Compliance and persistence with Alzheimer’s disease treatment: a retrospective analysis of multiregional hospital databases in Thailand

Figures & data

Figure 1. A hypothetical example of AD treatment refilling course illustrating measurements of compliance (MPR, Medication Possession Ratio) and persistence (time to non-persistence).

Figure 2. Identification of eligible study subjects from five hospitals’ databases in Thailand for compliance and persistence analyses.

Table 1. Distribution of study subject’s characteristics.

Characteristics of study subjects	Number of subjects (%)
Gender
Male	253 (36.3)
Female	445 (63.8)
Age (mean ± SD)	78.1 ± 7.8
60–69	96 (13.8)
70–79	259 (37.1)
80–89	293 (42.0)
90 and above	50 (7.2)
Medical institutions
Ramathibodi Hospital	395 (56.6)
Sunpasithiprasong Hospital	78 (11.2)
Buddhachinaraj Hospital	71 (10.2)
Chiangrai Prachanukroh Hospital	118 (16.9)
Suansaranrom Hospital	36 (5.2)
AD medications
Donepezil	339 (48.6)
Galantamine	79 (11.3)
Rivastigmine	111 (15.9)
Memantine	169 (24.2)
Single AD treatment	610 (87.4)
Switchers	72 (11.8)
Non-switchers	538 (88.2)
Combination AD treatment	88 (12.6)
Switchers	0 (0)
Non-switchers	88 (100)
Polypharmacy (prescription of ≥ five medications during 6 months preceding the index date)	478 (68.5)
Health insurance schemes
USC	67 (9.6)
SHI	3 (0.4)
CSMBS	517 (74.1)
Self-payment	111 (15.9)

Abbreviations. SD, Standard Deviation; AD, Alzheimer’s Disease; USC, Universal Coverage Scheme; SHI, Social Health Insurance; CSMBS, Civil Servant Medical Benefit Scheme.

Figure 3. A survival curve illustrating persistence probabilities with AD treatment over a 1-year observational period.

Table 2. Bivariate analyses exploring associations between patient characteristics and compliance with AD treatment.

Patient characteristics	Compliance (%)	Odds ratios of compliance (95% CI)	p-value of the Chi-square statistics
Gender			.224
Male	73.1	1
Female	68.8	0.81 (0.57–1.14)
Age			.867
60–69 years	67.7	1
70–79 years	69.9	1.11 (0.67–1.83)
80–89 years	71.0	1.17 (0.71–1.92)
90 years and above	74.0	1.36 (0.63–2.91)
University-affiliated hospital			<.001
Yes	65.3	1
No	76.9	1.77 (1.26–2.48)
Types of AD treatment			.530
Donepezil	69.0	1
Galantamine	72.2	1.16 (0.68–2.00)
Rivastigmine	75.7	1.40 (0.85–2.28)
Memantine	68.6	0.98 (0.66–1.46)
Multiple AD medications			<.001
Yes	85.2	1
No	68.2	0.37 (0.20–0.69)
Patch dosage form			.173
Yes	75.7	1
No	69.3	0.73 (0.46–1.16)
Polypharmacy (prescription of ≥ five medications during 6 months preceding the index date)			.307
Yes	71.6	1
No	67.7	0.83 (0.59–1.18)
Reimbursable for AD treatment			.531
Yes	71.0	1
No	68.5	0.89 (0.62–1.28)

Abbreviations. SD, Standard Deviation; 95% CI, 95% Confidence Interval; AD, Alzheimer’s Disease.

Table 3. Multivariate analyses of the patient characteristics selected from the bivariate analyses to investigate determinants of non-compliance and non-persistence.

Patient characteristics	Adjusted odds ratio* of non-compliance (95% CI)	Adjusted hazard ratios* of non-persistence (95% CI)
University-affiliated hospital
Yes	1.71 (1.21–2.42)	1.33 (1.12–1.58)
No	1	1
Multiple AD medications
Yes	1	–
No	2.52 (1.35–4.69)	–
Reimbursable for AD treatment
Yes	–	1
No	–	1.34 (1.11–1.62)

*adjusted for age and gender.

Abbreviations. SD, Standard Deviation; 95% CI, 95% Confidence Interval; AD, Alzheimer’s Disease.

Table 4. Bivariate analyses exploring associations between patient characteristics and persistence probabilities with AD treatment.

Patient characteristics	Persistence probabilities at 1 year (%)	95% CI of persistence probabilities	p-value of the log-rank statistics
Gender			.676
Male	20.1	15.8–25.7
Female	21.4	17.7–25.3
Age			.210
60–69 years	22.9	15.1–31.7
70–79 years	22.4	17.5–27.6
80–89 years	20.5	16.1–25.3
90 years and above	14.0	6.2–25.0
University-affiliated hospital			<.001
Yes	17.5	13.9–21.4
No	25.7	21.0–30.8
Types of AD treatment			.903
Donepezil	20.9	16.8–25.4
Galantamine	20.3	12.2–29.7
Rivastigmine	22.5	15.3–30.7
Memantine	20.7	15.0–27.1
Multiple AD medications			.744
Yes	14.8	8.3–23.0
No	22.0	18.8–25.3
Patch dosage form			.774
Yes	22.5	15.3–30.7
No	20.8	17.6–24.2
Polypharmacy (prescription of ≥ five medications during 6 months preceding the index date)			.948
Yes	21.1	17.6–24.9
No	20.9	15.8–26.5
Reimbursable for AD treatment			.002
Yes	23.8	20.2–27.5
No	13.3	8.8–18.6

Abbreviations. SD, Standard Deviation; 95% CI, 95% Confidence Interval; AD, Alzheimer’s Disease.

Table 5. Sensitivity analyses.

Sensitivity analyses	Mean MPR (SD)	% Compliance (95% CI)	Median time to non-persistence (days) (IQR)	1-year persistence probability (95% CI)
Excluding the datasets which captured the different period of prescribing information
Main analysis	0.83 (0.25)	70.3 (66.8–73.7)	177 (72–330)	21.1 (18.1–24.2)
After the exclusion	0.83 (0.25)	69.3 (65.7–72.8)	174 (70–324)	20.4 (17.4–23.5)
Varying the permissible gap of persistence analysis
Gap <15 days	–	–	129 (47–281)**	17.7 (15.0–20.7)
Gap <30 days (Main analysis)	–	–	177 (72–330)	21.1 (18.1–24.2)
Gap <45 days	–	–	208 (90–358)*	24.2 (21.1–27.4)
Gap <60 days	–	–	213 (99–NA)**	26.6 (23.4–29.9)

*p-value of the Kruskal-Wallis test <.05.

**p-value of the Kruskal-Wallis test <.001.

Abbreviations. SD, Standard Deviation; 95% CI, 95% Confidence Interval; IQR, Interquartile Range; AD, Alzheimer’s Disease.