Use of pegvaliase in the management of phenylketonuria: Case series of early experience in US clinics

Objective: To present a case series that illustrates real-world use of pegvaliase based on the initial experiences of US healthcare providers. Methods: Sixteen healthcare providers from 14 centers across the US with substantial clinical experience in treating patients with phenylketonuria (PKU) with pegvaliase in the two-plus years since FDA approval (May 2018) provided cases that exemplified important lessons from their initial experiences treating patients with pegvaliase. Key lessons from each case and takeaway points were discussed in both live and virtual meetings. Results: Fifteen cases of adults with PKU (eight males, seven females), representing a spectrum of age (18 to 53 years), previous PKU care, comorbidities, and socioeconomic situations were reviewed and discussed. Full extended case reports are included in the Supplement. The cases showed that treating patients with a daily injectable can be challenging due to a patient's financial problems, treatment challenges, and neuropsychological and psychiatric comorbidities, which can be identified before starting pegvaliase, but do not prohibit successful treatment. The authors agreed that patient education on adverse events (AEs), time to efficacy, dietary changes, and food preparation is an ongoing process that should start prior to initiating pegvaliase treatment. Treatment goals and planned dietary changes once efficacy is reached should be defined prior to treatment initiation and re-evaluated throughout the course of therapy. Each patient's titration schedule and dietary adjustments are unique, depending on occurrence of AEs and individual goals of treatment. Despite the AE profile of pegvaliase, all but two patients remained motivated to continue treatment and achieved efficacy (except one patient in whom titration was still ongoing). AEs occurring early in the treatment pathway may require prolongation of the titration phase and/or concomitant medication use, but do not seem indicative of future tolerability or eventual efficacy. Close follow-up of patients during titration and maintenance to help with dietary changes is important. Conclusion: This case series provides real-world experience on the use of pegvaliase. Until data from registries and independent research become available, the data presented herein can support appropriate management of patients receiving pegvaliase in clinical practice

Testing the organizational theory of innovation implementation effectiveness in a community pharmacy medication management program: a hurdle regression analysis

Abstract Background Many state Medicaid programs are implementing pharmacist-led medication management programs to improve outcomes for high-risk beneficiaries. There are a limited number of studies examining implementation of these programs, making it difficult to assess why program outcomes might vary across organizations. To address this, we tested the applicability of the organizational theory of innovation implementation effectiveness to examine implementation of a community pharmacy Medicaid medication management program. Methods We used a hurdle regression model to examine whether organizational determinants, such as implementation climate and innovation-values fit, were associated with effective implementation. We defined effective implementation in two ways: implementation versus non-implementation and program reach (i.e., the proportion of the target population that received the intervention). Data sources included an implementation survey administered to participating community pharmacies and administrative data. Results The findings suggest that implementation climate is positively and significantly associated with implementation versus non-implementation (AME = 2.65, p < 0.001) and with program reach (AME = 5.05, p = 0.001). Similarly, the results suggest that innovation-values fit is positively and significantly associated with implementation (AME = 2.17, p = 0.037) and program reach (AME = 11.79, p < 0.001). Some structural characteristics, such as having a clinical pharmacist on staff, were significant predictors of implementation and program reach whereas other characteristics, such as pharmacy type or prescription volume, were not. Conclusions Our study supported the use of the organizational theory of innovation implementation effectiveness to identify organizational determinants that are associated with effective implementation (e.g., implementation climate and innovation-values fit). Unlike broader environmental factors or structural characteristics (e.g., pharmacy type), implementation climate and innovation-values fit are modifiable factors and can be targeted through intervention—a finding that is important for community pharmacy practice. Additional research is needed to determine what implementation strategies can be used by community pharmacy leaders and practitioners to develop a positive implementation climate and innovation-values fit for medication management programs