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. We introduce the concept of horizontal equity-that individuals in similar situations should be treated similarly-into the SWF. Finally, we introduce anonymous altruism into individuals' utility functions-the desire to help others, without knowing their identity. RESULTS: Combined with the empirical link between disease severity and rarity, the Generalized Risk-Adjusted Cost-Effectiveness method demonstrates heightened willingness to pay for health gains for people with rare diseases, leading rational individuals to support orphan drug programs, our first pillar of support. Adding horizontal equity to the SWF further increases societal support for orphan drug programs. Anonymous altruism, focusing most strongly on those in the most-dire circumstances, leads to altruistic support for those with severe disorders. Because innovators' economic incentives lead them to focus on larger markets, anonymous altruistic individuals will increasingly prefer public investments into rare diseases over time, as private markets systematically produce gains for common diseases. CONCLUSIONS: We identified 3 supporting pillars for orphan drug programs: (1) individuals' propensity to prefer treatments for severe diseases; (2) the preference for horizontal equity in our social welfare; (3) anonymous altruism, the desire to help strangers, coupled with market incentives that underserve strangers with rare diseases.

A Roadmap for Improving Medicare's Application of Coverage With Evidence Development.

The Centers for Medicare and Medicaid Services' coverage with evidence development (CED) policy allows the agency to provide coverage for an item or service through a National Coverage Determination (NCD), conditional upon an agreement to collect evidence designed to address specific questions or uncertainties. The goals of this policy are to expedite beneficiary access to new items and services and to generate additional evidence on the impact of these items or services for Medicare beneficiaries. However, these goals have not been fully realized because of several issues with the way the policy has been implemented, including (1) a lack of clear criteria for when CED will be applied, (2) examples of CED data collection activities placing unnecessary burdens on clinicians and the potential for undue inducement on beneficiaries, and (3) a lack of clarity around the process and timeline for reconsidering and ending CED requirements. Additionally, there are cases in which the application of CED has failed to improve access to services for certain Medicare beneficiaries because no data collection activity was implemented in response to the CED requirement or because the NCD only allows the technology to be provided and studied in certain centers of excellence. We describe a roadmap for addressing these issues, which includes, for example, developing a framework to guide the application of coverage constraints in NCDs with CED requirements. Once these issues are addressed, the Centers for Medicare and Medicaid Services could consider expanding the use of CED to technologies that are not subject to NCDs.

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. METHODS: We describe standard cost-effectiveness analysis methods, the basis from which AS, PS, and FI make severity adjustments. We then develop how the Generalized Risk Adjusted Cost Effectiveness (GRACE) model assesses value for differing illness and disability severity. We compare AS, PS, and FI against value as defined by GRACE. RESULTS: AS, PS, and FI have major and unresolved differences between them in how they value various medical interventions. Compared with GRACE, they fail to properly incorporate illness severity or disability. They conflate gains in health-related quality of life and life expectancy incorrectly and confuse the magnitude of treatment gains with value per quality-adjusted life-year. Stair-step methods also introduce important ethical concerns. CONCLUSIONS: AS, PS, and FI disagree with each other in major ways, demonstrating that at most, one correctly describes patients' preferences. GRACE offers a coherent alternative, based on neoclassical expected utility microeconomic theory, and can be readily implemented in future analyses. Other approaches that depend on ad hoc ethical statements have yet to be justified using sound axiomatic approaches.

Prescription Drug Advertising and Drug Utilization: The Role of Medicare Part D.

This paper examines how direct-to-consumer advertising (DTCA) for prescription drugs influences utilization by exploiting a large and plausibly exogenous shock to DTCA driven by the introduction of Medicare Part D. Part D led to larger increases in advertising in geographic areas with higher concentrations of Medicare beneficiaries. We examine the impact of this differential increase in advertising on non-elderly individuals to isolate advertising effects from the direct effects of Part D. We find that exposure to advertising led to large increases in treatment initiation and improved medication adherence. Advertising also had sizeable positive spillover effects on non-advertised generic drugs. Our results imply significant spillovers from Medicare Part D on the under-65 population and an important role for non-price factors in influencing prescription drug utilization.

