Persistence and switching patterns of migraine prophylactic medications in Canada: A retrospective claims analysis comparing adherence and evaluating the economic burden of illness.

PURPOSE: To describe patient characteristics, treatment patterns, and the burden of illness among adult migraine patients in Canada prescribed migraine prophylactics. Little is known about the relative persistence of treatments in the real-world setting and the impact of migraine prophylactic therapy on patients. As a result, migraine care in Canada continues to inadequately serve patients suffering from frequent headache days, reflecting a large unmet need. METHODS: This retrospective study used Reformulary Group's longitudinal prescription claims database. Private payer data were analyzed to identify 2007 migraine prophylactic naïve patients, with a prior history of acute therapy, for tracking over 24 months to determine treatment patterns and costs. Patient flow is summarized in a Sankey diagram visualizing persistence and switching across different timepoints. RESULTS: Patient persistence to migraine prophylactic medications was low at 24.9% (n=500); Switching from index medications to another prophylactic medication was common (27%), however 50% of patients discontinued without switching. It was observed that acute treatment and opioid use were much lower when patients established and maintained therapy on migraine prophylactics. Overall, angiotensin receptor blockers and CGRP antagonists had high persistence but were underutilized therapies while the inverse was true for antidepressants and anticonvulsants. CONCLUSION: In a real-word setting, recognizing that many patients may discontinue preventative treatment completely after their first therapy, there is a need to employ migraine-specific prophylactics and/or tolerable medications early. Treatment guidelines aligned to costs savings and/or requiring step therapy may be inadvertently failing patients. Further, the impact of migraine on the day-to-day lives of patients and high societal costs such as its impact on productivity should be weighed in considering migraine's burden of illness and the benefits of treatment.

Impact of COVID-19 on hospital screening, diagnosis and treatment activities among prostate and colorectal cancer patients in Canada.

BACKGROUND: Suspension of cancer screening and treatment programs were instituted to preserve medical resources and protect vulnerable populations. This research aims to investigate the implications of COVID-19 on cancer management and clinical outcomes for patients with prostate and colorectal cancer in Canada. METHODS: We examined hospital cancer screening, diagnosis, treatment, length of stay, and mortality data among prostate and colorectal cancer patients between April 2017 and March 2021. Baseline trends were established with data between April 2017 and March 2020 for comparison with data collected between April 2020 and March 2021. Scenario analyses were performed to assess the incremental capacity requirements needed to restore hospital cancer care capacities to the pre-pandemic levels. RESULTS: For prostate cancer, A 12% decrease in diagnoses and 5.3% decrease in treatment activities were observed during COVID-19 between April 2020 and March 2021. Similarly, a 43% reduction in colonoscopies, 11% decrease in diagnoses and 10% decrease in treatment activities were observed for colorectal cancers. An estimated 1,438 prostate and 2,494 colorectal cancer cases were undiagnosed, resulting in a total of 620 and 1,487 unperformed treatment activities for prostate and colorectal cancers, respectively, across nine provinces in Canada. To clear the backlogs of unperformed treatment procedures will require an estimated 3%-6% monthly capacity increase over the next 6 months. INTERPRETATION: A concerted effort from all stakeholders is required to immediately ameliorate the backlogs of cancer detection and treatment activities. Mitigation measures should be implemented to minimize future interruptions to cancer care in Canada.

A Mechanistic Model for Predicting the Physical Stability of Amorphous Solid Dispersions.

In this paper, we establish a mechanistic model for the prediction of amorphous solid dispersion (ASD) stability. The novel approach incorporates fundamental physical parameters, principally supersaturation, diffusivity, and interfacial energy, to model crystallization in ASDs accounting for both kinetic and thermodynamic drivers. API dependent decoupling coefficients were also considered which allowed dynamic mechanical analysis to probe molecular mobility, with viscosity measurements, across an exceptionally broad range of temperatures to support ASD stability simulations. ASDs are multicomponent systems in which the amorphous form of active pharmaceutical ingredients (APIs) are molecularly dispersed within a carrier. This gives rise to a transiently supersaturated API solution upon dissolution which increases the driving force for oral absorption and results in increased bioavailability as compared to that of the crystalline API. A major shortcoming of ASDs, however, is that there is the potential for amorphous APIs to revert to their more stable crystalline form during storage, despite the use of polymer carriers to stabilize formulations and limit recrystallization. Hot melt extrusion (HME) has been employed as the preparation method for ASDs used in this study as it is well-suited for the formation of uniform dispersions. The ASDs were stored under controlled temperature conditions, in the absence of humidity, to determine recrystallization kinetics. Our mechanistic model, considering both crystal nucleation and growth processes, describes temporal ASD stability through a system of coupled differential equations that connect the physiochemical properties of the ASD system to drug recrystallization. The model and prolonged time scale of crystallization observed highlight the importance of considering both thermodynamic and kinetic factors in the preparation of stable ASDs. Experimental observations were found to be in good agreement with predictions of the model confirming its utility in predicting the temporal physical stability of amorphous solid dispersions through a mechanistic lens.

Elucidating the effect of crystallization on drug release from amorphous solid dispersions in soluble and insoluble carriers.

The development of amorphous solid dispersions (ASDs) is one way to overcome the bioavailability challenges of poorly water-soluble active pharmaceutical ingredients (APIs). An important consideration with ASD systems is that crystallization can occur during preparation, storage, and dissolution, thus reducing their bioavailability advantage. Currently, it is unclear whether the dissolution characteristics of the polymer carrier affects the dissolution performance of ASDs with intrinsic crystallization. Our aim was to differentiate the impact of a minor amount of intrinsic crystallinity (up to 10%) within soluble and insoluble carriers on ASD performance, using the area under the curve (AUC) values of non-sink dissolution profiles as a measure of dissolution performance that can inform in vivo bioavailability. In order to discern such differences, itraconazole (ITZ) ASDs were prepared by Hot Melt Extrusion (HME) with 50% (w/w) drug loading. PVP K12 and HPMCAS were used as the soluble and insoluble carriers in pH 1.2 dissolution media, respectively. Dissolution was also conducted in pH 6.8 buffer, wherein HPMCAS becomes soluble, to cross-validate experimental observations. Crystalline content was determined by differential scanning calorimetry (DSC) prior to dissolution. Soluble polymers differed from insoluble polymers in that crystals formed during processing and storage were released during dissolution which can undergo further growth causing a sharp decline in drug concentration in the dissolution medium. This led to a significant decrease in the AUC for soluble ASDs containing intrinsic crystallinity. In contrast, insoluble polymer carriers did not release the intrinsically formed crystals and the impact of subsequent crystal growth on dissolution performance was minimal for insoluble ASD systems. Furthermore, physical mixtures with spiked crystallinity were only found to reflect the dissolution performance of soluble ASDs exhibiting intrinsic crystallinity. Thus, in considering the impact of intrinsic crystallinity on ASD performance, the nature of the polymeric carrier in terms of solubility characteristics needs to be taken into account as there is significantly more variation in AUC with soluble carriers than insoluble carriers exhibiting intrinsic crystallinity.