Gregory F. Guzauskas’s research while affiliated with Harrington College of Design and other places

Background and Objectives Disease-modifying treatments (DMTs) such as gene therapy are currently under investigation as a potential treatment for Huntington disease (HD). Our objective was to estimate the long-term natural history of HD progression and explore the potential efficacy impacts and value of a hypothetical DMT using a decision-analytic modeling framework. Methods We developed a health state transition model that separately analyzed 40-year-old individuals with prefunctional decline (PFD, HD Integrated Staging System [HD-ISS] stage <3, total functional score [TFC] 13), active functional decline Shoulson and Fahn category 1 (SF1, HD-ISS stage 3, TFC 13-11), and SF2 (HD-ISS stage 3, TFC 10-7). Three-year outcomes from the TRACK-HD longitudinal study were linearly extrapolated to estimate the long-term health outcomes and costs of each population. For PFD individuals, we used the HD-ISS to predict the onset of functional decline. HD costs and quality-adjusted life years (QALYs) were estimated over a lifetime horizon by applying health state–specific costs and utilities derived from a related HD burden-of-illness study. We then estimated the long-term health impacts of hypothetical DMTs that slowed or delayed onset of functional decline. We conducted sensitivity analyses to assess model uncertainties. Results The expected life years for 40-year-old PFD, SF1, and SF2 populations were 20.46 (95% credible range [CR]: 19.05–22.30), 13.93 (10.82–19.08), and 10.99 (8.28–22.07), respectively. The expected QALYs for PFD, SF1, and SF2 populations were 15.93 (14.91–17.44), 8.29 (6.36–11.79), and 5.79 (4.14–12.91), respectively. The lifetime costs of HD were $508,200 ($310,300 to $803,700) for the PFD population,$1.15 million ($684,500 to$1.89 million) for SF1 individuals, and $1.07 million ($571,700 to $2.26 million) for SF2 individuals. Although hypothetical DMTs led to cost savings in the PFD population by delaying the cost burdens of functional decline, they increased costs in SF1 and SF2 populations by prolonging time spent in expensive progressive HD states. Discussion Our novel HD-modeling framework estimates HD progression over a lifetime and the associated costs and QALYs. Our approach can be used for future cost-effectiveness models as positive DMT clinical trial evidence becomes available.

Sickle cell disease (SCD) is an inherited, progressively debilitating blood disorder. Emerging gene therapies (GTx) may lead to a complete remission, the benefits of such can only be realized if GTx is affordable and accessible in the low-and middle-income countries (LMIC) with the greatest SCD burden. To estimate the health impacts and country-specific value-based prices (VBP) of a future gene therapy for SCD using a cost-utility model framework. We developed a lifetime Markov model to compare the costs and health outcomes of GTx versus standard of care for SCD. We modeled populations in seven LMICs and six high-income countries (HICs) estimating lifetime costs and disability-adjusted life-years (DALYs) in comparison to estimates of a country’s cost-effectiveness threshold. Each country’s unique VBP for GTx was calculated via threshold analysis. Relative to SOC treatment alone, we found that hypothetical GTx reduced the number of people symptomatic with SCD over time leading to fewer DALYs. Across countries, VBPs ranged from $3.6 million (US) to$700 (Uganda). Our results indicate a wide range of GTx prices are required if it is to be made widely available and may inform burden and affordability for ‘target product profiles’ of GTx in SCD.

Introduction Curative therapies (CTx) to achieve durable remission of HIV disease without the need for antiretroviral therapy (ART) are currently being explored. Our objective was to model the long‐term health and cost outcomes of HIV in various countries, the impact of future CTx on those outcomes and the country‐specific value‐based prices (VBPs) of CTx. Methods We developed a decision‐analytic model to estimate the future health economic impacts of a hypothetical CTx for HIV in countries with pre‐existing access to ART (CTx+ART), compared to ART alone. We modelled populations in seven low‐and‐middle‐income countries and five high‐income countries, accounting for localized ART and other HIV‐related costs, and calibrating variables for HIV epidemiology and ART uptake to reproduce historical HIV outcomes before projecting future outcomes to year 2100. Health was quantified using disability‐adjusted life‐years (DALYs). Base case, pessimistic and optimistic scenarios were modelled for CTx+ART and ART alone. Based on long‐term outcomes and each country's estimated health opportunity cost, we calculated the country‐specific VBP of CTx. Results The introduction of a hypothetical CTx lowered HIV prevalence and prevented future infections over time, which increased life‐years, reduced the number of individuals on ART, reduced AIDS‐related deaths, and ultimately led to fewer DALYs versus ART‐alone. Our base case estimates for the VBP of CTx ranged from $5400 (Kenya) up to$812,300 (United States). Within each country, the VBP was driven to be greater primarily by lower ART coverage, lower HIV incidence and prevalence, and higher CTx cure probability. The VBP estimates were found to be greater in countries where HIV prevalence was higher, ART coverage was lower and the health opportunity cost was greater. Conclusions Our results quantify the VBP for future curative CTx that may apply in different countries and under different circumstances. With greater CTx cure probability, durability and scale up, CTx commands a higher VBP, while improvements in ART coverage may mitigate its value. Our framework can be utilized for estimating this cost given a wide range of scenarios related to the attributes of a given CTx as well as various parameters of the HIV epidemic within a given country.