Recommendations to address key recruitment challenges of Alzheimer's disease clinical trials.

Clinical trials for Alzheimer's disease (AD) are slower to enroll study participants, take longer to complete, and are more expensive than trials in most other therapeutic areas. The recruitment and retention of a large number of qualified, diverse volunteers to participate in clinical research studies remain among the key barriers to the successful completion of AD clinical trials. An advisory panel of experts from academia, patient-advocacy organizations, philanthropy, non-profit, government, and industry convened in 2020 to assess the critical challenges facing recruitment in Alzheimer's clinical trials and develop a set of recommendations to overcome them. This paper briefly reviews existing challenges in AD clinical research and discusses the feasibility and implications of the panel's recommendations for actionable and inclusive solutions to accelerate the development of novel therapies for AD.

Value of Reducing Wait Times for Chimeric Antigen Receptor T-Cell Treatment: Evidence From Randomized Controlled Trial Data on Tisagenlecleucel for Diffuse Large B-Cell Lymphoma.

OBJECTIVES: This study aimed to quantify the value of reducing chimeric antigen receptor T-cell (CAR-T) treatment wait times on patients with refractory and relapsed aggressive blood cancer who can newly gain access to treatment or access treatment earlier in their disease course. METHODS: Using data from the JULIET clinical trial, we first identified the number of additional patients with diffuse large B-cell lymphoma that would have been treated with tisagenlecleucel CAR-T therapy if wait times were shortened. For these patients, we estimated mortality benefits using literature estimates of CAR-T effectiveness. Next, among patients who already received CAR-T, we estimated tumor burden progression over time using a linear probability regression model. The primary outcome variable was an indicator for having above-normal lactate dehydrogenase, and we controlled for time, use of bridging therapy, and time-invariant patient characteristics. The regression results, along with literature estimates relating lactate dehydrogenase to CAR-T effectiveness, were used to compute the survival benefits of earlier CAR-T treatment. RESULTS: Reducing wait times by 2 months increased the number of eligible patients receiving CAR-T by at least 10.7%. For patients already receiving tisagenlecleucel CAR-T, a 2-month reduction in wait times generated a 3.3% increase in survival gains per treated patient. Thus, among patients seeking treatment, the combined treatment efficacy increased by 14%, with approximately one-quarter of survival benefits accruing to existing patients receiving faster treatment. CONCLUSIONS: Delays affected not only access to CAR-T treatments but also treatment effectiveness. Our results highlight the survival benefits of expediting treatment access and may help explain some observed differences in CAR-T effectiveness across countries.

Access to Disease-Modifying Alzheimer's Therapies: Addressing Possible Challenges Using Innovative Payment Models.

OBJECTIVES: Aduhelm is the first approved disease-modifying therapies (DMT) for Alzheimer disease (AD). Nevertheless, under current payment models, AD DMTs-especially because they treat broader populations-will pose challenges to patient access since costs may accrue sooner than benefits do. New payment approaches may be needed to address this difference in timing. METHODS: We use the Future Elderly Model that draws on nationally representative data sets such as the Health and Retirement Study to estimate the potential benefits because of hypothetical AD DMTs in 4 stylized treatment scenarios for patients with mild cognitive impairment or mild AD, and develop a payment model to estimate the accrual of net costs and benefits to private and public payers. RESULTS: The modeled AD DMTs result in clinical benefit of 0.30 to 0.55 quality-adjusted life-years gained per patient in the baseline treatment scenario and 0.13 to 0.24 quality-adjusted life-years gained per patient in the least optimistic scenario. Private payers may observe a net loss in patients at the age of 61 to 65 years under the status quo (payment upon treatment). Constant and deferred installment payment models resolve this issue. CONCLUSIONS: Innovative payment solutions, such as installment payments, may be required to address misaligned incentives that AD DMTs may create among patients younger than the age of 65 years and may help address concerns about the timing and magnitude of costs and benefits accrued to private payers.

