March 2020

Association Between the Use of Surrogate Measures in Pivotal Trials and Health Technology Assessment Decisions: A Retrospective Analysis of NICE and CADTH Reviews of Cancer Drugs

Pinto A, Naci H, Neez E, Mossialos E
Value in Health. 2020;23(3):319 - 327.

To assess whether using surrogate versus patient-relevant endpoints in pivotal trials of cancer drugs was associated with health technology assessment recommendations in England (National Institute for Health and Care Excellence [NICE]) and Canada (Canadian Agency for Drugs and Technologies in Health [CADTH]).

Cancer drug approvals from 2012 to 2016 were categorized by demonstrating benefit on overall survival (OS), progression-free survival, disease response, or having no comparator. Approvals were analyzed by benefit category and health technology assessment recommendation. The association between benefit (surrogate vs OS) and recommending a drug was examined using descriptive statistics and linear probability models controlling for unmet need, orphan designation, and cost-effectiveness.

Of 42 cancer indications that NICE recommended, 15 (36%) demonstrated OS benefit. Cancer indications with OS benefit were less likely to receive a recommendation from NICE than those without (P = .04). In linear probability models, availability of OS benefit was no longer associated with a recommendation from NICE (P = .32). Cost-effective cancer drugs had a 55.6% (95% CI: 38.9%-72.3%) higher probability of receiving a recommendation from NICE than those that were not. In Canada, 15 of 37 (41%) cancer indications that were recommended showed OS benefit. There was no detectable association between surrogate measures and CADTH recommendations based on descriptive statistics (P = .62) or in linear probability models (P = .73).

When cost-effectiveness was considered, pivotal trial endpoints were not associated with NICE recommendations. Pivotal trial endpoints, unmet need, orphan status, and cost-effectiveness did not explain CADTH recommendations.

Value of Information Analytical Methods: Report 2 of the ISPOR Value of Information Analysis Emerging Good Practices Task Force

Rothery C, Strong M, Koffijberg H, Basu A, Ghabri S, Knies S, Murray J, Sanders Schmidler G, Steuten L, Fenwick E
Value in Health. 2020;23(3):277 - 286.

The allocation of healthcare resources among competing priorities requires an assessment of the expected costs and health effects of investing resources in the activities and of the opportunity cost of the expenditure. To date, much effort has been devoted to assessing the expected costs and health effects, but there remains an important need to also reflect the consequences of uncertainty in resource allocation decisions and the value of further research to reduce uncertainty. Decision making with uncertainty may turn out to be suboptimal, resulting in health loss. Consequently, there may be value in reducing uncertainty, through the collection of new evidence, to better inform resource decisions. This value can be quantified using value of information (VOI) analysis. This report from the ISPOR VOI Task Force describes methods for computing 4 VOI measures: the expected value of perfect information, expected value of partial perfect information (EVPPI), expected value of sample information (EVSI), and expected net benefit of sampling (ENBS). Several methods exist for computing EVPPI and EVSI, and this report provides guidance on selecting the most appropriate method based on the features of the decision problem. The report provides a number of recommendations for good practice when planning, undertaking, or reviewing VOI analyses. The software needed to compute VOI is discussed, and areas for future research are highlighted.

February 2020

Quebec Health-Related Quality-of-Life Population Norms Using the EQ-5D-5L: Decomposition by Sociodemographic Data and Health Problems

Poder T, Carrier N, Kouakou C
Value in Health. 2020;23(2):251 - 259.

Population norms for the EQ-5D-5L were published in Canada but only for Alberta province. The purpose of this study was to derive Quebec population norms from the EQ-5D-5L.

The data came from a larger study conducted between September 2016 and March 2018 using elicitation techniques for a quality-adjusted life-year project. The online survey was distributed randomly in the province of Quebec. To best describe the entire population, data were stratified by various sociodemographic characteristics such as age, gender, urban and rural populations, whether disadvantaged or not, immigrant or nonimmigrant, and health problems.

A total of 2704 (53.8%) respondents completed the EQ-5D-5L. Mean (95% confidence interval) and median (interquartile range) utility scores were 0.824 (0.818-0.829) and 0.867 (0.802-0.911), respectively. The EQ-VAS scores were estimated at 75.9 (75.2-76.6) and 80 (69-90). Subjects with lower scores were those who had a low or high body mass index; were smokers; were single, divorced, or widowed; had no children; were unemployed or sick; had lower education or lower annual income; and had a family or personal history of serious illness. Immigrants had higher scores. There was no difference in gender and urban or rural population. The score logically decreased with worsening health status, from a mean score of 0.896 (0.884-0.908) to 0.443 (0.384-0.501; P confidence interval: 0.867-0.876).

This is the first study to present utility score norms for EQ-5D-5L for the Quebec population. These results will be useful for comparison with quality-adjusted life-year studies to better interpret their results. Moreover, utility norms were provided for 21 health problems, which was rarely done.

Trends and Factors Associated With Insurer Approval of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Prescriptions

Doshi J, Li P, Puckett J, Pettit A, Raman S, Parmacek M, Rader D
Value in Health. 2020;23(2):209 - 216.

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is)—innovative yet costly cholesterol-lowering agents—have been subject to substantial prior authorization (PA) requirements and low approval rates. We aimed to investigate trends in insurer approval and reasons for rejection for PCSK9i prescriptions as well as associations between patients’ demographic, clinical, pharmacy, payer, and PCSK9i-specific plan/coverage factors and approval.

