Exploring the prospective acceptability of a healthy food incentive program from the perspective of people with type 2 diabetes and experiences of household food insecurity in Alberta, Canada.

OBJECTIVE: FoodRx is a 12-month healthy food prescription incentive program for people with type 2 diabetes (T2DM) and experiences of household food insecurity. In this study, we aimed to explore potential users' prospective acceptability (acceptability prior to program use) of the design and delivery of the FoodRx incentive and identify factors influencing prospective acceptability. DESIGN: We used a qualitative descriptive approach and purposive sampling to recruit individuals who were interested or uninterested in using the FoodRx incentive. Semi-structured interviews were guided by the theoretical framework of acceptability, and corresponding interview transcripts were analysed using differential qualitative analysis guided by the socioecological model. SETTING: Individuals living in Alberta, Canada. PARTICIPANTS: In total, fifteen adults with T2DM and experiences of household food insecurity. RESULTS: People who were interested in using the FoodRx incentive (n 10) perceived it to be more acceptable than those who were uninterested (n 5). We identified four themes that captured factors that influenced users' prospective acceptability: (i) participants' confidence, views and beliefs of FoodRx design and delivery and its future use (intrapersonal), (ii) the shopping routines and roles of individuals in participants' social networks (interpersonal), (iii) access to and experience with food retail outlets (community), and (iv) income and food access support to cope with the cost of living (policy). CONCLUSION: Future healthy food prescription programs should consider how factors at all levels of the socioecological model influence program acceptability and use these data to inform program design and delivery.

Patents and regulatory exclusivities on FDA-approved insulin products: A longitudinal database study, 1986-2019.

BACKGROUND: Insulin is the primary treatment for type 1 and some type 2 diabetes but remains costly in the United States, even though it was discovered more than a century ago. High prices can lead to nonadherence and are often sustained by patents and regulatory exclusivities that limit competition on brand-name products. We sought to examine how manufacturers have used patents and regulatory exclusivities on insulin products approved from 1986 to 2019 to extend periods of market exclusivity. METHODS AND FINDINGS: We used the publicly available Food and Drug Administration (FDA) Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) to identify all approved biosynthetic insulin products. Individual products approved under the same New Drug Application (NDA)-e.g., a vial and pen-were considered as separate products for the purposes of analysis. We recorded all patents and regulatory exclusivities listed in the Orange Book on each product and used Google Patents to extract the timing of patent application and whether patents were obtained on delivery devices or others aspects of the product. The primary outcome was the duration of expected protection, which was determined by subtracting the FDA approval date for each product from its last-to-expire patent or regulatory exclusivity (whichever occurred later). We performed a secondary analysis that considered overall protection on insulin lines-defined as groups of products approved under the same NDA with the same active ingredients manufactured by the same company. We also examined competition from follow-on insulin products-defined as products approved with the same active ingredients as originators but manufactured by different companies (approved via a specific drug approval pathway under section 505(b)(2) of the Food, Drug, and Cosmetic Act). During the study period, the FDA approved 56 individual products across 25 different insulin lines and 5 follow-ons across 3 different insulin lines. Thirty-three (59%) of the 56 products were drug-device combinations. Manufacturers of 9 products approved during the study period obtained patents filed after FDA approval that extended their duration of expected protection (by a median of 6 years). Approximately 63% of all patents on drug-device combinations approved during the study period were related to delivery devices. The median duration of expected protection on insulin products was 16.0 years, and the median protection on insulin lines was 17.6 years. An important limitation of our analysis is that manufacturers may continue to add patents on existing insulin products while competitors may challenge patents; therefore, periods of protection may change over time. CONCLUSIONS: Among several strategies that insulin manufacturers have employed to extend periods of market exclusivity on brand-name insulin products are filing patents after FDA approval and obtaining a large number of patents on delivery devices. Policy reforms are needed to promote timely competition in the pharmaceutical market and ensure that patients have access to low-cost drugs.

Patents and Regulatory Exclusivities on GLP-1 Receptor Agonists.

