Primary nonadherence to chronic disease medications: a meta-analysis

Figures & data

Figure 1 Prisma flow diagram for included studies.

Table 1 Description of included studies

Study and study location	Prescribed medication class	Duration of follow-up	Study design	Average/median age (years)	Database	Level of measurement	Predictors of primary nonadherence
Aznar-Lou et al;^Citation26 2017, Spain	Hypoglycemics Antihypertensives Lipid-lowering Antidepressants	1 month	R.cohort	52.4	Administrative	Prescription	No comorbidities, diseases other than diabetes, young female prescribing GP, GP in training
Bauer et al;^Citation15 2014, USA	Antidepressants	2 months	R.cohort	58	Administrative	Patient	Lack of involvement in decision making
Casebeer et al;^Citation27 2009, USA	Lipid-lowering	4 months	CT	58	Hospital	Patient	No social support: absence of educational programs
Chan et al;^Citation3 2004, Canada	Antihypertensives Lipid-lowering	60 months	R.cohort	70	Hospital	Patient	–
Cheetham et al;^Citation28 2013, USA	Lipid-lowering	3 months	R.cohort	57a	Administrative	Patient	Black race, polymedication
Derose et al;^Citation29 2013, USA	Lipid-lowering	3 months	RCT	56.1	Administrative	Patient	No social support: absence of text reminder, no drug coverage
Ewen et al;^Citation30 2015, Germany	Antihypertensives	6 months	P.cohort	62.7	Hospital	Patient	–
Fischer et al;^Citation31 2015, USA	Hypoglycemics Antihypertensives Lipid-lowering	0.5 months	RCT	53.2	Hospital	Patient	–
Fischer et al;^Citation12 2010, USA	Hypoglycemics Antihypertensives Lipid-lowering Antidepressants	12 months	R.cohort	44.3	Administrative	Prescription	New prescriptions
Freccero et al;^Citation32 2016, Sweden	Antidepressants	1 month	R.cohort	48.2	Administrative	Patient	Country of origin, young age, marital status (divorce)
van Geffen et al;^Citation33 2009, the Netherland	Antidepressants	1 month	R.cohort	48.5	Hospital	Patient	New prescriptions
Jackevicius et al;^Citation34 2008, Canada	Hypoglycemics Antihypertensives Lipid-lowering Antidepressants	1 month	R.cohort	76.3	Administrative	Prescription	Older age, higher income, more medications
Karter et al;^Citation35 2009, USA	Hypoglycemics Antihypertensives Lipid-lowering	2 months	R.cohort	61.2	Administrative	Patient	–
Kerner et al;^Citation36 2017, USA	Antihypertensives	1 month	P.cohort	63.9	Hospital	Patient	No social support: absence of messages and calls
Linnet et al;^Citation19 2012, Iceland	Hypoglycemics Antihypertensives Antidepressants	1 month	R.cohort	–	Administrative	Prescription	Cost
O’Connor et al;^Citation37 2014, USA	Hypoglycemics	2 months	RCT	61.7	Administrative	Patient	No social support: absence of telephone support
Raebel et al;^Citation25 2012, USA	Hypoglycemics Antihypertensives Lipid-lowering	1 month	R.cohort	59.2	Administrative	Patient	Race, smoking, less care contacts, comorbidities, cost
Shah et al;^Citation38 2008, USA	Hypoglycemics	1 month	R.cohort	49	Administrative	Patient	Cost, good health
Shah et al;^Citation39 2009, USA	Antihypertensives	1 month	R.cohort	47	Administrative	Patient	Female, comorbidities, older age, less severe disease
Shin et al;^Citation16 2012, USA	Hypoglycemics Antihypertensives Lipid-lowering Antidepressants	3 months	R.cohort	46.5	Administrative	Prescription	Minority race, lower income, greater number of prescriptions on the index date
Tamblyn et al;^Citation40 2014, Canada	Hypoglycemics Antihypertensives Lipid-lowering	9 months	P.cohort	61.6	Hospital	Prescription	New prescriptions, young age, cost, lower health visits
Thengilsdóttir et al;^Citation14 2015, Iceland	Lipid-lowering Antidepressants	12 months	R.cohort	58.7 45.4	Administrative	Prescription	Female gender, cost
Trinacty et al;^Citation41 2009, USA	Hypoglycemics	1 month	R.cohort	51	Administrative	Patient	–
Xing et al;^Citation42 2011, USA	Antidepressants	24 months	R.cohort	51.5	Administrative	Prescription	New prescriptions, young age

Notes: Database: the data source, that is, administrative (from large admin databases), hospital (from clinic or hospital records). Level of measurement: primary nonadherence could have been measured as the proportion of participants (patient level of measurement) failing to fill their prescription or the proportion of prescriptions not filled (prescription level of measurement).

a The age obtained from this particular study was a median value (unlike the others which were means).

Abbreviations: CT, controlled trial; GP, General Practitioner; PMNA, primary medication nonadherence; P.cohort, prospective cohort; R.cohort, retrospective cohort; RCT, randomized controlled trial.

Figure 2 (A) Risk-of-bias plot – experimental studies. (B) Risk-of-bias plot – observational studies.

