Cost-utility analysis of Dexcom G6 real-time continuous glucose monitoring versus FreeStyle Libre 1 intermittently scanned continuous glucose monitoring in adults with type 1 diabetes in Belgium.

AIMS/HYPOTHESIS: The aim of this study was to assess the long-term cost-effectiveness of Dexcom G6 real-time continuous glucose monitoring (rtCGM) with alert functionality compared with FreeStyle Libre 1 intermittently scanned continuous glucose monitoring (isCGM) without alerts in adults with type 1 diabetes in Belgium. METHODS: The IQVIA CORE Diabetes Model was used to estimate cost-effectiveness. Input data for the simulated baseline cohort were sourced from the randomised ALERTT1 trial (ClinicalTrials.gov. REGISTRATION NO: NCT03772600). The age of the participants was 42.9 ± 14.1 years (mean ± SD), and the baseline HbA1c was 57.8 ± 9.5 mmol/mol (7.4 ± 0.9%). Participants using rtCGM showed a reduction in HbA1c of 3.6 mmol/mol (0.36 percentage points) based on the 6-month mean between-group difference. In the base case, both rtCGM and isCGM were priced at €3.92/day (excluding value-added tax [VAT]) according to the Belgian reimbursement system. The analysis was performed from a Belgian healthcare payer perspective over a lifetime time horizon. Health outcomes were expressed as quality-adjusted life years. Probabilistic and one-way sensitivity analyses were used to account for parameter uncertainty. RESULTS: In the base case, rtCGM dominated isCGM, resulting in lower diabetes-related complication costs and better health outcomes. The associated main drivers favouring rtCGM were lower HbA1c, fewer severe hypoglycaemic events and reduced fear of hypoglycaemia. The results were robust under a wide range of one-way sensitivity analyses. In models where the price of rtCGM is €5.11/day (a price increase of 30.4%) or €12.34/day (a price increase of 214.8%), rtCGM was cost-neutral or reached an incremental cost-effectiveness ratio of €40,000 per quality-adjusted life year, respectively. CONCLUSIONS/INTERPRETATION: When priced similarly, Dexcom G6 rtCGM with alert functionality has both economic and clinical benefits compared with FreeStyle Libre 1 isCGM without alerts in adults with type 1 diabetes in Belgium, and appears to be a cost-effective glucose monitoring modality. Trial registration ClinicalTrials.gov NCT03772600.

Sales revenues for new therapeutic agents approved by the US Food and Drug Administration from 1995 to 2014: a retrospective study.

OBJECTIVES: To analyze worldwide sales of new therapeutic agents and to estimate the time it takes for product sales to exceed industry-wide average drug development costs. METHODS: Data obtained from company reports were analyzed to track worldwide sales of new medicines approved by the US Food and Drug Administration from 1995 to 2014. All sales figures were reported in 2019 US dollars. Kaplan-Meier curves were used to evaluate the time it took for discounted product sales to exceed the average costs associated with developing one new drug (accounting for the costs of failed trials), using published estimates of these costs. RESULTS: Based on data for 361 of 558 new therapeutic agents approved over the study period (median follow-up: 13.2 years), mean sales revenue per product was $15.2 billion through the end of 2019; the median was $6.7 billion. These products jointly generated global sales of $5.5 trillion since approval. Revenues were highly skewed, with the 25 best selling products (7%, 25/361) accounting for 38% of this amount ($2.1 trillion/$5.5 trillion). About 47% of products had discounted sales that exceeded the estimated industry-wide average costs of development within 5 years of approval, and 75% within 10 years. After attributing potential production, marketing, and other costs, these numbers dropped to 21% of products within 5 years of approval, and 46% within 10 years. CONCLUSIONS: Sales of new medicines approved from 1995 to 2014 were highly skewed, but a majority of products had net discounted sales that exceeded the industry-wide average costs of development within 10 years of approval. An understanding of how sales revenues accrue in the years after initial approval, alongside data on business costs, can inform discussions about how to incentivize private investment in innovation while ensuring affordable prices for patients and the health-care system.

Cost-effectiveness of point-of-care interventions to tackle inappropriate prescribing of antibiotics in high- and middle-income countries: a systematic review.

