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Background: Chikungunya virus (CHIKV) outbreaks, driven by the expanding habitat of the Aedes albopictus mosquito and global climate change, pose a significant threat to public health. Our study evaluates the effectiveness of emergency vaccination using a dynamic disease transmission model for a potential large-scale outbreak in Rome, Italy., Methods: The model incorporates a susceptible-exposed-infected-recovered (SEIR) framework for human and mosquito populations, taking into account temperature-dependent mosquito lifecycle dynamics, human-mosquito interactions, and various vaccination scenarios., Findings: Results indicate that emergency vaccination could significantly mitigate the impact of a CHIKV outbreak. Without vaccination, an outbreak is estimated to infect up to 6.21% of Rome's population, equating to approximately 170,762 individuals. Implementing rapid vaccination after detecting the virus in ten individuals and achieving 40% coverage could reduce infection rates by 82%, preventing 139,805 cases. Scenario and sensitivity analyses confirm that even with lower vaccination coverage rates, significant benefits are observed: at 10% coverage, the number of infections drops to 115,231, and at 20% coverage, it further reduces to 76,031. These scenarios indicate prevention of approximately 33% and 55% of infections, respectively., Conclusions: The findings highlight the critical role of timely vaccination interventions in outbreak settings, demonstrating that even modest coverage levels can markedly decrease the spread of CHIKV. This study underscores the importance of preparedness, early detection and adaptive response capabilities to manage emerging infectious diseases in urban centres, advocating for strategic vaccine stockpiling and rapid deployment mechanisms to enhance public health outcomes., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: GTV, AMR, and JCJ are paid employees of Valneva GmbH, the producer of the IXCHIQ vaccine discussed in the manuscript., (Copyright: © 2024 Sloof 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.)

Introduction: Chikungunya is a mosquito-borne arboviral disease posing an emerging global public health threat. Understanding the global burden of chikungunya is critical for designing effective prevention and control strategies. However, current estimates of the economic and health impact of chikungunya remain limited and are potentially underestimated. This study aims to provide a comprehensive overview of the chikungunya burden worldwide., Methods: We analysed the global burden of chikungunya between 2011 and 2020 and calculated disability-adjusted life years (DALYs) and direct and indirect costs using a data-driven simulation model. The main outcomes were the number of cases, the total DALY burden, and the direct and indirect costs of acute and chronic chikungunya between 2011 and 2020., Results: Our study revealed a total of 18.7 million chikungunya cases in 110 countries between 2011 and 2020, causing 1.95 million DALYs. Most of this burden was found in the Latin American and Caribbean region. The total economic burden caused by chikungunya over these 10 years was estimated at $2.8 billion in direct costs and $47.1 billion in indirect costs worldwide. Long-term chronic illness was the source of most costs and DALYs., Conclusion: Chikungunya has a higher disease burden than was previously estimated and costs related to the disease are substantial. Especially in combination with its unpredictable nature, chikungunya could significantly impact local health systems. Insights from this study could inform decision makers on the impact of chikungunya on population health and help them to appropriately allocate resources to protect vulnerable populations from this debilitating disease., Competing Interests: Competing interests: AMR and GTV are Valneva employees and own stock options of Valneva. MB is an employee of ASC Academics. ASC Academics has received consultancy fees for this project from Valneva Austria GmbH. MJP reports grants and honoraria from various pharmaceutical companies, including those developing, producing, and marketing vaccines. He holds stocks in Health-Ecore (Zeist, Netherlands) and PAG BV (Groningen, Netherlands), and advises ASC Academics (Groningen, Netherlands). KOM serves on the Scientific Advisory Board for Valneva., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chikungunya is a viral disease caused by a mosquito-borne alphavirus. The acute phase of the disease includes symptoms such as fever and arthralgia and lasts 7-10 days. However, debilitating symptoms can persist for months or years. Despite the substantial impact of this disease, a comprehensive assessment of its clinical picture is currently lacking., Methods: We conducted a systematic literature review on the clinical manifestations of chikungunya, their prevalence and duration, and related hospitalization. Embase and MEDLINE were searched with no time restrictions. Subsequently, meta-analyses were conducted to quantify pooled estimates on clinical outcomes, the symptomatic rate, the mortality rate, and the hospitalization rate. The pooling of effects was conducted using the inverse-variance weighting methods and generalized linear mixed effects models, with measures of heterogeneity reported., Results: The systematic literature review identified 316 articles. Out of the 28 outcomes of interest, we were able to conduct 11 meta-analyses. The most prevalent symptoms during the acute phase included arthralgia in 90% of cases (95% CI: 83-94%), and fever in 88% of cases (95% CI: 85-90%). Upon employing broader inclusion criteria, the overall symptomatic rate was 75% (95% CI: 63-84%), the chronicity rate was 44% (95% CI: 31-57%), and the mortality rate was 0.3% (95% CI: 0.1-0.7%). The heterogeneity between subpopulations was more than 92% for most outcomes. We were not able to estimate all predefined outcomes, highlighting the existing data gap., Conclusion: Chikungunya is an emerging public health concern. Consequently, a thorough understanding of the clinical burden of this disease is necessary. Our study highlighted the substantial clinical burden of chikungunya in the acute phase and a potentially long-lasting chronic phase. Understanding this enables health authorities and healthcare professionals to effectively recognize and address the associated symptoms and raise awareness in society., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: KR, TL, HSH, and GSG are employees of Asc Academics. Asc Academics has received consultancy fees for this project from Valneva Austria GmbH. AMR and GTV are Valneva employees and own stock options of Valneva. MJP reports grants and honoraria from various pharmaceutical companies, including those developing, producing, and marketing vaccines. He holds stocks in Health-Ecore (Zeist, Netherlands) and PAG BV (Groningen, Netherlands), and advises ASC Academics (Groningen, Netherlands). These competing interest will not alter adherence to PLOS policies on sharing data and materials., (Copyright: © 2024 Rama 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.)

