BACKGROUND:Implementation research generally assumes established evidence-based practices and prior piloting of implementation strategies, which may not be feasible during a public health emergency. We describe the use of a simulation model of the effectiveness of COVID-19 mitigation strategies to inform a stakeholder-engaged process of rapidly designing a tailored intervention and implementation strategy for individuals with serious mental illness (SMI) and intellectual/developmental disabilities (ID/DD) in group homes in a hybrid effectiveness-implementation randomized trial. METHODS:We used a validated dynamic microsimulation model of COVID-19 transmission and disease in late 2020/early 2021 to determine the most effective strategies to mitigate infections among Massachusetts group home staff and residents. Model inputs were informed by data from stakeholders, public records, and published literature. We assessed different prevention strategies, iterated over time with input from multidisciplinary stakeholders and pandemic evolution, including varying symptom screening, testing frequency, isolation, contact-time, use of personal protective equipment, and vaccination. Model outcomes included new infections in group home residents, new infections in group home staff, and resident hospital days. Sensitivity analyses were performed to account for parameter uncertainty. Results of the simulations informed a stakeholder-engaged process to select components of a tailored best practice intervention and implementation strategy. RESULTS:The largest projected decrease in infections was with initial vaccination, with minimal benefit for additional routine testing. The initial level of actual vaccination in the group homes was estimated to reduce resident infections by 72.4% and staff infections by 55.9% over the 90-day time horizon. Increasing resident and staff vaccination uptake to a target goal of 90% further decreased resident infections by 45.2% and staff infections by 51.3%. Subsequent simulated removal of masking led to a 6.5% increase in infections among residents and 3.2% among staff. The simulation model results were presented to multidisciplinary stakeholders and policymakers to inform the "Tailored Best Practice" package for the hybrid effectiveness-implementation trial. CONCLUSIONS:Vaccination and decreasing vaccine hesitancy among staff were predicted to have the greatest impact in mitigating COVID-19 risk in vulnerable populations of group home residents and staff. Simulation modeling was effective in rapidly informing the selection of the prevention and implementation strategy in a hybrid effectiveness-implementation trial. Future implementation may benefit from this approach when rapid deployment is necessary in the absence of data on tailored interventions. TRIAL REGISTRATION:ClinicalTrials.gov NCT04726371.

Objectives. Conventional value-of-information (VOI) analysis assumes complete uptake of an optimal decision. We employed an extended framework that includes value-of-implementation (VOM)-the benefit of encouraging adoption of an optimal strategy-and estimated how future trials of diagnostic tests for HIV-associated tuberculosis could improve public health decision making and clinical and economic outcomes. Methods. We evaluated the clinical outcomes and costs, given current information, of 3 tuberculosis screening strategies among hospitalized people with HIV in South Africa: sputum Xpert (Xpert), sputum Xpert plus urine AlereLAM (Xpert+AlereLAM), and sputum Xpert plus the newer, more sensitive, and costlier urine FujiLAM (Xpert+FujiLAM). We projected the incremental net monetary benefit (INMB) of decision making based on results of a trial comparing mortality with each strategy, rather than decision making based solely on current knowledge of FujiLAM's improved diagnostic performance. We used a validated microsimulation to estimate VOI (the INMB of reducing parameter uncertainty before decision making) and VOM (the INMB of encouraging adoption of an optimal strategy). Results. With current information, adopting Xpert+FujiLAM yields 0.4 additional life-years/person compared with current practices (assumed 50% Xpert and 50% Xpert+AlereLAM). While the decision to adopt this optimal strategy is unaffected by information from the clinical trial (VOI = $ 0 at $3,000/year-of-life saved willingness-to-pay threshold), there is value in scaling up implementation of Xpert+FujiLAM, which results in an INMB (representing VOM) of $650 million over 5 y. Conclusions. Conventional VOI methods account for the value of switching to a new optimal strategy based on trial data but fail to account for the persuasive value of trials in increasing uptake of the optimal strategy. Evaluation of trials should include a focus on their value in reducing barriers to implementation.Highlights:In conventional VOI analysis, it is assumed that the optimal decision will always be adopted even without a trial. This can potentially lead to an underestimation of the value of trials when adoption requires new clinical trial evidence. To capture the influence that a trial may have on decision makers' willingness to adopt the optimal decision, we also consider value-of-implementation (VOM), a metric quantifying the benefit of new study information in promoting wider adoption of the optimal strategy. The overall value-of-a-trial (VOT) includes both VOI and VOM.Our model-based analysis suggests that the information obtained from a trial of screening strategies for HIV-associated tuberculosis in South Africa would have no value, when measured using traditional methods of VOI assessment. A novel strategy, which includes the urine FujiLAM test, is optimal from a health economic standpoint but is underutilized. A trial would reduce uncertainties around downstream health outcomes but likely would not change the optimal decision. The high VOT (nearly $700 million over 5 y) lies solely in promoting uptake of FujiLAM, represented as VOM.Our results highlight the importance of employing a more comprehensive approach for evaluating prospective trials, as conventional VOI methods can vastly underestimate their value. Trialists and funders can and should assess the VOT metric instead when considering trial designs and costs. If VOI is low, the VOM and cost of a trial can be compared with the benefits and costs of other outreach programs to determine the most cost-effective way to improve uptake.

