To our knowledge, this analysis is the first claims-based evaluation of the effect of a prescription medication labeling change on medication adherence.16
While Target pharmacies have implemented a prescription medication label aimed at improving readability and understanding, we found little effect on medication adherence. When users of Target pharmacies were compared to patients who filled their prescriptions at non-Target pharmacies, we found no change in adherence in new users of chronic medications before and after implementation of the new label. Among prevalent users, we found changes in adherence that were small and inconsistent (a small reduction in the level of adherence and a small improvement in the monthly rate of change of adherence in the post-implementation period). The small magnitude and conflicting direction of these changes indicate that they are likely clinically unimportant.
These findings are not entirely surpirsing. Numerous studies have evaluated factors associated with medication non-adherence and have generally found adherence to be multi-factorial; cogntive, social, financial, and psychological explanations for non-adherence have been identified.23
However, analyses of interventions to improve adherence have generally found that simple strategies are rather ineffective, and multi-factorial and complex inteventions are needed to influence behavior.15,24
As a result, the change in labeling at Target pharmacies likely did not sufficiently address the multifactorial nature of medication non-adherence to affect meaningful behavioral change.
It may be that the label would be more likley to enhance medication safety than adherence. Some of the new features of the label, such as the colored rings to help patients identify which medication is for them, are focused on improving safety, and may have little effect on the quantity of medication purchased. Considering that the quality of pharmacologic care in the US is substandard,25,26
and there is evidence of both over-use and under-use of essential medications,25–27
improved labeling may encourage more appropriate use without measurably influencing adherence as we measured it.
While we did not find improved adherence in patients exposed to the new Target label, our claims-based methods for evaluating adherence may not have been sufficient to measure all aspects of adherence. Using claims to evaluate the frequency of refills is a commonly used approach to assess refill adherence with demonstrated validity; refill adherence using pharmacy claims correlates with other compliance measures as well as measures of drug presence (e.g., serum drug levels) or physiologic drug effects.28
Studies of refill adherence are conditional on a patient filling an intial prescription. This is unlikely to be an important limitation, as we would only expect the label to influence a patient once they have purchased an initial prescription, after which the patient is first exposed to the label. However, our adherence measures were not sensitive enough to ascertain nuanced measures of appropriate medication use such as timing of administration or administration on an empty or full stomach as directed. Further, we were unable to determine whether patients exposed to the new label were more likely to adhere to written warnings and to avoid contraindications. Before concluding that the Target label offered no clinical benefit, more nuanced evaluation of medication use would be useful to evaluate the effect on adherence, and additional study of the effect of the new label on safety and adverse effects is needed.
Our study is limited by the sample we studied, commercially-insured patients. The label may have been more effective in improving understanding15
and stimulating adherence in Medicaid beneficiaries or the uninsured, who often exhibit lower health literacy, and our study did not evaluate these populations. In addition, we censored data from all seniors on January 1, 2006 because we lost full records for a large percentage of patients after implementation of Medicare Part D. Shortening this window for analysis may also have limited our ability to identify changes in adherence in elderly patients, another population that may benefit from clearer labels and larger font. Further studies in elderly and low health literacy populations are needed before concluding that the Target label does not affect adherence.
Our obsevational methods were also unable to fully account for selection bias. It is possible that sicker or older patients selected Target pharmacies after learning about the new label designs. However, we matched exposed and unexposed patients on socio-demographic characteristics and adjusted for individual health characteristics in our models, and expect that the null finding in this study could not be explained by selection bias alone. We also saw a secular trend of improved adherence in the post period among new users, but we do not expect that it should have biased our study, and the difference-in-difference model controlled for these trends.
In conclusion, our evaluation of pharmacy claims in two large health plans did not find a clinically meaningful influence of an intervention to improve prescription medication labeling upon medication adherence. Further studies of the effect of the new label on medication safety and health outcomes are needed to assess the importance of label design on medication use. While we cannot rule out any benefit on adherence with the methods we used, these findings should inform pharmacies, insurers, and policy-makers, who may advocate for improved labeling. While efforts to improve labeling may enhance appropriate medication use, providers and payors should have reasonable expectations about how overall drug consumption will be affected. More importantly, these data should further encourage physicians to improve their communication with patients about medication use. They should not rely on patients to get their information from medication labels alone, even those with innovative designs, if appropriate adherence is the goal.