It Is Time to Reconsider the 3% Discount Rate.

OBJECTIVES: Health technology assessment (HTA) guidance often recommends a 3% real annual discount rate, the appropriateness of which has received limited attention. This article seeks to identify an appropriate rate for high-income countries because it can influence projected cost-effectiveness and hence resource allocation recommendations. METHODS: The author conducted 2 Pubmed.gov searches. The first sought articles on the theory for selecting a rate. The second sought HTA guidance documents. RESULTS: The first search yielded 21 articles describing 2 approaches. The "Ramsey Equation" sums contributions by 4 factors: pure time preference, catastrophic risk, wealth effect, and macroeconomic risk. The first 3 factors increase the discount rate because they indicate future impacts are less important, whereas the last, suggesting greater future need, decreases the discount rate. A fifth factor-project-specific risk-increases the discount rate but does not appear in the Ramsey Equation. Market interest rates represent a second approach for identifying a discount rate because they represent competing investment returns and hence opportunity costs. The second search identified HTA guidelines for 32 high-income countries. Twenty-two provide no explicit rationale for their recommended rates, 8 appeal to market interest rates, 3 to consistency, and 3 to Ramsey Equation factors. CONCLUSIONS: Declining consumption growth and real interest rates imply HTA guidance should reduce recommended discount rates to 1.5 to 2+%. This change will improve projected cost-effectiveness for therapies with long-term benefits and increase the impact of accounting for long-term drug price dynamics, including reduced prices attending loss of market exclusivity.

The Impact on Cost-Effectiveness of Accounting for Generic Drug Pricing: Four Case Studies.

OBJECTIVES: Guidance on the conduct of health technology assessments rarely recommends accounting for anticipated future price declines that can follow loss of marketing exclusivity. This article explores when it is appropriate to account for generic pricing and whether it can influence cost-effectiveness estimates. METHODS: This article presents 4 case studies. Case study 1 considers a hypothetical drug used by a first patient cohort at branded prices and by subsequent, "downstream" cohorts at generic prices. Case study 2 explores whether statin assessments should account for generic prices for downstream cohorts that gain access after the initial cohort. Case study 3 uses a simplified spreadsheet model to assess the impact of accounting for generic pricing for inclisiran, used when statins insufficiently reduce cholesterol. Case study 4 amends this model for a hypothetical, advanced, follow-on treatment displacing inclisiran. RESULTS: Assessments should include generic pricing even if the first cohort using a drug pays branded prices and only downstream cohorts pay generic prices (case study 1). Because eventual generic pricing for statins did not depend on decisions for downstream cohorts, assessing reimbursement for those cohorts could safely omit generic pricing (case study 2). For inclisiran (case study 3), including generic pricing notably improved estimated cost-effectiveness. Displacing inclisiran with an advanced therapy (case study 4) modestly affected estimated cost-effectiveness. CONCLUSIONS: Although this analysis relies on simplified and hypothetical models, it demonstrates that accounting for generic pricing might substantially reduce estimated cost-effectiveness ratios. Doing so when warranted is crucial to improving health technology assessment validity.

A review of HTA guidelines on societal and novel value elements.

OBJECTIVES: Health technology assessment (HTA) organizations vary in terms of how they conduct assessments. We assess whether and to what extent HTA bodies have adopted societal and novel elements of value in their economic evaluations. METHODS: After categorizing "societal" and "novel" elements of value, we reviewed fifty-three HTA guidelines. We collected data on whether each guideline mentioned each societal or novel element of value, and if so, whether the guideline recommended the element's inclusion in the base case, sensitivity analysis, or qualitative discussion in the HTA. RESULTS: The HTA guidelines mention on average 5.9 of the twenty-one societal and novel value elements we identified (range 0-16), including 2.3 of the ten societal elements and 3.3 of the eleven novel value elements. Only four value elements (productivity, family spillover, equity, and transportation) appear in over half of the HTA guidelines, whereas thirteen value elements are mentioned in fewer than one-sixth of the guidelines, and two elements receive no mention. Most guidelines do not recommend value element inclusion in the base case, sensitivity analysis, or qualitative discussion in the HTA. CONCLUSIONS: Ideally, more HTA organizations will adopt guidelines for measuring societal and novel value elements, including analytic considerations. Importantly, simply recommending in guidelines that HTA bodies consider novel elements may not lead to their incorporation into assessments or ultimate decision making.

