Multinational Analysis of Estimated Health Care Costs Related to Extended-Interval Fixed Dosing of Checkpoint Inhibitors.

Importance: New dosing options for immune checkpoint inhibitors have recently been approved by the US Food and Drug Administration (FDA), including fixed dosing with extended intervals. Although the dose intensity appears the same, there is expected to be some waste with extended-interval dosing, as some drug remains in the bloodstream once a decision to stop treatment is made. The economic impact of extended-interval fixed dosing is unknown compared with standard-interval fixed dosing. Objective: To analyze the potential health care costs of using extended-interval fixed dosing instead of standard-interval fixed dosing. Design, Setting, and Participants: This economic evaluation used a pharmacoeconomic model to simulate 2 cohorts of patients with platinum-resistant metastatic urothelial cancer receiving pembrolizumab as second-line therapy at different dosing intervals using 2020 pricing data. Data were analyzed from 2020 to 2022. Exposures: The simulated patients received FDA-approved regimens of either 200 mg every 3 weeks or 400 mg every 6 weeks. Main Outcomes and Measures: The progression-free survival curve from the KEYNOTE-045 trial was used to estimate treatment duration. Drug, imaging, and administration costs were included in analyses. Sensitivity analyses were performed to assess how different imaging frequencies would affect the model results. The potential overall costs of using the 2 different dosing strategies were assessed. The base case was set in the US, while sensitivity analyses were set in several other countries. Results: In the base case analysis, dosing every 6 weeks instead of every 3 weeks resulted in an estimated 8.9% increase in pembrolizumab costs for the health care payer. Accounting for a decrease in infusion costs would result in an estimated net additional cost of $7483 per patient in the US (7.9% cost increase). In the US, this would amount to an increase of approximately $28 million annually for health care payers. Similar percentages in cost estimate increases were found for health care payers around the world, such as in Israel, where the net additional cost would be $5491 per patient. Conclusions and Relevance: This economic evaluation assessed and quantified the potential increased costs related to extended-interval fixed dosing of pembrolizumab. The model method could be applied to other diseases and other drugs for which there has been a movement toward extended-interval dosing. Results may differ in other diseases owing to differing disease courses and patient profiles.

Mortality, hospital days and expenditures attributable to ambient air pollution from particulate matter in Israel.

BACKGROUND: Worldwide, ambient air pollution accounts for around 3.7 million deaths annually. Measuring the burden of disease is important not just for advocacy but also is a first step towards carrying out a full cost-utility analysis in order to prioritise technological interventions that are available to reduce air pollution (and subsequent morbidity and mortality) from industrial, power generating and vehicular sources. METHODS: We calculated the average national exposure to particulate matter particles less than 2.5 µm (PM2.5) in diameter by weighting readings from 52 (non-roadside) monitoring stations by the population of the catchment area around the station. The PM2.5 exposure level was then multiplied by the gender and cause specific (Acute Lower Respiratory Infections, Asthma, Circulatory Diseases, Coronary Heart Failure, Chronic Obstructive Pulmonary Disease, Diabetes, Ischemic Heart Disease, Lung Cancer, Low Birth Weight, Respiratory Diseases and Stroke) relative risks and the national age, cause and gender specific mortality (and hospital utilisation which included neuro-degenerative disorders) rates to arrive at the estimated mortality and hospital days attributable to ambient PM2.5 pollution in Israel in 2015. We utilised a WHO spread-sheet model, which was expanded to include relative risks (based on more recent meta-analyses) of sub-sets of other diagnoses in two additional models. RESULTS: Mortality estimates from the three models were 1609, 1908 and 2253 respectively in addition to 184,000, 348,000 and 542,000 days hospitalisation in general hospitals. Total costs from PM2.5 pollution (including premature burial costs) amounted to $544 million, $1030 million and $1749 million respectively (or 0.18 %, 0.35 % and 0.59 % of GNP). CONCLUSIONS: Subject to the caveat that our estimates were based on a limited number of non-randomly sited stations exposure data. The mortality, morbidity and monetary burden of disease attributable to air pollution from particulate matter in Israel is of sufficient magnitude to warrant the consideration of and prioritisation of technological interventions that are available to reduce air pollution from industrial, power generating and vehicular sources. The accuracy of our burden estimates would be improved if more precise estimates of population exposure were to become available in the future.

Erratum to: The burden of smoking in Israel-attributable mortality and costs (2014).

[This corrects the article DOI: 10.1186/2045-4015-3-28.].

The burden of smoking in Israel-attributable mortality and costs (2014).

