Dealing with Time in Health Economic Evaluation: Methodological Issues and Recommendations for Practice

Time is an important aspect of health economic evaluation, as the timing and duration of clinical events, healthcare interventions and their consequences all affect estimated costs and effects. These issues should be reflected in the design of health economic models. This article considers three important aspects of time in modelling: (1) which cohorts to simulate and how far into the future to extend the analysis; (2) the simulation of time, including the difference between discrete-time and continuous-time models, cycle lengths, and converting rates and probabilities; and (3) discounting future costs and effects to their present values. We provide a methodological overview of these issues and make recommendations to help inform both the conduct of cost-effectiveness analyses and the interpretation of their results. For choosing which cohorts to simulate and how many, we suggest analysts carefully assess potential reasons for variation in cost effectiveness between cohorts and the feasibility of subgroup-specific recommendations. For the simulation of time, we recommend using short cycles or continuous-time models to avoid biases and the need for half-cycle corrections, and provide advic

Burden of paediatric respiratory syncytial virus disease and potential effect of different immunisation strategies: a modelling and cost-effectiveness analysis for England.

BACKGROUND: Vaccines and prophylactic antibodies against respiratory syncytial virus (RSV) are in development and likely to be available in the next 5-10 years. The most efficient way to use these products when they become available is an important consideration for public health decision makers. METHODS: We performed a multivariate regression analysis to estimate the burden of RSV in children younger than 5 years in England (UK), a representative high-income temperate country, and used these results to assess the potential effect of different RSV immunisation strategies (targeting vaccination for infants, or pregnant women, or prophylactic antibodies for neonates). We did a cost-effectiveness analysis for these strategies, implemented either separately or concurrently, and assessed the effect of restricting vaccination to certain months of the year. FINDINGS: We estimated that RSV is responsible for 12 primary care consultations (95% CI 11·9-12·1) and 0·9 admissions to hospital annually per 100 children younger than 5 years (95% CI 0·89-0·90), with the major burden occurring in infants younger than 6 months. The most cost-effective strategy was to selectively immunise all children born before the start of the RSV season (maximum price of £220 [95% uncertainty interval (UI) 208-232] per vaccine, for an incremental cost-effectiveness ratio of £20 000 per quality-adjusted life-year). The maximum price per fully protected person that should be paid for the infant, newborn, and maternal strategies without seasonal restrictions was £192 (95% UI 168-219), £81 (76-86), and £54 (51-57), respectively. INTERPRETATION: Nearly double the number of primary care consultations, and nearly five times the number of admissions to hospital occurred with RSV compared with influenza. RSV vaccine and antibody strategies are likely to be cost-effective if they can be priced below around £200 per fully protected person. A seasonal vaccination strategy is likely to provide the most direct benefits. Herd effects might render a year-round infant vaccination strategy more appealing, although it is currently unclear whether such a programme would induce herd effects. FUNDING: UK National Institute for Health Research

Dealing with Time in Health Economic Evaluation: Methodological Issues and Recommendations for Practice

Time is an important aspect of health economic evaluation, as the timing and duration of clinical events, healthcare interventions and their consequences all affect estimated costs and effects. These issues should be reflected in the design of health economic models. This article considers three important aspects of time in modelling: (1) which cohorts to simulate and how far into the future to extend the analysis; (2) the simulation of time, including the difference between discrete-time and continuous-time models, cycle lengths, and converting rates and probabilities; and (3) discounting future costs and effects to their present values. We provide a methodological overview of these issues and make recommendations to help inform both the conduct of cost-effectiveness analyses and the interpretation of their results. For choosing which cohorts to simulate and how many, we suggest analysts carefully assess potential reasons for variation in cost effectiveness between cohorts and the feasibility of subgroup-specific recommendations. For the simulation of time, we recommend using short cycles or continuous-time models to avoid biases and the need for half-cycle corrections, and provide advice on the correct conversion of transition probabilities in state transition models. Finally, for discounting, analysts should not only follow current guidance and report how discounting was conducted, especially in the case of differential discounting, but also seek to develop an understanding of its rationale. Our overall recommendations are that analysts explicitly state and justify their modelling choices regarding time and consider how alternative choices may impact on results

Evaluating food safety management systems in Singapore: A controlled interrupted time-series analysis of foodborne disease outbreak reports

Food catering service establishments are often implicated in foodborne disease outbreaks. We evaluated the effects of implementing Food Safety Management Systems (FSMS) in food catering service establishments in Singapore on two outcome measures: foodborne disease outbreaks and food hygiene violations. Using a controlled interrupted time-series study design, we estimated the change in the average level of these outcome measures following implementation, and compared the pre- and post-intervention trends. There were 42 foodborne disease outbreaks and 521 food hygiene violations associated with catering service establishments from 2012 to 2018. Eighteen months after FSMS implementation, we observed a 78.4% decrease (IRR: 0.216, 95% CI: 0.050 to 0.940, p=0.041) in the average level of foodborne outbreaks in food catering service establishments. There was no significant effect on reported hygiene violations. Our study suggests that the FSMS implementation was successful in reducing foodborne outbreaks

Using Economic Evidence to Set Healthcare Priorities in Low-Income and Lower-Middle-Income Countries: A Systematic Review of Methodological Frameworks.

