Search

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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.

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., Competing Interests: Competing interests: Michael Hill reports grants from Boehringer-Ingelheim to the University of Calgary for the TEMPO-2 and ACT-GLOBAL trials; from Biogen to the University of Calgary; from NoNO to the University of Calgary for the ESCAPE-NA1 and ESCAPE-NEXT trials; from the Canadian Institutes of Health Research to the University of Calgary for the ESCAPE-NA1 and ESCAPE-NEXT trials; from Medtronic to the University of Calgary for the HERMES collaboration; and from Alberta Innovates to the University of Calgary for the QuICR Alberta Stroke Program (some of the funds were used for the ESCAPENA1 trial). He has received consulting fees from Sun Pharmaceutical Industries and BrainsGate for adjudication of clinical trial outcomes. He reports US Patents 62/086,077 and 10,916,346, both licensed to Circle Neurovascular Imaging. He has been chair of the Data and Safety Monitoring Committee for the RACECAT trial (end 2020), the Oncovir Hiltonol trial (end 2023) and the DUMAS trial (end 2023). He is a member of the Data and Safety Monitoring Board for the ARTESIA trial (end 2023) and the BRAIN-AF trial (ongoing). He is president of the Canadian Neurological Sciences Federation and a member of the board of directors of the Canadian Stroke Consortium. He holds private stock in Circle Cardiovascular Imaging and PureWeb. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

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., Competing Interests: AO serves as a fellow in the Office of the Assistant Secretary for Planning and Evaluation. ASK is a member of the PLOS Medicine Editorial Board and has served as an expert witness in litigation against Gilead relating to tenofovir-containing products. Outside the scope of the work, WBF serves as a consultant for the non-profit Alosa Health and as an expert witness in litigation against inhaler manufacturers. WBF also served as a consultant to Aetion., (Copyright: © 2023 Olsen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.

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., (Copyright © 2023 Longwoods Publishing.)

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.

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 m 2 ) 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., (Copyright © 2022 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

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., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

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., (Copyright © 2022 Longwoods Publishing.)

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., Competing Interests: Competing interests: Mina Tadrous has received consultant fees from the Canadian Agency for Drugs and Technologies in Health and Green Shield Canada. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

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.

Background: Few studies have categorized high-cost patients (defined by accumulated health care spending above a predetermined percentile) into distinctive groups for which potentially actionable interventions may improve outcomes and reduce costs. We sought to identify homogeneous groups within the persistently high-cost population to develop a taxonomy of subgroups that may be targetable with specific interventions., Methods: We conducted a retrospective analysis in which we identified adults (≥ 18 yr) who lived in Alberta between April 2014 and March 2019. We defined "persistently high-cost users" as those in the top 1% of health care spending across 4 data sources (the Discharge Abstract Database for inpatient encounters; Practitioner Claims for outpatient primary care and specialist encounters; the Ambulatory Care Classification System for emergency department encounters; and the Pharmaceutical Information Network for medication use) in at least 2 consecutive fiscal years. We used latent class analysis and expert clinical opinion in tandem to separate the persistently high-cost population into subgroups that may be targeted by specific interventions based on their distinctive clinical profiles and the drivers of their health system use and costs., Results: Of the 3 919 388 adults who lived in Alberta for at least 2 consecutive fiscal years during the study period, 21 115 (0.5%) were persistently high-cost users. We identified 9 subgroups in this population: people with cardiovascular disease ( n = 4537; 21.5%); people receiving rehabilitation after surgery or recovering from complications of surgery ( n = 3380; 16.0%); people with severe mental health conditions ( n = 3060; 14.5%); people with advanced chronic kidney disease ( n = 2689; 12.7%); people receiving biologic therapies for autoimmune conditions ( n = 2538; 12.0%); people with dementia and awaiting community placement ( n = 2520; 11.9%); people with chronic obstructive pulmonary disease or other respiratory conditions ( n = 984; 4.7%); people receiving treatment for cancer ( n = 832; 3.9%); and people with unstable housing situations or substance use disorders ( n = 575; 2.7%)., Interpretation: Using latent class analysis supplemented with expert clinical review, we identified 9 policy-relevant subgroups among persistently high-cost health care users. This taxonomy may be used to inform policy, including identifying interventions that are most likely to improve care and reduce cost for each subgroup., Competing Interests: Competing interests: None declared., (© 2022 CMA Impact Inc. or its licensors.)

