Valuing the Societal Impact of Medicines and Other Health Technologies: A User Guide to Current Best Practices.

This study argues that value assessment conducted from a societal perspective should rely on the Generalized Cost-Effectiveness Analysis (GCEA) framework proposed herein. Recently developed value assessment inventories - such as the Second Panel on Cost-Effectiveness's "impact inventory" and International Society of Pharmacoeconomics Outcomes Research (ISPOR) "value flower" - aimed to more comprehensively capture the benefits and costs of new health technologies from a societal perspective. Nevertheless, application of broader value elements in practice has been limited in part because quantifying these elements can be complex, but also because there have been numerous methodological advances since these value inventories have been released (e.

CHRONOS-4: phase 3 study of copanlisib plus rituximab-based immunochemotherapy in relapsed indolent B-cell lymphoma.

Copanlisib, a pan-class I phosphatidylinositol 3-kinase inhibitor with predominant activity against the α and δ isoforms, previously demonstrated durable responses as monotherapy and improved progression-free survival (PFS) in combination with rituximab in patients with relapsed indolent non-Hodgkin lymphoma (iNHL). CHRONOS-4 was a phase 3, randomized, double-blind, placebo-controlled study to investigate the efficacy and safety of copanlisib in combination with standard immunochemotherapy in patients with relapsed iNHL. Patients (n = 524) were randomized (1:1) to copanlisib (60 mg IV) plus immunochemotherapy (rituximab and bendamustine [R-B] or placebo plus R-B).

Three Pillars of Support for Orphan Drug Programs: Individual Valuations, Societal Valuations, and Anonymous Altruism.

Objectives: To identify and describe potential societal and individual sources of support for orphan drug programs.

Methods: The Generalized Risk-Adjusted Cost-Effectiveness method shows that acute illness and disability severity increase individuals' willingness to pay for health gains. We develop a social welfare function (SWF) that incorporates individuals' own values, combined with politically or ethically determined weights.

Values Beyond "Health" in Budget-Constrained Healthcare Systems.

Objectives: Most current methods to value healthcare treatments only incorporate measures such as quality-adjusted life-years, combining gains in health-related quality of life and life expectancy in specific ways. Failure of these methods to recognize other dimensions of value has led to calls for methods to include additional values that are associated with the healthcare treatments but not captured directly by quality-adjusted life-years. This article seeks to provide methodologically sound ways to incorporate additional health-related outcomes, focusing on budget-constrained healthcare systems, in which using standard welfare economics methods are often eschewed.

Risk preferences over health: Empirical estimates and implications for medical decision-making.

Mainstream health economic theory implies that an expected gain in health-related quality of life (HRQoL) produces the same value for consumers, regardless of baseline health. Several strands of recent research call this implication into question. Generalized Risk-Adjusted Cost-Effectiveness (GRACE) demonstrates theoretically that baseline health status influences value, so long as consumers are not risk-neutral over health.

On the (Near) Equivalence of Welfarist and Extra-Welfarist Methods to Value Healthcare With Implications for Assessing Equity.

Objectives: While welfarist economics (WE) methods rely wholly on individuals' valuations, extra-welfarist (EW) methods seek alternative measures of value. Major reviews of the EW literature conclude that EW studies almost universally replace "utility" with "health" as the maximand. This analysis seeks to understand what conclusions are necessary and sufficient to make EW and WE methods concurrent and discusses implications for measuring social value.

Reimagining Patient Data Access for Researchers.

Objectives: Widespread use of electronic health records (EHRs) now makes it feasible to expand beyond health insurance claims data to include full EHR data for health economics and outcomes research (HEOR) studies. We seek to develop ways to maximize researcher access to such data while strongly protecting patients' privacy rights.

Methods: We analyzed alternative organizational structures and intellectual property rights assignments as they now exist and compared these with structures and intellectual property rights assignments that would maximize access to data for HEOR studies and minimize transactions costs.

Methods to Adjust Willingness-to-Pay Measures for Severity of Illness.

Objectives: Both private sector organizations and governmental health agencies increasingly use illness severity measures to adjust willingness-to-pay thresholds. Three widely discussed methods-absolute shortfall (AS), proportional shortfall (PS), and fair innings (FI)-all use ad hoc adjustments to cost-effectiveness analysis methods and "stair-step" brackets to link illness severity with willingness-to-pay adjustments. We assess how these methods compare with microeconomic expected utility theory-based methods to value health gains.

A guide to extending and implementing generalized risk-adjusted cost-effectiveness (GRACE).

The generalized risk-adjusted cost-effectiveness (GRACE) model generalizes conventional cost-effectiveness analysis (CEA) by introducing diminishing returns to Health-Related Quality of Life (QoL). This changes CEA practice in three ways: (1) Willingness to pay (WTP) increases exponentially with untreated illness severity or pre-existing permanent disability, and WTP ends up lower for mild diseases but higher for severe diseases compared with conventional CEA; (2) Average treatment effectiveness should be adjusted for uncertainty in outcomes; and (3) The marginal rate of substitution between life expectancy and QoL varies with health state. Implementing GRACE requires new parameters describing risk preferences over QoL, the marginal rate of substitution between life expectancy (LE) and QoL, and the variance and skewness of treatment outcomes distributions.

