Model parameter estimation and uncertainty analysis: a report of the ISPOR-SMDM modeling good research practices task force working group - 6

A model’s purpose is to inform medical decisions and health care resource allocation. Modelers employ quantitative methods to structure the clinical, epidemiological, and economic evidence base and gain qualitative insight to assist decision makers in making better decisions. From a policy perspective, the value of a model-based analysis lies not simply in its ability to generate a precise point estimate for a specific outcome but also in the systematic examination and responsible reporting of uncertainty surrounding this outcome and the ultimate decision being addressed. Different concepts relating to uncertainty in decision modeling are explored. Stochastic (first-order) uncertainty is distinguished from both parameter (second-order) uncertainty and from heterogeneity, with structural uncertainty relating to the model itself forming another level of uncertainty to consider. The article argues that the estimation of point estimates and uncertainty in parameters is part of a single process and explores the link between parameter uncertainty through to decision uncertainty and the relationship to value-of-information analysis. The article also makes extensive recommendations around the reporting of uncertainty, both in terms of deterministic sensitivity analysis techniques and probabilistic methods. Expected value of perfect information is argued to be the most appropriate presentational technique, alongside cost-effectiveness acceptability curves, for representing decision uncertainty from probabilistic analysis

Cost-Effectiveness of Long-Acting Injectable HIV Preexposure Prophylaxis in the United States: A Cost-Effectiveness Analysis

Background: The HIV Prevention Trials Network (HPTN) 083 trial demonstrated the superiority of long-acting injectable cabotegravir (CAB-LA) compared with oral emtricitabine–tenofovir disoproxil fumarate (F/TDF) for HIV preexposure prophylaxis (PrEP). Objective: To identify the maximum price premium (that is, greatest possible price differential) that society should be willing to accept for the additional benefits of CAB-LA over tenofovir-based PrEP among men who have sex with men and transgender women (MSM/TGW) in the United States. Design: Simulation, cost-effectiveness analysis. Data Sources: Trial and published data, including estimated HIV incidence (5.32, 1.33, and 0.26 per 100 person-years for off PrEP, generic F/TDF and branded emtricitabine–tenofovir alafenamide (F/TAF), and CAB-LA, respectively); 28% 6-year PrEP retention. Annual base-case drug costs: $360 and$16 800 for generic F/TDF and branded F/TAF. Fewer side effects with branded F/TAF versus generic F/TDF were assumed. Target Population: 476 700 MSM/TGW at very high risk for HIV (VHR). Time Horizon: 10 years. Perspective: Health care system. Intervention: CAB-LA versus generic F/TDF or branded F/TAF for HIV PrEP. Outcome Measures: Primary transmissions, quality-adjusted life-years (QALYs), costs (2020 U.S. dollars), incremental cost-effectiveness ratios (ICERs; U.S. dollars per QALY), maximum price premium for CAB-LA versus tenofovir-based PrEP. Results of Base-Case Analysis: Compared with generic F/ TDF (or branded F/TAF), CAB-LA increased life expectancy by 28 000 QALYs (26 000 QALYs) among those at VHR. Branded F/ TAF cost more per QALY gained than generic F/TDF compared with no PrEP. At 10 years, CAB-LA could achieve an ICER of at most $100 000 per QALY compared with generic F/TDF at a maximum price premium of$3700 per year over generic F/TDF (CAB-LA price <$4100 per year). Results of Sensitivity Analysis: In a PrEP-eligible population at high risk for HIV, rather than at VHR (n = 1 906 800; off PrEP incidence: 1.54 per 100 person-years), CAB-LA could achieve an ICER of at most$100 000 per QALY versus generic F/TDF at a maximum price premium of $1100 per year over generic F/TDF (CAB-LA price <$1500 per year). Limitation: Uncertain clinical and economic benefits of averting future transmissions. Conclusion: Effective oral PrEP limits the additional price society should be willing to pay for CAB-LA

Phase Behavior of Type-II Superconductors with Quenched Point Pinning Disorder: A Phenomenological Proposal

A general phenomenology for phase behaviour in the mixed phase of type-II superconductors with weak point pinning disorder is outlined. We propose that the ``Bragg glass'' phase generically transforms via two separate thermodynamic phase transitions into a disordered liquid on increasing the temperature. The first transition is into a glassy phase, topologically disordered at the largest length scales; current evidence suggests that it lacks the long-ranged phase correlations expected of a ``vortex glass''. This phase has a significant degree of short-ranged translational order, unlike the disordered liquid, but no quasi-long range order, in contrast to the Bragg glass. This glassy phase, which we call a ``multi-domain glass'', is confined to a narrow sliver at intermediate fields, but broadens out both for much larger and much smaller field values. The multi-domain glass may be a ``hexatic glass''; alternatively, its glassy properties may originate in the replica symmetry breaking envisaged in recent theories of the structural glass transition. Estimates for translational correlation lengths in the multi-domain glass indicate that they can be far larger than the interline spacing for weak disorder, suggesting a plausible mechanism by which signals of a two-step transition can be obscured. Calculations of the Bragg glass-multi-domain glass and the multi-domain glass-disordered liquid phase boundaries are presented and compared to experimental data. We argue that these proposals provide a unified picture of the available experimental data on both high-T$_c$ and low-T$_c$ materials, simulations and current theoretical understanding.Comment: 70 pages, 9 postscript figures, modified title and minor changes in published versio

