Distinguishing patterns in the dynamics of long-term medication use by Markov analysis: beyond persistence

Abstract

BackgroundIn order to accurately distinguish gaps of varying length in drug treatment for chronic conditions from discontinuation without resuming therapy, short-term observation does not suffice. Thus, the use of inhalation corticosteroids (ICS) in the long-term, during a ten-year period is investigated. To describe medication use as a continuum, taking into account the timeliness and consistency of refilling, a Markov model is proposed.MethodsPatients, that filled at least one prescription in 1993, were selected from the PHARMO medical record linkage system (RLS) containing >95% prescription dispensings per patient originating from community pharmacy records of 6 medium-sized cities in the Netherlands.The probabilities of continuous use, the refilling of at least one ICS prescription in each year of follow-up, and medication free periods were assessed by Markov analysis. Stratified analysis according to new use was performed.ResultsThe transition probabilities of the refilling of at least one ICS prescription in the subsequent year of follow-up, were assessed for each year of follow-up and for the total study period.The change of transition probabilities in time was evaluated, e.g. the probability of continuing ICS use of starters in the first two years (51%) of follow-up increased to more than 70% in the following years. The probabilities of different patterns of medication use were assessed: continuous use (7.7%), cumulative medication gaps (1–8 years 69.1%) and discontinuing (23.2%) during ten-year follow-up for new users. New users had lower probability of continuous use (7.7%) and more variability in ICS refill patterns than previous users (56%).ConclusionIn addition to well-established methods in epidemiology to ascertain compliance and persistence, a Markov model could be useful to further specify the variety of possible patterns of medication use within the continuum of adherence. This Markov model describes variation in behaviour and patterns of ICS use and could also be useful to investigate continuous use of other drugs applied in chronic diseases.

Triptan persistency among newly initiated users in a pharmacy claims database

“…It was found that 39% of new users received only one triptan prescription, but it is unclear whether the four-month interval used can predict a migraineur's future attack frequency. Other medication persistency literature has noted that observation periods longer than one year may be necessary to accurately differentiate treatment gaps from medication discontinuation (20).…”

“…Even then, prescription refill patterns may not accurately reflect migraine frequency patterns. Medication persistency in other chronic-episodic conditions, such as asthma, has been described in terms of continuous refills, taking into account the timeliness and consistency of refilling at each point in the timeline (20,21). Similarly, at each point in a patient's refill history, the placement of switching patterns may be identified by comparing lapses in sustained medication use against observable uptakes of alternative treatments.…”

Measuring adherence with medications: time is of the essence

“…5 Markov models have described transitions in adherence over time. 11 At least two investigators have described measurement algorithms that assess refill adherence over shorter time intervals than the traditional PDC, similar to the question posed by Bijlsma and colleagues. 12,13 Both studies demonstrated that time-varying adherence correlated more strongly than fixed-time adherence with measures of drug effect (such as blood pressure and glycemic control).…”

“…Survival analysis has been used to assess the time to discontinuation of a medication . Markov models have described transitions in adherence over time . At least two investigators have described measurement algorithms that assess refill adherence over shorter time intervals than the traditional PDC, similar to the question posed by Bijlsma and colleagues .…”

Reduced risk of decompensation and death associated with use of statins in patients with alcoholic cirrhosis. A nationwide case‐cohort study

“…The method is explained in the Data S1. Briefly, we determined the likelihood of being in a period with stable dosing of statins for each patient and clustered the patients into four groups . Moreover, if a patient had three consecutive periods with stable dosing of statins they entered a sub‐cohort for further analysis (Figure S2).…”