Algorithm for Refill Adherence Measure Calculation:Continuous Multiple-Interval Gap (CMG) MeasureOur CMG measure was calculated using the following algorithm, illustrated in Appendix Figure
Example of Calculation of Refill Adherence Measure.
1. Looking retrospectively 12 months from the patient’s clinic visit, our VA pharmacy record details specific dates of when a medicine was first filled, dates of each fill and refill (noted by thin arrows in Appendix Figure
), and days of supply the prescription would last if taken as prescribed (shaded boxes in Appendix Figure
). For the purpose of determining if the patient was already taking a medication chronically prior to the 12 month observation period (and when it would be expected to require refill within the 12 month observation period), prescription records were also evaluated for 90 days prior to the 12 month observation period. For the purpose of determining if medications not refilled recently prior to the time of the appointment were inappropriately late refill requests, or if these medications were not expected to be continued chronically, prescription refill records were also evaluated for 90 days after the clinic visit.
2. Next, if the patient was taking the medicine exactly as prescribed at full dose, which date would the patient expected to be without medication (“supply end” noted by * in Appendix Figure
3. Then, all days that occur between the date of supply end and the next refill date are considered to be “gap days” (white boxes in Appendix Figure
), that is, days where the patient would be expected to be experiencing a gap in medication supply because had not refilled early enough.
4. To generate the CMG for each BP medication class, the total number of gap days for medications in each class was summed, and then divided by the total number of days that patient was prescribed the medications in that class, to yield the following measure:
5. To generate the composite CMG, the total number of gap days for all BP medications (all classes, excluding loop diuretics for reasons explained below) was summed, and then divided by the total number of days the patient was prescribed each medication. Therefore, the composite CMG is not a simple average of the CMG calculated for each BP medication class; instead, it takes into account (and thus is weighted by) the duration of time the patient was prescribed each medication. Thus, a single medication (or a single class) of short duration would not have equal influence as a long-standing chronically prescribed BP medication.
This ratio of total gap days to total prescribed days yields the CMG, which is measure of proportion of days without adequate medication, also known as a ratio of non-possession. For example, a CMG of 0.2 or 20% means the patient refilled the medication in a manner that left 20% of days without an adequate medication supply to take. The CMG can also be interpreted as a proportion of time the patient misses their medications, with a CMG of 20% meaning that on average, the patient missed 20% of the doses, or 1 day or dose in 5. Prior literature has established that a lack of medication possession of
20% is clinically significant refill non-adherence
In order for our pharmacy adherence measure to better reflect adherence as indicated by refills the patient requested, we excluded new medications with only one fill for the CMG calculation because first prescriptions in the VA health system are filled automatically without effort required by the patient. New medications were identified as having a total expected supply to patient of
90 days in the study period year, with less than 2 fills. Using the rich and connected VA database of inpatient, outpatient, and pharmacy data, multiple sources of oversupply were also accounted for, including days of hospitalization and early refills which include early medication fills written as part of discharge orders
Of note, our refill adherence measure including refill data for all classes of antihypertensives excluding only loop diuretics, because loop diuretics can be taken for reasons such as congestive heart failure or edema with directions and instructions changing frequently by prescribers to treat acute exacerbations (such as increased loop diuretic for 3–4 days, before transition to a stable dose). Thus, the refill record for loop diuretics was not thought to reflect adherence as an antihypertensive treatment. In summary, classes of antihypertensives that were evaluated and included for patients in this study included: angiotensin converting enzyme (ACE) inhibitors, beta blockers, calcium channel blockers, alpha receptor blockers, hydralazine, aldosterone receptor blockers, sympathetic blockers, thiazide diuretics, potassium-sparing diuretics, renin-inhibitors, and minoxidil.