BACKGROUND: Tobacco use is the single most preventable cause of death, incurring huge resource costs in terms of treating morbidity and lost productivity. This paper estimates smoking attributable mortality (SAM) as health costs in 2014 in Israel. METHODS: Longitudinal data on prevalence of smokers and ex-smokers were combined with diagnostic and gender specific data on Relative Risks (RR) to gender and disease specific population attributable risks (PAR). PAR was then applied to mortality and hospitalization data from 2011, adjusted by population growth to 2014 to calculate SAM and hospitalization days (SAHD) caused by active smoking. These were used as a base for calculating deaths, hospital days and costs attributable to passive smoking, smoking by pregnant women, residential fires and productivity losses based on international literature. RESULTS: The lagged model estimated active SAM in Israel in 2014 to be 7,025 deaths. Cardio-vascular causes accounted for 45.0% of SAM, malignant neoplasms (39.2%) and respiratory diseases (15.5%). Lung cancer alone accounted for 24.1% of SAM. There were an estimated 793, 17 and 12 deaths from passive smoking, mothers-to-be smoking and residential fires. Total SAM is around 7,847 deaths (95% CI 7,698-7,997) in 2014. We estimated 319,231 active SAHD days (95% CI 313,135-325,326). Respiratory care accounted for around one-half of active SAHD (50.5%). Cardio-Vascular causes for 33.5% and malignant neoplasms (13.2%). Lung cancer only for 4.6%. Total SAHD was around 356,601 days including 36,049 days from passive smoking. Estimated direct acute care costs of 356,601 days in a general hospital amount to around 849 (95% CI 832-865) million NIS ($244 million). Non acute care costs amount to an additional 830 million NIS ($238 million). The total health service costs amount to 1,678 million NIS (95% CI 1,646-1,710) or $482 million, 0.2% of GNP. Productivity losses account for a further 1,909 million NIS ($548 million), giving an overall smoking related cost of 3,587 million NIS (95% CI 3,519-3,656) or $1,030 million, 0.41% of GNP). CONCLUSIONS: Smoking causes a considerable burden in Israel, both in terms of the expected 7,847 lives lost and the financial costs of around 3.6 million NIS ($1,030 million or 0.42% of GNP).

Cost-utility analysis of interventions to reduce the burden of cervical cancer in Israel.

Using World health Organization, CHOosing Interventions that are Cost Effective (WHO-CHOICE) methodology, cost-utility ratios were calculated for various interventions (Papanicolaou [Pap] smear, human papillomavirus [HPV]-DNA testing, visual inspection with acetic acid [VIA] and vaccination against HPV) at various frequencies to reduce the burden of cervical cancer and condyloma (in the case of the HPV vaccination) in Israel, which has a low prevalence of cervical cancer. All of the screening and/or vaccine interventions were very cost-effective. Attempts should be made to raise compliancy with Pap smears from the current opportunistic 12.1% per annum to screen everyone aged 20-64 once every 5 years in combination with HPV-DNA testing for persons aged 30-64 both before and/or after HPV vaccination is introduced. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in Israel" Vaccine Volume 31, Supplement 8, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.

Cost effectiveness of strategies to combat breast, cervical, and colorectal cancer in sub-Saharan Africa and South East Asia: mathematical modelling study.

OBJECTIVE: To determine the costs and health effects of interventions to combat breast, cervical, and colorectal cancers in order to guide resource allocation decisions in developing countries. SETTING: Two World Health Organization sub-regions of the world: countries in sub-Saharan Africa with very high adult and high child mortality (AfrE); and countries in South East Asia with high adult and high child mortality (SearD). DESIGN: Cost effectiveness analysis of prevention and treatment strategies for breast, cervical, and colorectal cancer, using mathematical modelling based on a lifetime population model. DATA SOURCES: Demographic and epidemiological data were taken from the WHO mortality and global burden of disease databases. Estimates of intervention coverage, effectiveness, and resource needs were based on clinical trials, treatment guidelines, and expert opinion. Unit costs were taken from the WHO-CHOICE price database. MAIN OUTCOME MEASURES: Cost per disability adjusted life year (DALY) averted, expressed in international dollars ($Int) for the year 2005. RESULTS: In both regions certain interventions in cervical cancer control (screening through cervical smear tests or visual inspection with acetic acid in combination with treatment) and colorectal cancer control (increasing the coverage of treatment interventions) cost <$Int2000 per DALY averted and can be considered highly cost effective. In the sub-Saharan African region screening for colorectal cancer (by colonoscopy at age 50 in combination with treatment) costs $Int2000-6000 per DALY averted and can be considered cost effective. In both regions certain interventions in breast cancer control (treatment of all cancer stages in combination with mammography screening) cost $Int2000-6000 per DALY averted and can also be considered cost effective. Other interventions, such as campaigns to eat more fruit and vegetable or subsidies in colorectal cancer control, are not cost effective according to the criteria defined. CONCLUSION: Highly cost effective interventions to combat cervical and colorectal cancer are available in the African and Asian sub-regions. In cervical cancer control, these include screening through smear tests or visual inspection in combination with treatment. In colorectal cancer, increasing treatment coverage is highly cost effective (screening through colonoscopy is cost effective in the African sub-region). In breast cancer control, mammography screening in combination with treatment of all stages is cost effective.

