The indirect costs of human papillomavirus-related cancer in Central and Eastern Europe: years of life lost and productivity costs.

BACKGROUND: Human papilloma virus (HPV) is a common cause of several types of cancer, including head and neck (oral cavity, pharynx, oropharynx, hypopharynx, nasopharynx, and larynx), cervical, vulval, vaginal, anal, and penile cancers. As HPV vaccines are available, there is potential to prevent HPV-related disease burden and related costs. METHOD: A model was developed for nine Central Eastern European (CEE) countries (Bulgaria, Croatia, Czechia, Hungary, Poland, Romania, Serbia, Slovakia, Slovenia). This model considered cancer patients who died from 11 HPV-related cancers (oropharynx, oral cavity, nasopharynx, hypopharynx, pharynx, anal, larynx, vulval, vaginal, cervical, and penile) in 2019. Due to data limitations, Bulgaria only included four cancer types. The model estimated the number of HPV-related deaths and years of life lost (YLL) based on published HPV-attributable fractions. YLL was adjusted with labor force participation, retirement age and then multiplied by mean annual earnings, discounted at a 3% annual rate to calculate the present value of future lost productivity (PVFLP). RESULTS: In 2019, there were 6,832 deaths attributable to HPV cancers resulting in 107,846 YLL in the nine CEE countries. PVFLP related to HPV cancers was estimated to be €46 M in Romania, €37 M in Poland, €19 M in Hungary, €15 M in Czechia, €12 M in Croatia, €10 M in Serbia, €9 M in Slovakia, €7 M in Bulgaria and €4 M in Slovenia. CONCLUSIONS: There is a high disease burden of HPV-related cancer-related deaths in the CEE region, with a large economic impact to society due to substantial productivity losses. It is critical to implement and reinforce public health measures with the aim to reduce the incidence of HPV-related diseases, and the subsequent premature cancer deaths. Improving HPV screening and increasing vaccination programs, in both male and female populations, could help reduce this burden.

Determining the Relationship Between Seizure-Free Days and Other Predictors of Quality of Life in Patients with Dravet Syndrome and Their Carers from FFA Registration Studies.

INTRODUCTION: Dravet syndrome (DS) is a rare, lifelong epileptic encephalopathy characterised by frequent and severe seizures associated with premature mortality. Typically diagnosed in infancy, patients also experience progressive behavioural, motor-function and cognitive decline. Twenty percent of patients do not reach adulthood. Quality of life (QoL) is impaired for both patients and their carers. Reducing convulsive seizure frequency, increasing convulsive seizure-free days (SFDs) and improving patient/carer QoL are primary treatment goals in DS. This study explored the relationship between SFDs and patients' and carers' QoL to inform a cost-utility analysis of fenfluramine (FFA). METHODS: In FFA registration studies, patients (or their carer proxies) completed the Paediatric QoL inventory (PedsQL). These data were mapped to EuroQol-5 Dimensions Youth version (EQ-5D-Y) to provide patient utilities. Carer utilities were collected using EQ-5D-5L and mapped to EQ-5D-3L to align patient and carer QoL on the same scale. Linear mixed-effects and panel regression models were tested and Hausman tests identified the most appropriate approach for each group. On this basis, a linear mixed-effects regression model was used to examine the relationships between patient EQ-5D-Y and clinically relevant variables (age, frequency of SFDs per 28 days, motor impairments and treatment dose). A linear panel regression model examined the relationship between SFDs and carer QoL. RESULTS: After adjustment for age and underlying comorbidities, the patient regression model showed that SFDs per 28 days was a significant predictor of QoL. Each additional patient-SFD increased utility by 0.005 (p < 0.001). The carer linear panel model also showed that increasing SFDs per 28 days was a significant predictor of improved QoL. Each additional SFD increased carer utility by 0.014 (p < 0.001). CONCLUSION: This regression framework highlights that SFDs are significantly correlated with both patients' and carers' QoL. Treatment with effective antiseizure medications that increase SFDs directly improves QoL for patients and their carers.

Indirect Costs Due to Lung Cancer-Related Premature Mortality in Four European Countries.

INTRODUCTION: Lung cancer accounts for approximately 20% of all cancer-related deaths and for the loss of 3.2 million disability-adjusted life years (DALYs) annually across Europe. The present study investigated the productivity losses resulting from premature deaths due to lung cancer in four European countries. METHODS: The human capital approach (HCA) was used to estimate indirect cost of productivity losses due to premature death due to lung cancer (ICD-10 codes C33-34 malignant neoplasm of trachea, bronchus, and lung) in Belgium, the Netherlands, Norway, and Poland. Years of productive life lost (YPLL) and present value of future lost productivity (PVFLP) were calculated using national age-specific mortality, wages, and employment rates. Data were sourced from the World Health Organization, Eurostat, and the World Bank. RESULTS: In 2019, there were 41,468 lung cancer deaths in the included countries resulting in 59,246 YPLL and more than €981 million in productivity losses due to premature mortality. From 2010 to 2015, the PVFLP of lung cancer decreased by 14% in Belgium, 13% in the Netherlands, 33% in Norway, and 19% in Poland. From 2015 to 2019, the PVFLP of lung cancer decreased by 26% in Belgium, 27% in the Netherlands, 14% in Norway, and 38% in Poland. CONCLUSION: The results from this study illustrate a decreasing trend in productivity costs of premature mortality due to lung cancer, as illustrated by the decreasing PVFLP between 2010 and 2019. This trend could be driven by a shift in the distribution of deaths towards older age groups due to advancements in the preventative and treatment landscape. These results provide an economic measure of the lung cancer burden which may assist decision-makers in allocating scarce resources amongst competing priorities in the included countries.