Background: We aimed to quantify patients' benefit-risk preferences for attributes associated with human epidermal growth factor receptor 2 (HER2)-targeted breast cancer treatments and estimate minimum acceptable benefits (MABs), denominated in additional months of progression-free survival (PFS), for given treatment-related adverse events (AEs)., Methods: We conducted an online discrete-choice experiment (DCE) among patients with self-reported advanced/metastatic breast cancer in the United States, United Kingdom, and Japan (N = 302). In a series of nine DCE questions, respondents chose between two hypothetical treatment profiles created by an experimental design. Profiles were defined by six attributes with varying levels: PFS, nausea/vomiting, diarrhea, liver function problems, risk of heart failure, and risk of serious lung damage and infections. Data were analyzed using an error component random-parameters logit model., Results: Among the attributes, patients placed the most importance on a change in PFS from 5 to 26 months; change from no diarrhea to severe diarrhea was the least important. Avoiding a 15% risk of heart failure had the largest MAB (5.8 additional months of PFS), followed by avoiding a 15% risk of serious lung damage and infections (4.6 months), possible severe liver function problems (4.2 months), severe nausea/vomiting (3.7 months), and severe diarrhea (2.3 months) compared with having none of the AEs. The relative importance of 21 additional months of PFS (increasing from 5 to 26 months) increased for women with HER2-negative disease and those with children., Conclusions: Patients valued PFS gain higher than the potential risk of AEs when deciding between hypothetical breast cancer treatments., (© 2022. The Author(s).)

Background: Evidence-based reassurances addressing vaccine-related concerns are crucial to promoting primary vaccination, completion of the primary series, and booster vaccination. By summarizing and comparing the reactogenicity of COVID-19 vaccines authorized by the European Medicines Agency, this analysis aims to support in-formed decision-making by the lay public and help overcome vaccine hesitancy., Research Design and Methods: A systematic literature review identified 24 records reporting solicited adverse events for AZD1222, BNT162b2, mRNA-1273, NVX-Cov2373, and VLA2001 in individuals aged 16 or older. Network meta-analyses were conducted for each solicited adverse events reported for at least two vaccines that were not compared head-to-head but could be connected through a common comparator., Results: A total of 56 adverse events were investigated through network meta-analyses within a Bayesian framework with random-effects models. Overall, the two mRNA vaccines were found to be the most reactogenic vaccines. VLA2001 had the highest likelihood of being the least reactogenic vaccine after the first and second vaccine dose, especially for systemic adverse events after the first dose., Conclusions: The reduced chance of experiencing an adverse event with some COVID-19 vaccines may help to overcome vaccine hesitancy in population groups with concerns about the side effects of vaccines.