Estimating optimal willingness to pay thresholds for cost-effectiveness analysis: A generalized method.

Operationalizing cost-effectiveness analysis (CEA) requires that decisionmakers select maximum willingness to pay thresholds (K). We generalize previous methods used to estimate K using highly flexible hyperbolic absolute risk aversion (HARA) utility functions that encompass a wide range of risk behavior. For HARA utility, we calculate formulas for relative risk aversion (r*) and relative prudence (π ), using literature-based estimates to calibrate our HARA model.

Health Technology Assessment With Diminishing Returns to Health: The Generalized Risk-Adjusted Cost-Effectiveness (GRACE) Approach.

Objectives: Cost-effectiveness analysis (CEA) embeds an assumption at odds with most economic analysis-that of constant returns to health in the creation of happiness (utility). We aim to reconcile it with the bulk of economic theory.

Methods: We generalize the traditional CEA approach, allow diminishing returns to health, and align CEA with the rest of the health economics literature.

Is the Choice of Cost-Effectiveness Threshold in Cost-Utility Analysis Endogenous to the Resulting Value of Technology? A Systematic Review.

Background: Cost-utility analysis (CUA) is widely used for health technology assessment; however, concerns exist that cost-utility analysts may suggest higher cost-effectiveness thresholds (CETs) to compensate for technologies of relatively lower value.

Objective: We explored whether selection of a CUA study's CET was endogenous to estimated incremental cost-effectiveness ratios (ICERs).

Methods: We systematically reviewed the US cost-effectiveness literature between 2000 and 2017 where studies with explicit CET and ICERs were included.

Health technology assessment with risk aversion in health.

Standard cost-effectiveness models compare incremental cost increases to incremental average gains in health, commonly expressed in Quality-Adjusted Life Years (QALYs). Our research generalizes earlier models in several ways. We introduce risk aversion in Quality of Life (QoL), which leads to "willingness-to-pay" thresholds that rise with illness severity, potentially by an order of magnitude.

Feasibility of Measuring Preferences for Chemotherapy Among Early-Stage Breast Cancer Survivors Using a Direct Rank Ordering Multicriteria Decision Analysis Versus a Time Trade-Off.

Objectives: Chemotherapy is increasingly a preference-based choice among women diagnosed with early-stage breast cancer. Multicriteria decision analysis (MCDA) is a promising but underutilized method to facilitate shared decision making. We explored the feasibility of conducting an MCDA using direct rank ordering versus a time trade-off (TTO) to assess chemotherapy choice in a large population-based sample.

A New Method to Determine the Optimal Willingness to Pay in Cost-Effectiveness Analysis.

Objective: To provide a new approach to estimate optimal willingness to pay (WTP) for health technology assessment (HTA).

Study Design: This analysis specified utility as a function of income and calibrated it using estimates of relative risk aversion, from which the optimal WTP (K) can be determined using Garber and Phelps' results (1997).

Methods: This analysis used the highly flexible Weibull utility function, calibrated with estimates of relative risk aversion (r*) derived from multiple data sources.

Valuing Health: Evolution, Revolution, Resistance, and Reform.

A number of methods have sought to determine the value of interventions and services that promote health, even when no agreement exists on the proper way to determine and define "value." Previous valuation efforts began simply by counting deaths or measuring life expectancy, slowly evolving to the widespread use of cost-effectiveness analysis (CEA) as the de facto normative standard for medical interventions. Users of CEA recognize that the method is incomplete.

Vision for a systems architecture to integrate and transform population health.

Entities involved in population health often share a common mission while acting independently of one another and perhaps redundantly. Population health is in everybody's interest, but nobody is really in charge of promoting it. Across governments, corporations, and frontline operations, lack of coordination, lack of resources, and lack of reliable, current information have often impeded the development of situation-awareness models and thus a broad operational integration for population health.

Resource allocation in decision support frameworks.

Background: Cost-benefit and cost-effectiveness analysis place limits on the dimensions of value that the models can incorporate. Cost-benefit analysis requires monetization of all measures of value (including life), a task sometimes deemed either difficult to accomplish or even repugnant. Cost-effectiveness analyses include health care gains in natural units (e.

The impact of gene expression profile testing on confidence in chemotherapy decisions and prognostic expectations.

Purpose: Little is known about whether gene expression profile (GEP) testing and specific recurrence scores (e.g., medium risk) improve women's confidence in their chemotherapy decision or perceived recurrence risk.

Toward Alignment in the Reporting of Economic Evaluations of Diagnostic Tests and Biomarkers: The AGREEDT Checklist.

Objectives: General frameworks for conducting and reporting health economic evaluations are available but not specific enough to cover the intricacies of the evaluation of diagnostic tests and biomarkers. Such evaluations are typically complex and model-based because tests primarily affect health outcomes indirectly and real-world data on health outcomes are often lacking. Moreover, not all aspects relevant to the evaluation of a diagnostic test may be known and explicitly considered for inclusion in the evaluation, leading to a loss of transparency and replicability.