Importance: Glucagon-like peptide 1 (GLP-1) receptor agonists were first approved for the treatment of type 2 diabetes in 2005. Demand for these drugs has increased rapidly in recent years, as indications have expanded, but they remain expensive. Objective: To analyze how manufacturers of brand-name GLP-1 receptor agonists have used the patent and regulatory systems to extend periods of market exclusivity. Evidence Review: The annual US Food and Drug Administration's (FDA) Approved Drug Products With Therapeutic Equivalence Evaluations was used to identify GLP-1 receptor agonists approved from 2005 to 2021 and to record patents and nonpatent statutory exclusivities listed for each product. Google Patents was used to extract additional data on patents, including whether each was obtained on the delivery device or another aspect of the product. The primary outcome was the duration of expected protection from generic competition, defined as the time elapsed from FDA approval until expiration of the last-to-expire patent or regulatory exclusivity. Findings: On the 10 GLP-1 receptor agonists included in the cohort, drug manufacturers listed with the FDA a median of 19.5 patents (IQR, 9.0-25.8) per product, including a median of 17 patents (IQR, 8.3-22.8) filed before FDA approval and 1.5 (IQR, 0-2.8) filed after FDA approval. Fifty-four percent of all patents listed on GLP-1 receptor agonists were on the delivery devices rather than active ingredients. Manufacturers augmented patent protection with a median of 2 regulatory exclusivities (IQR, 0-3) obtained at approval and 1 (IQR, 0.3-4.3) added after approval. The median total duration of expected protection after FDA approval, when accounting for both preapproval and postapproval patents and regulatory exclusivities, was 18.3 years (IQR, 16.0-19.4). No generic firm has successfully challenged patents on GLP-1 receptor agonists to gain FDA approval. Conclusions and Relevance: Patent and regulatory reform is needed to ensure timely generic entry of GLP-1 receptor agonists to the market.

Premarket Development Times for Innovative Vaccines--To What Extent Are the Coronavirus Disease 2019 (COVID-19) Vaccines Outliers?

One reason expressed in surveys of people reporting coronavirus disease 2019 (COVID-19) vaccine hesitancy is how rapidly these vaccines have reached the market. To estimate the length of time the COVID-19 vaccine spent in research and development as compared to other novel vaccines, we apply previously established methods for estimating medical product development times, using the key associated patent filings cited by the manufacturer as the marker of when commercial development activity began. Applying these methods to a cohort of recently approved innovative vaccines and comparing them to the first-approved COVID-19 vaccine (BioNTech/Pfizer), we found key patent filings for the technology in this COVID-19 vaccine occurred 10.0 years prior to regulatory authorization. By this metric, the development timelines for innovative vaccines have been shortening since the 1980s, and the COVID-19 vaccine comfortably fits within this pattern. Vaccine development timelines have now even drawn to parity with many of the most commonly used drugs.

COVID-19 and the prevalence of drug shortages in Canada: a cross-sectional time-series analysis from April 2017 to April 2022.

BACKGROUND: In March 2020, the Government of Canada introduced measures to reduce intensifying shortages of prescription drugs during the beginning of the COVID-19 pandemic. We sought to assess the extent to which a decline in drug shortages was observed in the months after this policy change. METHODS: Our data source was the Drug Shortages Canada Database, which reports shortages by drug product, including shortage start and duration. Using a cross-sectional design, we tracked shortage rates of drug products using a 30-day moving average from Apr. 15, 2017, to Apr. 1, 2022. We used autoregressive integrated moving average modelling with a ramp function to determine the significance of trend changes after policy implementation. RESULTS: We found that of the 13 329 drug products at risk for shortage, 44.7% (n = 5953) had at least 1 shortage event in the past 5 years. Average daily shortage prevalence rates rose from 901 in April 2017 to a peak of 2345 by April 2020. Significant declines (p = 0.02) ensued shortly thereafter, dropping to a rate of 1611 shortages by the end of the first year after policy implementation. However, we did not observe a significant reduction in shortage rates in the second year (p = 0.2), with rates plateauing below 1500 and then rising back above 1600 by the end of March 2022. INTERPRETATION: Drug shortages are common in Canada, including during the initial months of the COVID-19 pandemic. We observed substantial improvements after the implementation of the new measures, but gains appear to have plateaued. Continued vigilance is needed to sustain improvements.