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., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: The private versus public contribution to developing new health knowledge and interventions is deeply contentious. Proponents of commercial innovation highlight its role in late-stage clinical trials, regulatory approval, and widespread distribution. Proponents of public innovation point out the role of public institutions in forming the foundational knowledge undergirding downstream innovation. The rapidly evolving COVID-19 situation has brought with it uniquely proactive public involvement to characterize, treat, and prevent this novel health treat. How has this affected the share of research by industry and public institutions, particularly compared to the experience of previous pandemics, Ebola, H1N1 and Zika?, Methods: Using Embase, we categorized all publications for COVID-19, Ebola, H1N1 and Zika as having any author identified as affiliated with industry or not. We placed all disease areas on a common timeline of the number of days since the WHO had declared a Public Health Emergency of International Concern with a six-month lookback window. We plotted the number and proportion of publications over time using a smoothing function and plotted a rolling 30-day cumulative sum to illustrate the variability in publication outputs over time., Results: Industry-affiliated articles represented 2% (1,773 articles) of publications over the 14 months observed for COVID-19, 7% (278 articles) over 7.1 years observed for Ebola, 5% (350 articles) over 12.4 years observed for H1N1, and 3% (160 articles) over the 5.7 years observed for Zika. The proportion of industry-affiliated publications built steadily over the time observed, eventually plateauing around 7.5% for Ebola, 5.5% for H1H1, and 3.5% for Zika. In contrast, COVID-19's proportion oscillated from 1.4% to above 2.7% and then declined again to 1.7%. At this point in the pandemic (i.e., 14 months since the PHEIC), the proportion of industry-affiliated articles had been higher for the other three disease areas; for example, the proportion for H1N1 was twice as high., Conclusions: While the industry-affiliated contribution to the biomedical literature for COVID is extraordinary in its absolute number, its proportional share is unprecedentedly low currently. Nevertheless, the world has witnessed one of the most remarkable mobilizations of the biomedical innovation ecosystem in history., Competing Interests: The authors have declared that no competing interests exist.