Alzheimer's disease medication use and adherence patterns by race and ethnicity.

BACKGROUND: We examined racial and ethnic differences in medication use for a representative US population of patients with Alzheimer's disease and related dementias (ADRD). METHODS: We examined cholinesterase inhibitors and memantine initiation, non-adherence, and discontinuation by race and ethnicity, using data from the 2000-2016 Health and Retirement Study linked with Medicare and Medicaid claims. RESULTS: Among newly diagnosed ADRD patients (n = 1299), 26% filled an ADRD prescription ≤90 days and 36% ≤365 days after diagnosis. Among individuals initiating ADRD-targeted treatment (n = 1343), 44% were non-adherent and 24% discontinued the medication during the year after treatment initiation. Non-Hispanic Blacks were more likely than Whites to not adhere to ADRD medication therapy (odds ratio: 1.50 [95% confidence interval: 1.07-2.09]). DISCUSSION: Initiation of ADRD-targeted medications did not vary by ethnoracial group, but non-Hispanic Blacks had lower adherence than Whites. ADRD medication non-adherence and discontinuation were substantial and may relate to cost and access to care. HIGHLIGHTS: Initiation of anti-dementia medications among newly diagnosed Alzheimer's disease and related dementias (ADRD) patients was low in all ethnoracial groups. ADRD medication non-adherence and discontinuation were substantial and may relate to cost and access to care. Compared to Whites, Blacks and Hispanics had lower use, poorer treatment adherence, and more frequent discontinuation of ADRD medication, but when controlling for disease severity and socioeconomic factors, racial disparities diminish. Our findings demonstrate the importance of adjusting for socioeconomic characteristics and disease severity when studying medication use and adherence in ADRD patients.

Cost-effectiveness of exome and genome sequencing for children with rare and undiagnosed conditions.

PURPOSE: This study aimed to estimate the cost-effectiveness of exome sequencing (ES) and genome sequencing (GS) for children. METHODS: We modeled costs, diagnoses, and quality-adjusted life years (QALYs) for diagnostic strategies for critically ill infants (aged <1 year) and children (aged <18 years) with suspected genetic conditions: (1) standard of care (SOC) testing, (2) ES, (3) GS, (4) SOC followed by ES, (5) SOC followed by GS, (6) ES followed by GS, and (7) SOC followed by ES followed by GS. We calculated the 10-year incremental cost per additional diagnosis, and lifetime incremental cost per QALY gained, from a health care perspective. RESULTS: First-line GS costs $15,048 per diagnosis vs SOC for infants and $27,349 per diagnosis for children. If GS is unavailable, ES represents the next most efficient option compared with SOC ($15,543 per diagnosis for infants and $28,822 per diagnosis for children). Other strategies provided the same or fewer diagnoses at a higher incremental cost per diagnosis. Lifetime results depend on the patient's assumed long-term prognosis after diagnosis. For infants, GS ranged from cost-saving (vs all alternatives) to $18,877 per QALY (vs SOC). For children, GS (vs SOC) ranged from $119,705 to $490,047 per QALY. CONCLUSION: First-line GS may be the most cost-effective strategy for diagnosing infants with suspected genetic conditions. For all children, GS may be cost-effective under certain assumptions. ES is nearly as efficient as GS and hence is a viable option when GS is unavailable.

Do Cost-Effectiveness Analyses Account for Drug Genericization? A Literature Review and Assessment of Implications.