Reimagining Pharmaceutical Market Exclusivities: Should the Duration of Guaranteed Monopoly Periods Be Value Based?

OBJECTIVES: To describe the main features of a pharmaceutical market in which the duration of guaranteed monopoly periods would correspond to a new pharmaceutical product's value. METHODS: After reviewing patent and regulatory exclusivity-based mechanisms for protecting prescription drug markets from competition to incentivize drug innovation in developed countries, we model market protection mechanisms within the current framework to give the longest-lasting market protections to drug developers that bring the most affordable products to market with highest public health and clinical value. RESULTS: An approach tying pharmaceutical market exclusivity to value would have 3 main features. First, it would be based on regulatory exclusivity (ie, the drug regulator refrains from authorizing generic entry for a certain amount of time), rather than patents. Second, the duration of exclusivity period would be pegged to the magnitude of a product's anticipated health impact and its proposed price by using modified methods from the field of health technology assessment. Third, the duration of the value-based exclusivity period would be reassessed routinely 3 years after the product's launch to account for its real-world effectiveness. CONCLUSIONS: Linking a drug's proposed price to the duration of its regulatory-based exclusivities would both incentivize the development of high impact, low-cost products and motivate drug developers to introduce these products at lower prices.

A Method for Approximating Future Entry of Generic Drugs.

OBJECTIVES: To develop and test a method for approximating generic entry of top-selling drugs. METHODS: The procedure involved 1) identifying products' key patents as those with a patent term restoration extension (whenever relevant) or otherwise as the first expiring patent listed in the US Food and Drug Administration's patent register, 2) determining whether the key patent had been extended through an associated pediatric extension, 3) identifying other regulatory exclusivities associated with the drug, and 4) categorizing key patents as active ingredient (or extended) patents versus secondary patents. The accuracy and precision of the procedure's predictions were then tested against a database containing the timing of generic entry for 170 top-selling drugs that lost market exclusivity between 2000 and 2012, on the basis of Medicaid data. RESULTS: Overall, the procedure predicted a median market exclusivity period of 12.5 years (interquartile range [IQR] 7.25-14.5) compared with the median actual period of 12.5 years (IQR 8.5-14.75 years). Among the 131 drugs (77%) with active ingredient patents, the median predicted market exclusivity was 12.25 years (IQR 7.5-14.5) compared with a median actual period of 13.0 years (IQR 10.0-14.75). Among the 38 (22%) drugs protected only by secondary patents, the median predicted market exclusivity was 16.0 years (IQR 6.75-19.5), but the median actual market exclusivity was only 8.25 years (IQR 6.25-13.5). CONCLUSIONS: The procedure approximated median actual exclusivity with reasonable accuracy and precision for drugs with active ingredient patents, but substantially overestimated exclusivity for drugs with only secondary patents.

In which developing countries are patents on essential medicines being filed?