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., (Copyright © 2021 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Before the first generic version of a drug is marketed, patent litigation often occurs. The process begins when generic manufacturers notify the US Food and Drug Administration (FDA) of their intent to market a generic copy of a brand-name drug protected by patents, which they allege to be invalid or not infringed (called a Paragraph IV certification). Assuming the brand-name manufacturer responds with litigation within 45 days, a 30-month stay period is triggered, which bars the FDA from authorizing generic entry until the stay period expires or litigation is resolved in favor of the generic manufacturer. To understand whether 30-month stays delay generic entry, we examined the timing of major legal events leading to generic entry for a cohort of 46 generic drugs, including the timing of Paragraph IV certification filings, stay period expirations, the FDA approvals of generics, and generic product launches. We found Paragraph IV certifications were filed a median of 5.2 years after the brand drug's FDA approval. There was a median of 3.2 years between the stay period expiration and subsequent generic launch. Because stay periods generally expire well in advance of when generic entry typically occurs, 30-month stays are unlikely to delay the timing of generic entry. Patent litigation could begin even earlier, however, if litigation was allowed to start immediately following a brand-name drug's FDA approval; but by law currently, the soonest this can begin is 4 years after the brand drug's FDA approval. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Before generic versions of new drugs reach the market, patent litigation often occurs. Once litigation has been initiated, a 30-month regulatory stay period is triggered that bars the US Food and Drug Administration (FDA) from approving the generic application until litigation resolves or the stay period expires. WHAT QUESTION DID THIS STUDY ADDRESS? What is the timing of key legal events in the regulatory approval process for generic drugs in relation to the eventual launch of the generic product? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? We identified the typical timing of the initiation of patent litigation and expiration of the 30-month stay period prior to the eventual launch of generic products. Litigation is often initiated as soon as legally possible (i.e., 4 years after the launch of the brand product), and stay periods typically expire well before generic entry occurs. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? Stay periods are unlikely to delay generic entry directly because stay expirations often occur well before the time of generic launch. Allowing the submission of generic drug applications immediately following a brand drug's FDA approval would facilitate earlier patent dispute resolution and prevent unnecessary delays in the anticipated generic product launch date., (© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Background: A range of first-line similarly effective medications ranging in price are recommended for treating uncomplicated hypertension. Considering drug costs alone, thiazides and thiazide-like diuretics are the most cost-efficient option. We determined incident prescribing of thiazides for newly diagnosed hypertension as first-line treatment in Alberta, factors that predicted receiving thiazides vs more costly medications, and how much could be saved if more patients were prescribed thiazides., Methods: Using a retrospective cohort design, factors predicting receiving thiazides vs other agents were determined using mixed effects logistic regression. Cost savings were simulated by shifting patients from other antihypertensive medications to thiazides and calculating the difference., Results: Within our cohort of 89,548 adults, only 12% received thiazides as first-line treatment whereas 44% received angiotensin converting enzyme inhibitors, 17% received angiotensin receptor blockers, 16% received calcium channel blockers, and 10% received β-blockers. Antihypertensive medications were typically prescribed by office-based, general practitioners (88%). Being male and receiving a prescription from a physician with ≥ 20 years of practice and a high clinical workload were associated with increased odds of receiving nonthiazides. In the extreme case that all patients received thiazides as their first prescription, spending would have been reduced by a maximum of 95% (CAD$1.8 million)., Conclusions: Only 12% of Albertan adults with incident, uncomplicated hypertension were prescribed thiazides as first-line treatment. With the opportunity for drug cost savings, future research should evaluate the risk of adverse events and side effects across the drug classes and whether the costs associated with managing those risks could offset the savings achieved through increased thiazide use., (© 2021 The Authors.)

Background: Drug repurposing (i.e., finding novel uses for existing drugs) is essential for maximizing medicines' therapeutic utility, but obtaining regulatory approval for new indications is costly. Policymakers have therefore created temporary indication-specific market exclusivities to incentivize drug innovators to run new clinical investigations. The effectiveness of these exclusivities is poorly understood., Objective: To determine whether generic entry impacts the probability of new indication additions., Methods: For a cohort of all new small-molecule drugs approved by the FDA between July 1997 and May 2020, we tracked new indications added for the subset of drugs that experienced generic entry during the observation period and then analyzed how the probability of a new indication changed with the number of years since/to generic entry., Results: Of the 197 new drugs that subsequently experienced generic entry, only 64 (32%) had at least one new indication added. The probability of a new indication addition peaked above 4% between 7 and 8 years prior to generic entry and then to dropped to near zero 15 years after FDA approval. We show that the limited duration of exclusivity reduces the number of secondary indications significantly., Conclusion: Status quo for most drug innovators is creating novel one-indication products. Despite indication-specific exclusivities, the imminence of generic entry still has a detectable impact on reducing the chances of new indication additions. There is much room for improvement when it comes to incentivizing clinical investigations for new uses and unlocking existing medicines' full therapeutic potential.