Measuring the COVID-19 Mortality Burden in the United States : A Microsimulation Study.

BACKGROUND: Fully assessing the mortality burden of the COVID-19 pandemic requires measuring years of life lost (YLLs) and accounting for quality-of-life differences. OBJECTIVE: To measure YLLs and quality-adjusted life-years (QALYs) lost from the COVID-19 pandemic, by age, sex, race/ethnicity, and comorbidity. DESIGN: State-transition microsimulation model. DATA SOURCES: Health and Retirement Study, Panel Study of Income Dynamics, data on excess deaths from the Centers for Disease Control and Prevention, and nursing home death counts from the Centers for Medicare & Medicaid Services. TARGET POPULATION: U.S. population aged 25 years and older. TIME HORIZON: Lifetime. PERSPECTIVE: Individual. INTERVENTION: COVID-19 pandemic through 13 March 2021. OUTCOME MEASURES: YLLs and QALYs lost per 10 000 persons in the population. The estimates account for the age, sex, and race/ethnicity of decedents, along with obesity, smoking behavior, lung disease, heart disease, diabetes, cancer, stroke, hypertension, dementia, and nursing home residence. RESULTS OF BASE-CASE ANALYSIS: The COVID-19 pandemic resulted in 6.62 million QALYs lost (9.08 million YLLs) through 13 March 2021, with 3.6 million (54%) lost by those aged 25 to 64 years. The greatest toll was on Black and Hispanic communities, especially among men aged 65 years or older, who lost 1138 and 1371 QALYs, respectively, per 10 000 persons. Absent the pandemic, 38% of decedents would have had average or above-average life expectancies for their subgroup defined by age, sex, and race/ethnicity. RESULTS OF SENSITIVITY ANALYSIS: Accounting for uncertainty in risk factors for death from COVID-19 yielded similar results. LIMITATION: Estimates may vary depending on assumptions about mortality and quality-of-life projections. CONCLUSION: Beyond excess deaths alone, the COVID-19 pandemic imposed a greater life expectancy burden on persons aged 25 to 64 years, including those with average or above-average life expectancies, and a disproportionate burden on Black and Hispanic communities. PRIMARY FUNDING SOURCE: National Institute on Aging.

Crosswalk between the Mini-Mental State Examination and the Telephone Interview for Cognitive Status (TICS-27/30/40).

BACKGROUND: We develop a crosswalk between the Mini-Mental State Examination (MMSE) and Telephone Interview for Cognitive Status (TICS)-27, TICS-30, and TICS-40 for adults 65 years and older. METHODS: We examined the scores of 1809 participants, with and without cognitive impairment, who completed the MMSE and the TICS assessment in the 2016 Health and Retirement Study and the 2016 Harmonized Cognitive Assessment Protocol study. Crosswalks between MMSE and TICS-27/30/40 were developed via equipercentile equating. RESULTS: We present crosswalks for MMSE and TICS-27/30/40 for the 65+ population representative of the US elderly. While monotonic, the pattern of the TICS-30 to MMSE crosswalk differs from the other two crosswalks (MMSE to TICS-27/40). CONCLUSION: Our analysis offers an empirical crosswalk between two commonly used cognitive measures-the MMSE and TICS. Our findings suggest the need for validated and robust measures that allow for the comparison of scores on different cognitive scales.