Background: With the introduction of investigational human epidermal growth factor receptor 2 (HER2) targeting treatments, thorough understanding of breast cancer with different HER2 expression levels is critical. The aim of this study was to compare clinicopathologic characteristics and survival of patients with metastatic breast cancer according to the level of HER2 expression., Methods: Women with distant metastatic breast cancer during 2008-2016 were selected from PALGA, the Dutch Pathology Registry, and linked to the PHARMO Database Network. Breast cancer samples were categorised as HER2 immunohistochemistry score 0 (IHC0), HER2-low or HER2+., Results: Among women with hormone receptor (HR) positive metastatic breast cancer (n = 989), 373 (38%) cancers were HER2 IHC0, 472 (48%) were HER2-low and 144 (15%) were HER2+. Among HR negative patients (n = 272), the proportion of HER2 IHC0, HER2-low and HER2+ was 110 (40%), 104 (38%) and 58 (21%) respectively. Within the HR + cohort, patients with HER2 IHC0 or HER2-low cancer were significantly older compared to HER2+ patients. This age difference was not seen in the HR-cohort. The localisation of distant metastases differed significantly between HER2 IHC0 or HER2-low versus HER2+ cases. Survival rates did not differ markedly by subtypes., Conclusion: Substantial proportion of patients had a HER2-low breast cancer. No clear differences in survival were found when comparing HER2 and HR status. Getting more granular insights in the level of HER2 expression and addressing HER2-low as a separate category could help to assess the impact of emerging treatment strategies. Therefore, more detailed information on HER2 expression should be routinely reported., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The development of accelerated approval programs for high morbidity and unmet need conditions has driven the use of single-arm studies in drug development. Regulatory and health technology assessment (HTA) agencies are recognizing that high-quality external control arms (ECAs), built using real-world data, can reduce uncertainties arising from single-arm studies. This review compared 7 case studies of regulatory and HTA agencies' evaluations of oncology ECAs., Methods: Food and Drug Administration multidisciplinary reviews for oncology submissions from 2014 to 2021 were screened to identify 7 cases (2 blinatumomab indications, avelumab, and erdafitinib, entrectinib, trastuzumab deruxtecan, and idecabtagene vicleucel) with ECAs to support efficacy claims. Regulatory (Food and Drug Administration, European Medicines Agency, Health Canada) and HTA (pan-Canadian Oncology Drug Review, National Institute for Health and Care Excellence, Federal Joint Committee, Haute Autorité de Santé, and Pharmaceutical Benefits Advisory Committee) submissions for these cases were reviewed. The decision makers' ECA critiques and the level of influence on the decision were analyzed and categorized., Results: Across case studies, selection bias and confounding were the most common ECA critiques. Nevertheless, agreement in critiques between and among regulators and HTA bodies was low. ECA influence on agencies' decisions also varied., Conclusions: Evaluating the same ECA evidence, agencies focused on methodologic issues (ie, selection bias and confounding), but were often not aligned on their critiques. Further research is needed to fully characterize how agencies evaluate ECAs. This study is a first step in critically evaluating agencies' critiques of ECAs and highlights the need for future guidance development around ECA design and generation., (Copyright © 2022. Published by Elsevier Inc.)

Background : Currently literature on the impact of patent expiry on drug prices is lacking. Objective : To determine the impact of patent expiration and generic entry on drug prices in the Netherlands. Methods : Prescription and price data from 1999 up to and including December 2016 were collected from two national databases. The overall price ratio of drugs prices up to 48 months after patent expiration was compared to the price in the month before expiry. Sub-analyses were performed to provide insights in generic uptake, length of market exclusivity and price development for originators and generics separately. Results : In total 250 drugs faced patent expiration during the study period. Forty-eight months after patent expiration the median price ratio decreased to 0.59 (IQR = 0.23-0.86) compared to the month prior patent expiry. Major differences in price developments were observed depending on the level of revenue prior to patent expiration and the time of patent expiration with ratios ranging from 0.08 (IQR = 0.07-0.16) to 0.81 (IQR = 0.62-0.97). Prior to patent expiry, the price decreased by 2.3% annually while having market exclusivity for 11.3 years on average. Conclusion : This study showed that the median drug price after patent expiration decreased by 41% after 4 years. The results of this study can be used to provide more reliable estimates on drug prices over its lifecycle and can be implemented in economic evaluations to inform the cost-effectiveness and long-term budget impact of new drugs., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Objective: The aim of this study was to evaluate the impact of patent expiry on drug prices by means of a systematic literature review., Methods: A systematic literature search was performed in PubMed to identify all published literature on the impact of patent expiration on drug prices. Additional literature was identified using a less distinct syntax in Google Scholar and EconLit. Data extraction followed a standardized assessment form containing the domains study type, study aim, reported outcomes, number of drugs and drug classes assessed, and originators or generics assessed., Results: The 16 identified studies that assessed impact of patent expiry on drug prices showed that price developments after patent expiration varied between countries. The included studies assessed price developments for the USA, Canada, Australia, the UK, the Netherlands, Germany and France, Spain, Italy, Norway, Sweden and Denmark. The number of drugs included within different studies ranged between 1 and 219. The identified studies indicated that drug prices decreased significantly after patent expiry with drug price ratios ranging from 6.6 to 66% 1-5 years after patent expiry., Conclusion: Drug prices decrease significantly after patent expiry. The extent of this price reduction varied greatly between products and countries. For this reason, country-specific analyses on price developments after patent expiry should be used when these are considered in decision making. Future research should be dedicated to gathering more country-specific data to reduce the uncertainty with regard to price developments.