OBJECTIVES: We investigated how health technology assessment (HTA) organizations around the world have handled drug genericization (an allowance for future generic drug entry and subsequent drug price declines) in their guidelines for cost-effectiveness analyses (CEAs). We also analyzed a large sample of published CEAs to examine prevailing practices in the field. METHODS: We reviewed 43 HTA guidelines to determine whether and how they addressed drug genericization in their CEAs. We also selected a sample of 270 US-based CEAs from the Tufts Medical Center's CEA Registry, restricting the sample to studies on pharmaceuticals published from 1991 to 2019 and to analyses taking a lifetime time horizon. We determined whether each CEA examined genericization (and if so, whether in base case or sensitivity analyses), and how inclusion of genericization influenced the estimated incremental cost-effectiveness ratios. RESULTS: Fourteen (33%) of the 43 HTA guidelines mention genericization for CEAs and 4 (9%) recommend that base case analyses include assumptions about future drug price changes due to genericization. Most published CEAs (95%) do not include assumptions about future generic prices for intervention drugs. Only 2% include such assumptions about comparator drugs. Most studies (72%) conduct sensitivity analyses on drug prices unrelated to genericization. CONCLUSIONS: The omission of assumptions about genericization means that CEAs may misrepresent the long run opportunity costs for drugs. The field needs clearer guidance for when CEAs should account for genericization, and for the inclusion of other price dynamics that might influence a drug's cost-effectiveness.

The Impact of Broader Value Elements on Cost-Effectiveness Analysis: Two Case Studies.

OBJECTIVES: This study aimed to explore the impact of including broader value elements in cost-effectiveness analyses by presenting 2 case studies, one on human papillomavirus (HPV) infection and one on early-stage Hodgkin's lymphoma (ESHL). METHODS: We identified broader value elements (eg, patient and caregiver time, spillover health effects, productivity) from the Second Panel's Impact Inventory and the ISPOR Special Task Force's value flower. We then evaluated the cost-effectiveness of HPV vaccination versus no vaccination (case 1) and combined modality therapy (CMT) versus chemotherapy alone for treatment of adult ESHL (case 2) using published simulation models. For each case study, we compared incremental cost-effectiveness ratios considering health sector impacts only (the "base-case" scenario) with incremental cost-effectiveness ratios incorporating broader value elements. RESULTS: For vaccination of US girls against HPV before sexual debut versus no vaccination, the base-case result was $38 334 per disability-adjusted life-year averted. Including each broader value element made cost-effectiveness progressively more favorable, with HPV vaccination becoming cost-saving (ie, reducing costs and averting more disability-adjusted life-years) when the analysis incorporated productivity costs. For CMT versus chemotherapy alone in patients with ESHL, the base-case result indicated that CMT was cost-saving. Including all elements made this treatment's net monetary benefits (the sum of its averted resource costs and the net value of its health impacts) less favorable, even as the contribution from CMT's near-term health benefits grew. CONCLUSIONS: Including broader value elements can substantially influence cost-effectiveness ratios, although the direction and the magnitude of their impact can differ across interventions and disease context.

Dementia Diagnosis Disparities by Race and Ethnicity.

BACKGROUND: Dementia is often underdiagnosed and this problem is more common among some ethnoracial groups. OBJECTIVE: The objective of this study was to examine racial and ethnic disparities in the timeliness of receiving a clinical diagnosis of dementia. RESEARCH DESIGN: This was a prospective cohort study. SUBJECTS: A total of 3966 participants age 70 years and above with probable dementia in the Health and Retirement Study, linked with their Medicare and Medicaid claims. MEASURES: We performed logistic regression to compare the likelihood of having a missed or delayed dementia diagnosis in claims by race/ethnicity. We analyzed dementia severity, measured by cognition and daily function, at the time of a dementia diagnosis documented in claims, and estimated average dementia diagnosis delay, by race/ethnicity. RESULTS: A higher proportion of non-Hispanic Blacks and Hispanics had a missed/delayed clinical dementia diagnosis compared with non-Hispanic Whites (46% and 54% vs. 41%, P<0.001). Fully adjusted logistic regression results suggested more frequent missed/delayed dementia diagnoses among non-Hispanic Blacks (odds ratio=1.12; 95% confidence interval: 0.91-1.38) and Hispanics (odds ratio=1.58; 95% confidence interval: 1.20-2.07). Non-Hispanic Blacks and Hispanics had a poorer cognitive function and more functional limitations than non-Hispanic Whites around the time of receiving a claims-based dementia diagnosis. The estimated mean diagnosis delay was 34.6 months for non-Hispanic Blacks and 43.8 months for Hispanics, compared with 31.2 months for non-Hispanic Whites. CONCLUSIONS: Non-Hispanic Blacks and Hispanics may experience a missed or delayed diagnosis of dementia more often and have longer diagnosis delays. When diagnosed, non-Hispanic Blacks and Hispanics may have more advanced dementia. Public health efforts should prioritize racial and ethnic underrepresented communities when promoting early diagnosis of dementia.