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. RESULTS: This simple change has far-reaching implications for the practice of CEA. First, optimal cost-effectiveness thresholds should systematically rise for more severe diseases and fall for milder ones. We provide formulae for estimating how these thresholds vary with health-related quality of life (QoL) in the sick state. Practitioners can also use our approach to account for treatment outcome uncertainty. Holding average benefits fixed, risk-averse consumers value interventions more when they reduce outcome uncertainty ('insurance value') and/or when they provide a chance at positively skewed outcomes ('value of hope'). Finally, we provide a coherent way to combine improvements in QoL and life expectancy (LE) when people have diminishing returns to QoL. CONCLUSION: This new approach obviates the need for increasingly prevalent and ad hoc exceptions to CEA for end-of-life care, rare disease, and very severe disease (eg, cancer). Our methods also show that the value of improving QoL for disabled people is greater than for comparable non-disabled people, thus resolving an ongoing and mathematically legitimate objection to CEA raised by advocates for disabled people. Our Generalized Risk-Adjusted Cost-Effectiveness (GRACE) approach helps align HTA practice with realistic preferences for health and risk.

Challenging Assumptions of Outcomes and Costs Comparing Peritoneal and Hemodialysis.

OBJECTIVES: Policy makers have suggested increasing peritoneal dialysis (PD) would improve end-stage kidney disease (ESKD) outcomes and reduce Medicare spending compared with hemodialysis (HD). We compared mortality, hospitalizations, and Medicare spending between PD and HD among uninsured adults with incident ESKD. METHODS: Using an instrumental variable design, we exploited a natural experiment encouraging PD among the uninsured. Uninsured patients usually receive Medicare at dialysis month 4. For those initiating PD, Medicare covers the first 3 dialysis months, including predialysis services in the calendar month when dialysis started. Starting dialysis later in a calendar month increases predialysis coverage that is essential for PD catheter placements. The policy encourages PD incrementally when ESKD develops later in the month. Dialysis start day appears to be unrelated to patient characteristics and effectively "randomizes patients" to dialysis modality, mitigating selection bias. RESULTS: Starting dialysis later in the month was associated with an increased PD uptake: every week later in the month was associated with an absolute increase of 0.8% (95% confidence interval [CI] 0.6%-0.9%) at dialysis day 1 and 0.5% (95% CI 0.3%-0.7%) at dialysis month 12. We observed no significant absolute difference between PD and HD for 12-month mortality (-0.9%, 95% CI -3.3% to 0.8%), hospitalizations during months 7 to 12 (-0.05, 95% CI -0.20 to 0.07), and Medicare spending during months 7 to 12 (-$702, 95% CI -$4004 to $2909). CONCLUSIONS: In an instrumental variable analysis, PD did not result in improved outcomes or lower costs than HD.

Predicting quantity and quality of life with the Future Elderly Model.

The Future Elderly Model (FEM) is a microsimulation model designed to forecast health status, longevity, and a variety of economic outcomes. Compared to traditional actuarial models, microsimulation models provide greater opportunities for policy forecasting and richer detail, but they typically build upon smaller samples of data that may mitigate forecasting accuracy. We perform validation analyses of the FEM's mortality and quality of life forecasts using a version of the FEM estimated exclusively on early waves of data from the Health and Retirement Study. First, we compare FEM mortality and longevity projections to the actual mortality and longevity experience observed over the same period of time. We also compare the FEM results to actuarial forecasts of mortality and longevity during the same time. We find that FEM projections are generally in line with observed mortality rates and closely match longevity. Then, we assess the FEM's performance at predicting quality of life and longitudinal outcomes, two features missing from traditional actuarial models. Our analysis suggests the FEM performs at least as well as actuarial forecasts of mortality, while providing policy simulation features that are not available in actuarial models.

Adoption of Digital Health Technologies in the Practice of Behavioral Health: Qualitative Case Study of Glucose Monitoring Technology.