BACKGROUND: This article is based upon data gathered during a study conducted in partnership with the World Intellectual Property Organization on the patent status of products appearing on the World Health Organization's 2013 Model List of Essential Medicines (MLEM). It is a statistical analysis aimed at answering: in which developing countries are patents on essential medicines being filed? METHODS: Patent data were collected by linking those listed in the United States and Canada's medicine patent registers to corresponding patents in developing countries using two international patent databases (INPADOC and Derwent) via a commerical-grade patent search platform (Thomson Innovation). The respective supplier companies were then contacted to correct and verify our data. We next tallied the number of MLEM patents per developing country. Spearman correlations were done to assess bivariate relationships between variables, and a multivariate regression model was developed to explain the number of MLEM patents in each country using SPSS 23.0. RESULTS: A subset of 20 of the 375 (5%) products on the 2013 MLEM fit our inclusion criteria. The patent estate reports (i.e., the global list of patents for a given drug) varied greatly in their number with a median of 48 patents (interquartile range [IQR]: 26-76). Their geographic reach had a median of 15% of the developing countries sampled (IQR: 8-28%). The number of developing countries covered appeared to increase with the age of the patent estate (r = .433, p = 0.028). The number of MLEM patents per country was significantly positively associated with human development index (HDI), gross domestic income (GDI) per capita, total healthcare expenditure per capita, population size, the Rule of Law Index, and average education level. Population size, GDI per capita, and healthcare expenditure (in % of national expenditure) were predictors of the number of MLEM patents in countries (p = 0.001, p = 0.001, p = 0.009, respectively). Population size was the most important predictor (ß = 0.59), followed by income (GDI per capita) (ß = 0.32), and healthcare expenditure (ß = 0.15). Holding the other factors constant, (i) 14.3 million more people, (ii) $833.33 more per capita (GDI), or (iii) 0.88% more of national spending on healthcare resulted in 1 additional essential medicine patent. CONCLUSION: Population was a powerful predictor of the number of patent filings in developing countries along with GDI and healthcare expenditure. The age and historical context of the patent estate may make a difference in the number of patents and countries covered. Broad surveillance and benchmarking of the global medicine patent landscape is valuable for detecting significant shifts that may occur over time. With improved international medicine patent transparency by companies and data available through third parties, such studies will be increasingly feasible.

Could patents interfere with the development of a cardiovascular polypill?

BACKGROUND: The Wellcome Trust, the World Health Organization, and cardiologists have advocated for the idea of a "polypill" containing multiple cardiovascular drugs to be co-formulated into a single pill for over a decade. Some cardiologists have asserted that the drugs commonly considered for inclusion into such a polypill are older and therefore free of patent protection. We tested this assertion. This project was requested by the World Heart Federation (WHF). METHODS, DATA AND MATERIALS: Two cardiologists from the WHF provided a list of 48 cardiovascular drugs for evaluation. We designated the United States and Canada as the base jurisdictions for this patent study. We linked patent data from these countries' national medicine patent registers to patent information in over 96 other countries using Derwent and INPADOC via Thomson Innovation. We expanded our study beyond the aforementioned data linkage through a systematic search of the World Intellectual Property Organization's PatentScope, which was based primarily upon the drugs' active ingredient names. RESULTS: In the United States and Canada, eight of the drugs were only available in the patent-protected, brand name formulation in one or both countries. Another 21 drugs had relevant patents, but generic equivalents were nevertheless available. Only 19 drugs (40 %) appeared entirely post-patent. Broadening the co-formulation searches globally, the overwhelming majority of drugs (40/48) were mentioned in patent applications for cardiovascular drug combinations. CONCLUSION: The assertion that most of these cardiovascular drugs are post-patent is accurate, but only in the sense that many of the original patents on these active ingredients have expired and that generic alternatives are usually available. The landscape of patents covering novel (co-) formulations is far more complex, however. Most research and development for cardiovascular combination medicines are likely to be undertaken by companies whose original patents on the active ingredient will soon expire or have recently expired. Cardiologists looking to accelerate polypill development may consider approaching such companies to partner.

Modes of delivery in preventive intervention studies: a rapid review.

BACKGROUND: This review was commissioned to generate broad discussion about how to select intervention delivery modes when designing a complex, preventive intervention aimed at chronic disease through the promotion of physical activity, healthy diet and/or medication adherence. In this context, we asked, what are the delivery modes? What are the important design considerations? And how do these compare (e.g. strengths, limitations)? MATERIALS AND METHODS: This review utilized the methods of rapid review, an emerging methodology arising from health technology assessment. The search strategy was applied in Embase and MEDLINE. A qualitative, narrative synthesis was performed on included articles. RESULTS: After screening, 21 articles remained for synthesis (10 systematic reviews, including 1 review of reviews; four trials or studies; three commentaries or conference proceedings; and 2 were scoping projects). Our synthesis determined that major categories of design considerations when selecting intervention delivery modes include attention to the (i) candidate mode types, (ii) settings and social environment, (iii) intensity and timing, (iv) provider, (v) study population and participants, (vi) cost, (vii) behaviour change technique and (viii) theoretical basis. CONCLUSION: An array of modes of delivery is available for each of the intervention strategies under consideration (i.e. physical activity, dietary change and medication adherence). No single delivery mode was clearly more appropriate or more effective than another, each having unique strengths and limitations. Delivery mode decisions that take the above-mentioned factors (i-viii) into account will be more fit-for-purpose than those that do not.