Prevention, screening and treatment of colorectal cancer: a global and regional generalized cost effectiveness analysis.

BACKGROUND: Regional generalized cost-effectiveness estimates of prevention, screening and treatment interventions for colorectal cancer are presented. METHODS: Standardised WHO-CHOICE methodology was used. A colorectal cancer model was employed to provide estimates of screening and treatment effectiveness. Intervention effectiveness was determined via a population state-transition model (PopMod) that simulates the evolution of a sub-regional population accounting for births, deaths and disease epidemiology. Economic costs of procedures and treatment were estimated, including programme overhead and training costs. RESULTS: In regions characterised by high income, low mortality and high existing treatment coverage, the addition of screening to the current high treatment levels is very cost-effective, although no particular intervention stands out in cost-effectiveness terms relative to the others.In regions characterised by low income, low mortality with existing treatment coverage around 50%, expanding treatment with or without screening is cost-effective or very cost-effective. Abandoning treatment in favour of screening (no treatment scenario) would not be cost effective.In regions characterised by low income, high mortality and low treatment levels, the most cost-effective intervention is expanding treatment. CONCLUSIONS: From a cost-effectiveness standpoint, screening programmes should be expanded in developed regions and treatment programmes should be established for colorectal cancer in regions with low treatment coverage.

Issues in estimating smoking attributable mortality in Israel.

BACKGROUND: The US Centres for Disease Control provides a widely used online user-friendly computational program, called SAMMEC (Smoking Attributable Mortality, Morbidity and Economic Costs) to produce estimates of tobacco-related mortality. However, the SAMMEC tool loses accuracy because it lacks flexibility in deciding which diseases enter into the calculations, has estimates of relative risk (RR) attributable to smoking based on old studies, and does not allow for the latency period that occurs between initial exposure and mortality. METHODS: Smoking attributable mortality (SAM) due to active smoking in Israel was estimated with the approach used by SAMMEC taking into account past and present smoking prevalence (lag-times) as well as using new and expanded disease categories. RESULTS: Around 50.3% of the increase from the un-lagged SAM estimate of 3859 deaths to the final SAM estimate of 8664 deaths in 2003 is attributable to the introduction of lag times. More robust estimates of risk accounted for a further 29.6% of the increase. While 21.2% is attributable to the inclusion of additional disease categories, only 1.5% was attributable to the widening of existing diseases categories. CONCLUSION: This difference in estimates is attributable to expansion of the list of diseases included, updating the estimates of RR for smoking-attributable death, and the use of smoking prevalence from previous years to more accurately reflect the effect of tobacco use on disease occurrence. There is a need to establish an 'authority' to implement a multi-faceted intervention strategy to decrease the considerable burden from smoking in Israel.

Standardized mortality ratios by region of residence, Israel, 1987-1994: a tool for public health policy.

BACKGROUND: Standardized mortality ratios (SMRs) are used internationally to compare health status across regions and to identify high risk areas for investigation of specific diseases, for funding determination, and for planning purposes. OBJECTIVE: To ascertain regional differences in SMRs by sub-District in Israel for 1987-1994. METHOD: The indirect method of standardization of mortality rates with adjustment for age, gender, and continent of birth was used to calculate SMRs by major cause of death, by sub-District of residence for the Jewish population of Israel. RESULTS: SMRs for all causes of death ranged from regions with low rates (Petah Tikva, Sharon, Rehovot, Ashkelon, and Jerusalem) to those with high rates (Zefat/Golan, Hadera, Yizreel, Ramla, Haifa, Tel Aviv, and Be'er Sheva) (all p<0.0001). Zefat's SMRs are elevated for acute myocardial infarction, stroke, diabetes, and motor vehicle accidents (MVAs). Haifa's SMRs are high for all cardiovascular diseases, liver disease, MVAs, and lung cancer. Be'er Sheva residents had high SMRs for diabetes, liver disease, MVAs, some categories of cardiovascular disease, cervical cancer, and homicide. Yizreel had high SMRs for diabetes, hypertension, stroke, liver disease, and MVAs. Tel Aviv had elevated SMRs for septicemia, acute MI, perinatal causes, and colon, lung and breast cancer. Jerusalem (p<0.0001) and Kinneret residents (p<0.05) had low SMRs for everything except congenital anomalies. CONCLUSIONS: Regional SMR differences, adjusted for age, gender, and ethnicity, may be due to socioeconomic, nutritional, environmental, occupational, or health care factors. SMRs provide a tool to identify regions for epidemiological investigation and priorities for preventive interventions. Regional health monitoring should be undertaken routinely on mortality data, as well as other national databases, as part of national health monitoring.