BACKGROUND: Evaluation of patients with serious mental illness (SMI) relies largely on patient or caregiver self-reported symptoms. New digital technologies are being developed to better quantify the longitudinal symptomology of patients with SMI and facilitate disease management. However, as these new technologies become more widely available, psychiatrists may be uncertain about how to integrate them into daily practice. To better understand how digital tools might be integrated into the treatment of patients with SMI, this study examines a case study of a successful technology adoption by physicians: endocrinologists' adoption of digital glucometers. OBJECTIVE: This study aims to understand the key facilitators of and barriers to clinician and patient adoption of digital glucose monitoring technologies to identify lessons that may be applicable across other chronic diseases, including SMIs. METHODS: We conducted focus groups with practicing endocrinologists from 2 large metropolitan areas using a semistructured discussion guide designed to elicit perspectives of and experiences with technology adoption. The thematic analysis identified barriers to and facilitators of integrating digital glucometers into clinical practice. Participants also provided recommendations for integrating digital health technologies into clinical practice more broadly. RESULTS: A total of 10 endocrinologists were enrolled: 60% (6/10) male; a mean of 18.4 years in practice (SD 5.6); and 80% (8/10) working in a group practice setting. Participants stated that digital glucometers represented a significant change in the treatment paradigm for diabetes care and facilitated more effective care delivery and patient engagement. Barriers to the adoption of digital glucometers included lack of coverage, provider reimbursement, and data management support, as well as patient heterogeneity. Participant recommendations to increase the use of digital health technologies included expanding reimbursement for clinician time, streamlining data management processes, and customizing the technologies to patient needs. CONCLUSIONS: Digital glucose monitoring technologies have facilitated more effective, individualized care delivery and have improved patient engagement and health outcomes. However, key challenges faced by the endocrinologists included lack of reimbursement for clinician time and nonstandardized data management across devices. Key recommendations that may be relevant for other diseases include improved data analytics to quickly and accurately synthesize data for patient care management, streamlined software, and standardized metrics.

Lifetime Economic Burden of Crohn's Disease and Ulcerative Colitis by Age at Diagnosis.

BACKGROUND & AIMS: Understanding the burden of Crohn's disease (CD) and ulcerative colitis (UC) is important for measuring treatment value. We estimated lifetime health care costs incurred by patients with CD or UC by age at diagnosis. METHODS: We collected data from 78,620 patients with CD, 85,755 with UC, and propensity score-matched control subjects from the Truven Health MarketScan insurance claims databases (2008‒2015). Total medical (inpatient, outpatient) and pharmacy costs were captured. Cost variations over a lifetime were estimated in cost-state Markov models by age at diagnosis, adjusted to 2016 U.S. dollars and discounted at 3% per annum. We measured lifetime total and lifetime incremental cost (the difference between costs of CD or UC patients vs matched controls). RESULTS: For CD, the lifetime incremental cost was $707,711 among patients who received their diagnosis at 0‒11 years, and $177,614 for patients 70 years or older, averaging $416,352 for a diagnosis at any age. Lifetime total cost was $622,056, consisting of outpatient ($273,056), inpatient ($164,298), pharmacy ($163,722), and emergency room (ER) ($20,979) costs. For UC, the lifetime incremental cost was $369,955 among patients who received their diagnosis at 0‒11 years, and $132,396 for individuals 70 years or older, averaging $230,102 for a diagnosis at any age. Lifetime total cost was $405,496, consisting of outpatient ($163,670), inpatient ($123,190), pharmacy ($105,142), and ER ($13,493) costs. Therefore, the prevalent populations of patients with CD or UC in the United States in 2016 are expected to incur lifetime total costs of $498 billion and $377 billion, respectively. CONCLUSIONS: Using a Markov model, we estimated lifetime costs for patients with CD or UC to exceed previously published estimates. Individuals who receive a diagnosis of CD or UC at an early age (younger than 11 years) incur the highest lifetime cost burden. Advancing management strategies may significantly improve patient outcomes and reduce lifetime health care spending.

Early Delays in Insurance Coverage and Long-term Use of Home-based Peritoneal Dialysis.