BACKGROUND: Antimicrobial resistance (AMR) is propagated by widespread inappropriate use of antibiotics. In response, point-of-care interventions (POCIs) have been developed in primary care to preserve antibiotic effectiveness. Many of these POCIs are adopted based on their clinical value. However, assessment of their cost-effectiveness is crucial as well. OBJECTIVES: To summarize the evidence on cost-effectiveness of POCIs aimed at tackling inappropriate antibiotic prescriptions in primary care in middle- and high-income countries. We also evaluate the quality of the evidence with particular attention to how these economic evaluations faced the challenge of capturing the impact of these POCIs on AMR. METHODS: Six scientific databases (MEDLINE, Embase, Web of Science, NHS EED, NHS HTA, the Cochrane Library) were searched for eligible articles published from 1999 to 2022. Their quality was appraised by means of the Drummond and CHEERS checklist. RESULTS: Twenty-nine articles met the selection criteria. Using their own (implicit) definitions of cost-effectiveness, evidence reported that point-of-care testing, scoring tools, electronic interventions, communication training, and multidimensional and educational interventions are more cost-effective than standard care. In contrast, studies found dipstick testing and audit-and-feedback interventions to be not cost-effective. Data synthesis took a narrative approach as eligible studies were not similar and/or reliable enough to pool their results through meta-analysis. CONCLUSIONS: More high-quality evidence is needed to attain a thorough understanding of the cost-effectiveness of POCIs. Heterogeneity in terms of interventions and efficiency measures complicates comparing and generalizing results. Methodological recommendations are urgently needed to economically evaluate POCIs, focusing on how AMR should be accounted for.

To be or not to be: Future lives in economic evaluation.

Sometimes healthcare will affect the health of people living in the future, or their chance of coming into existence. Should such outcomes be valued in health-economic evaluation? Guidelines implicitly recommend their inclusion but this rule has counterintuitive implications and is not consistently applied in practice. We suggest making a distinction between "necessary" and "potential" future lives in Health Technology Assessment. Necessary lives will exist independent of our healthcare choices and should be included. Potential lives are choice-dependent and should be excluded. This rule offers intuitive solutions within the HTA framework, and it changes the cost-effectiveness of several interventions where necessary future lives are affected.

Rationing of a scarce life-saving resource: Public preferences for prioritizing COVID-19 vaccination.

In the face of limited COVID-19 vaccine supply, governments have had to identify priority groups for vaccination. In October 2020, when it was still uncertain whether COVID-19 vaccines would be shown to work in trials, we conducted a discrete choice experiment and a best-worst ranking exercise on a representative sample of 2060 Belgians in order to elicit their views on how to set fair vaccination priorities. When asked directly, our respondents prioritized the groups that would later receive priority: essential workers, the elderly or those with pre-existing conditions. When priorities were elicited indirectly, through observing choices between individuals competing for a vaccine, different preferences emerged. The elderly were given lower priority and respondents divided within two clusters. While both clusters wanted to vaccinate the essential workers in the second place, one cluster (N = 1058) primarily wanted to target virus spreaders in order to control transmission whereas the other cluster (N = 886) wanted to prioritize those who were most at risk because of a pre-existing health condition. Other strategies to allocate a scarce resource such as using a "lottery", "first-come, first-served" approach or highest willingness-to-pay received little support.

Cost-effectiveness of mental health interventions during and after pregnancy: A systematic review.

BACKGROUND: Mental health problems during and after pregnancy such as depression, anxiety, post-traumatic stress disorder (PTSD), or addiction are common and can have lifelong implications for both parents and offspring. This review investigates the cost-effectiveness of interventions tackling these problems, assesses the methodological quality of included studies, and indicates suggestions for further research. METHODS: Thirteen databases were searched for economic evaluations of interventions related to antenatal, perinatal, and postnatal mental health conditions, published between 2000 and September 2021, in high-income countries. RESULTS: Thirty-nine studies met all inclusion criteria. Interventions considered were screening programs, pharmacological treatments, and various forms of psychosocial and psychological support. Six studies reported that the intervention was cost-saving. Eighteen were cost-effective and seven likely to be cost-effective. Only six studies included health outcomes for the child; one study considered paternal health. The time horizon for which costs and consequences were considered was for most evaluations limited to 1 year (n = 18) or 2 years (n = 11) postpartum. CONCLUSIONS: Given the importance of the subject, a relatively low number of studies have investigated the cost-effectiveness of interventions tackling mental health problems during and after pregnancy. The scant evidence available suggests good overall value for money. Likely, cost-effectiveness is underestimated as costly long-term consequences on offspring are systematically excluded. No evidence was found for several frequently occurring conditions. Further research is required to obtain reliable, long-term effectiveness data and to address the methodological challenges related to measuring all relevant health outcomes for all parties affected.