Balancing Value with Affordability: Cell Immunotherapy for Cancer Treatment in the U.S.

Despite the Centers for Medicare and Medicaid Services' recent approval to increase payments for inpatient-delivered chimeric antigen receptor T-cell therapy (CAR-T) for adult lymphoma, reimbursement remains far below the costs of the product and overall treatment of the therapy. We surveyed 92 CAR-T-certified centers in the U.S. to assess the perceived financial viability and related challenges for treating adult patients with lymphoma. Of 92 certified CAR-T centers in the U.S., 20 (22%) directors or chief medical officers responded. More than three quarters of facilities reported treating patients in an inpatient setting, and 60% reported that the majority of their patients were covered under commercial/private insurance. The financial viability rating across centers (median: 62; interquartile range: 48-69; scale 1-100) signals that economic sustainability of institutional programs for adult lymphoma is a concern. These dynamics may limit access to CAR-T for Medicare beneficiaries and lead to greater outpatient use of the therapy, which may limit access for medically complex patients.

Orphan Drugs Offer Larger Health Gains but Less Favorable Cost-effectiveness than Non-orphan Drugs.

BACKGROUND: Orphan drugs offer important therapeutic options to patients suffering from rare conditions, but are typically considerably more expensive than non-orphan drugs, leading to questions about their cost-effectiveness. OBJECTIVE: To compare the value of orphan and non-orphan drugs approved by the FDA from 1999 through 2015. DESIGN: We searched the PubMed database to identify estimates of incremental health gains (measured in quality-adjusted life-years, or QALYs) and incremental costs that were associated with orphan and non-orphan drugs compared with preexisting care. We excluded pharmaceutical industry-funded studies from the dataset. When a drug was approved for multiple indications, we considered each drug-indication pair separately. We then compared incremental QALY gains, incremental costs, and incremental cost-effectiveness ratios for orphan and non-orphan drugs using the Mann-Whitney U (MWU) test (to compare median values of the different distributions) and the Kolmogorov-Smirnov (KS) test (to compare the shape of different distributions). RESULTS: We identified estimates for 49 orphan drug-indication pairs, and for 169 non-orphan drug-indication pairs. We found that orphan drug-indication pairs offered larger median incremental health gains than non-orphan drug-indication pairs (0.25 vs. 0.05 QALYs; MWU p = 0.0093, KS p = 0.02), but were associated with substantially higher costs ($47,652 vs. $2870; MWU p < 0.001, KS p < 0.001) and less favorable cost-effectiveness ($276,288 vs. $100,360 per QALY gained; MWU p = 0.0068, KS p = 0.009). CONCLUSIONS: Our study suggests that orphan drugs often offer larger health gains than non-orphan drugs, but due to their substantially higher costs they tend to be less cost-effective than non-orphan drugs. Our findings highlight the challenge faced by health care payers to provide patients appropriate access to orphan drugs while achieving value from drug spending.

Measuring "Fearonomic Effects" in Valuing Therapies: An Application to COVID-19 in China.