Effectiveness of individual-focused interventions to prevent chronic disease.

BACKGROUND: The burden of chronic disease is projected to assume crisis proportions in most parts of the world by the middle of the century, focusing attention on the need for preventive interventions. We identify and review published research on primary prevention individual-level interventions in current practice and describe and discuss the limitations of the current evidence. The report facilitates prioritizing a research agenda for potential interventions that might be investigated within cohort studies. MATERIALS AND METHODS: This study is a rapid review. Computerized database searches (PubMed and EMBASE) were performed in October 2012 to identify articles on primary prevention interventions that are directed at the individual level. Potentially, relevant International Agency of Research on Cancer handbooks and monographs were also reviewed. The review includes articles reported in English on the efficacy or effectiveness of a preventive intervention in an adult population. It excludes articles on alcohol or tobacco smoking. RESULTS: Many chronic disease interventions directed at individuals report a protective effect in the short term and some evidence for the efficacy of chemoprevention in chronic disease prevention exists. Evidence these effects persist in the longer term is inconsistent. CONCLUSIONS: There are currently only limited evidence-based preventions for most chronic diseases, for which a summary is available in Table A1 (see Appendix B). Most individual-level intervention research studies have been conducted using case-control designs and some small, randomized studies. There are fewer impediments to lifestyle modifications when compared to prevention using chemoprevention and vaccination or other methods of prevention of persistent infection.

Social network risk factors and COVID-19 vaccination: A cross-sectional survey study.

BACKGROUND: Social networks have an important impact on our health behaviours, including vaccination. People's vaccination beliefs tend to mirror those of their social network. As social networks are homogenous in many ways, we sought to determine in the context of COVID-19 which factors were most predictive of belonging to a mostly vaccinated or unvaccinated social group. METHODS: We conducted a cross-sectional survey among Canadian residents in November and December 2021. Participants were asked about the vaccination status of their social networks their beliefs relating to COVID-19, and various sociodemographic factors. Respondents were split into three groups based on social network vaccination: low-, medium-, and high-risk. Chi-squared tests tested associations between factors and risk groups, and an ordinal logistic model was created to determine their direction and strength. RESULTS: Most respondents (81.1 %) were classified as low risk (i.e., a mostly vaccinated social network) and few respondents (3.7 %) were classified as high-risk (i.e., an unvaccinated social group). Both the chi-square test (29.2 % difference between the low- and high- risk groups [1.8 % vs. 31.0 %], p < 0.001) and the ordinal logistic model (odds ratio between the low- and high-risk groups: 14.45, p < 0.01) found that respondents' perceptions of COVID-19 as a "not at all serious" risk to Canadians was the most powerful predictor of belonging to a predominantly unvaccinated social circle. The model also found that those in mostly unvaccinated social circles also more often reported severe COVID-19 symptoms (odds ratio between the low- and high-risk groups: 2.26, p < 0.05). CONCLUSION: Perception of COVID-19 as a threat to others may signal communities with lower vaccination coverage and higher risk of severe outcomes. This may have implications for strategies to improve public outreach, messaging, and planning for downstream consequences of low intervention uptake.

Patent Challenges And Litigation On Inhalers For Asthma And COPD.

Between 1986 and 2020 the Food and Drug Administration (FDA) approved fifty-three brand-name inhalers for asthma and chronic obstructive pulmonary disease (COPD), but by the end of 2022 only three of those inhalers faced independent generic competition. Manufacturers of brand-name inhalers have created long periods of market exclusivity by obtaining multiple patents, many on the delivery devices rather than the active ingredients, and by introducing new devices that contain old active ingredients. Limited generic competition for inhalers has raised questions about whether the Drug Price Competition and Patent Term Restoration Act of 1984, also known as the Hatch-Waxman Act, for challenging patents is adequately facilitating the entry of complex generic drug-device combinations. For the fifty-three brand-name inhalers approved during the period 1986-2020, generic manufacturers filed challenges authorized by the Hatch-Waxman Act, which are known as paragraph IV certifications, on only seven products (13 percent). The median time from FDA approval to first paragraph IV certification was fourteen years. Paragraph IV certifications resulted in approved generics for only two products, each of which experienced fifteen years of market exclusivity before generic approval. Reform of the generic drug approval system is critical to ensuring the timely availability of competitive markets for generic drug-device combinations such as inhalers.

