A practical approach for adoption of a hub and spoke model for cell and gene therapies in low- and middle-income countries: framework and case studies.

In the rapidly evolving landscape of biotechnologies, cell and gene therapies are being developed and adopted at an unprecedented pace. However, their access and adoption remain limited, particularly in low- and middle-income countries (LMICs). This study aims to address this critical gap by exploring the potential of applying a hub and spoke model for cell and gene therapy delivery in LMICs. We establish the identity and roles of relevant stakeholders, propose a hub and spoke model for cell and gene therapy delivery, and simulate its application in Brazil and the Middle East and North Africa. The development and simulation of this model were informed by a comprehensive review of academic articles, grey literature, relevant websites, and publicly available data sets. The proposed hub and spoke model is expected to expand availability of and access to cell and gene therapy in LMICs and presents a comprehensive framework for the roles of core stakeholders, laying the groundwork for more equitable access to these lifesaving therapies. More research is needed to explore the practical adoption and implications of this model.

The potential long-term comparative effectiveness of larotrectinib vs standard of care for treatment of metastatic TRK fusion thyroid cancer, colorectal cancer, and soft tissue sarcoma.

BACKGROUND: Larotrectinib is approved for patients with metastatic TRK fusion cancers, including differentiated thyroid (DTC), colorectal cancer (CRC), and soft tissue sarcoma (STS). Given the basket clinical trial design of larotrectinib, direct comparisons against standard of care in each of the mentioned cancers have not been assessed. Also, owing to the limited duration of follow-up in clinical trials, long-term outcomes for treatments are generally not known or estimated. OBJECTIVE: To compare expected life-years (LYs) and quality-adjusted life-years (QALYs) for patients with metastatic DTC, CRC, and STS who are eligible to receive larotrectinib against patients with unknown NTRK gene fusion status receiving standard-of-care therapy. METHODS: We developed a partitioned survival model to estimate the long-term comparative effectiveness of larotrectinib and standard of care for 3 tumor types. Larotrectinib survival data, assessed by independent review committee, were derived from an updated July 2020 analysis of 19, 8, and 23 adult patients (aged ≥ 18 years) with metastatic TRK fusion DTC, CRC, and STS, respectively. The DTC survival data also included 2 patients aged less than 18 years for a total of 21 patients. Survival estimates for standard of care were derived from published clinical trials. Progressionfree and overall survival for all treatments were estimated using survival distributions (Exponential, Weibull, Log-logistic, and Lognormal) fit to the available data. The final exponential form was selected based on goodness-of-fit and clinical plausibility. QALYs were estimated by adjusting the time spent in the preprogression and postprogression health states by utility weights derived from publicly available literature. RESULTS: Patients receiving larotrectinib experienced more LYs and QALYs compared with those receiving standard-of-care treatments across all 3 assessed cancer types. In DTC, patients receiving larotrectinib had 7.15-8.26 additional LYs (5.87-6.12 QALYs); in CRC, patients receiving larotrectinib had 1.26-1.27 additional LYs (1.00 QALYs); and in STS, patients receiving larotrectinib had 5.56 additional LYs (1.99 QALYs). CONCLUSIONS: Compared with standard of care in metastatic TRK wild-type cancers, larotrectinib is estimated to result in improved LY and QALY outcomes based on parametric extrapolations of intrial survival data. Because patient-level data were unavailable for adjusted analyses, a cross-trial comparison was performed. Given the limitations of this analytic approach and the small sample size for larotrectinib in trials, future studies should reassess the comparative effectiveness of larotrectinib vs standard of care as treated patients accrue and long-term survival data mature. DISCLOSURES: K. Suh, J. Carlson, and S. Sullivan report consulting fees from Bayer US LLC. F. Xia and T. Williamson are employees of Bayer US LLC. This study was funded by Bayer US LLC. The sponsor had no role in the design of the study and did not have any role in the execution, analyses, interpretation of the data, or decision to submit results.

Cost-Effectiveness of the COVID-19 Test, Trace and Isolate Program in Colombia.

BACKGROUND: During the COVID-19 pandemic, Test-Trace-Isolate (TTI) programs have been recommended as a risk mitigation strategy. However, many governments have hesitated to implement them due to their costs. This study aims to estimate the cost-effectiveness of implementing a national TTI program to reduce the number of severe and fatal cases of COVID-19 in Colombia. METHODS: We developed a Markov simulation model of COVID-19 infection combined with a Susceptible-Infected-Recovered structure. We estimated the incremental cost-effectiveness of a comprehensive TTI strategy compared to no intervention over a one-year horizon, from both the health system and the societal perspective. Hospitalization and mortality rates were retrieved from Colombian surveillance data. We included program costs of TTI intervention, health services utilization, PCR diagnosis test, productivity loss, and government social program costs. We used the number of deaths and quality-adjusted life years (QALYs) as health outcomes. Sensitivity analyses were performed. FINDINGS: Compared with no intervention, the TTI strategy reduces COVID-19 mortality by 67%. In addition, the program saves an average of $1,045 and $850 per case when observed from the social and the health system perspective, respectively. These savings are equivalent to two times the current health expenditures in Colombia per year. INTERPRETATION: The TTI program is a highly cost-effective public health intervention to reduce the burden of COVID-19 in Colombia. TTI programs depend on their successful and speedy implementation. FUNDING: This study was supported by the Colombian Ministry of Health through award number PUJ-04519-20 received by EPQ AVO and SDS declined to receive any funding support for this study. The contents are the responsibility of all the individual authors.