OBJECTIVES: To develop a checklist that helps quantify the economic impact associated with fear of contagion and to illustrate how one might use the checklist by presenting a case study featuring China during the coronavirus disease 2019 (COVID-19) outbreak. METHODS: Based on "fearonomic effects," a qualitative framework that conceptualizes the direct and indirect economic effects caused by the fear of contagion, we created a checklist to facilitate empirical estimation. As a case study, we first identified relevant sectors affected by China's lockdown policies implemented just before the Lunar New Year (LNY) week. To quantify the immediate impact, we then estimated the projected spending levels in 2020 in the absence of COVID-19 and compared these projections with actual spending during the LNY week. Data sources used include Chinese and global websites. To characterize uncertainty, we reported upper and lower bound estimates and calculated midpoints for each range. RESULTS: The COVID-19 epidemic is estimated to cost China's economy $283 billion ($196-369 billion), that is, ¥2.0 trillion renminbi (¥1.4-¥2.6 trillion), during the LNY week. Reduced restaurant and movie theater business ($106 [$103-$109] billion, 37.5% [36.4%-38.5%]) and reduced public transportation utilization ($96 [$13-$179] billion dollars, 33.9% [4.6%-63.3%]) explain most of this loss, followed by travel restrictions and the resulting loss of hotel business and tourism ($80.36 billion, 28.4%). CONCLUSION: Our checklist can help quantify the immediate and near-term impact of COVID-19 on a country's economy. It can also help researchers and policy makers consider the broader economic and social consequences when valuing future vaccines and treatments.

Using QALYs versus DALYs to measure cost-effectiveness: How much does it matter?

OBJECTIVES: Quality-adjusted life-years (QALYs) and disability-adjusted life-years (DALYs) are commonly used in cost-effectiveness analysis (CEA) to measure health benefits. We sought to quantify and explain differences between QALY- and DALY-based cost-effectiveness ratios, and explore whether using one versus the other would materially affect conclusions about an intervention's cost-effectiveness. METHODS: We identified CEAs using both QALYs and DALYs from the Tufts Medical Center CEA Registry and Global Health CEA Registry, with a supplemental search to ensure comprehensive literature coverage. We calculated absolute and relative differences between the QALY- and DALY-based ratios, and compared ratios to common benchmarks (e.g., 1× gross domestic product per capita). We converted reported costs into US dollars. RESULTS: Among eleven published CEAs reporting both QALYs and DALYs, seven focused on pharmaceuticals and infectious disease, and five were conducted in high-income countries. Four studies concluded that the intervention was "dominant" (cost-saving). Among the QALY- and DALY-based ratios reported from the remaining seven studies, absolute differences ranged from approximately $2 to $15,000 per unit of benefit, and relative differences from 6-120 percent, but most differences were modest in comparison with the ratio value itself. The values assigned to utility and disability weights explained most observed differences. In comparison with cost-effectiveness thresholds, conclusions were consistent regardless of the ratio type in ten of eleven cases. CONCLUSIONS: Our results suggest that although QALY- and DALY-based ratios for the same intervention can differ, differences tend to be modest and do not materially affect comparisons to common cost-effectiveness thresholds.

Preparing the health-care system to pay for new Alzheimer's drugs.

Biogen's announcement last fall that it will seek U.S. Food and Drug Administration approval for its Alzheimer's disease (AD) treatment, aducanumab, 7 months after the drug was declared a failure, buoyed patients and families, but put health payers and policymakers on alert. Whether aducanumab succeeds, other disease-modifying therapies for AD will follow, and the health-care system is unprepared for the reimbursement and access challenges. Novel AD therapies are much needed, but we cannot assume substantial cost offsets. With forethought and preparation, however, the health-care system can accommodate new AD drugs. First, we urge the use of cost-effectiveness of new Alzheimer's treatments as a starting point for setting value-based prices. Second, payments for new AD therapies should ideally incorporate a performance warranty, which helps apportion risk associated with initial therapy value estimates between drug manufacturers and payers. Third, we urge consideration of "subscription" payment agreements to address system affordability issues.

Patient selection in palliative surgery: Defining value.

Proper patient selection for palliative surgery requires a challenging and often complex decision-making process. Optimally, proposed palliative procedures must be undertaken with an intent to provide the greatest possible value to patients at the end of life. This review describes the process of patient selection and identifies psychosocial, biochemical, and functional markers that can complement sound surgical judgment.

Does the Institute for Clinical and Economic Review Revise Its Findings in Response to Industry Comments?