COVID-19 Vaccine's Speed to Market and Vaccine Hesitancy: A Cross-Sectional Survey Study.

Background: This paper aims to assess the extent to which the COVID-19 vaccine's speed to market affected Canadian residents' decision to remain unvaccinated. Method: A cross-sectional survey conducted in late 2021 asked participants whether they had received the vaccine and their reasons for abstaining. Results: Of the 2,712 participants who completed the survey, 8.9% remained unvaccinated. Unvaccinated respondents who selected "They made the vaccine too fast" (59.8%), were significantly more likely to identify as white, believe that the COVID-19 pandemic was not serious and have an unvaccinated social circle. Conclusion: Should the COVID-19 vaccine rapid regulatory process be expanded, more patients may refuse treatment than if traditional timelines are followed.

Neighbourhood deprivation, distance to nearest comprehensive stroke centre and access to endovascular thrombectomy for ischemic stroke: a population-based study.

BACKGROUND: Endovascular thrombectomy (EVT) has revolutionized ischemic stroke care. We aimed to assess whether neighbourhood socioeconomic status is predictive of access to EVT after receipt of alteplase for ischemic stroke among patients living in Alberta, Canada, and whether this relation is mediated by the distance a person lives to the nearest comprehensive stroke centre (CSC). METHODS: We performed a retrospective study including all people older than 18 years living in Alberta who were admitted to hospital with an ischemic stroke and who received intravenous alteplase treatment between Jan. 1, 2017, and Dec. 31, 2019. Data were obtained through administrative data sets. The primary outcome was treatment with EVT. We assigned neighbourhood deprivation quintile based on the Material and Social Deprivation Index. We used logistic regression modelling to assess for a relation between deprivation and treatment with EVT. We adjusted for age, sex, stroke severity and distance to the nearest CSC. We calculated the average causal mediation effect of distance to the nearest CSC on the relation between neighbourhood deprivation level and treatment with EVT. RESULTS: The study cohort consisted of 1335 patients, of whom 181 (13.6%) had missing data and were excluded from the main regression analysis. Endovascular thrombectomy was performed or attempted in 314 patients (23.5%). In the primary model, patients from the most deprived neighbourhoods were less likely than those from less deprived neighbourhoods to have received EVT (adjusted odds ratio 0.43, 95% confidence interval 0.24 to 0.77). Neighbourhood deprivation level was not significantly associated with EVT when distance to the nearest CSC was included as a covariate. Mediation analysis suggested that 48% of the total effect that neighbourhood deprivation level had on the odds of receiving EVT was attributable to the distance a person lived from the nearest CSC. INTERPRETATION: The results suggest that people from more deprived neighbourhoods in Alberta were less likely to be treated with EVT than those from less deprived neighbourhoods. Improving access to EVT for people living in remote locations may improve the equitable distribution of this treatment.

Patterns and Patients' Characteristics Associated With Use of Sodium-Glucose Cotransporter-2 Inhibitors Among Adults With Type 2 Diabetes: A Population-based Cohort Study.

