence measured by pharmacy refill	At 12 mo (n = 948), mean adherence was Provider education: 0.89 (SD = 0.14) Provider education and alert: 0.89 (SD = 0.14) Provider education and alert and patient education: 0.88 (SD = 0.16) P = 0.71	0.02
Rozenfeld et al (1999) [31]	RCT/US	33 men and women Intervention: n = 17, mean age 66 (12) yr Control: n = 16, mean age 65 (10) yr	Pharmacist counseling at VAMC cardiology clinic with medication history, recommendations to cardiologists, medication counseling, drug information, therapeutic drug monitoring and follow-up, and continuity of care vs. Usual Care at VAMC outpatient pharmacy	Therapeutic coverage with optimal ≥ 80%, partial 20% to 80%, and poor < 20% measured by EEM	At 1 mo Intervention: 83.2% (SD = 19.9) Control: 78.0% (SD = 25.5) P = 1.00	0.24
Schroeder et al (2005) [49]	RCT/UK	245 men and women with hypertension Intervention: n = 128, mean age 67.9 (10.3) yr Control: n = 117, mean age 68.2 (9.4) yr	20-min nurse-led educational intervention and 10-min follow-up 2 mo later vs. Usual Care	Percentage days correct number of doses of prescribed doses taken on time measured by EEM	At 6 mo, mean percentage adherence was Intervention: 87.2% (SD = 20.1) Control: 90.2% (SD = 16.2) P = 0.63	0.16
Solomon et al (1998) [50]	RCT/US	133 men and women with hypertension Intervention: n = 63, mean age 66.3 (10.0) yr Control: n = 70, mean age 67.3 (11.0) yr 98 men with COPD Intervention: n = 43, mean age 69.3 (5.9) yr Control: n = 55, mean age 69.3 (9.2) yr	Pharmacy resident met 5 times for recommendations to physicians, patient education and counseling, patient assessment and follow-up vs. Usual Care	Adherence measured by 4-item dichotomous self- report scale (lower score is better adherence)	At 6 mo, in hypertension arm mean adherence was Intervention: 0.23 (SD = 0.054) Control: 0.61 (SD = 0.094) P < 0.05 In COPD arm, no significant group differences	4.93 Unable to compute
Stromberg et al (2006) [51]	RCT/ Sweden	154 men and women with heart failure Intervention: n = 82, mean age 70 (10) yr Control: n = 72, mean age 70 (11) yr	45-min interactive computer educational session plus Usual Care (educational session with a heart failure clinic nurse) vs. Usual Care	How often a dose of diuretics was skipped measured on a 1-item, 3-point self-report scale	At 1 mo, adherence improved more in intervention subjects (n = 72) than control subjects (n = 65); P = 0.01 At 6 mo, no significant group differences	0.43 Unable to compute
Sturgess et al (2003) [52]	Cluster RCT/UK	10 pharmacies Intervention: n = 5 with 110 men and women, mean age 73.1 (5.0) yr Control: n = 5 with 81 men and women, mean age 74.2 (6.3) yr	Pharmacist assessed patients individually to identify actual and potential drug-related problems during home visits vs. Usual Care	Adherence measured by self-report	At 18 mo, proportion adherent was Intervention: n = 75, 47.3% Control: n = 35, 14.7% P < 0.05	0.98
Taylor et al (2003) [53]	RCT/US	69 men and women Intervention: n = 33, mean age 64.4 (13.7) yr Control: n = 36, mean age 66.7 (12.3) yr	Pharmacist provided medical record review, medication history review, pharmacotherapeutic evaluation, patient education and monitoring vs. Usual Care	≥ 80% of prescribed doses taken in the previous week/month measured by self-report	At 12 mo, proportion adherent was Intervention: 100% Control: 88.9% P = 0.115	0.38
Varma et al (1999) [54]	RCT/UK	83 men and women with heart failure Intervention: n = 42, mean age 75.50 (6.44) yr Control: n = 41, mean age 76.36 (7.12) yr	Pharmacist provided education on heart failure, its treatment, and life- style changes to control symptoms; encouraged monitoring of symptoms and adherence with prescribed medication therapy vs. Usual Care	Using a minimum of 6 mo continuous data, adherence defined as 80%– 120% of prescribed doses taken measured by pharmacy refill Underadherence: < 80% Overadherence: > 120%	At 12 mo, adherence with at least 1 heart failure drug was Intervention: 77% (10/13) Control: 30% (3/10) P = 0.039	1.26
Vivian (2002) [55]	RCT/US	56 men with hypertension Intervention: n = 27, mean age 64.0 (10.9) yr Control: n = 29, mean age 65.5 (7.8) yr	Pharmacist at VAMC hypertension clinic met with patients monthly for appropriate changes in prescribed drugs, adjustments in dosages, and drug counseling vs. Usual Care	Refilling drugs within 2 wk of the scheduled refill date measured by pharmacy refill	At 6 mo, proportion adherent was Intervention: 85% (22/26) Control: 93% (25/27) P > 0.42	−0.43
Volume et al (2001) [56]	Cluster RCT/ Canada	16 pharmacies Intervention: n = 8 with 159 men and women, mean age 73.89 (6.09) yr Control: n = 8 with 204 men and women, mean age 73.18 (6.11) yr	Pharmacist spoke with patients in person or by telephone to assess, plan, and document actions related to pharmaceutical care vs. Usual Care	Adherence measured on a 4-item dichotomous self- report scale	At 12 mo Intervention: 0.56 (SD = 0.75) Control: 0.47 (SD = 0.69) P > 0.05	Unable to compute
Williams et al (2004) [57]	RCT/US	417 men and women with depression and diabetes Intervention: n = 205, mean age 70.1 (6.9) yr Control: n = 212, mean age 70.3 (7.1) yr	Depression care management program with care manager providing education, problem-solving treatment, and support vs. Usual Care	Taking diabetes medication as prescribed measured on a 5-point self-report scale	At 12 mo, mean adherence was Intervention: n = 193, 1.16 (SD = 0.53) Control: n = 200, 1.19 (SD = 0.50) P > 0.20	0.06
Wu et al (2006) [58]	RCT/ Hong Kong	442 men and women Intervention: n = 219, mean age 71.2 (9.4) yr Control: n =223, mean age 70.5 (11.1) yr	Pharmacist assessed patients individually via a telephone call between clinic visits vs. Usual Care	Adherence defined as 80%–120% of prescribed doses taken measured by self-report	At 24 mo, proportion nonadherent at enrollment who remained nonadherent was Intervention: 7% (7/102) Control: 18% (19/104) P < 0.001	0.58
					At 24 mo, proportion adherent at enrollment who remained adherent was Intervention: 81% (95/117) Control: 58% (69/119) P = 0.038	0.68

CI = confidence interval; COPD = chronic obstructive pulmonary disease; EEM = electronic event monitoring; OR = odds ratio; RCT = randomized controlled trial; RR = relative risk; SD = standard deviation; VAMC = Veterans Affairs Medical Center.

^*Number in parentheses is standard deviation.