Evidence of sample use among new users of statins: implications for pharmacoepidemiology

Abstract

Background: Epidemiologic studies of prescription medications increasingly rely on large administrative health care databases. These data do not capture patients' use of medication samples. This could potentially bias studies of short-term effects where date of initiation may be inaccurate.

Objectives: To assess the extent of sample use among patients initiating statin therapy.

Research design: Retrospective cohort of patients who filled a first prescription for a statin after at least 6 months of statin-free period in 2007-2010. Low-density lipoprotein (LDL) values obtained within the 15 days preceding the first prescription were analyzed using a 2-component Gaussian mixture model to look for evidence of prior treatment.

Subjects: A total of 26,033 statin initiators with at least 1 LDL laboratory result within the 15 days preceding the prescription fill.

Measures: Estimators for the proportion of patients filling a new prescription already on treatment.

Results: Among 9256 patients filling a branded statin, LDL distribution was bimodal, consisting of 2 Gaussian distributions: one, which made up 13.4% of the total population, had much lower LDL values (mean=71.8 mg/dL) compared with the second (mean=148.0 mg/dL), suggesting drug use before first dispensed prescription. Among 16,777 patients filling a generic statin, LDL levels were substantially higher with no evidence of bimodality that would suggest prior sample use.

Conclusions: These results provide indirect evidence that the initial period of branded medication use may often be missed when using pharmacy claims data to define drug initiation. Further research is needed to examine approaches to better identify incident medication use when assessing short-term effects.

Figure 1

Schematic of the statin user cohort study design. Not all patients had LDL₂ in the primary cohort.

Figure 2

Flow diagram of the cohort creation process: new users of statins, ≥40 years of age, United States, 2007-2010

Figure 3

The distribution of last LDL before first statin prescription fill in patients with at least 1 LDL lab prior to first statin prescription fill. ((a) Results from mixture model analysis: λ =proportion, μ =mean (mg/dL), σ =standard deviation (mg/dL), D =distribution; (b) Left panel: Patients filling a prescription for branded drug; Right panel: patients filling a prescription for generic drug)

Figure 4

The distributions of 2 sequential LDLs before first statin prescription fill in patients with 2 or more LDL labs prior to first statin prescription fill. ((a) Results from mixture model analysis: λ =proportion, μ =mean (mg/dL), σ =standard deviation (mg/dL), D =distribution; (b) (Top panels: the last LDL, LDL₁; Bottom panels: the older LDL, LDL₂; Left panels: Patients filling a prescription for branded drug; Right panels: patients filling a prescription for generic drug)