Differences in Evidentiary Requirements Between European Medicines Agency and European Health Technology Assessment of Oncology Drugs—Can Alignment Be Enhanced?

ObjectivesNational health technology assessments (HTAs) across Europe show differences in evidentiary requirements from assessments by the European Medicines Agency (EMA), affecting time to patient access for drugs after marketing authorization. This article analyzes the differences between EMA and HTA bodies’ evidentiary requirements for oncology drugs and provides recommendations on potential further alignment to minimize and optimally manage the remaining differences.MethodsInterviews were performed with representatives and drug assessment experts from EMA and HTA bodies to identify evidentiary requirements for several subdomains and collect recommendations for potentially more efficiently addressing differences. A comparative analysis of acceptability of the evidence by EMA and the HTA bodies and for potential further alignment between both authorities was conducted.ResultsAcceptability of available evidence was higher for EMA than HTA bodies. HTA bodies and EMA were aligned on evidentiary requirements in most cases. The subdomains showing notable differences concerned the acceptance of limitation of the target population and extrapolation of target populations, progression-free survival and (other) surrogate endpoints as outcomes, cross-over designs, short trial duration, and clinical relevance of the effect size. Recommendations for reducing or optimally managing differences included joint early dialogues, joint relative effectiveness assessments, and the use of managed entry agreements.ConclusionsDifferences between assessments of EMA and HTA bodies were identified in important areas of evidentiary requirements. Increased alignment between EMA and HTA bodies is suggested and recommendations for realization are discussed.     

Assessment of University Students’ Suboptimal Health and Social Media Use: Implications for Health Regulatory Authorities

Journal of Community Health - This study aimed to assess the patterns of social media usage amongst university students at Ajman University (AU) and to explore health issues in relation to social...     

Who Does the Numbers? The Role of Third-Party Technology Assessment to Inform Health Systems' Decision-Making about the Funding of Health Technologies

Background:  There is an increasing number of health-care systems using economic evaluations to inform decisions about the reimbursement of health technologies. There are usually two separate elements of this process: assembling relevant evidence and undertaking analyses (technology assessment), and decision-making. In most systems, technology assessment is undertaken by the manufacturer of the technology. In a few, "third-party" assessment is used.
Methods:  In the United Kingdom, the National Institute for Health and Clinical Excellence used a combination of third-party and manufacturer assessments between 1999 and 2005. After this point, a Single Technology Appraisal program (using manufacturer-based assessment) was instituted for some technologies. Here the role of third-party assessment is considered in this from of decision-making. The article reviews the requirements of economic evaluation to support decision-making, and considers the extent to which each type of assessment is likely to meet these requirements. It also attempts to address whether the two forms of assessment differ in their impact on decision-making using a comparison of the decisions made by National Institute for Health and Clinical Excellence (NICE) (under its multiple-technology appraisal system) and the Scottish Medicines Consortium (SMC), which relies on manufacturer assessment.
Results:  The comparison is limited by the small number of technologies considered by both bodies. Nevertheless, it suggests that there are potentially important differences between the two bodies, with NICE generally placing more restrictions of the use of technologies.
Conclusions:  The article concludes that there are potential advantages to third-party assessment, but its cost and timing may preclude its use for all new technologies. A hybrid arrangement is suggested where third-party assessment is used in particular circumstances.     

The Causal Mediation Formula—A Guide to the Assessment of Pathways and Mechanisms

Recent advances in causal inference have given rise to a general and easy-to-use formula for assessing the extent to which the effect of one variable on another is mediated by a third. This Mediation Formula is applicable to nonlinear models with both discrete and continuous variables, and permits the evaluation of path-specific effects with minimal assumptions regarding the data-generating process. We demonstrate the use of the Mediation Formula in simple examples and illustrate why parametric methods of analysis yield distorted results, even when parameters are known precisely. We stress the importance of distinguishing between the necessary and sufficient interpretations of "mediated-effect" and show how to estimate the two components in nonlinear systems with continuous and categorical variables.     

