Improving the accuracy of medication adherence measures using linked prescription and dispensation data: findings from the ESOSVAL cohort of patients treated with osteoporosis drugs

Figures & data

Figure 1. (a) Example of calculation of PDC using dispensation only data. PDC is calculated using either a fixed interval or a last-refill interval. (b) Example of calculation of PDC using linked dispensation and prescription data. PDC is calculated using either any gap or a three-month prescription gap.

Table 1. Definitions used in this study.

Concept	Definitions	Acronym
Primary non-adherence	Failure to have a new prescription filled (discrete event).	None
Early non-adherence	Failure to have the initial prescriptions (typically the two first prescriptions) filled (discrete event).	None
Secondary adherence	Ongoing process that measures whether or not the patient fills dispensations as prescribed during a period of follow-up and assessment.	None
Follow-up period	Total length of the period in which PDC is formally calculated, f.i., 6 months, 12 months, etc. This is the formal definition of the period in which adherence is measured, normally stated in the Title and the Methods section of the studies.	None
Assessment period	Effective period in which PDC is estimated within the follow-up period. For instance, when censoring patient time during the follow-up for any reason, the assessment period is shorter than the follow-up. If no patients are censored during the follow-up period, both follow-up and assessment periods coincide.	None
Proportion of days covered	Total number of days covered with medication during a specified assessment period divided by the number of days in patient’s assessment period.	PDC
PDC using dispensation-only data and fixed interval	PDC calculated with information on dispensations only, where the assessment period is equivalent to the follow-up period (except for reasonable censoring due to death, exclusion from insurance or other losses to follow-up unrelated to medication use).	PDC-DFI
PDC using dispensation-only data and a last-refill interval	PDC calculated with information on dispensations only, where the assessment period is censored at the time of the last dispensation within the follow-up period.	PDC-DLR
PDC using prescription and dispensation data and censoring any prescription gap	PDC calculated using linked prescription and dispensation data. Any gap in days’ supply coinciding with gaps in prescription (days not covered with prescription) is censored from the calculation of PDC.	PDC-PD
PDC using prescription and dispensation data and censoring when prescription gaps are 3 months or longer	PDC calculated using linked prescription and dispensation data. Periods equal to or longer than 3 months without prescriptions are censored and thus not included either in the numerator or in the denominator for the calculation of PDC.	PDC-PD3

f.i.: for instance.

Figure 2. Differences between using dispensation only data or linked dispensation and prescription data with regard to the identification of the index date and patient inclusion for PDC calculation.

Table 2. Baseline characteristics of the ESOSVAL cohort.

	New users (N = 712)		Experienced users (N = 1548)		Total (N = 2260)
	N	%	N	%
Age
50–64	380	53.4	771	49.8	1151
65–99	332	46.6	777	50.2	1109
Sex
Women	568	79. 8	1447	93.5	2015
Men	144	20.2	101	6.5	245
Education
No studies	188	29.2	496	35.2	684
Primary	287	44.6	618	43.8	905
Second/univ	169	26.2	297	21.0	366
Family history of hip fracture
No	485	82.6	1021	79.9	1506
Yes	102	17.4	256	20.1	358
Previous fracture
No	553	77.7	1258	81.3	1811
Yes	159	22.3	290	18.7	349
Body mass index
<20 kg/m^2	11	1.6	26	1.8	37
20.0–24.9 kg/m^2	190	28.2	397	26.7	587
25.0–29.9 kg/m^2	285	42.22	622	41.9	907
≥30 kg/m^2	189	28.0	439	29.6	628
Falls (≥1 in the last year)
No	486	72.4	1055	72.6	1541
Yes	185	27.6	399	27.4	584
10 year risk of hip fracturea
<3%	525	77.8	1098	74.0	1623
≥3%	150	22.2	386	26.0	536
Other osteopenic diseases^b
No	562	78.9	1241	80.2	1803
Yes	150	21.1	307	19.8	457
Glucocorticoid use^c
No	694	97.5	1515	97.9	2209
Yes	18	2.5	33	2.1	51
Other osteopenic drugs
No	407	57.16	809	52.26	1216
Yes	305	42.84	739	47.74	1044
BMD testing
No	416	58.4	979	63.2	1315
Yes	296	41.6	569	36.8	865
Bone mineral density (T-score)
Normal	30	10.3	78	14	108
−1 to −2.5	128	44.0	279	50.1	407
≤ −2.5	133	45.7	200	35.9	333
Sedentarism
No	540	79.8	1218	81.6	1758
Yes	137	20.2	274	18.4	411
Polypharmacy
≤6	269	37.8	327	21.1	596
>6	443	62.2	1221	78.9	1664
Calcium and/or vitamin D supplements
No	201	28.2	494	31.9	695
Yes	511	71.8	1054	68.1	1565
Copayment
No	533	74.9	1253	80.9	1586
Yes	179	25.1	295	19.1	474
Antiosteoporotic treatment
Bisphosphonates^d	599	84.1	1206	77.9	1805
PTH^e	10	1.4	30	1.9	40
Raloxifene	38	5.3	180	11.6	218
Ranelate	65	9.1	132	8.5	197

BMD: bone mineral density.

^aFracture Risk Assessment Tool (FRAX).

^bType I diabetes, rheumatoid arthritis, untreated long-standing hyperthyroidism, chronic malnutrition or malabsorption, chronic obstructive pulmonary disease, renal disease, prolonged immobility, organ transplantation, and chronic liver disease.

^c≥5 mg per day of prednisone or equivalent for at least 3 months in the previous year.

^dBisphosphonates (alendronate, risedronate, ibandronate).

^ePTH, parathyroid hormone (1–34 and 1–84).

Missing data: educational level (205), family history of hip fracture (396), BMI (101), falls (135), FRAX (101), sedentarism (91).

