The estimated costs and benefits of a hypothetical supervised consumption site in Providence, Rhode Island.

BACKGROUND: Overdose deaths have increased dramatically in the United States, including in Rhode Island. In July 2021, the Rhode Island government passed legislation supporting a two-year pilot program authorizing supervised consumption sites (SCSs) in response to this crisis. We estimated the costs and benefits of a hypothetical SCS in Providence, Rhode Island. METHODS: We utilized a decision analytic mathematical model to compare costs and outcomes for people who inject drugs under two scenarios: (1) a SCS that includes syringe services provision, and (2) a syringe service program only (i.e., status quo). We assumed 0.95% of injections result in overdose, the SCS would serve 400 clients monthly and have a net cost of $783,899 annually, 46% of overdoses occurring outside of the SCS result in an ambulance run and 43% result in an emergency department (ED) visit, 0.79% of overdoses occurring within the SCS result in an ambulance run and ED visit, and the SCS would lead to a 25.7% reduction in fatal overdoses near the site. The model was developed from a modified societal perspective with a one-year time horizon. RESULTS: A hypothetical SCS in Providence would prevent approximately 2 overdose deaths, 261 ambulance runs, 244 ED visits, and 117 inpatient hospitalizations for emergency overdose care annually compared to a scenario that includes a syringe service program only. The SCS would save $1,104,454 annually compared to the syringe service program only, accounting only for facility costs and short-term costs of emergency overdose care and ignoring savings associated with averted deaths. Influential parameters included the percentage of injections resulting in overdose, the total annual injections at the SCS, and the percentage of overdoses outside of the SCS that result in an ED visit. CONCLUSION: A SCS in would result in substantial cost savings due to prevention of costly emergency overdose care.

Adult lifetime cost of hemophilia B management in the US: payer and societal perspectives from a decision analytic model.

AIMS: Hemophilia B (HB) is a rare congenital disorder characterized by bleeding-related complications which are managed by prophylactic or post-bleeding event ("on-demand") replacement of clotting factor IX (FIX). The standard of care for severe HB is life-long prophylaxis with standard half-life (SHL) or extended half-life (EHL) products given every 2-3 or 7-14 days, respectively. FIX treatment costs in the US have been investigated, but the lifetime costs of HB treatment have not been well characterized, particularly related to the impact of joint health deterioration and associated health resource utilization. We developed a decision-analytic model to explore outcomes, costs and underlying cost drivers associated with FIX treatment options over the lifetime of an adult with severe or moderately severe HB. MATERIALS AND METHODS: With participation from clinicians, health technology assessment specialists and patient advocates, a Markov model was constructed to estimate bleeding events and costs associated with health states including "bleed into joint", "bleed not into joint", "no bleed" and "death". Sub-models of joint health were based on 0, 1, or ≥2 areas of chronic joint damage. US third-party payer and societal perspectives were considered with a lifetime horizon; sensitivity analyses tested the robustness of primary findings. RESULTS: Total adult lifetime costs per patient with severe and moderately severe HB were $21,086,607 for SHL FIX prophylaxis, $22,987,483 for EHL FIX prophylaxis, and $20,971,826 for on-demand FIX treatment. For FIX prophylaxis, the cost of FIX treatment accounts for >90% of the total HB treatment costs. CONCLUSIONS: This decision analytic model demonstrated significant economic burden associated with the current HB treatment paradigm.

Estimating the cost-effectiveness of an infant 13-valent pneumococcal conjugate vaccine national immunization program in China.

BACKGROUND: The burden of pneumococcal disease in China is high, and a 13-valent pneumococcal conjugate vaccine (PCV13) recently received regulatory approval and is available to Chinese infants. PCV13 protects against the most prevalent serotypes causing invasive pneumococcal disease (IPD) in China, but will not provide full societal benefits until made broadly available through a national immunization program (NIP). OBJECTIVE: To estimate clinical and economic benefits of introducing PCV13 into a NIP in China using local cost estimates and accounting for variability in vaccine uptake and indirect (herd protection) effects. METHODS: We developed a population model to estimate the effect of PCV13 introduction in China. Modeled health states included meningitis, bacteremia, pneumonia (PNE), acute otitis media, death and sequelae, and no disease. Direct healthcare costs and disease incidence data for IPD and PNE were derived from the China Health Insurance and Research Association database; all other parameters were derived from published literature. We estimated total disease cases and associated costs, quality-adjusted life years (QALYs), and deaths for three scenarios from a Chinese Payer Perspective: (1) direct effects only, (2) direct+indirect effects for IPD only, and (3) direct+indirect effects for IPD and inpatient PNE. RESULTS: Scenario (1) resulted in 370.3 thousand QALYs gained and 12.8 thousand deaths avoided versus no vaccination. In scenarios (2) and (3), the PCV13 NIP gained 383.2 thousand and 3,580 thousand QALYs, and avoided 13.1 thousand and 147.5 thousand deaths versus no vaccination, respectively. In all three scenarios, the vaccination cost was offset by cost reductions from prevented disease yielding net costs of ¥29,362.32 million, ¥29,334.29 million, and ¥13,524.72 million, respectively. All resulting incremental cost-effectiveness ratios fell below a 2x China GDP cost-effectiveness threshold across a range of potential vaccine prices. DISCUSSION: Initiation of a PCV13 NIP in China incurs large upfront costs but is good value for money, and is likely to prevent substantial cases of disease among children and non-vaccinated individuals.