Table 2 Pooled estimates

Study and study location	Prescribed medication class	Number of study prescriptions	Primary nonadherence rate (%)	95% CI
Aznar-Lou et al;^Citation26 2017, Spain	Hypoglycemics	8,270	13.2	12.5–14.0
	Antihypertensives	74,346	7.5	7.3–7.7
	Lipid-lowering	69,602	8.8	8.6–9.0
	Antidepressants	97,635	11.5	11.3–11.7
Bauer et al;^Citation15 2014, USA	Antidepressants	1,523	4.3	3.3–5.4
Casebeer et al;^Citation27 2009, USA	Lipid-lowering	913	43.2	39.9–46.4
Chan et al;^Citation3 2004, Canada	Antihypertensives	1,700	33.5	31.3–35.8
	Lipid-lowering	1,700	71.0	68.8–73.1
Cheetham et al;^Citation28 2013, USA	Lipid-lowering	19,826	15.4	14.9–15.9
Derose et al;^Citation29 2013, USA	Lipid-lowering	5,216	18.4	17.4–19.5
Ewen et al;^Citation30 2015, Germany	Antihypertensives	100	2.0	0.2–7.0
Fischer et al;^Citation31 2015, USA	Hypoglycemics	346	6.4	4.0–9.5
	Antihypertensives	2,065	3.3	2.6–4.2
	Lipid-lowering	528	6.4	4.5–8.9
Fischer et al;^Citation12 2010, USA	Hypoglycemics	5,525	21.9	20.8–23.0
	Antihypertensives	30,211	19.5	19.0–19.9
	Lipid-lowering	12,963	19.9	19.2–20.6
	Antidepressants	11,767	21.4	20.6–22.1
Freccero et al;^Citation32 2016, Sweden	Antidepressants	11,624	14.9	14.3–15.6
van Geffen et al;^Citation33 2009, the Netherland	Antidepressants	965	4.3	3.1–5.7
Jackevicius et al;^Citation34 2008, Canada	Hypoglycemics	146	13.7	8.6–20.4
	Antihypertensives	5,337	6.4	5.8–7.1
	Lipid-lowering	758	5.2	3.7–7.0
	Antidepressants	43	32.6	19.1–48.5
Karter et al;^Citation35 2009, USA	Hypoglycemics	8,191	4.0	3.6–4.5
	Antihypertensives	12,712	3.2	2.9–3.5
	Lipid-lowering	6,426	8.5	7.8–9.2
Kerner et al;^Citation36 2017, USA	Antihypertensives	9	22.2	2.8–60.0
Linnet et al;^Citation19 2012, Iceland	Hypoglycemics	760	8.7	6.8–10.9
	Antihypertensives	4,127	8.6	7.7–9.5
	Antidepressants	4,492	6.6	5.9–7.4
O’Connor et al;^Citation37 2014, USA	Hypoglycemics	2,378	13.3	11.9–14.7
Raebel et al;^Citation25 2012, USA	Hypoglycemics	1,521	11.3	9.8–13.0
	Antihypertensives	4,721	7.0	6.3–7.8
	Lipid-lowering	4,607	12.6	11.6–13.6
Shah et al;^Citation38 2008, USA	Hypoglycemics	1,132	15	13.0–17.2
Shah et al;^Citation39 2009, USA	Antihypertensives	3,240	17.1	15.8–18.5
Shin et al;^Citation16 2012, USA	Hypoglycemics	14,417	12.6	12.0–13.1
	Antihypertensives	48,982	7.8	7.5–8.0
	Lipid-lowering	22,249	22.3	21.8–22.9
	Antidepressants	27,383	7.7	7.4–8.0
Tamblyn et al;^Citation40 2014, Canada	Hypoglycemics	979	29.1	26.3–32.1
	Antihypertensives	3,108	32.2	30.5–33.8
	Lipid-lowering	2,794	33.6	31.9–35.4
Thengilsdóttir et al;^Citation14 2015, Iceland	Lipid-lowering	2,132	6.2	5.2–7.3
	Antidepressants	8,553	8.0	7.4–8.6
Trinacty et al;^Citation41 2009, USA	Hypoglycemics	1,906	10.0	8.7–11.5
Xing et al;^Citation42 2011, USA	Antidepressants	557	13.1	10.4–16.2
Pooled random estimate		550,485	14.6	13.1–16.2

Table 3 Subgroup analysis

Subgroup	PMNA (95% CI)	N
Medication
Hypoglycemics	13.2 (9.6–16.8)	45,571
Antihypertensives	12.4 (9.5–15.3)	190,658
Lipid-lowering	20.8 (16.0–25.6)	149,714
Antidepressants	10.8 (8.2–13.4)	164,542
Duration of follow-up
≤3 months	10.0 (8.7–11.4)	467,483
>3 months	25.3 (19.7–30.9)	83,002
Study design
R.cohort	13.5 (11.8–15.2)	532,049
P.cohort, CT, RCT	18.9 (11.0–26.8)	18,436
Average age, years
50 or less	14.8 (11.4–18.2)	199,011
51–60	11.4 (9.8–12.9)	295,714
>60	20.4 (14.9–25.8)	46,381
Data source
Administrative database	11.7 (10.2–13.3)	535,278
Hospital database	24.0 (12.0–35.9)	15,207
Level of measurement
Prescription	14.5 (12.7–16.4)	457,136
Patient	14.8 (11.4–18.2)	93,349
Risk of bias
Low risk	12.9 (11.2–14.5)	493,728
Unclear/high risk	17.3 (13.0–21.5)	56,757
Location
North America	17.0 (14.4–19.5)	267,879
Europe	8.5 (7.1–9.9)	282,606
Absence of social support
Yes	20.5 (14.4–26.6)	27,769
No	13.1 (11.4–14.8)	522,716

Abbreviations: CT, controlled trial; N, total number of prescriptions; PMNA, primary medication nonadherence; P.cohort, prospective cohort; RCT, randomized controlled trial; R.cohort, retrospective cohort.

Figure 3 Forest plot for primary medication nonadherence.

Notes: (a) hypoglycemics; (b) anti-hypertensives; (c) lipid-lowering; (d) anti-depressants.
Abbreviation: ES, effect size.

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