Track E Implementation Science, Health Systems and Economics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138412/1/jia218443.pd

Cost-effectiveness of canine vaccination to prevent human rabies in rural tanzania

Background: The annual mortality rate of human rabies in rural Africa is 3.6 deaths per 100 000 persons. Rabies can be prevented with prompt postexposure prophylaxis, but this is costly and often inaccessible in rural Africa. Because 99% of human exposures occur through rabid dogs, canine vaccination also prevents transmission of rabies to humans.&lt;p&gt;&lt;/p&gt; Objective: To evaluate the cost-effectiveness of rabies control through annual canine vaccination campaigns in rural sub-Saharan Africa.&lt;p&gt;&lt;/p&gt; Design: We model transmission dynamics in dogs and wildlife and assess empirical uncertainty in the biological variables to make probability-based evaluations of cost-effectiveness.&lt;p&gt;&lt;/p&gt; Data Sources: Epidemiologic variables from a contact-tracing study and literature and cost data from ongoing vaccination campaigns.&lt;p&gt;&lt;/p&gt; Target Population: Two districts of rural Tanzania: Ngorongoro and Serengeti.&lt;p&gt;&lt;/p&gt; Time Horizon: 10 years.&lt;p&gt;&lt;/p&gt; Perspective: Health policymaker.&lt;p&gt;&lt;/p&gt; Intervention: Vaccination coverage ranging from 0% to 95% in increments of 5%.&lt;p&gt;&lt;/p&gt; Outcome Measures: Life-years for health outcomes and 2010 U.S. dollars for economic outcomes.&lt;p&gt;&lt;/p&gt; Results of Base-Case Analysis: Annual canine vaccination campaigns were very cost-effective in both districts compared with no canine vaccination. In Serengeti, annual campaigns with as much as 70% coverage were cost-saving.&lt;p&gt;&lt;/p&gt; Results of Sensitivity Analysis: Across a wide range of variable assumptions and levels of societal willingness to pay for life-years, the optimal vaccination coverage for Serengeti was 70%. In Ngorongoro, although optimal coverage depended on willingness to pay, vaccination campaigns were always cost-effective and life-saving and therefore preferred.&lt;p&gt;&lt;/p&gt; Limitation: Canine vaccination was very cost-effective in both districts, but there was greater uncertainty about the optimal coverage in Ngorongoro.&lt;p&gt;&lt;/p&gt; Conclusion: Annual canine rabies vaccination campaigns conferred extraordinary value and dramatically reduced the health burden of rabies.&lt;p&gt;&lt;/p&gt

Disease-modifying drugs for knee osteoarthritis: can they be cost-effective?

SummaryObjectiveDisease-modifying osteoarthritis drugs (DMOADs) are under development. Our goal was to determine efficacy, toxicity, and cost thresholds under which DMOADs would be a cost-effective knee OA treatment.DesignWe used the Osteoarthritis Policy Model, a validated computer simulation of knee OA, to compare guideline-concordant care to strategies that insert DMOADs into the care sequence. The guideline-concordant care sequence included conservative pain management, corticosteroid injections, total knee replacement (TKR), and revision TKR. Base case DMOAD characteristics included: 50% chance of suspending progression in the first year (resumption rate of 10% thereafter) and 30% pain relief among those with suspended progression; 0.5%/year risk of major toxicity; and costs of $1,000/year. In sensitivity analyses, we varied suspended progression (20–100$1,000–$7,000). Outcomes included costs, quality-adjusted life expectancy, incremental cost-effectiveness ratios (ICERs), and TKR utilization.ResultsBase case DMOADs added 4.00 quality-adjusted life years (QALYs) and$230,000 per 100 persons, with an ICER of $57,500/QALY. DMOADs reduced need for TKR by 15$3,000/year achieved ICERs below $100,000/QALY if the likelihoods of suspended progression and pain relief were 20$5,000, these ICERs were attained if the likelihoods of suspended progression and pain relief were both 60%.ConclusionsCost, suspended progression, and pain relief are key drivers of value for DMOADs. Plausible combinations of these factors could reduce need for TKR and satisfy commonly cited cost-effectiveness criteria