Next-Generation Sequencing Panels for the Diagnosis of Colorectal Cancer and Polyposis Syndromes: A Cost-Effectiveness Analysis.

PURPOSE: To evaluate the cost effectiveness of next-generation sequencing (NGS) panels for the diagnosis of colorectal cancer and polyposis (CRCP) syndromes in patients referred to cancer genetics clinics. PATIENTS AND METHODS: We developed a decision model to evaluate NGS panel testing compared with current standard of care in patients referred to a cancer genetics clinic. We obtained data on the prevalence of genetic variants from a large academic laboratory and calculated the costs and health benefits of identifying relatives with a pathogenic variant, in life-years and quality-adjusted life-years (QALYs). We classified the CRCP syndromes according to their type of inheritance and penetrance of colorectal cancer. One-way and probabilistic sensitivity analyses were conducted to assess uncertainty. RESULTS: Evaluation with an NGS panel that included Lynch syndrome genes and other genes associated with highly penetrant CRCP syndromes led to an average increase of 0.151 year of life, 0.128 QALY, and $4,650 per patient, resulting in an incremental cost-effectiveness ratio of $36,500 per QALY compared with standard care and a 99% probability that this panel was cost effective at a threshold of $100,000 per QALY. When compared with this panel, the addition of genes with low colorectal cancer penetrance resulted in an incremental cost-effectiveness ratio of $77,300 per QALY. CONCLUSION: The use of an NGS panel that includes genes associated with highly penetrant CRCP syndromes in addition to Lynch syndrome genes as a first-line test is likely to provide meaningful clinical benefits in a cost-effective manner at a $100,000 per QALY threshold.

A model of cost-effectiveness of tissue plasminogen activator in patient subgroups 3 to 4.5 hours after onset of acute ischemic stroke.

STUDY OBJECTIVE: The European Cooperative Acute Stroke Study III (ECASS III) showed that recombinant tissue plasminogen activator (rtPA) administered 3 to 4.5 hours after acute ischemic stroke led to improvement in patient disability versus placebo. We evaluate the long-term incremental cost-effectiveness of rtPA administered 3 to 4.5 hours after acute ischemic stroke onset versus no treatment according to patient clinical and demographic factors. METHODS: We developed a disease-based decision analytic model to project lifetime outcomes of patients post-acute ischemic stroke from the payer perspective. Clinical data were derived from the ECASS III trial, longitudinal cohort studies, and health state preference studies. Cost data were based on Medicare reimbursement and other published sources. We performed probabilistic sensitivity analyses to evaluate uncertainty in the analysis. RESULTS: rtPA in a hypothetical cohort resulted in a gain of 0.07 years of life (95% credible range 0.0005 to 0.17) and 0.24 quality-adjusted life-years (95% credible range 0.01 to 0.60) and a difference in cost of $1,495 (95% credible range -$4,637 to $6,100) compared with placebo. The incremental cost-effectiveness ratio for all patients was $6,255 per quality-adjusted life-year gained; for patients younger than 65 years, cost saving; for patients aged 65 years or older, $35,813 per quality-adjusted life-year; for patients with baseline National Institutes of Health Stroke Scale (NIHSS) score 0 to 9, $16,322 per quality-adjusted life-year; for patients with NIHSS score 10 to 19, $37,462 per quality-adjusted life-year; and for patients with NIHSS score greater than or equal to 20, $2,432 per quality-adjusted life-year. The majority of other subgroups such as sex, history of stroke, and history of hypertension were either cost saving or cost-effective, with the exceptions of diabetes and atrial fibrillation. CONCLUSION: The results indicate that rtPA in the 3- to 4.5-hour therapeutic window provides improvement in long-term patient outcomes in most patient subgroups and is a good economic value versus no treatment.

Meeting the governance challenges of next-generation biorepository research.

Advances in clinical translational research have led to an explosion of interest in infrastructure development and data sharing facilitated by biorepositories of specimens and linked health information. These efforts are qualitatively different from the single-center sample collections that preceded them and pose substantial new ethics and regulatory challenges for investigators and institutions. New research governance approaches, which can address current and anticipated challenges, promote high-quality research, and provide a robust basis for ongoing research participation, are urgently required.

A novel GLRA1 mutation associated with an atypical hyperekplexia phenotype.

Hyperekplexia (MIM #149400) is a rare neurological disorder characterized by an exaggerated startle response, infantile hypertonia and hyperreflexia without spasticity, a hesitant gait that usually improves by 3 years of age, and nocturnal myoclonus. Familial hyperekplexia is usually autosomal dominant resulting from mutations in the inhibitory glycine receptor subunit alpha 1 (GLRA1) gene on chromosome 5q. We identified a 3-generation family with progressively severe phenotypes of hyperekplexia. All affected family members were found to be heterozygous for a novel arginine271proline mutation in GLRA1. Long-term follow-up of the affected members of the third generation, now aged 6 and 7 years, reveals enhanced startle responses and persistent hypertonia of the extremities without clonus or a catch, tight heel cords and abnormal toe-walking gait, and plantar flexor reflexes. The 7-year-old child recently reponded well to a benzodiazepine. Future studies are warranted to examine whether this new missense mutation is solely responsible for this atypical phenotype.