Policy makers in low-income and lower-middle-income countries (LMICs) are increasingly looking to develop 'evidence-based' frameworks for identifying priority health interventions. This paper synthesises and appraises the literature on methodological frameworks--which incorporate economic evaluation evidence--for the purpose of setting healthcare priorities in LMICs. A systematic search of Embase, MEDLINE, Econlit and PubMed identified 3968 articles with a further 21 articles identified through manual searching. A total of 36 papers were eligible for inclusion. These covered a wide range of health interventions with only two studies including health systems strengthening interventions related to financing, governance and human resources. A little under half of the studies (39%) included multiple criteria for priority setting, most commonly equity, feasibility and disease severity. Most studies (91%) specified a measure of 'efficiency' defined as cost per disability-adjusted life year averted. Ranking of health interventions using multi-criteria decision analysis and generalised cost-effectiveness were the most common frameworks for identifying priority health interventions. Approximately a third of studies discussed the affordability of priority interventions. Only one study identified priority areas for the release or redeployment of resources. The paper concludes by highlighting the need for local capacity to conduct evaluations (including economic analysis) and empowerment of local decision-makers to act on this evidence

Cost-effectiveness of Pharmaceutical-based Pandemic Influenza Mitigation Strategies1

Population prepandemic vaccine and antiviral treatment strategies may be cost-effective

Pertussis vaccination in a cohort of older Australian adults following a cocooning vaccination program

Background While recommendations to vaccinate adults against pertussis exist, information on uptake for adult tetanus-diphtheria-pertussis vaccine (Tdap) among older adults is limited. Methods We used data from the 45 and Up Study, a prospective cohort of adults aged ≥45 years who completed a questionnaire between 2012 and 2014 asking about pertussis vaccination. We evaluated Tdap uptake following a program providing free vaccine for adults in contact with young children between 2009 and 2012. Results Among 91,432 adults (mean age = 66.3 years, SD = 9.6), 3.1% (n = 2823) reported receiving Tdap prior to the program. This increased seven-fold to 21.8% (n = 19898) after the program finished. Tdap coverage was almost twice as high in women compared to men and among adults more likely to be grandparents than those not. Conclusion These findings suggest that funding for a targeted program can help to substantially increase vaccination coverage as well as decrease disparities in the uptake of Tdap in different sub-groups.This study was funded by the Australian National Health and Medical Research Council (NHMRC) grant no 1048180. AD received a PhD scholarship from the NHMRC. BL, JK, EB receive fellowships from the NHMRC

Dealing with Time in Health Economic Evaluation: Methodological Issues and Recommendations for Practice

Time is an important aspect of health economic evaluation, as the timing and duration of clinical events, healthcare interventions and their consequences all affect estimated costs and effects. These issues should be reflected in the design of health economic models. This article considers three important aspects of time in modelling: (1) which cohorts to simulate and how far into the future to extend the analysis; (2) the simulation of time, including the difference between discrete-time and continuous-time models, cycle lengths, and converting rates and probabilities; and (3) discounting future costs and effects to their present values. We provide a methodological overview of these issues and make recommendations to help inform both the conduct of cost-effectiveness analyses and the interpretation of their results. For choosing which cohorts to simulate and how many, we suggest analysts carefully assess potential reasons for variation in cost effectiveness between cohorts and the feasibility of subgroup-specific recommendations. For the simulation of time, we recommend using short cycles or continuous-time models to avoid biases and the need for half-cycle corrections, and provide advice on the correct conversion of transition probabilities in state transition models. Finally, for discounting, analysts should not only follow current guidance and report how discounting was conducted, especially in the case of differential discounting, but also seek to develop an understanding of its rationale. Our overall recommendations are that analysts explicitly state and justify their modelling choices regarding time and consider how alternative choices may impact on results

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Newborn screening and earlier intervention with deaf children: issues for the developing world

The universal screening of newborn children for permanent hearing loss has become a standard health and educational service in many, if not most, developed countries. Developed nations, however, represent the minority of the world's population. Universal newborn hearing screening (UNHS) is far less frequently available in developing countries where hearing loss is often disproportionately prevalent. This chapter considers the issues associated with the development of newborn screening programs in developing countries, where the vast majority of the world's deaf children live. These issues include whether to screen all newborns or to employ a targeted approach of seeking only those children with known risk factors for hearing loss, the articulation of UNHS programs with appropriate support services for children and families, and the availability and quality of subsequent intervention in developing-country contexts. The question of economic affordability and the sustainability of expensive programs of screening in very poor countries is also considered, as are the ethical issues associated with providing (or not providing) access to such programs. It is concluded that successfully implemented UNHS programs stand to provide enormous benefits to deaf and hard-of-hearing (DHH) children and their families in developing countries. It is argued that such benefits will only accrue, however, if programs are well implemented and combined with adequate and effective follow-up