Background: The cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention (CDC) Tier 1 genomic conditions is unknown. Objective: To estimate the cost-effectiveness of simultaneous genomic screening for Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH). Design: Decision analytic Markov model. Data sources: Published literature. Target population: Separate age-based cohorts (ages 20 to 60 years at time of screening) of racially and ethnically representative U.S. adults. Time horizon: Lifetime. Perspective: U.S. health care payer. Intervention: Population genomic screening using clinical sequencing with a restricted panel of high-evidence genes, cascade testing of first-degree relatives, and recommended preventive interventions for identified probands. Outcome measures: Incident breast, ovarian, and colorectal cancer cases; incident cardiovascular events; quality-adjusted survival; and costs. Results of base-case analysis: Screening 100 000 unselected 30-year-olds resulted in 101 (95% uncertainty interval [UI], 77 to 127) fewer overall cancer cases and 15 (95% UI, 4 to 28) fewer cardiovascular events and an increase of 495 quality-adjusted life-years (QALYs) (95% UI, 401 to 757) at an incremental cost of $33.9 million (95$27.0 million to $41.1 million). The incremental cost-effectiveness ratio was$68 600 per QALY gained (95% UI, $41 800 to$88 900). Results of sensitivity analysis: Screening 30-, 40-, and 50-year-old cohorts was cost-effective in 99%, 88%, and 19% of probabilistic simulations, respectively, at a $100 000-per-QALY threshold. The test costs at which screening 30-, 40-, and 50-year-olds reached the$100 000-per-QALY threshold were 413, 290, and $166, respectively. Variant prevalence and adherence to preventive interventions were also highly influential parameters. Limitations: Population averages for model inputs, which were derived predominantly from European populations, vary across ancestries and health care environments. Conclusion: Population genomic screening with a restricted panel of high-evidence genes associated with 3 CDC Tier 1 conditions is likely to be cost-effective in U.S. adults younger than 40 years if the testing cost is relatively low and probands have access to preventive interventions. Primary funding source: National Human Genome Research Institute.

Background : Population genomic screening for familial hypercholesterolemia (FH) in unselected individuals can prevent premature cardiovascular disease. Objective : To estimate the clinical and economic outcomes of population-wide FH genomic screening versus no genomic screening. Methods : We developed a decision tree plus 10-state Markov model evaluating the identification of patients with an FH variant, statin treatment status, LDL-C levels, MI, and stroke to compare the costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness of population-wide FH genomic screening. FH variant prevalence (0.4%) was estimated from the Geisinger MyCode Community Health Initiative (MyCode). Genomic test costs were assumed to be $200. Age and sex-based estimates of MI, recurrent MI, stroke, and recurrent stroke were obtained from Framingham risk equations. Additional outcomes independently associated with FH variants were derived from a retrospective analysis of 26,025 participants screened for FH. Sensitivity and threshold analyses were conducted to evaluate model assumptions and uncertainty. Results : FH screening was most effective at younger ages; screening unselected 20-year-olds lead to 111 QALYs gained per 100,000 individuals screened at an incremental cost of$20 M. The incremental cost-effectiveness ratio (ICER) for 20-year-olds was $181,000 per QALY, and there was a 38$100,000 per QALY willingness-to-pay threshold. If genomic testing cost falls to $100, the ICER would be$91,000 per QALY. Conclusion : Population FH screening is not cost-effective at current willingness to pay thresholds. However, reducing test costs, testing at younger ages, or including FH within broader multiplex screening panels may improve clinical and economic value.