Transferability of health technology assessment reports in Latin America: an exploratory survey of researchers and decision makers.

INTRODUCTION: HTA agencies, especially in developing countries, are under resourced and unable to conduct the desired amount of assessments. Adapting HTA reports (HTAs) from other jurisdictions is an alternative for saving resources. OBJECTIVES: To explore HTA transferability experiences in Latin-America and Caribbean (LAC): are decision makers (DMs) using HTAs from other jurisdictions? Are researchers adapting HTAs when developing local reports? How useful is the information found in HTAs from other jurisdictions? METHODS: Web-based survey sent to 13031 HTA researchers and DMs. RESULTS: We received 671 responses from 19 countries. DMs reported using HTAs from other jurisdictions to guide decisions in the majority of the situations: 52.6 percent HTAs from outside LAC (e.g., Europe), 23.1 percent from other LAC countries, and only 24.3 percent HTAs from their own countries. 63 percent of researchers reported using HTAs from other jurisdictions. Usefulness scored significantly higher for HTAs from other jurisdictions as compared to local HTAs (7.1 versus 6.0 in a 1-10 scale; p < .01). Both DMs and researchers considered the information regarding safety and effectiveness more applicable than the information on social aspects, or economic evaluation. Barriers that limit transferability had significantly different scores for HTAs from other LAC countries as compared to those from regions outside LAC (i.e., poor methodological quality 6.7 versus 5.3, different epidemiological context 6.0 versus 7.4; all p < .01). CONCLUSIONS: HTAs from outside the region are commonly used. However, DMs and researchers agreed that HTAs from LAC had the greatest potential for transferability, provided that barriers such as poor methodological quality could be overcome.

Health technology assessment for resource allocation decisions: are key principles relevant for Latin America?

OBJECTIVES: A set of fifteen key principles (KP) has been recently proposed to guide decisions on the structure of HTA programs, the methods of HTA, the processes for conducting HTA and the use of HTA findings in decision-making. The objective of this research is to explore whether these KPs are relevant and useful in Latin America (LA), and to what extent they are being applied. METHODS: A Web-based survey was sent to 11,792 HTA researchers and users in LA to explore the perceived relevance of each KP, its current level of application and the gap between these two. RESULTS: We received 1,142 responses from nineteen LA countries (9.7 percent response rate). The subgroup of KP related to Methods and to the Use of HTA received the higher mean scores in the relevance scale (9.00 and 8.94). Level of current application scored low in all KP (3.2 to 4.9). Higher gaps were observed in principles related to the use of HTA in decision making and to the processes for conducting HTA. Countries with more developed HTA showed higher scores in the degree of current application (5.3 versus 3.4, p < .01) and lower gaps (3.84 versus 5.21, p < .01). Researchers, compared with research users, scored the relevance of the KPs higher. CONCLUSIONS: KPs seem to be very relevant to most HTA researchers and users in LA. However, the current level of application was considered uniformly poor. Higher gaps were observed in KPs related to the link between HTA and decision making, highlighting one of the major challenges for the countries in the region.

Effectiveness of screening examinations to detect unrecognized exercise-induced bronchoconstriction.

OBJECTIVE: To determine if a physician-administered physical examination and screening questionnaire accurately detects exercise-induced bronchoconstriction (EIB) in adolescent athletes. STUDY DESIGN: Cross-sectional study of 256 adolescents participating in organized sports from 3 suburban high schools. The number of persons screened positive for EIB by physical examination and questionnaire was compared with the number of persons with EIB diagnosed by a "gold standard" test that consisted of a 7-minute exercise challenge followed by serial spirometry. RESULTS: We diagnosed EIB in 9.4% of adolescent athletes. The screening history identified persons with symptoms or a previous diagnosis suggestive of EIB in 39.5% of the participants, but only 12.9% of these persons actually had EIB. Among adolescents with a negative review of symptoms of asthma or EIB, 7.8% had EIB. Among adolescents with no previous diagnosis of asthma, allergic rhinitis, or EIB, 7.2% had EIB diagnosed by exercise challenge. Persons who screened negative on all questions about symptoms or history of asthma, EIB, and allergic rhinitis accounted for 45.8% of the adolescents with EIB. CONCLUSIONS: EIB occurs frequently in adolescent athletes, and screening by physical examination and medical history does not accurately detect it.