Integrating Alternative Social Value Judgments Into Cost-Effectiveness Analysis of Vaccines: An Application to Varicella-Zoster Virus Vaccination.

OBJECTIVES: Cost-effectiveness analyses (CEA) are based on the value judgment that health outcomes (eg, quantified in quality-adjusted life-years; QALYs) are all equally valuable irrespective of their context. Whereas most published CEAs perform extensive sensitivity analysis on various parameters and assumptions, only rarely is the influence of the QALY-equivalence assumption on cost-effectiveness results investigated. We illustrate how the integration of alternative social value judgments in CEA can be a useful form of sensitivity analysis. METHODS: Because varicella-zoster virus (VZV) vaccination affects 2 distinct diseases (varicella zoster and herpes zoster) and likely redistributes infections across different age groups, the program has an important equity dimension. We used a cost-effectiveness model and disentangled the share of direct protection and herd immunity within the total projected QALYs resulting from a 50-year childhood VZV program in the UK. We use the UK population's preferences for QALYs in the vaccine context to revalue QALYs accordingly. RESULTS: Revaluing different types of QALYs for different age groups in line with public preferences leads to a 98% change in the projected net impact of the program. The QALYs gained among children through direct varicella protection become more important, whereas the QALYs lost indirectly through zoster in adults diminish in value. Weighting of vaccine-related side effects made a large difference. CONCLUSIONS: Our study shows that a sensitivity analysis in which alternative social value judgments about the value of health outcomes are integrated into CEA of vaccines is relatively straightforward and provides important additional information for decision makers to interpret cost-effectiveness results.

Economic Evaluation of Vaccines: Belgian Reflections on the Need for a Broader Perspective.

OBJECTIVES: The standard framework of economic evaluation of health programs, which is increasingly used for policy funding decisions, is insufficiently equipped to reflect the full range of health and economic benefits conferred by vaccines and thus undervalues vaccination. METHODS: In 2019, a group of Belgian health economic and clinical experts, supported by 2 senior international vaccination experts (1 American, 1 Belgian), convened 4 roundtable meetings to highlight which particular value elements of vaccination remain neglected in economic evaluations. RESULTS: They concluded that the standard economic evaluation framework fails to reflect the full value of vaccination with respect to prevention of complications linked to some vaccine-preventable diseases, health gains for caregivers, herd effects, changes in exposure to and distribution of serotypes, the effect on antimicrobial resistance, productivity gains for caregivers and patients, and the distributive implications of vaccination programs. CONCLUSIONS: Here, suggestions are made regarding how these shortcomings can be addressed in future economic evaluations of vaccines and how a more level playing field between vaccines and other health programs can be created.

The cognitive footprint of medication: A review of cognitive assessments in clinical trials.

WHAT IS KNOWN AND OBJECTIVE: Polypharmacy is common, and many medications have cognitive side effects. Such effects can be transient and subside when the drug in question is discontinued or can be long-lasting with effects present for years afterwards. Although formal assessment of cognition is feasible and often undertaken in neuropsychiatric trials, these effects are usually neglected in the evaluation of any non-neuropsychiatric health intervention. Medication effects can be assessed within a cognitive footprint framework, to account for the magnitude and the duration of cognitive side effects, with some likely to have a greater and more lasting effect than others. COMMENT: Adverse event reporting suggests that many medications may be indirectly associated with cognitive effects, for example due to headaches, somnolence and 'dizziness'; however, inferring causation from adverse event reporting can be problematic. In order to better understand the impact of investigational drug and concomitant medications effect on cognition, it would be essential to ensure cognition is prioritized in drug development evaluation. It is suggested that simple instruments that can be easily incorporated into existing trial designs are used to assess the cognitive footprint of medication. WHAT IS NEW AND CONCLUSION: We present an overview of existing measures of cognition that can be integrated into drug trials in order to provide a cognitive footprint. Like quality of life testing, such tests should be administered as a standard throughout the key assessment stages of the design of the trial to ensure that any effects on this equally important outcome are also documented. Furthermore, employing routine cognition testing may also enable researchers to identify unanticipated beneficial and non-beneficial effects on cognition. Provision of such a cognitive footprint profile of drugs may provide the necessary evidence to enable decision-makers to make informed decisions on risk-benefit analysis that can subsequently make trade-offs between different drug regimens.

Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018.

IMPORTANCE: The mean cost of developing a new drug has been the subject of debate, with recent estimates ranging from $314 million to $2.8 billion. OBJECTIVE: To estimate the research and development investment required to bring a new therapeutic agent to market, using publicly available data. DESIGN AND SETTING: Data were analyzed on new therapeutic agents approved by the US Food and Drug Administration (FDA) between 2009 and 2018 to estimate the research and development expenditure required to bring a new medicine to market. Data were accessed from the US Securities and Exchange Commission, Drugs@FDA database, and ClinicalTrials.gov, alongside published data on clinical trial success rates. EXPOSURES: Conduct of preclinical and clinical studies of new therapeutic agents. MAIN OUTCOMES AND MEASURES: Median and mean research and development spending on new therapeutic agents approved by the FDA, capitalized at a real cost of capital rate (the required rate of return for an investor) of 10.5% per year, with bootstrapped CIs. All amounts were reported in 2018 US dollars. RESULTS: The FDA approved 355 new drugs and biologics over the study period. Research and development expenditures were available for 63 (18%) products, developed by 47 different companies. After accounting for the costs of failed trials, the median capitalized research and development investment to bring a new drug to market was estimated at $985.3 million (95% CI, $683.6 million-$1228.9 million), and the mean investment was estimated at $1335.9 million (95% CI, $1042.5 million-$1637.5 million) in the base case analysis. Median estimates by therapeutic area (for areas with ≥5 drugs) ranged from $765.9 million (95% CI, $323.0 million-$1473.5 million) for nervous system agents to $2771.6 million (95% CI, $2051.8 million-$5366.2 million) for antineoplastic and immunomodulating agents. Data were mainly accessible for smaller firms, orphan drugs, products in certain therapeutic areas, first-in-class drugs, therapeutic agents that received accelerated approval, and products approved between 2014 and 2018. Results varied in sensitivity analyses using different estimates of clinical trial success rates, preclinical expenditures, and cost of capital. CONCLUSIONS AND RELEVANCE: This study provides an estimate of research and development costs for new therapeutic agents based on publicly available data. Differences from previous studies may reflect the spectrum of products analyzed, the restricted availability of data in the public domain, and differences in underlying assumptions in the cost calculations.

Ethical Considerations for Movement Mapping to Identify Disease Transmission Hotspots.

Traditional public health methods for detecting infectious disease transmission, such as contact tracing and molecular epidemiology, are time-consuming and costly. Information and communication technologies, such as global positioning systems, smartphones, and mobile phones, offer opportunities for novel approaches to identifying transmission hotspots. However, mapping the movements of potentially infected persons comes with ethical challenges. During an interdisciplinary meeting of researchers, ethicists, data security specialists, information and communication technology experts, epidemiologists, microbiologists, and others, we arrived at suggestions to mitigate the ethical concerns of movement mapping. These suggestions include a template Data Protection Impact Assessment that follows European Union General Data Protection Regulations.

Cost-effectiveness of ovarian stimulation with gonadotrophin and clomiphene citrate in an intrauterine insemination programme for subfertile couples.