We sought to compare expected and observed biosimilar and generic entry dates among new drugs approved by the US Food and Drug Administration (FDA) between 2000 and 2012. We defined expected biosimilar and generic entry dates as the later of the expiration of the key patent term or statutory exclusivity (12 years for biologics, 5 years for small molecule drugs not indicated for a rare disease, and 7 years for small molecule drugs indicated for a rare disease; plus 6 months if a pediatric extension had been granted). For drugs with expected entry prior to 2019, we calculated the proportion with observed biosimilar or generic entry. The expected biosimilar entry dates were estimated to be a median of 12.3 years (interquartile range (IQR) 12.0-14.0, n = 60) after FDA approval. The 12-year biologic statutory exclusivity period comprised 98% of the median expected protection period. By contrast, expected generic entry was estimated to be a median of 12.2 years (IQR 8.4-14.0, n=268), or 7.2 years after the 5-year small molecule statutory exclusivity (59% of the total expected market protection period). By 2019, observed biosimilar entry occurred in 12% of cases (3/25) and observed generic entry in 65% (101/155). We concluded that expected US market exclusivity periods are similar for biologic and small molecule drugs. Statutory exclusivity plays a more substantial role in market exclusivity protection for biologics. Biosimilar competition, currently lagging behind generic competition, will likely increase as the biosimilar market becomes established., (© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.)

The clinical trial landscape for Coronavirus 2019 (COVID-19) is radically different from that of previous epidemics. Compared with H1N1, Ebola, and Zika, COVID-19 had an order of magnitude more clinical trials within the first 3 months following the declaration of a Public Health Emergency of International Concern (PHEIC). These trials have started much faster, are more geographically diverse, and are less likely to be funded by industry. However, the almost simultaneous design and initiation of hundreds of trials with 0.3 million participants across 78 countries creates the potential for congestion and inefficiencies and enhances risks for investors. Thus, an international coordination mechanism for clinical trials could be valuable in this and other situations., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Delays in market entry of generic drugs are common. This study sought to identify the prevalence of delayed entry, the reasons for the delays, and the delays' effects on Medicaid spending in a recent cohort of brand-name medications. We estimated excess Medicaid spending in 2010-16 in the delayed quarter-years after accounting for market average predictions of brand-name market share, ratios of generic to brand-name prices, and Medicaid rebates (60 percent for brand-name and 15 percent for generic drugs). Among sixty-nine brand-name drugs that were predicted to lose market exclusivity, generic entry occurred either before or within a quarter-year of the expected date for thirty-eight products (55 percent), was delayed by more than one quarter for twenty products (29 percent), and did not occur for eleven products (16 percent). For the thirty-one products (45 percent) for which generic entry was delayed by more than one quarter or did not occur, Medicaid spent an estimated excess of $761 million over seven years ($109 million annually). Patent litigation was the most common cause of generic entry delays. Policies that expedite the resolution of patent challenges are needed to ensure the timely entry of generic drugs.

Lexchin has criticized Health Canada's recently published draft guidance on accelerated drug review, expressing concern over agency conflicts of interest and observing that priority review and notice of compliance with conditions correlate poorly with therapeutic benefit. Although agency operations may be imperfect, perhaps the most important finding of Lexchin's research is that only 11% of newly approved drugs provide meaningful benefit over standard treatments. To improve the expedited review process in light of these findings, we suggest eliminating user fees and fully funding the review process with public monies, reserving the use of expedited approval pathways for when preliminary measures of benefit are so large that traditional approval thresholds can be met earlier in the clinical trial process, improving labelling to quantitatively communicate drug benefits and risks, and avoiding the use of titles such as "priority" review, which could imply a magnitude of clinical superiority that has not been established., (Copyright © 2020 Longwoods Publishing.)