BACKGROUND: The Institute for Clinical and Economic Review (ICER) has gained prominance through its work conducting health technology assessments of pharmaceuticals in the United States. OBJECTIVE: To understand the influence of industry comments on pharmaceutical value assessments conducted by ICER. METHODS: We reviewed 15 ICER reports issued from 2017 through 2019. We quantified ICER's revisions to its cost-effectiveness analysis (CEA) estimates between release of its draft and revised evidence reports and whether ratios shifted across ICER-specified categories of high, intermediate, or low value. We also reviewed industry-submitted comments recommending revision to ICER's CEAs, noting ICER's response as no change, text revised, assumption(s) revised, or conclusion revised. We evaluated each comment in terms of clarity, whether it offered an alternative to ICER's approach, and whether it characterized the expected impact of revision on ICER's analysis. RESULTS: We identified 53 ICER-reported ratios. Of these, 45 (84.9%) changed between the draft and revised report, but 26 changes (57.8%) were small (<10%). Six ratios shifted across value categories. We identified 256 industry comments recommending that ICER revise its CEA. Of these, 159 (62%) lacked clarity, 145 (57%) offered no alternative, and 243 (95%) did not characterize their impact on ICER's estimated ratio. Ninety-one comments (35.5%) caused ICER to revise its assumptions, but only 5 (2.0%) caused ICER to revise its conclusions. Four of these 5 comments characterized their impact on ICER's findings. CONCLUSIONS: Changes in ICER's estimates of cost-effectiveness between its draft and revised evidence reports are generally modest. Greater precision in industry comments could increase the influence of industry critiques, thus enhancing the dialogue around pharmaceutical value.

Challenges with Forecasting Budget Impact: A Case Study of Six ICER Reports.

BACKGROUND: Payers frequently rely on budget impact model (BIM) results to help determine drug coverage policy and its effect on their bottom line. It is unclear whether BIMs typically overestimate or underestimate real-world budget impact. OBJECTIVE: We examined how different modeling assumptions influenced the results of 6 BIMs from the Institute for Clinical and Economic Review (ICER). STUDY DESIGN: Retrospective analysis of pharmaceutical sales data. METHODS: From ICER reports issued before 2016, we collected estimates of 3 BIM outputs: aggregate therapy cost (ie, cost to treat the patient population with a particular therapy), therapy uptake, and price. We compared these against real-world estimates that we generated using drug sales data. We considered 2 classes of BIM estimates: those forecasting future uptake of new agents, which assumed "unmanaged uptake," and those describing the contemporaneous market state (ie, estimates of current, managed uptake and budget impact for compounds already on the market). RESULTS: Differences between ICER's estimates and our own were largest for forecasted studies. Here, ICER's uptake estimates exceeded real-world estimates by factors ranging from 7.4 (sacubitril/valsartan) to 54 (hepatitis C treatments). The "unmanaged uptake" assumption (removed from ICER's approach in 2017) yields large deviations between BIM estimates and real-world consumption. Nevertheless, in some cases, ICER's BIMs that relied on current market estimates also deviated substantially from real-world sales data. CONCLUSIONS: This study highlights challenges with forecasting budget impact. In particular, assumptions about uptake and data source selection can greatly influence the accuracy of results.

Risk-Targeted Lung Cancer Screening: A Cost-Effectiveness Analysis.