Background. Management of postmenopausal women with HR+ mBC includes monitoring with tumor markers, CT scans, and bone scans. DiviTum®TKa is a blood-based biomarker assay developed to monitor and predict treatment response in hormone receptor positive metastatic breast cancer (HR+ mBC). Uptake of DiviTum®TKa monitoring may decrease usage of traditional monitoring technologies and potentially avoid prolongation of futile treatments. Our objective was to estimate budget impacts of the assay on monitoring utilization and cancer treatment on a postmenopausal HR+ mBC population in a 1,000,000 member U.S. health plan. Methods. We developed a budget impact model comparing inclusion of DiviTum®TKa to standard monitoring practices vs. standard monitoring practices alone. The modeled population was post-menopausal women with HR+ mBC who receive 1st-line treatment with CDK4/6 inhibitors (CDK4/6i) + an aromatase inhibitor (AI). We explored two scenarios: (1) uptake of DiviTum®TKa reduces the frequency of traditional mBC monitoring tools, and 2) in addition to scenario 1, DiviTum®TKa predicts treatment futility 1 month in advance of radiological disease progression. We assumed patients were 100% adherent to DiviTum®TKa and traditional monitoring schedules, which were based on clinical guidelines and expert opinion. DiviTum®TKa’s impact on therapy utilization was based on published literature and expert opinion. Modeled costs included DiviTum®TKa, NCCN-recommended treatments, imaging, biomarker testing, and adverse events. Unit costs were based on CMS fee schedules and wholesale acquisition costs. Annual rates of incident and recurrent post-menopausal HR+ mBC were estimated from SEER and publicly available data. We calculated total and per-member per-month (PMPM) costs with a 3-year time horizon. Results. Each year, 17 women who progressed to mBC and 4 who developed de novo mBC were treated 1st-line with CDK4/6i+AI. In scenario 1 (monitoring only), addition of 404 DiviTum®TKa assays led to 203 fewer CT scans, 93 fewer bone scans, and 60 fewer biomarker tests over 3 years. In scenario 2 (impact on therapy), mean time on treatment with CDK 4/6i + AI therapy was 28 months without DiviTum®TKa testing; with DiviTum®TKa, 27 months; this led to treatment-related cost savings due to avoidance of time on futile therapy. Spend on DiviTum®TKa testing was $161,600. Accounting only for test costs (Scenario 1) resulted in incremental cost of$38,000 and a PMPM of $0.001. Accounting for time spent on futile therapy (Scenario 2) resulted in incremental cost savings of$465,600 and a PMPM cost-savings of $0.013. In one-way sensitivity analysis, results were most sensitive to DiviTum®TKa and CT scan costs, the proportion of mBC patients treated with CDK4/6i+AI, and CDK4/6i costs. Conclusions. In this analysis, use of DiviTum®TKa reduced use of a substantial proportion of traditional monitoring. If use of DiviTum®TKa can also predict lack of benefit from costly CDK4/6i therapy and clinicians act on that information in a timely fashion, this can result in substantial cost savings to patients and health plans. In this 2nd scenario, net savings on adding a new test to care were ~3X the spend on the test itself. Following approval and commercial introduction of DiviTum®TKa, future research on practice patterns will be necessary to validate our analysis. Scenario 1WithoutDiviTum®TKaWithDiviTum®TKaDifferenceDifferencePMPMTotal Cost$14,518,99814,556,98437,9860.001Monitoring284,680322,66637,9860.001Treatment13,703,86713,703,8670$0.000Adverse Events$530,451530,4510$0.000Scenario 2WithoutDiviTum®TKaWithDiviTum®TKaDifferenceDifferencePMPMTotal Cost$14,518,998$14,053,431-$465,567-0.013Monitoring284,680311,17926,5000.001Treatment13,703,867$13,209,240-$494,627-$0.014Adverse Events$530,451533,0132,561$0.000 Citation Format: Gregory F. Guzauskas, Josh J. Carlson, Robert A. Dann, Scott D. Ramsey. The budget impact of the DiviTum®TKa assay in postmenopausal women with hormone receptor positive metastatic breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-03-05.

Purpose Genomic screening for Lynch syndrome (LS) could prevent colorectal cancer (CRC) by identifying high-risk patients and instituting intensive CRC screening. We estimated the cost-effectiveness of a population-wide LS genomic screening vs family history–based screening alone in an unselected US population. Methods We developed a decision-analytic Markov model including health states for precancer, stage-specific CRC, and death and assumed an inexpensive test cost of $200. We conducted sensitivity and threshold analyses to evaluate model uncertainty. Results Screening unselected 30-year-olds for LS variants resulted in 48 (95$24.6 million (95% CR = $20.3 million-$29.1 million). The incremental cost-effectiveness ratio was $132,200, with an 8$100,000 and $150,000 per QALY willingness-to-pay thresholds, respectively. Conclusion Population LS screening may be cost-effective in younger patient populations under a$150,000 willingness-to-pay per QALY threshold and with a relatively inexpensive test cost. Further reductions in testing costs and/or the inclusion of LS testing within a broader multiplex screening panel are needed for screening to become highly cost-effective.