We examined trends in PCSK9i approval rates and reasons for rejection using medical and prescription claims from 2015 to 2017 for individuals who received a PCSK9i prescription. We used multinomial logistic regression to estimate quarterly risk-adjusted approval rates for initial PCSK9i prescriptions and approval for any PCSK9i prescription within 30, 90, and 180 days of the initial PCSK9i prescription. For a 2016 subsample for whom we had PCSK9i-specific plan policy data, we examined factors associated with approval including PCSK9i-specific plan formulary coverage, step therapy requirements, and number of PA criteria.

The main sample included 12 309 patients (mean age 64.8 years [SD = 10.8], 52.1% female, 51.5% receiving Medicare) and was similar in characteristics to the 2016 subsample (n = 6091). Approval rates varied across quarters but remained low (initial prescription, 13%-23%; within 90 days, 28%-44%). Over time, rejections owing to a lack of formulary coverage decreased and rejections owing to PA requirements increased. Lack of formulary coverage and having ≥11 PA criteria in the plan policy were associated with lower odds of PCSK9i prescription approval.

These findings confirm ongoing PCSK9i access issues and offer a baseline for comparison in future studies examining the impact of recent efforts to improve PCSK9i access.

Why Reinvent the Wheel? Use or Modification of Existing Clinical Outcome Assessment Tools in Medical Product Development s

Papadopoulos E, Bush E, Eremenco S, Coons S
Value in Health. 2020;23(2):151 - 153.

Assessment of clinical benefit in treatment trials can be made through report by a clinician, a patient, or a nonclinician observer (eg, caregiver) or through a performance-based assessment. The US Food and Drug Administration (FDA) published a final guidance for industry for one type of clinical outcome assessment (COA)—patient-reported outcome (PRO) measures—in 2009 that described how FDA reviews PRO measures for their adequacy to support medical product–labeling claims. Many of the principles described in the PRO Guidance could be applicable to the other types of COAs, including instruments completed by clinicians (ie, clinician-reported outcome assessments) and nonclinician observers (ie, observer-reported outcome assessments). FDA guidance describing the regulatory expectations for all COA types including performance outcome assessments, which are based on the patient’s performance of a defined task or activity, is in progress to meet requirements described within the 21st Century Cures Act and PDUFA VI. This communication highlights potential ways in which existing instruments might be modified or used “as is” to conform to good measurement principles. An industry and a regulatory perspective are described.


January 2020

Do Social Values and Institutional Context Shape the Use of Economic Evaluation in Reimbursement Decisions? An Empirical Analysis

Torbica A, Fornaro G, Tarricone R, Drummond M
Value in Health. 2020;23(1):17 - 24.

To investigate whether the use of economic evaluation (EE) in healthcare decision making is influenced by the social values and institutional context in a given country.

We developed and tested a conceptual framework for the 36 Organisation for Economic Co-operation and Development (OECD) countries. The countries were divided into two groups based on the extent of their use of EE in drug reimbursement. The key social values were efficiency, equity, and personal responsibility, measured in an international survey. Countries were classified based on their institutional context in terms of their general welfare paradigm/type of healthcare system and the administrative tradition to which they belong. We performed correlation tests and ran path analysis regression models to test our hypotheses.

EE high users included significantly more Beveridge-type systems (50% vs 31%) and fewer Bismarck-type (15% vs 56%). Napoleonic tradition countries seemed to reject personal responsibility in health (r = -0.511, P = .009), whereas Germanic tradition countries embraced it (r = 0.572, P = .003); Anglo-American tradition countries exhibited a significant association with efficiency (r = 0.444, P = .026), whereas Scandinavian tradition countries appeared to reject it as a criterion for rationing in healthcare (r = -0.454, P = .023). No significant direct association was found between social values and use of EE.

Our exploratory analysis suggests that institutional context and, indirectly, social values may play a role in shaping the use of EE in healthcare decision making. Because of the differences among countries in terms of institutional context, which may in part be influenced by social values, it is unlikely that there will ever be a single, harmonious approach to the use of EE.


Health Years in Total: A New Health Objective Function for Cost-Effectiveness Analysis

Basu A, Carlson J, Veenstra D
Value in Health. 2020;23(1):96 -103.

To find an alternative for quality-adjusted life-year (QALY) and equal value of life (EVL) measures. Despite the importance of QALY in cost-effectiveness analysis (CEA)—because it captures the effects of both life expectancy and health-related quality of life (QOL) and enables comparisons across interventions and disease areas—its potential to be discriminatory towards patients with lower QOL presents a critical challenge that has resulted in the exclusion of its use in some public decision making (eg, US Medicare) on healthcare in the United States. Alternatives to QALY, such as EVL, have not gained traction because EVL fails to recognize the QOL gains during added years of life.

We present a new metric for effectiveness for CEA, health years in total (HYT), which overcomes both the specific distributional issue raised by QALY and the efficiency challenges of EVL.

The HYT framework separates life expectancy changes and QOL changes on an additive scale. HYT have the same axiomatic foundations as QALY and perform better than both QALY, in terms of the discriminatory implications, and EVL, in terms of capturing QOL gains during added years of life. HYT are straightforward to calculate within a CEA model. We found that thresholds of $34 000/HYT and $89 000/HYT correspond to CEA thresholds of $50 000/QALY and $150 000/QALY, respectively.

The HYT framework may provide a viable alternative to both the QALY and the EVL; its application to diverse healthcare technologies and stakeholder assessments are important next steps in its development and evaluation.

IHTA Around the World: Broadening Our Understanding of Cross-Country Differences 

Torbica A
Value in Health. 2020;23(1):1 - 2.

The attitudes toward the use of health technology assessment (HTA) in healthcare decision making vary widely between the United States and Europe and often even within Europe. Some countries use HTA extensively, others hardly at all. Some countries have independent HTA agencies; others adopt different institutional models. Some countries that conduct economic evaluations as part of HTA stress the use of quality-adjusted life-years (QALYs); others use other concepts of value.


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