Real-world impact of reminder packaging on antihypertensive treatment adherence and persistence

Figures & data

Figure 1 Study design.

Notes: The index date for first VAL-HCT-RP was defined as the first fill of Diovan^® HCT-RP, which occurred after October 28, 2009 (the date the packaging was released into the marketplace). The period of time that patients were identified for study inclusion based on their first fill of VAL-HCT-RP was considered as the enrollment period, which ranged from October 28, 2009 through January 31, 2010, allowing for patients to be followed for 6 months pre-index and post-index Diovan HCT-RP prescription.
Abbreviations: RP, reminder packaging; non-RP, without reminder packaging; VAL-HCT, valsartan-hydrochlorothiazide combination.

Table 1 Baseline characteristics: after match

Characteristics	RP (n = 4633)		non-RP (n = 4633)		P valuea	Standardized difference
Demographic characteristics
Age (mean, SD)	62.07	12.60	62.02	12.16	0.8262	0.45
Female (n, %)	2900	62.59	2889	62.36	0.8250	0.49
Region (n, %)
Midwest	849	18.33	901	19.45		2.87
Northeast	675	14.57	677	14.61	0.6556	0.12
South	2711	58.52	2656	57.33		2.40
West	398	8.59	399	8.61		0.08
Adherence in pre-index period (mean, SD)
MPR	82.43	18.63	82.57	19.39	0.6910	0.77
Refill timing (days)	8.77	14.61	8.84	13.55	0.7971	0.51
Prescription counts in pre-index period (mean, SD)
Unique HTN Rx classes (n)	0.62	0.79	0.62	0.79	0.8183	0.44
Unique HTN Rxs (n)	0.64	0.82	0.63	0.82	0.7718	0.55
Unique non-HTN Rx classes (n)	4.41	3.62	4.47	3.75	0.4224	1.55
Unique non-HTN Rxs (n)	4.61	3.89	4.68	4.05	0.3072	1.97
Comorbidity in pre-index period
Cardiovascular CDS Ib,c (mean, SD)	1.38	1.69	1.37	1.67	0.8649	0.33
Non-cardiovascular CDS IIb,d (mean, SD)	2.24	2.25	2.27	2.30	0.5337	1.25
Other diseases (n, %)
Renal disease	2	0.04	3	0.06	1.0000	0.93
End-stage renal disease	1	0.02	1	0.02	1.0000	0.00
Cystic fibrosis	2	0.04	1	0.02	1.0000	1.20
Liver failure	7	0.15	9	0.19	0.8036	1.04
Transplantation	0	0.00	1	0.02	–	–
Thyroid disorders	587	12.67	592	12.78	0.8987	0.32
Pain and inflammation	837	18.07	828	17.87	0.8180	0.51
Pain	1020	22.02	1009	21.78	0.7957	0.57
Depression	928	20.03	911	19.66	0.6730	0.92
Psychotic illness	78	1.68	84	1.81	0.6771	0.99
Bipolar disorder	4	0.09	3	0.06	1.0000	0.79
Human immunodeficiency virus	114	2.46	102	2.20	0.4368	1.72
Anxiety and tension	613	13.23	565	12.20	0.1094	3.11

Notes:

a t-test for continuous variables and Chi-square test for categorical variables;

b CDS is calculated by assigning a weight (score) to each drug class to correspond to disease complexity and severity. It is an aggregate of the assigned weights based on medication use, but not on frequency of use;

c CDS I is derived based on hypertensive (excluding valsartan-hydrochlorothiazide claims) and cardiac medications, by assigning scores suggested by Von Korff et al.²¹ Range (0–7);

d CDS II is derived based on medications of epilepsy, tuberculosis, rheumatologic conditions, hyperlipidemia, malignancies, Parkinson’s disease, diabetes, glaucoma, ulcer, respiratory illness, gout, acne, migraines, Crohn’s disease, and coronary disease by assigning scores suggested by Von Kroff et al.²¹ Range (0–27) Standardized difference = 100 * (x1 − x2)/√ {(s12 + s22)/2}, where x1 = mean of group 1, x2 = mean of group 2, s1 = standard deviation of group 1, and s2 = standard deviation of group 2.

Abbreviations: CDS, chronic disease score; ESRD, end-stage renal disease; HIV, human immunodeficiency virus; HTN, hypertension; MPR, medication possession ratio; RP, reminder packaging; Rx, prescription; SD, standard deviation; non-RP, without reminder packaging.

Figure 2 Reminder packaging dispensed to patients.

Table 2 Adherence and persistency outcomes

Outcome	RP (n = 4633)		non-RP (n = 4633)		P valuea
	Mean	SD	Mean	SD
Adherence (mean, SD)
MPR	79.6	(18.7)	73.2	(21.3)	<0.0001
PDC	65.2	(26.2)	62.7	(25.1)	<0.0001
Persistence (mean, SD)
Time to discontinuation (days)	195.9	(115.8)	174.0	(118.6)	<0.0001
Refill timing (days)	10.4	(16.5)	15.6	(20.0)	<0.0001

Notes: Refill timing: time between successive refills of valsartan-hydrochlorothiazide.

a Paired t-test. Matching was based on propensity scores.

Abbreviations: MPR, medication possession ratio; PDC, proportion of days covered; RP, reminder packaging; SD, standard deviation; non-RP, without reminder packaging.

Figure 3 Time-to-event (treatment discontinuation) analysis.

Table 3 Outcomes stratified by pre-index medication possession ratio categories

Pre-period MPR categories (%)	RP					non-RP					P valuea
	Pre-period (n = 4633)			Post-period (n = 4633)		Pre-period (n = 4633)			Post-period (n = 4633)
	n	Mean	SD	Mean	SD	n	Mean	SD	Mean	SD
MPR
0–19	3	10.89	(7.58)	58.73	(26.88)	2	4.83	(0.16)	41.21	(8.36)	0.6105
20–39	144	30.76	(5.52)	62.24*	(21.07)	153	34.29	(4.06)	57.32*	(19.66)	0.0008
40–59	466	50.20	(5.18)	66.31*	(20.66)	584	50.28	(5.29)	60.84*	(20.46)	0.0001
60–79	1098	70.92	(5.32)	76.18*	(18.93)	905	70.23	(5.83)	66.12*	(20.15)	0.0001
80–100	2922	94.51	(5.98)	83.95*	(16.18)	2989	95.15	(5.90)	78.65*	(19.74)	0.0001
Refill timing (days)
0–19	3	93.67	(29.57)	27.37	(21.82)	2	88.00	(16.97)	43.33	(15.08)	0.6118
20–39	144	67.76	(19.56)	24.52*	(24.52)	153	56.25	(11.84)	0.12*	(23.10)	0.0001
40–59	466	29.33	(6.56)	20.40*	(21.57)	584	29.08	(6.69)	25.17*	(22.75)	0.0004
60–79	1098	11.69	(3.40)	12.48	(17.42)	905	12.32	(4.22)	20.31*	(20.71)	0.0001
80–100	2922	1.40	(2.00)	7.35*	(13.36)	2989	1.36	(2.06)	11.61*	(17.73)	0.0001

Notes:

* P < 0.05 versus pre-period values (paired t-test).

a Statistical test: unpaired t-test for pre-post difference scores.

Abbreviations: MPR, medication possession ratio; non-RP, without reminder packaging; RP, reminder packaging; SD, standard deviation.

Von KorffMWagnerEHSaundersKA chronic disease score from automated pharmacy dataJ Clin Epidemiol1992451971573438

 PubMed Web of Science ®Google Scholar