Table 3. Mean PDC and categorical PDC at 12 months using dispensation-only data and using linked prescription and dispensation data.

	New users	Experienced users
Mean PDC
Dispensation-only data	N = 696	N = 1517
PDC-DFI	63.1 (60.5–65.6)	80.0 (78.7–81.2)
PDC-DLR	86.0 (84.5–87.6)	88.9 (88.1–89.7)
Linked prescription and dispensation data	N = 712	N = 1548
PDC-PD3	78.3 (76.2–80.3)	81.0 (79.8–82.3)
PDC-PD	81.0 (78.9–83.1)	83.0 (81.7–84.2)
Categorical PDC
Dispensation-only data	N = 696	N = 1517
PDC-DFI
<20%	18.4 (15.7–21.5)	4.8 (3.9–6.1)
≥80%	46.1 (42.4–49.8)	67.0 (64.6–69.4)
PDC-DLR
<20%	1.3 (0.7–2.4)	0.07 (0.0–0.5)
≥80%	75.3 (71.9–78.4)	81.0 (79.0–82.9)
Linked prescription and dispensation data	N = 712	N = 1548
PDC-PD3
<20%	6.0 (4.5–8.0)	4.9 (3.9–6.1)
≥80%	65.0 (61.4–68.5)	70.1 (67.8–72.3)
PDC-PD
<20%	6.0 (4.5–8.0)	4.8 (3.8–6.0)
≥80%	69.7 (66.2–72.9)	73.8 (71.6–76.0)

Abbreviations. PDC, Proportion of days covered; PDC-DFI, PDC, calculated with dispensation-only data and a fixed interval of assessment; PDC-DLR, PDC, calculated with dispensation-only data and an interval of assessment censored at the moment of the last refill; PDC-PD, PDC, calculated with linked prescription and dispensation data and censoring any period of gaps in prescription from the calculation of PDC; PDC-PD3, PDC, calculated with linked prescription and dispensation data and censoring any period of 3 month gaps or longer in prescription from the calculation of PDC.

Table 4 Mean PDC and categorical PDC at 24 months using dispensation-only data and using linked prescription and dispensation data.

	New users	Experienced users
Mean PDC
Dispensation-only data	N = 696			N = 1517
PDC-DFI	56.6 (54.0–59.2)			74.1 (72.7–75.5)
PDC-DLR	81.2 (79.5–83.0)			85.7 (84.7–86.6)
Linked prescription and dispensation data	N = 712			N = 1548
PDC-PD3	77.1 (75.2–79.1)			80.3 (79.1–81.5)
PDC-PD	79.0 (77.0–81.0)			82.1 (80.8–83.3)
Categorical PDC
Dispensation-only data	N = 696			N = 1517
PDC-DFI
<20%	23.1 (20.1–26.4)			6.1 (5.0–7.5)
≥80%	35.3 (31.9–39.0)			57.0 (54.4–59.4)
PDC-DLR
<20%	1.7 (1.0–3.0)			0.7 (0.4–1.3)
≥80%	64.9 (61.3–68.4)			73.9 (71.6–76.0)
Linked prescription and dispensation data	N = 712			N = 1548
PDC-PD3
<20%	7.7 (6.0–9.9)			5.7 (4.6–7.0)
≥80%	61.7 (58.0–65.2)			67.8 (65.5–70.1)
PDC-PD
<20%	5.5 (4.0–7.4)			4.5 (3.5–5.6)
≥80%	60.3 (56.6–63.8)			68.0 (65.7–70.3)

Abbreviations. PDC, Proportion of days covered; PDC-DFI, PDC, calculated with dispensation-only data and a fixed interval of assessment; PDC-DLR, PDC, calculated with dispensation-only data and an interval of assessment censored at the moment of the last refill; PDC-PD, PDC, calculated with linked prescription and dispensation data and censoring any period of gaps in prescription from the calculation of PDC; PDC-PD3, PDC, calculated with linked prescription and dispensation data and censoring any period of 3 month gaps or longer in prescription from the calculation of PDC.

Figure 3. Patient misclassification in our cohort using dispensation data only versus using prescription and dispensation data.

Appendix 1. Periods of effective assessment when the follow-up is defined at 24 months using different PDC calculation methods.

PDC	New users		Experienced users
	Periods of follow-up and effective assessment (months)
	Formal follow-up	Effective assessment period	Formal follow-up	Effective assessment period
Dispensation-only data
PDC-DFI	24	23.78	24	23.95
PDC-DLR	24	17.01	24	20.75
Prescription and dispensation data
PDC-PD3	24	24 (16.3)	24	24 (20.82)
PDC-PD	24	24 (15.94)	24	24 (20.38)

Abbreviations. PDC, Proportion of days covered; PDC-DFI, PDC, calculated with dispensation-only data and a fixed interval of assessment; PDC-DLR, PDC, calculated with dispensation-only data and an interval of assessment censored at the moment of the last refill; PDC-PD, PDC, calculated with linked prescription and dispensation data and censoring any period of gaps in prescription from the calculation of PDC; PDC-PD3, PDC, calculated with linked prescription and dispensation data and censoring any period of 3 month gaps or longer in prescription from the calculation of PDC.

In the case of estimators built using dispensation-only data, the effective assessment period is shorter than the formal follow-up period, due to censoring for deaths and disenrollment in the case of PDC-DFI, and to additionally censoring the time between the last dispensation and the end of the formal follow-up period in the case of PDC-PLR. The denominator of the formula for calculating the PDC is therefore shorter than the formal follow-up period. When linking prescription and dispensation data, the follow-up period remains stable (24 months), and the denominator for the calculation of the PDC is adjusted by gaps in prescription (figures in brackets).