Canada recently entered into two multinational trade agreements (i.e., the Canada, United States, and Mexico Trade Agreement; and the Comprehensive Economic and Trade Agreement with the European Union). The resulting federal policy changes will prolong periods of market protection afforded to eligible brand-name prescription drugs by extending competition-blocking patent and data exclusivity terms. While previous studies have analysed these two policy changes in isolation, it remains unknown what the total combined impact will be in a typical year. Our objective was to design an analytic approach that can assess more than one change to a country's market protections and then to apply this methodology to the Canadian context. We find that the collective impact of these policy changes will be to extend the regulatory protection period for new drugs from an average of 10.0 years to 11.1 years. Depending upon the model's assumptions and all contingencies considered, an 11% increase equated to an average of $410 million annually (with a minimum estimate of $40 million and a maximum of $1.4 billion). Despite this uncertainty reflected in the range of possible financial impacts, we conclude that such methodological approaches could be useful for rapidly evaluating potential policy changes prior to adoption, which may further assist in budget planning to mitigate increased cost to the downstream health authorities most impacted by these trade concessions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: After new prescription drugs reach the market, manufacturers sometimes create modified versions of them. These new formulations can expand patient treatment options, but they may also be protected by later-expiring patents or data exclusivities, which can lead to later generic entry for the new formulations compared with the original product., Objective: To quantify how frequently manufacturers introduce new formulations of existing drugs and how often these new formulations earn additional years of market exclusivity beyond that of the original product., Methods: Using a cohort design and FDA databases, we assessed how frequently manufacturers introduced new formulations of 17 new small-molecule drugs approved in 2002 and when generic entry for the new formulations and original product occurred., Results: Through 2017, nine (53%) drugs approved in 2002 had been connected to 21 new formulations, most (11/21, 53%) introduced before 2007. Generic entry was observed in 6 of 9 (67%) cases and occurred more than 2 years later for the new formulations in 3 of the cases., Conclusions: Our results suggest that the introduction of new formulations of brand-name drugs occurs in about half of cases and sometimes provides manufacturers with a lengthy period of additional market exclusivity beyond that of the original product., Disclosures: This work was funded by the Laura and John Arnold Foundation. Kesselheim and Sarpatwari also receive support from the Harvard-MIT Center for Regulatory Science and the Engelberg Foundation. Beall has nothing to disclose.

Background: Most new brand-name drugs are protected by patents from generic competition, but these patents are occasionally granted in error. Invalidating such patents has traditionally been accomplished via court litigation by generic manufacturers, which is expensive and time consuming. In 2011, Congress created an administrative alternative to court litigation of patents, called inter partes review, intended to be much faster and less expensive., Objective: To evaluate the use of inter partes review to challenge pharmaceutical patents, including the number of challenges, the number of associated drug products, and the extent to which challengers have been successful., Methods: We obtained data pertaining to inter partes review proceedings, including identity of patent challenger, duration of proceedings, and outcome, from September 16, 2012 through April 24, 2017 from UnifiedPatents.com, and combined it with information about drug products and their associated patents, including patent type, contained in the US Food and Drug Administration's Orange Book., Results: Generic drug manufacturers have embraced the new inter partes review process, succeeding in overturning all challenged claims in 43% of the patents they have targeted since 2011, and some challenged claims in an additional 8%. Inter partes review for drug patents has consistently been completed within 12 months, as required by statute. Successful challenges have been brought most frequently against drug patents covering new formulations or methods of use, rather than drug patents covering active ingredients., Conclusion: In the pharmaceutical market, the inter partes review process can meaningfully contribute to ensuring that invalid patents do not block timely availability of generic drugs.

Patents temporarily protect brand-name drugs from generic competition, but some of the 20-year patent term is used up before marketing approval. To compensate for patent life lost to clinical testing and regulatory review, current law provides patent term restoration (PTR) of up to 5 years. Examining 170 top-selling drugs with a first generic equivalent approved between 2000 and 2012, we found that 49% (83 drugs) received a PTR extension (median extension: 2.75 years) yielding a median total exclusivity period of 13.75 years, compared with 10.0 years for the 87 nonextended drugs. Because PTR substantially prolongs market exclusivity periods, policies that extend non-patent exclusivity periods (which generally run concurrently with patent exclusivity) for less than the extended patent terms of drugs will have little practical impact., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2018 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