OBJECTIVES: Our aim in this study was to describe patterns and patient-level factors associated with use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) among adults with diabetes being treated in Alberta, Canada. METHODS: Using linked administrative data sets from 2014 to 2019, we defined a retrospective cohort of adults with prevalent or incident type 2 diabetes with indications for SGLT2i use and who did not have advanced kidney disease (glomerular filtration rate <30 mL/min per 1.73 m2) or previous amputation. We describe medication dispensation patterns of SGLT2is over time in the overall cohort and among the subgroup with cardiovascular disease (CVD). Multivariable logistic regression was used to determine patients' characteristics associated with SGLT2i use. RESULTS: Of the 341,827 patients with diabetes (mean age, 60.7 years; 45.6% female), 107,244 (31.3%) had CVD. The proportion of patients with an SGLT2i prescription increased in a linear fashion to a maximum of 10.8% (95% confidence interval [CI], 10.7% to 10.9%) of the eligible cohort by the end of the observation period (March 2019). The proportion of filled prescriptions was similar for patients with CVD (10.4%; 95% CI, 10.1% to 10.6%) and for those without CVD (10.9%; 95% CI, 10.8% to 11.0%). Patients' characteristics associated with lower odds of filling an SGLT2i prescription included female sex, older age and lower income. CONCLUSIONS: The use of SGLT2is is increasing among patients with diabetes but remains low even in those with CVD. Policy and practice changes to increase prescribing, especially in older adults, may help to reduce morbidity and mortality related to cardiovascular and renal complications.

Patents And Regulatory Exclusivities On Inhalers For Asthma And COPD, 1986-2020.

Inhalers are the mainstay of treatment for asthma and chronic obstructive pulmonary disease (COPD). These products face limited generic competition in the US and remain expensive. To better understand the strategies that brand-name inhaler manufacturers have employed to preserve their market dominance, we analyzed all patents and regulatory exclusivities granted to inhalers approved by the Food and Drug Administration between 1986 and 2020. Of the sixty-two inhalers approved, fifty-three were brand-name products, and these brand-name products had a median of sixteen years of protection from generic competition. Only one inhaler contained an ingredient with a new mechanism of action. More than half of all patents were on the inhaler devices, not the active ingredients or other aspects of these drug-device combinations. Manufacturers augmented periods of brand-name market exclusivity by moving active ingredients from one inhaler device into another ("device hops"). The median time from approval of an originator product to the last-to-expire patent or regulatory exclusivity of branded follow-ons was twenty-eight years (across device hops on fourteen originator products). Regulatory and patent reform is critical to ensure that the rewards bestowed on brand-name inhaler manufacturers better reflect the added clinical benefit of new products.

Patent "Evergreening" of Medicine-Device Combination Products: A Global Perspective.

Background: Patenting medicine-delivery devices (inhalers and pens) is controversial when it extends market protections beyond that of the underlying therapeutic agent. We evaluated how common device patenting is, internationally. Method: Using a product sample (n = 88) and an international patent database, we assessed the issue's scope. Results: When comparing the 88 patent portfolios for each product in each country, Canada was found to be among the most impacted, with 90% of the portfolios containing at least one device patent and 35% of the portfolios containing device patents exclusively. Conclusion: Patenting of delivery devices impacts major pharmaceutical manufacturing centres worldwide. International consensus among stakeholders (regulators and payors) is needed on which device modifications represent meaningful clinical value.

Laboratory testing and antihypertensive medication adherence following initial treatment of incident, uncomplicated hypertension: A real-world data analysis.

In this study on medication adherence among newly diagnosed patients with uncomplicated, incident hypertension, we conducted a retrospective cohort study using available administrative and laboratory data from April 1, 2012 to March 31, 2017 in Alberta, Canada to understand the extent to which baseline laboratory assessment and/or subsequent follow-up was associated with persistence with antihypertensive therapy. We determined the frequency of baseline and follow-up testing and compared the rates of medication persistence by patient-, neighbourhood-, and treatment-related factors. Of 103 232 patients with newly diagnosed, uncomplicated hypertension who filled their first prescription within our study timeframe, 52.5% were non-persistent within 6 months. Persistent patients were more often female and residing in neighbourhoods with higher social status (with exception to rurality). Aside from older age, the strongest predictor of persistence was performance of laboratory testing related to hypertension with an apparent effect in which higher levels of medication persistence were seen with more frequent laboratory testing. We concluded that medication persistence was far from optimal, dropping off considerably after 6 months for more than half of patients. Medication persistence is a substantial barrier to realizing the full societal benefits of antihypertensive treatment. Ongoing follow up with patients, including laboratory testing, may be a critical component of better long term treatment persistence.