Ovarian stimulation with low-dose human menopausal gonadotrophin (HMG) is superior to clomiphene citrate in intrauterine insemination (IUI) cycles with respect to clinical pregnancy rate, but it is unclear whether HMG is also the more cost-effective option. The aim of this study was to compare the cost-effectiveness of ovarian stimulation with low-dose subcutaneously administred HMG (37.5-75 IU per day) to orally administred clomiphene citrate (50 mg/day from day 3-7) in an IUI programme for subfertile couples. A cost-effectiveness analysis was conducted using the results of a randomized trial, including 620 IUI cycles. The primary outcome was the incremental cost-effectiveness ratio (ICER) of using HMG versus clomiphene citrate. Results are presented from the healthcare payer perspective. The total cost per patient associated with one IUI treatment with HMG is €764, whereas it is €558 if clomiphene citrate is used, resulting in an incremental cost of €206 for HMG per treatment. The incremental clinical pregnancy rate of using HMG instead of clomiphene citrate, however, is also 5.7 percentage points higher, resulting in an ICER of HMG versus clomiphene citrate of €3615 per additional clinical pregnancy achieved. On average, HMG was found to be more cost-effective than clomiphene citrate.

Public preferences for prioritizing preventive and curative health care interventions: a discrete choice experiment.

BACKGROUND: Setting fair health care priorities counts among the most difficult ethical challenges our societies are facing. OBJECTIVE: To elicit through a discrete choice experiment the Belgian adult population's (18-75 years; N = 750) preferences for prioritizing health care and investigate whether these preferences are different for prevention versus cure. METHODS: We used a Bayesian D-efficient design with partial profiles, which enables considering a large number of attributes and interaction effects. We included the following attributes: 1) type of intervention (cure vs. prevention), 2) effectiveness, 3) risk of adverse effects, 4) severity of illness, 5) link between the illness and patient's health-related lifestyle, 6) time span between intervention and effect, and 7) patient's age group. RESULTS: All attributes were statistically significant contributors to the social value of a health care program, with patient's lifestyle and age being the most influential ones. Interaction effects were found, showing that prevention was preferred to cure for disease in young adults, as well as for severe and lethal disease in people of any age. However, substantial differences were found in the preferences of respondents from different age groups, with different lifestyles and different health states. CONCLUSIONS: Our study suggests that according to the Belgian public, contextual factors of health gains such as patient's age and health-related lifestyle should be considered in priority setting decisions. The studies, however, revealed substantial disagreement in opinion between different population subgroups.

Kicking against the pricks: vaccine sceptics have a different social orientation.

BACKGROUND: In any country, part of the population is sceptical about the utility of vaccination. To develop successful vaccination programmes, it is important to study and understand the defining characteristics of vaccine sceptics. Research till now mainly focused either on the underlying motives of vaccine refusal, or on socio-demographic differences between vaccine sceptics and non-sceptics. It remained till now unexplored whether both groups differ in terms of basic psychological dispositions. METHODS: We held a population survey in a representative sample of the population in Flanders, Belgium (N = 1050), in which we investigated whether respondents' attitude to vaccination was associated with their basic disposition toward other community members or society in general, as measured by the Triandis and Gelfand social orientation scale. RESULTS: We found that sceptics and non-sceptics have a different social orientation, even when several variables are controlled for. More specifically, vaccine sceptics scored significantly lower on both horizontal individualism and horizontal collectivism, indicating a lower disposition to see others as equals. CONCLUSION: These findings need confirmation in the context of different countries. Such insights can be valuable to optimize the design of effective communication strategies on vaccination programmes.

The sexual ethics of HPV vaccination for boys.

Human papillomavirus (HPV) is one of the most common sexually transmitted infections. It is a leading cause of cervical cancer in women but the virus is increasingly being linked to several other cancers in men and women alike. Since the introduction of safe and effective but also expensive vaccines, many developed countries have implemented selective vaccination programs for girls. Some however argue that these programs should be expanded to include boys, since (1) HPV constitutes non-negligible health risks for boys as well and (2) protected boys will indirectly also protect girls. In this paper we approach this discussion from an ethical perspective. First, on which moral grounds can one justify not reimbursing vaccination for the male sex? We develop an ethical framework to evaluate selective vaccination programs and conclude that, in the case of HPV, efficiency needs to be balanced against non-stigmatization, non-discrimination and justice. Second, if vaccination programs were to be expanded to boys as well, do the latter then also have a moral duty to become immunized? Two arguments in favor of such a moral duty are well known in vaccination ethics: the duty not to harm others and to contribute to the public good of public health. However, we argue that these are not particularly convincing in the context of HPV. In contrast, we believe a third, more powerful but also more controversial argument is possible. In our view, the sexual mode of transmission of HPV constitutes an additional reason to believe that boys in fact may have a moral obligation to accept vaccination.