Low- and middle-income countries are implementing COVID-19 vaccination strategies in light of varying vaccine efficacies and costs, supply shortages, and resource constraints. Here, we use a microsimulation model to evaluate clinical outcomes and cost-effectiveness of a COVID-19 vaccination program in South Africa. We varied vaccination coverage, pace, acceptance, effectiveness, and cost as well as epidemic dynamics. Providing vaccines to at least 40% of the population and prioritizing vaccine rollout prevented >9 million infections and >73,000 deaths and reduced costs due to fewer hospitalizations. Model results were most sensitive to assumptions about epidemic growth and prevalence of prior immunity to SARS-CoV-2, though the vaccination program still provided high value and decreased both deaths and health care costs across a wide range of assumptions. Vaccination program implementation factors, including prompt procurement, distribution, and rollout, are likely more influential than characteristics of the vaccine itself in maximizing public health benefits and economic efficiency.

BACKGROUND:Health-care resource constraints in low-income and middle-income countries necessitate the identification of cost-effective public health interventions to address COVID-19. We aimed to develop a dynamic COVID-19 microsimulation model to assess clinical and economic outcomes and cost-effectiveness of epidemic control strategies in KwaZulu-Natal province, South Africa.METHODS:We compared different combinations of five public health interventions: health-care testing alone, where diagnostic testing is done only for individuals presenting to health-care centres; contact tracing in households of cases; isolation centres, for cases not requiring hospital admission; mass symptom screening and molecular testing for symptomatic individuals by community health-care workers; and quarantine centres, for household contacts who test negative. We calibrated infection transmission rates to match effective reproduction number (Re) estimates reported in South Africa. We assessed two main epidemic scenarios for a period of 360 days, with an Re of 1·5 and 1·2. Strategies with incremental cost-effectiveness ratio (ICER) of less than US$3250 per year of life saved were considered cost-effective. We also did sensitivity analyses by varying key parameters (Re values, molecular testing sensitivity, and efficacies and costs of interventions) to determine the effect on clinical and cost projections.FINDINGS:When Re was 1·5, health-care testing alone resulted in the highest number of COVID-19 deaths during the 360-day period. Compared with health-care testing alone, a combination of health-care testing, contact tracing, use of isolation centres, mass symptom screening, and use of quarantine centres reduced mortality by 94%, increased health-care costs by 33%, and was cost-effective (ICER $340 per year of life saved). In settings where quarantine centres were not feasible, a combination of health-care testing, contact tracing, use of isolation centres, and mass symptom screening was cost-effective compared with health-care testing alone (ICER $590 per year of life saved). When Re was 1·2, health-care testing, contact tracing, use of isolation centres, and use of quarantine centres was the least costly strategy, and no other strategies were cost-effective. In sensitivity analyses, a combination of health-care testing, contact tracing, use of isolation centres, mass symptom screening, and use of quarantine centres was generally cost-effective, with the exception of scenarios in which Re was 2·6 and when efficacies of isolation centres and quarantine centres for transmission reduction were reduced.INTERPRETATION:In South Africa, strategies involving household contact tracing, isolation, mass symptom screening, and quarantining household contacts who test negative would substantially reduce COVID-19 mortality and would be cost-effective. The optimal combination of interventions depends on epidemic growth characteristics and practical implementation considerations.FUNDING:US National Institutes of Health, Royal Society, Wellcome Trust.