BACKGROUND: Uninsured patients with end-stage renal disease face barriers to peritoneal dialysis (PD), a type of home dialysis that is associated with improved quality of life and reduced Medicare costs. Although uninsured patients using PD at dialysis start receive retroactive Medicare coverage for required predialysis services, coverage only applies for the calendar month of dialysis start. Thus, initiating dialysis later in the month yields longer retroactive coverage. OBJECTIVES: To examine whether differences in retroactive Medicare were associated with decreased long-term PD use. RESEARCH DESIGN: We exploited the dialysis start date using a regression discontinuity design on a national cohort from the US Renal Data System. SUBJECTS: 36,256 uninsured adults starting dialysis between January 1, 2006 and December 31, 2014. MEASURES: PD use at dialysis days 1, 90, 180, and 360. RESULTS: Starting dialysis on the first versus last day of the calendar month was associated with an absolute decrease in PD use of 2.7% [95% confidence interval (CI), 1.5%-3.9%], or a relative decrease of 20% (95% CI, 12%-27%) at dialysis day 360. The absolute decrease was 5.5% (95% CI, 3.5%-7.2%) after Medicare established provider incentives for PD in 2011 and 7.2% (95% CI, 2.5%-11.9%) after Medicaid expansion in 2014. Patients were unlikely to switch from hemodialysis to PD after the first month of dialysis (probability of 6.9% in month 1, 1.5% in month 2, and 0.9% in month 4). CONCLUSIONS: Extending retroactive coverage for preparatory dialysis services could increase PD use and reduce overall Medicare spending in the uninsured.

Does Medicare Coverage Improve Cancer Detection and Mortality Outcomes?

Medicare is a large government health insurance program in the United States that covers about 60 million people. This paper analyzes the effects of Medicare insurance on health for a group of people in urgent need of medical care: people with cancer. We used a regression discontinuity design to assess impacts of near-universal Medicare insurance at age 65 on cancer detection and outcomes, using population-based cancer registries and vital statistics data. Our analysis focused on the three tumor sites for which screening is recommended both before and after age 65: breast, colorectal, and lung cancer. At age 65, cancer detection increased by 72 per 100,000 population among women and 33 per 100,000 population among men; cancer mortality also decreased by nine per 100,000 population for women but did not significantly change for men. In a placebo check, we found no comparable changes at age 65 in Canada. This study provides the first evidence to our knowledge that near-universal access to Medicare at age 65 is associated with improvements in population-level cancer mortality.

How Does Treating Chronic Hepatitis C Affect Individuals in Need of Organ Transplants in the United Kingdom?

OBJECTIVES: To estimate the impact of cures for chronic hepatitis C (CHC) infection on organ donation in the United Kingdom. Curing CHC infection reduces the need for liver transplants and enables cured individuals to donate organs of all types. METHODS: We adapted a double-queuing model of organ allocation to estimate the effects of CHC infection cures on liver, lung, heart, and kidney transplants in the United Kingdom. We assumed that cured individuals would donate organs at similar rates as the general population and no longer require liver transplants because of CHC infection. We estimated how curing CHC infection influences waitlist lengths for each organ and the annual net present value to society on the basis of quality-adjusted life-years gained through additional transplants under opt-in and opt-out organ donation policies. RESULTS: Curing CHC generates the most value for patients on the liver waitlist, because it increases the number of transplantable livers and reduces the need for transplants. Under the current opt-in policy, liver waitlist length falls by 24%, generating £34.3 million of annual net present value. Growth in the number of uninfected lungs, hearts, and kidneys generates an additional £19.2 million annually, with £18.7 million from kidneys. Implementing the opt-out policy, liver waitlist length would decrease by 75%, implying that treating CHC eliminates one-third of the excess liver waitlist due to an opt-in policy. CONCLUSIONS: Treating CHC has large positive spillovers to uninfected individuals by reducing the need for liver transplants and allowing cured individuals to donate organs. These spillovers have not been included in traditional value assessments of CHC treatment.

Using Information on Patient Adherence to Antipsychotic Medication to Understand Their Adherence to Other Medications.