Background: Targeting low-dose computed tomography (LDCT) for lung cancer screening to persons at highest risk for lung cancer mortality has been suggested to improve screening efficiency. Objective: To quantify the value of risk-targeted selection for lung cancer screening compared with National Lung Screening Trial (NLST) eligibility criteria. Design: Cost-effectiveness analysis using a multistate prediction model. Data Sources: NLST. Target Population: Current and former smokers eligible for lung cancer screening. Time Horizon: Lifetime. Perspective: Health care sector. Intervention: Risk-targeted versus NLST-based screening. Outcome Measures: Incremental 7-year mortality, life expectancy, quality-adjusted life-years (QALYs), costs, and cost-effectiveness of screening with LDCT versus chest radiography at each decile of lung cancer mortality risk. Results of Base-Case Analysis: Participants at greater risk for lung cancer mortality were older and had more comorbid conditions and higher screening-related costs. The incremental lung cancer mortality benefits during the first 7 years ranged from 1.2 to 9.5 lung cancer deaths prevented per 10 000 person-years for the lowest to highest risk deciles, respectively (extreme decile ratio, 7.9). The gradient of benefits across risk groups, however, was attenuated in terms of life-years (extreme decile ratio, 3.6) and QALYs (extreme decile ratio, 2.4). The incremental cost-effectiveness ratios (ICERs) were similar across risk deciles ($75 000 per QALY in the lowest risk decile to $53 000 per QALY in the highest risk decile). Payers willing to pay $100 000 per QALY would pay for LDCT screening for all decile groups. Results of Sensitivity Analysis: Alternative assumptions did not substantially alter our findings. Limitation: Our model did not account for all correlated differences between lung cancer mortality risk and quality of life. Conclusions: Although risk targeting may improve screening efficiency in terms of early lung cancer mortality per person screened, the gains in efficiency are attenuated and modest in terms of life-years, QALYs, and cost-effectiveness. Primary Funding Source: National Institutes of Health (U01NS086294).

Early-stage Hodgkin lymphoma in the modern era: simulation modelling to delineate long-term patient outcomes.

We developed a novel simulation model integrating multiple data sets to project long-term outcomes with contemporary therapy for early-stage Hodgkin lymphoma (ESHL), namely combined modality therapy (CMT) versus chemotherapy alone (CA) via 18 F-fluorodeoxyglucose positron emission tomography response-adaption. The model incorporated 3-year progression-free survival (PFS), probability of cure with/without relapse, frequency of severe late effects (LEs), and 35-year probability of LEs. Furthermore, we generated estimates for quality-adjusted life years (QALYs) and unadjusted survival (life years, LY) and used model projections to compare outcomes for CMTversusCA for two index patients. Patient 1: a 25-year-old male with favourable ESHL (stage IA); Patient 2: a 25-year-old female with unfavourable ESHL (stage IIB). Sensitivity analyses assessed the impact of alternative assumptions for LE probabilities. For Patient 1, CMT was superior to CA (CMT incremental gain = 0·11 QALYs, 0·21 LYs). For Patient 2, CA was superior to CMT (CA incremental gain = 0·37 QALYs, 0·92 LYs). For Patient 1, the advantage of CMT changed minimally when the proportion of severe LEs was reduced from 20% to 5% (0·15 QALYs, 0·43 LYs), whereas increasing the severity proportion for Patient 2's LEs from 20% to 80% enhanced the advantage of CA (1·1 QALYs, 6·5 LYs). Collectively, this detailed simulation model quantified the long-term impact that varied host factors and alternative contemporary treatments have in ESHL.

Use and Misuse of Cost-Effectiveness Analysis Thresholds in Low- and Middle-Income Countries: Trends in Cost-per-DALY Studies.

OBJECTIVES: To determine what thresholds are most often cited in the cost-effectiveness literature for low- and middle-income countries (LMICs), given various recommendations proposed and used in the literature to date, and thereafter to assess whether studies appropriately justified their use of threshold values. METHODS: We reviewed the contents of the Tufts Medical Center Global Health Cost-Effectiveness Analysis Registry, a repository of all English language cost-per-disability-adjusted life-year averted studies indexed in PubMed. Our review included all catalogued cost-per-disability-adjusted life-year studies published from 2000 through 2015. We restricted attention to studies that investigated interventions in LMICs. RESULTS: Our analysis identified 381 studies (80%) focused on LMICs. Of these studies, 250 (66%) cited the World Health Organization's 1 to 3 times gross domestic product per capita threshold. A full-text review of 60 (24%) of these articles (randomly selected) revealed that none justified use of this threshold in the particular country or countries studied beyond citing (generic) guideline documents. CONCLUSIONS: Cost-effectiveness analysis can help inform health care spending, but its value depends on incorporating assumptions that are valid for the applicable setting. Rather than rely on commonly used, generic economic thresholds, we encourage authors to use context-specific thresholds that reflect local preferences.