For thirty-five years the Orphan Drug Act of 1983 has provided incentives for pharmaceutical manufacturers to develop drugs to treat rare diseases-conditions that affect fewer than 200,000 people in the US. One key statutory incentive is an exclusive seven-year marketing right for the rare disease indication, which has been heralded as driving a dramatic increase in the number of rare disease treatments. However, most new drugs are also protected by patents. In this study we assessed all new small-molecule drugs approved in the period 1985-2014 that had at least one indication for an orphan-designated disease as of January 1, 2017. We found that orphan drug exclusivity outlasted the last expiring patent in 33 percent of cases overall, and in a smaller percentage of cases for each successive ten-year drug cohort: from 50 percent for drugs approved in 1985-94 to 35 percent for those approved in 1995-2004 and 18 percent for those approved in 2005-14. The Orphan Drug Act's market exclusivity incentive has played an increasingly smaller role in protecting rare disease drugs from competition, while rare disease drugs have substantially increased as a fraction of all new drug approvals.

Patent protection on medicines may frustrate access by blocking generic competition. Nevertheless, circumstances may still allow for generic procurement to occur anyway, especially for humanitarian cause. But to what extent does this occur? And which legal flexibilities may facilitate such procurement? We attempted to design a replicable methodology that involved linking antiretroviral (ARV) patent data (1260 patents for 12 medicines) from a World Intellectual Property Organization patent study on the 2013 World Health Organization's (WHO) Model List of Essential Medicines to all available matching procurement records in the WHO's Global Price Reporting Mechanism. We then cross-referenced these with lists of legal flexibilities which facilitate generic access where patents have been granted (e.g., supplier companies' patent non-enforcement policies, voluntary and compulsory licenses) to estimate plausible relevance. The patent data corresponded to 1924 generic procurement transactions (1.34 billion units) from 85 countries. While patents were relatively less common in these countries (the median coverage was 20%), over half (53%) of the generic procurements nevertheless aligned with patent protection in the exporting and/or importing country. The disproportionately high relevance of patents despite their lower numbers can be explained by their presence in key medicine-exporting countries and/or those with larger populations. We noted, however, that developing countries still seemed able to buy generic versions of these essential ARVs. A combination of legal flexibilities may have played important roles, but voluntary licensing agreements (VLs) between originator companies and generic ones appeared to align with the largest volumes of generic procurement where we estimated patent protection. If true, VLs may warrant proportionate attention from observers as a heavily relied upon international mechanism for facilitating generic access so that the implications can be better understood; however, we hope others repeat similar studies to investigate whether these results hold with different methodologies and samples of patented medicines, contexts, and timeframes., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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 (β = 0.59), followed by income (GDI per capita) (β = 0.32), and healthcare expenditure (β = 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.

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.

Background: Lack of access to insulin and poor health outcomes are issues for both low and high income countries. This has been accompanied by a shift from relatively inexpensive human insulin to its more expensive analogs, marketed by three to four main global players. Nonetheless, patent-based market exclusivities are beginning to expire there for the first generation insulin analogs. This paper adds a global dimension to information on the U.S. patent landscape for insulin by reviewing the patent status of insulins with emphasis on the situation outside the US and Europe., Methods: Using the term "insulin", we searched for patents listed on the United States Food and Drug Administration's (USFDA) Orange Book and the Canadian Online Drug Product Database Online Query and its Patent Register. With this information, we expanded the search globally using the World Intellectual Property Organization (WIPO) PatentScope database, the European Patent Office's INPADOC database and various country-specific Patent Offices., Results: Patent protected insulins marketed in the U.S. and other countries are facing an imminent patent-expiration "cliff' yet the three companies that dominate the global insulin market are continuing to file for patents in and outside the U.S, but very rarely in Africa. Only a few local producers in the so-called "pharmerging" markets (e.g., Brazil, India, China) are filing for global patent protection on their own insulins. There is moderate, but statistically significant association between patent filings and diabetes disease burden., Conclusions: The global market dominance by a few companies of analog over human insulin will likely continue even though patents on the current portfolio of insulin analogs will expire very soon. Multinationals are continuing to file for more insulin patents in the bigger markets with large disease burdens and a rapidly emerging middle class. Off-patent human insulins can effectively manage diabetes. A practical way forward would be find (potential) generic manufacturers globally and nudge them towards opportunities to diversify their national insulin markets with acceptable off-patent products for export.

