Distributional Cost-Effectiveness of Equity-Enhancing Gene Therapy in Sickle Cell Disease in the United States.

BACKGROUND: Gene therapy is a potential cure for sickle cell disease (SCD). Conventional cost-effectiveness analysis (CEA) does not capture the effects of treatments on disparities in SCD, but distributional CEA (DCEA) uses equity weights to incorporate these considerations. OBJECTIVE: To compare gene therapy versus standard of care (SOC) in patients with SCD by using conventional CEA and DCEA. DESIGN: Markov model. DATA SOURCES: Claims data and other published sources. TARGET POPULATION: Birth cohort of patients with SCD. TIME HORIZON: Lifetime. PERSPECTIVE: U.S. health system. INTERVENTION: Gene therapy at age 12 years versus SOC. OUTCOME MEASURES: Incremental cost-effectiveness ratio (ICER) (in dollars per quality-adjusted life-years [QALYs] gained) and threshold inequality aversion parameter (equity weight). RESULTS OF BASE-CASE ANALYSIS: Gene therapy versus SOC for females yielded 25.5 versus 15.7 (males: 24.4 vs. 15.5) discounted lifetime QALYs at costs of $2.8 million and $1.0 million (males: $2.8 million and $1.2 million), respectively, with an ICER of $176 000 per QALY (full SCD population). The inequality aversion parameter would need to be 0.90 for the full SCD population for gene therapy to be preferred per DCEA standards. RESULTS OF SENSITIVITY ANALYSIS: SOC was favored in 100.0% (females) and 87.1% (males) of 10 000 probabilistic iterations at a willingness-to-pay threshold of $100 000 per QALY. Gene therapy would need to cost less than $1.79 million to meet conventional CEA standards. LIMITATION: Benchmark equity weights (as opposed to SCD-specific weights) were used to interpret DCEA results. CONCLUSION: Gene therapy is cost-ineffective per conventional CEA standards but can be an equitable therapeutic strategy for persons living with SCD in the United States per DCEA standards. PRIMARY FUNDING SOURCE: Yale Bernard G. Forget Scholars Program and Bunker Endowment.

Evolution of Value in American College of Cardiology/American Heart Association Clinical Practice Guidelines.

BACKGROUND: In January 2014, the American College of Cardiology/American Heart Association released a policy statement arguing for the inclusion of cost-effectiveness analysis (CEA) and value assessments in clinical practice guidelines. It is unclear whether subsequent guidelines changed how they incorporated such concepts. METHODS: We analyzed guidelines of cardiovascular disease subconditions with a guideline released before and after 2014. We counted the words (total and per page) for 8 selected value- or CEA-related terms and compared counts and rates of terms per page in the guidelines before and after 2014. We counted the number of recommendations with at least 1 reference to a CEA or a CEA-related article to compare the ratios of such recommendations to all recommendations before and after 2014. We looked for the inclusion of the value assessment system recommended by the writing committee of the American College of Cardiology/American Heart Association policy statement of 2014. RESULTS: We analyzed 20 guidelines of 10 different cardiovascular disease subconditions. Seven of the 10 cardiovascular disease subconditions had guidelines with a greater term per page rate after 2014 than before 2014. Across all 20 guidelines, the proportion of recommendations with at least 1 reference to a CEA changed from 0.44% to 1.99% (P<0.01). The proportion of recommendations with at least 1 reference to a CEA-related article changed from 1.02% to 3.34% (P<0.01). Only 3 guidelines used a value assessment system. CONCLUSIONS: The proportion of recommendations with at least 1 reference to a CEA or CEA-related article was low before and after 2014 for most of the subconditions, however, with substantial variation in this finding across the guidelines included in our analysis. There is a need to organize existing CEA information better and produce more policy-relevant CEAs so guideline writers can more easily make recommendations that incentivize high-value care and caution against using low-value care.

Epidemiologic Impacts in Acute Infectious Disease Associated with Catastrophic Climate Events Related to Global Warming in the Northeast of Mexico.

Rising global temperatures and seawater temperatures have led to an increase in extreme weather patterns leading to droughts and floods. These natural phenomena, in turn, affect the supply of drinking water in some communities, which causes an increase in the prevalence of diseases related to the supply of drinking water. The objective of this work is to demonstrate the effects of global warming on human health in the population of Monterrey, Mexico after Hurricane Alex. We interpolated data using statistical downscaling of climate projection data for 2050 and 2080 and correlated it with disease occurrence. We found a remarkable rise in the incidence of transmissible infectious disease symptoms. Gastrointestinal symptoms predominated and were associated with drinking of contaminated water like tap water or water from communal mobile water tanks, probably because of the contamination of clean water, the disruption of water sanitation, and the inability to maintain home hygiene practices.

Dependence of COVID-19 Policies on End-of-Year Holiday Contacts in Mexico City Metropolitan Area: A Modeling Study.