Background We projected the clinical and economic impact of alternative testing strategies on COVID-19 incidence and mortality in Massachusetts using a microsimulation model. Methods We compared five testing strategies: 1) PCR-severe-only: PCR testing only patients with severe/critical symptoms; 2) Self-screen: PCR-severe-only plus self-assessment of COVID-19-consistent symptoms with self-isolation if positive; 3) PCR-any-symptom: PCR for any COVID-19-consistent symptoms with self-isolation if positive; 4) PCR-all: PCR-any-symptom and one-time PCR for the entire population; and, 5) PCR-all-repeat: PCR-all with monthly re-testing. We examined effective reproduction numbers (Re, 0.9-2.0) at which policy conclusions would change. We used published data on disease progression and mortality, transmission, PCR sensitivity/specificity (70/100%) and costs. Model-projected outcomes included infections, deaths, tests performed, hospital-days, and costs over 180-days, as well as incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year [QALY]). Results In all scenarios, PCR-all-repeat would lead to the best clinical outcomes and PCR-severe-only would lead to the worst; at Re 0.9, PCR-all-repeat vs. PCR-severe-only resulted in a 63% reduction in infections and a 44% reduction in deaths, but required >65-fold more tests/day with 4-fold higher costs. PCR-all-repeat had an ICER <$100,000/QALY only when Re[≥]1.8. At all Re values, PCR-any-symptom was cost-saving compared to other strategies. Conclusions Testing people with any COVID-19-consistent symptoms would be cost-saving compared to restricting testing to only those with symptoms severe enough to warrant hospital care. Expanding PCR testing to asymptomatic people would decrease infections, deaths, and hospitalizations. Universal screening would be cost-effective when paired with monthly retesting in settings where the COVID-19 pandemic is surging.

ABSTRACT Importance: Approximately 356,000 people stay in homeless shelters nightly in the US. These individuals are at high risk for COVID-19. Objective: To assess clinical outcomes, costs, and cost-effectiveness of strategies for COVID-19 prevention and management among sheltered homeless adults. Design: We developed a dynamic microsimulation model of COVID-19. We modeled sheltered homeless adults in Boston, Massachusetts, using cohort characteristics and costs from Boston Health Care for the Homeless Program. Disease progression, transmission, and clinical outcomes data were from published literature and national databases. We examined surging, growing, and slowing epidemics (effective reproduction numbers [Re] 2.6, 1.3, and 0.9). Costs were from a health care sector perspective; time horizon was 4 months. Setting & Participants: Simulated cohort of 2,258 adults residing in homeless shelters in Boston. Interventions: We assessed combinations of daily symptom screening with same-day polymerase chain reaction (PCR) testing of screen-positive individuals, universal PCR testing every 2 weeks, hospital-based COVID-19 care, alternate care sites [ACSs] for mild/moderate COVID-19 management, and moving people from shelters to temporary housing, compared to no intervention. Main Outcomes: Infections, hospital-days, costs, and cost-effectiveness. Results: Compared to no intervention, daily symptom screening with ACSs for those with pending tests or confirmed COVID-19 and mild/moderate disease leads to 37% fewer infections and 46% lower costs when Re=2.6, 75% fewer infections and 72% lower costs when Re=1.3, and 51% fewer infections and 51% lower costs when Re=0.9. Adding universal PCR testing every 2 weeks further decreases infections in all epidemic scenarios, with incremental cost per case prevented of $1,000 (Re=2.6), $27,000 (Re=1.3), and $71,000 (Re=0.9). In all scenarios, moving shelter residents to temporary housing with universal PCR testing every 2 weeks is most effective but substantially more costly than other options. Results are most sensitive to the cost and sensitivity of PCR testing and the efficacy of ACSs in preventing transmission. Conclusions & Relevance: Daily symptom screening and ACSs for sheltered homeless adults will substantially decrease COVID-19 cases and reduce costs compared to no intervention. In a surging epidemic, adding universal PCR testing every 2 weeks further decreases cases at modest incremental cost and should be considered. Keywords: Homelessness, COVID-19, cost-effectiveness analysis, simulation model