Exorbitant price increases for critical off-patent medicines have received considerable media attention in recent months, leading to an investigation by the U.S. Senate. However, much of this attention has focused upon the companies that initiated the price increases, all of whom had recently acquired the drugs in question. Overlooked are upstream interventions with the originators of these drugs to prevent generics trolling in the first place. Using the particular example of Eli Lilly and Company's efforts to divest itself of cycloserine, a flawed process that paved the way for the recent price hike by Rodelis Therapeutics, this article highlights the responsibilities of drug originators, and safeguards to ensure similar rights transfers do not affect ongoing affordable access.

Background: Not all new drug products are truly new. Some are the result of marginal innovation and incremental patenting of existing products, but in such a way that confers no major therapeutic improvement. This phenomenon, pejoratively known as "evergreening", can allow manufacturers to preserve market exclusivity, but without significantly bettering the standard of care. Other studies speculate that evergreening is especially problematic for medicine/device combination products, because patents on the device component may outlast expired patents on the medicine component, and thereby keep competing, possibly less-expensive generic products off the market., Materials and Methods: We focused on four common conditions that are often treated by medicine/device product combinations: asthma and chronic obstructive pulmonary disease (COPD), diabetes, and severe allergic reactions. The patent data for a sample of such products (n = 49) for treating these conditions was extracted from the United States Food and Drug Administration's Orange Book. Additional patent-related data (abstracts, claims, etc) were retrieved using LexisNexis TotalPatent. Comparisons were then made between each product's device patents and medicine patents., Results: Unexpired device patents exist for 90 percent of the 49 medicine/device product combinations studied, and were the only sort of unexpired patent for 14 products. Overall, 55 percent of the 235 patents found by our study were device patents. Comparing the last-to-expire device patent to that of the last-to-expire active ingredient patent, the median additional years of patent protection afforded by device patents was 4.7 years (range: 1.3-15.2 years)., Conclusion: Incremental, patentable innovation in devices to extend the overall patent protection of medicine/device product combinations is very common. Whether this constitutes "evergreening" depends on whether these incremental innovations and the years of extra patent protection they confer are proportionately matched by therapeutic improvements in the standard of care, which is highly debatable.

Compulsory licensing has been widely suggested as a legal mechanism for bypassing patents to introduce lower-cost generic antiretrovirals for HIV/AIDS in developing countries. Previous studies found that compulsory licensing can reduce procurement prices for drugs, but it is unknown how the resulting prices compare to procurements through the Global Fund to Fight AIDS, Tuberculosis, and Malaria; UNICEF; and other international channels. For this study we systematically constructed a case-study database of compulsory licensing activity for antiretrovirals and compared compulsory license prices to those in the World Health Organization's (WHO's) Global Price Reporting Mechanism and the Global Fund's Price and Quality Reporting Tool. Thirty compulsory license cases were analyzed with 673 comparable procurements from WHO and Global Fund data. Compulsory license prices exceeded the median international procurement prices in nineteen of the thirty case studies, often with a price gap of more than 25 percent. Compulsory licensing often delivered suboptimal value when compared to the alternative of international procurement, especially when used by low-income countries to manufacture medicines locally. There is an ongoing need for multilateral and charitable actors to work collectively with governments and medicine suppliers on policy options., (Project HOPE—The People-to-People Health Foundation, Inc.)

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., (© 2014 Stichting European Society for Clinical Investigation Journal Foundation.)