Short Assessment of Health Literacy��Spanish and English: A Comparable Test of Health Literacy for Spanish and English Speakers

Objective. The intent of the study was to develop and validate a comparable health literacy test for Spanish‐speaking and English‐speaking populations. Study Design. The design of the instrument, named the Short Assessment of Health Literacy—Spanish and English (SAHL‐S&E), combined a word recognition test, as appearing in the Rapid Estimate of Adult Literacy in Medicine (REALM), and a comprehension test using multiple‐choice questions designed by an expert panel. We used the item response theory (IRT) in developing and validating the instrument. Data Collection. Validation of SAHL‐S&E involved testing and comparing the instrument with other health literacy instruments in a sample of 201 Spanish‐speaking and 202 English‐speaking subjects recruited from the Ambulatory Care Center at the University of North Carolina Healthcare System. Principal Findings. Based on IRT analysis, 18 items were retained in the comparable test. The Spanish version of the test, SAHL‐S, was highly correlated with other Spanish health literacy instruments, Short Assessment of Health Literacy for Spanish‐Speaking Adults (r=0.88, p<.05) and the Spanish Test of Functional Health Literacy in Adults (TOFHLA) (r=0.62, p<.05). The English version, SAHL‐E, had high correlations with REALM (r=0.94, p<.05) and the English TOFHLA (r=0.68, p<.05). Significant correlations were found between SAHL‐S&E and years of schooling in both Spanish‐ and English‐speaking samples (r=0.15 and 0.39, respectively). SAHL‐S&E displayed satisfactory reliability of 0.80 and 0.89 in the Spanish‐ and English‐speaking samples, respectively. IRT analysis indicated that the SAHL‐S&E score was highly reliable for individuals with a low level of health literacy. Conclusions. The new instrument, SAHL‐S&E, has good reliability and validity. It is particularly useful for identifying individuals with low health literacy and could be used to screen for low health literacy among Spanish and English speakers.     

Do Reimbursement Recommendations by the Canadian Agency for Drugs and Technology in Health Translate Into Coverage Decisions for Orphan Drugs in the Canadian Province of Ontario?

ObjectivesUnlike other high-income countries, Canada has no national policy for drugs treating rare diseases (orphan drugs). Nevertheless, in 2022, the Canadian government committed to creating a national strategy to make access to these drugs more consistent. Our aim was to study whether recommendations made by the Canadian Agency for Drugs and Technology in Health (CADTH) translated into coverage decisions for orphan drugs in Ontario, the largest Canadian province. This study is the first to look at this question for orphan drugs, which are at the center of policy attention.MethodsWe included 155 orphan drug-indication pairs approved and marketed in Canada between October 2002 and April 2022. Cohen’s kappa was used to test the agreement across health technology assessment (HTA) recommendations and coverage decisions in Ontario. Logistic regression was used to test which factors, relevant to decision-makers, might be associated with funding in Ontario.ResultsWe found only fair agreement between CADTH’s recommendations and coverage decisions in Ontario. Although a positive and statistically significant association between favorable HTA recommendations and coverage was found, more than half of the drugs with a negative HTA recommendation were available in Ontario, predominately through specialized funds. Successful pan-Canadian pricing negotiations were a strong predictor of coverage in Ontario.ConclusionsDespite efforts to harmonize access to drugs across Canada, considerable room for improvement remains. Introducing a national strategy for orphan drugs could help increase transparency, consistency, promote collaborations, and make access to orphan drugs a national priority.     

A decade of adaptation: Regulatory contributions of the World Health Organization to the Global Action Plan for Influenza Vaccines (2006–2016)

The Global Action Plan (GAP) for Influenza Vaccines is a decade-long initiative that brings together a diverse range of stakeholders to work towards reducing anticipated global shortage of influenza vaccines and ensuring more equitable access to vaccines during the next influenza pandemic. Since its inception in 2006, significant progress has been made towards all the main objectives of GAP, namely: (1) an increase in seasonal vaccine use, (2) an increase in vaccine production, and (3) progress in research and development of more effective vaccines. The Technology Transfer Initiative (TTI), conceived and managed by WHO under the GAP, contributed to increasing regional influenza vaccine production capacity. This was achieved by facilitating technology transfer in 14 low- and middle-income countries, through grants to manufacturers to establish or strengthen influenza vaccine production capacity and support to their national regulatory authorities. Five of the countries subsequently licensed locally produced influenza vaccines; two pandemic and three seasonal vaccines received WHO prequalification. The success of GAP can be largely attributed to the regulatory support provided by WHO to both manufacturers and regulators. This support had two components: (1) direct regulatory support to GAP/TTI, and (2) support to GAP-related WHO programmes, such as the Pandemic Influenza Vaccine Deployment Initiative in 2010 and the Pandemic Influenza Preparedness Framework since 2013, especially in non-vaccine-producing countries. Temporary adaptation of the assessment process for influenza vaccines in the WHO Vaccine Prequalification Programme to the A(H1N1) pandemic situation in 2009 was instrumental to the success of the WHO Pandemic Influenza Vaccine Deployment Initiative in its attempt to meet the demand for pandemic vaccines in countries that received donated vaccines.     