Background Decisions around US college and university operations will affect millions of students and faculty amidst the COVID-19 pandemic. We examined the clinical and economic value of different COVID-19 mitigation strategies on college campuses. Methods We used the Clinical and Economic Analysis of COVID-19 interventions (CEACOV) model, a dynamic microsimulation that tracks infections accrued by students and faculty, accounting for community transmissions. Outcomes include infections, $/infection-prevented, and $/quality-adjusted-life-year ($/QALY). Strategies included extensive social distancing (ESD), masks, and routine laboratory tests (RLT). We report results per 5,000 students (1,000 faculty) over one semester (105 days). Results Mitigation strategies reduced COVID-19 cases among students (faculty) from 3,746 (164) with no mitigation to 493 (28) with ESD and masks, and further to 151 (25) adding RLTq3 among asymptomatic students and faculty. ESD with masks cost $168/infection-prevented ($49,200/QALY) compared to masks alone. Adding RLTq3 ($10/test) cost $8,300/infection-prevented ($2,804,600/QALY). If tests cost $1, RLTq3 led to a favorable cost of $275/infection-prevented ($52,200/QALY). No strategies without masks were cost-effective. Conclusion Extensive social distancing with mandatory mask-wearing could prevent 87% of COVID-19 cases on college campuses and be very cost-effective. Routine laboratory testing would prevent 96% of infections and require low cost tests to be economically attractive.

Background: To improve early infant HIV diagnosis (EID) programs, options include replacing laboratory-based tests with point-of-care (POC) assays or investing in strengthened systems for sample transport and result return. Setting: We used the CEPAC-Pediatric model to examine clinical benefits and costs of 3 EID strategies in Zimbabwe for infants 6 weeks of age. Methods: We examined (1) laboratory-based EID ( LAB) , (2) strengthened laboratory-based EID ( S-LAB) , and (3) POC EID (POC). LAB/S-LAB and POC assays differed in sensitivity ( LAB / S-LAB 100%, POC 96.9%) and specificity ( LAB / S-LAB 99.6%, POC 99.9%). LAB/S-LAB/POC algorithms also differed in: probability of result return (79%/91%/98%), time until result return (61/53/1 days), probability of initiating antiretroviral therapy (ART) after positive result (52%/71%/86%), and total cost/test ($18.10/$30.47/$30.71). We projected life expectancy (LE) and average lifetime per-person cost for all HIV-exposed infants. We calculated incremental cost-effectiveness ratios (ICERs) from discounted (3%/year) LE and costs in $/year-of-life saved (YLS), defining cost effective as an ICER <$580/YLS (reflecting programs providing 2 vs. 1 ART regimens). In sensitivity analyses, we varied differences between S-LAB and POC in result return probability, result return time, ART initiation probability, and cost. Results: For infants who acquired HIV, LAB/S-LAB/POC led to projected one-year survival of 67.3%/69.9%/75.6% and undiscounted LE of 21.74/22.71/24.49 years. For all HIV-exposed infants, undiscounted LE was 63.35/63.38/63.43 years, at discounted lifetime costs of $200/220/240 per infant . In cost-effectiveness analysis, S-LAB was an inefficient use of resources; the ICER of POC vs. LAB was $830/YLS. Conclusions: Current EID programs will attain greater benefit from investing in POC EID rather than strengthening laboratory-based systems.