Background. Mexico City Metropolitan Area (MCMA) has the largest number of COVID-19 (coronavirus disease 2019) cases in Mexico and is at risk of exceeding its hospital capacity in early 2021. Methods. We used the Stanford-CIDE Coronavirus Simulation Model (SC-COSMO), a dynamic transmission model of COVID-19, to evaluate the effect of policies considering increased contacts during the end-of-year holidays, intensification of physical distancing, and school reopening on projected confirmed cases and deaths, hospital demand, and hospital capacity exceedance. Model parameters were derived from primary data, literature, and calibrated. Results. Following high levels of holiday contacts even with no in-person schooling, MCMA will have 0.9 million (95% prediction interval 0.3-1.6) additional COVID-19 cases between December 7, 2020, and March 7, 2021, and hospitalizations will peak at 26,000 (8,300-54,500) on January 25, 2021, with a 97% chance of exceeding COVID-19-specific capacity (9,667 beds). If MCMA were to control holiday contacts, the city could reopen in-person schools, provided they increase physical distancing with 0.5 million (0.2-0.9) additional cases and hospitalizations peaking at 12,000 (3,700-27,000) on January 19, 2021 (60% chance of exceedance). Conclusion. MCMA must increase COVID-19 hospital capacity under all scenarios considered. MCMA's ability to reopen schools in early 2021 depends on sustaining physical distancing and on controlling contacts during the end-of-year holiday.

How do Covid-19 policy options depend on end-of-year holiday contacts in Mexico City Metropolitan Area? A Modeling Study.

BACKGROUND: With more than 20 million residents, Mexico City Metropolitan Area (MCMA) has the largest number of Covid-19 cases in Mexico and is at risk of exceeding its hospital capacity in late December 2020. METHODS: We used SC-COSMO, a dynamic compartmental Covid-19 model, to evaluate scenarios considering combinations of increased contacts during the holiday season, intensification of social distancing, and school reopening. Model parameters were derived from primary data from MCMA, published literature, and calibrated to time-series of incident confirmed cases, deaths, and hospital occupancy. Outcomes included projected confirmed cases and deaths, hospital demand, and magnitude of hospital capacity exceedance. FINDINGS: Following high levels of holiday contacts even with no in-person schooling, we predict that MCMA will have 1·0 million (95% prediction interval 0·5 - 1·7) additional Covid-19 cases between December 7, 2020 and March 7, 2021 and that hospitalizations will peak at 35,000 (14,700 - 67,500) on January 27, 2021, with a >99% chance of exceeding Covid-19-specific capacity (9,667 beds). If holiday contacts can be controlled, MCMA can reopen in-person schools provided social distancing is increased with 0·5 million (0·2 - 1·0) additional cases and hospitalizations peaking at 14,900 (5,600 - 32,000) on January 23, 2021 (77% chance of exceedance). INTERPRETATION: MCMA must substantially increase Covid-19 hospital capacity under all scenarios considered. MCMA's ability to reopen schools in mid-January 2021 depends on sustaining social distancing and that contacts during the end-of-year holiday were well controlled. FUNDING: Society for Medical Decision Making, Gordon and Betty Moore Foundation, and Wadhwani Institute for Artificial Intelligence Foundation. RESEARCH IN CONTEXT: Evidence before this study: As of mid-December 2020, Mexico has the twelfth highest incidence of confirmed cases of Covid-19 worldwide and its epidemic is currently growing. Mexico's case fatality ratio (CFR) - 9·1% - is the second highest in the world. With more than 20 million residents, Mexico City Metropolitan Area (MCMA) has the highest number and incidence rate of Covid-19 confirmed cases in Mexico and a CFR of 8·1%. MCMA is nearing its current hospital capacity even as it faces the prospect of increased social contacts during the 2020 end-of-year holidays. There is limited Mexico-specific evidence available on epidemic, such as parameters governing time-dependent mortality, hospitalization and transmission. Literature searches required supplementation through primary data analysis and model calibration to support the first realistic model-based Covid-19 policy evaluation for Mexico, which makes this analysis relevant and timely.Added value of this study: Study strengths include the use of detailed primary data provided by MCMA; the Bayesian model calibration to enable evaluation of projections and their uncertainty; and consideration of both epidemic and health system outcomes. The model projects that failure to limit social contacts during the end-of-year holidays will substantially accelerate MCMA's epidemic (1·0 million (95% prediction interval 0·5 - 1·7) additional cases by early March 2021). Hospitalization demand could reach 35,000 (14,700 - 67,500), with a >99% chance of exceeding current capacity (9,667 beds). Controlling social contacts during the holidays could enable MCMA to reopen in-person schooling without greatly exacerbating the epidemic provided social distancing in both schools and the community were maintained. Under all scenarios and policies, current hospital capacity appears insufficient, highlighting the need for rapid capacity expansion.Implications of all the available evidence: MCMA officials should prioritize rapid hospital capacity expansion. MCMA's ability to reopen schools in mid-January 2021 depends on sustaining social distancing and that contacts during the end-of-year holiday were well controlled.