How Is Evidence on Test Performance Synthesized for Economic Decision Models of Diagnostic Tests? A Systematic Appraisal of Health Technology Assessments in the UK Since 1997

ObjectivesThe study aims to assess how evidence on diagnostic test accuracy is synthesized and used to inform economic decision modeling for HTA.MethodsAll reports evaluating diagnostic test via an economic decision model published by the NHS Research and Development Health Technology Assessment (HTA) program since 1997 were identified. The methods for evidence synthesis of diagnostic test accuracy data and its use in economic decision modeling in this sample were reviewed.ResultsForty-four HTA reports out of 474 concerned diagnostic accuracy, of which 11 did not do any economic evaluation. Of the remaining 33 HTAs, 14 conducted meta-analyses of diagnostic accuracy in the clinical review but only 8 used such pooled estimates to inform the decision model. A number of meta-analysis methods ranging in complexity were applied to estimate diagnostic accuracy. Nevertheless, when it came to informing the economic decision model, the majority of reviews used independent meta-analytic estimates of sensitivity and specificity.ConclusionsOften, very simplistic methods to estimate diagnostic test accuracy were used for purposes of informing an economic decision model. The assumptions made by the simplistic methods are usually invalid which may lead to suboptimal decisions being made. It is desirable that decision modelers become aware of the rapid evolution of meta-analysis methods in this area; however, further research is still required to identify how the pooled results obtained from the different meta-analysis models should best be used to inform economic decision models.     

A Health Economics Approach to US Value Assessment Frameworks—Summary and Recommendations of the ISPOR Special Task Force Report [7]

This summary section first lists key points from each of the six sections of the report, followed by six key recommendations. The Special Task Force chose to take a health economics approach to the question of whether a health plan should cover and reimburse a specific technology, beginning with the view that the conventional cost-per-quality-adjusted life-year metric has both strengths as a starting point and recognized limitations. This report calls for the development of a more comprehensive economic evaluation that could include novel elements of value (e.g., insurance value and equity) as part of either an “augmented” cost-effectiveness analysis or a multicriteria decision analysis. Given an aggregation of elements to a measure of value, consistent use of a cost-effectiveness threshold can help ensure the maximization of health gain and well-being for a given budget. These decisions can benefit from the use of deliberative processes. The six recommendations are to: 1) be explicit about decision context and perspective in value assessment frameworks; 2) base health plan coverage and reimbursement decisions on an evaluation of the incremental costs and benefits of health care technologies as is provided by cost-effectiveness analysis; 3) develop value thresholds to serve as one important input to help guide coverage and reimbursement decisions; 4) manage budget constraints and affordability on the basis of cost-effectiveness principles; 5) test and consider using structured deliberative processes for health plan coverage and reimbursement decisions; and 6) explore and test novel elements of benefit to improve value measures that reflect the perspectives of both plan members and patients.     

Health Technology Assessment–Informed Decision Making by the Federal Joint Committee/Institute for Quality and Efficiency in Health Care in Germany and the National Institute for Health and Care Excellence in England: The Role of Budget Impact

ObjectivesThis study aimed to test (official) evaluation criteria including the potential role of budget impact (BI) on health technology assessment (HTA) outcomes published by the Federal Joint Committee (Gemeinsamer Bundesausschuss [GBA]) and the Institute for Quality and Efficiency in Health Care (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen [IQWiG]) in Germany as well as the National Institute for Health and Care Excellence (NICE) in England.MethodsData were extracted from all publicly available GBA decisions and IQWiG assessments as well as NICE single technology appraisals between January 2011 and June 2018, and information with regard to evaluation criteria used by these agencies was collected. Data were analyzed using logistic regression to estimate the effect of the BI on the HTA outcomes while controlling for criteria used by GBA/IQWiG and NICE.ResultsNICE recommendations are largely driven by the incremental cost-effectiveness ratio and, if applicable, by end-of-life criteria (P < .01). While IQWiG assessments are significantly affected by the availability of randomized controlled trials and patient-relevant endpoints (P < .01), GBA appraisals primarily focus on endpoints (P < .01). The BI correlated with NICE single technology appraisals (inverted-U relationship, P < .1) and IQWiG recommendations (increasing linear relationship, P < .05), but not with GBA decisions (P > .1). Nevertheless, given that IQWiG assessments seem to be more rigorous than GBA appraisals regarding the consideration of evidence-based evaluation criteria, decisions by GBA might be negatively associated with the BI.ConclusionsResults reveal that GBA/IQWiG and NICE follow their official evaluation criteria consistently. After controlling for all significant variables, the BI seems to have an (independent) effect on HTA outcomes as well.     