PURPOSE: To assess how patient adherence to atypical antipsychotic medications is associated with adherence to concurrently used medications that treat other serious mental illnesses (SMIs), type-2 diabetes, or hypertension. METHODS: Among patients who had been diagnosed with an SMI (i.e., bipolar disorder, major depressive disorder, or schizophrenia) in the previous year, we used health-insurance claims data to measure adherence based on medication fills. Patients diagnosed with an SMI were required to have 1) a prescription for an atypical oral antipsychotic, and 2) another SMI therapy or oral anti-diabetic or antihypertensive agent in the same year. The patient's concurrent adherence to an antipsychotic and one of 23 other medications was measured by the proportion of days covered (PDC) over a one-year period. Patients were considered adherent when the PDC was ≥ 80%. The strength of the association between their atypical antipsychotic adherence and their concurrent medication adherence was evaluated using the following metrics: accuracy, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: The average (standard deviation) age of patients (N = 129,614) was 44.8 (14.8) years and 62.2% of patients were female. The median accuracy based on atypical antipsychotic adherence to the other 23 medications was 67% (range, 55-71%; statistically different from 50% accuracy in all cases, P < 0.001). Accuracy was higher than physician predictions of adherence from previous studies (53%). The negative predictive value of antipsychotic adherence (75%; range, 62-88%) was generally higher than the PPV (62%; range, 43-67%; all, P < 0.001). CONCLUSION: Information on patient adherence to antipsychotics provides significant insight into adherence to other medications often used by patients with SMI. Because NPV is higher than PPV, adherence to antipsychotics is likely to be a necessary but not sufficient condition for patients with SMI regarding adherence to non-SMI medications.

Defining Elements of Value in Health Care-A Health Economics Approach: An ISPOR Special Task Force Report [3].

The third section of our Special Task Force report identifies and defines a series of elements that warrant consideration in value assessments of medical technologies. We aim to broaden the view of what constitutes value in health care and to spur new research on incorporating additional elements of value into cost-effectiveness analysis (CEA). Twelve potential elements of value are considered. Four of them-quality-adjusted life-years, net costs, productivity, and adherence-improving factors-are conventionally included or considered in value assessments. Eight others, which would be more novel in economic assessments, are defined and discussed: reduction in uncertainty, fear of contagion, insurance value, severity of disease, value of hope, real option value, equity, and scientific spillovers. Most of these are theoretically well understood and available for inclusion in value assessments. The two exceptions are equity and scientific spillover effects, which require more theoretical development and consensus. A number of regulatory authorities around the globe have shown interest in some of these novel elements. Augmenting CEA to consider these additional elements would result in a more comprehensive CEA in line with the "impact inventory" of the Second Panel on Cost-Effectiveness in Health and Medicine. Possible approaches for valuation and inclusion of these elements include integrating them as part of a net monetary benefit calculation, including elements as attributes in health state descriptions, or using them as criteria in a multicriteria decision analysis. Further research is needed on how best to measure and include them in decision making.

Approaches to Aggregation and Decision Making-A Health Economics Approach: An ISPOR Special Task Force Report [5].

The fifth section of our Special Task Force report identifies and discusses two aggregation issues: 1) aggregation of cost and benefit information across individuals to a population level for benefit plan decision making and 2) combining multiple elements of value into a single value metric for individuals. First, we argue that additional elements could be included in measures of value, but such elements have not generally been included in measures of quality-adjusted life-years. For example, we describe a recently developed extended cost-effectiveness analysis (ECEA) that provides a good example of how to use a broader concept of utility. ECEA adds two features-measures of financial risk protection and income distributional consequences. We then discuss a further option for expanding this approach-augmented CEA, which can introduce many value measures. Neither of these approaches, however, provide a comprehensive measure of value. To resolve this issue, we review a technique called multicriteria decision analysis that can provide a comprehensive measure of value. We then discuss budget-setting and prioritization using multicriteria decision analysis, issues not yet fully resolved. Next, we discuss deliberative processes, which represent another important approach for population- or plan-level decisions used by many health technology assessment bodies. These use quantitative information on CEA and other elements, but the group decisions are reached by a deliberative voting process. Finally, we briefly discuss the use of stated preference methods for developing "hedonic" value frameworks, and conclude with some recommendations in this area.