A Comprehensive Comparison of Additional Benefit Assessment Methods Applied by Institute for Quality and Efficiency in Health Care and European Society for Medical Oncology for Time-to-Event Endpoints After Significant Phase III Trials—A Simulation Study

ObjectivesAfter a successful Marketing Authorization Application for clinical trials with time-to-event endpoints, the degree of the added benefit from new treatments remains unknown and needs to be assessed. Unfortunately, until now no clear definition for added benefit determination of a treatment exists. Nevertheless, European authorities / societies have developed 2 “additional benefit assessment” methods, which have up to now not been compared: the European Society for Medical Oncology (ESMO) developed a dual rule considering relative and absolute benefit. The German Institute for Quality and Efficiency in Health Care (IQWiG) developed a method using upper 95% hazard ratio confidence interval.MethodsWe evaluate and compare both methods in an extensive simulation study including different censoring rates, failure time distributions, and treatment effects for sample size calculation. The methods’ performance is assessed via Receiver Operating Characteristic curves, Spearman correlation, and percentage of achieved maximal scores.ResultsThe results show that IQWiG’s method has in many situations a lower maximal scoring proportion than ESMO’s rule, that is, up to 28.5% versus 94.7%. Various failure time distributions lead to strongly changed maximal scoring percentages for ESMO. High positive correlation between the methods is present for moderate treatment effects.ConclusionsIQWiG’s method is usually more conservative than ESMO’s. ESMO’s rule tends to be more susceptible for various failure time distributions. Using the lower confidence interval limit seems to be a better solution resulting in a higher true-positive rate without increasing the false-positive rate. Thus, IQWiG’s method might need to be adapted accordingly to achieve a better overall classification.     

How to Increase Fruit and Vegetable Consumption: A Multistakeholder Approach for Improved Health Outcomes—A Report from the Alliance for Food & Health

Nutrition is the fundamental bridge between food and health. Inadequate fruit and vegetable (FV) consumption has been linked to an increase in global noncommunicable diseases, which places a greater burden on health systems (1) Hall JN, Moore S, Harper SB, Lynch JW. Global variability in fruit and vegetable consumption. American Journal of Preventive Medicine. 2009;36(5):402–409. https://doi.org/10.1016/j.amepre.2009.01.029. PMID:19362694.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]. Despite much emphasis from the World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO) on the benefits of increased FV consumption, neither results nor an understanding of the complexity of food security and the actions of a diverse array of stakeholders needed to achieve outcomes have been attained. To address this challenge, the Alliance for Food &; Health (AFH) uses a multistakeholder approach to engage cross-sector solutions. This paper, the first in a series, addresses the global challenge of FV consumption by examining and synthesizing current practices and outcomes and providing actionable recommendations for government, private-sector, and civil-society stakeholders. To effectively reduce the global noncommunicable disease (NCD) burden, it is critical that stakeholders work in concordance with the WHO/FAO Second International Conference on Nutrition commitments (Table 1), United Nations (UN) Decade of Action on Nutrition Action Areas (Table 2), and the UN Sustainable Development Goals (SDGs) applicable to this issue (Table 3). AFH's top line recommendations (Table 4) align with multiple UN SDGs (2) United Nations Department of Public Information. Sustainable development goals; 2015. Available from: https://sustainabledevelopment.un.org/?menu=1300. [Google Scholar]. All recommendations connect with the following three SDGs: #2: “Zero Hunger,” #3: “Good Health and Well-Being,” and #17: “Partnerships for the Goals.” This indicates AFH's integration of the food, agriculture, and global health communities in efforts to combat NCDs. A variety of recommendations align with #9: “Industry, Innovation, and Infrastructure,” #11: “Sustainable Cities and Communities,” and #12: “Responsible Consumption and Production.”