Assessing the impact of kidney cancer-related premature mortality and productivity loss in Greece and Portugal.

OBJECTIVE: In 2018, 371,750 people were diagnosed with kidney cancer globally, constituting 2.2% of all cancer diagnoses. Since 2010, the number of kidney cancer deaths in Europe have decreased in people under 65. However, this is not the case in Greece and Portugal. This study estimated the mortality and lost productivity due to premature mortality from kidney cancer in Greece and Portugal. METHODS: Years of life lost (YLL) and present value of future lost productivity (PVFLP) due to kidney cancer mortality (ICD-10 code: C64 - Malignant neoplasm of kidney, except renal pelvis) were calculated using the human capital approach. Age-specific mortality, mean earnings, and labor force participation rates were used in these calculations. RESULTS: In 2019, there were 564 and 454 kidney cancer deaths in Greece and Portugal, respectively, resulting in 5,871 (3,636 in males and 2,234 in females) and 5,397 (3,100 in males and 2,297 in females) YLL, respectively. YPLL and annual PVFLP were estimated to be 1,326 and €14.8 M in Greece and 1,278 and €11.8 M in Portugal, respectively. CONCLUSION: YLL and PVFLP due to kidney cancer mortality are substantial in Greece and Portugal. These results provide new evidence to assist decision-makers in allocating resources to reduce cancer burden.

Breast cancer-related mortality in Central and Eastern Europe: years of life lost and productivity costs.

BACKGROUND: Breast cancer (BC) poses a public health challenge as the most commonly diagnosed cancer among women globally. While BC mortality has declined across Europe in the past three decades, an opposite trend has been reported in some transitional European countries. This analysis estimates the mortality burden and the cost of lost productivity due to BC deaths in nine Central and Eastern Europe (CEE) countries: Bulgaria, Croatia, Czech Republic, Hungary, Poland, Romania, Serbia, Slovakia, and Slovenia, that have defied the favorable cancer mortality trends. These estimates may provide relevant evidence to aid decision-makers in the prioritization of BC-targeted policies. METHODS: The human capital approach (HCA) was used to estimate years of life lost (YLL) and productivity losses due to premature death from BC (ICD-10 code: C50 Malignant neoplasm of breast). YLL and present value of future lost productivity (PVFLP) were calculated using age and gender-specific mortality, wages, and employment rates. Data were sourced from the World Health Organization (WHO), Eurostat, and the World Bank. RESULTS: In 2019, there were 19,726 BC deaths in the nine CEE countries. This study estimated BC deaths resulted in 267,184 YLL. Annual PVFLP was estimated to be €85 M in Poland, €46 M in Romania, €39 M in Hungary, €21 M in Slovakia, €18 M in Serbia, €16 M in Czech Republic, €15 M in Bulgaria, €13 M in Croatia, and €7 M in Slovenia. CONCLUSION: Premature death from BC leads to substantial YLL and productivity losses. Lost productivity costs due to premature BC-related mortality exceeded €259 million in 2019 alone. The data modeled provide important evidence toward resource allocation priorities for BC prevention, screening, and treatment that could potentially decrease productivity losses. Careful consideration should be given to BC-specific policies, such as surveillance programs and the availability of new treatments in CEE countries to decrease the medical and financial burden of the disease.

Lost productivity due to head and neck cancer mortality in Hungary, Poland, and Romania.

BACKGROUND/AIMS: Head and neck cancer (HNC) describes a range of malignant tumours that arise from the epithelium of the mucous membranes in the head and neck region, including the oral cavity, pharynx, larynx, nasal cavity, and paranasal sinuses. In Hungary, oral cancer is among the top ten causes of cancer-related death (Diz et al., 2017 [1]). In Romania, HNC mortality has increased by more than 50 % in the last decade, and in Poland, HNC is the seventh most common type of cancer (Diz et al., 2017, Pinkas et al., 2022 [1,2]). To inform priorities for cancer control, this analysis estimated the mortality burden and cost of lost productivity due to premature HNC-deaths in Hungary, Poland, and Romania. The model used years of life lost (YLL), years of productive life lost (YPLL) and present value of future lost productivity (PVFLP). METHODS: We modelled patients who died from HNC in Hungary, Poland, and Romania in a single year and utilised epidemiological inputs and economic inputs to estimate YLL, YPLL, PVFLP and PVFLP/death. RESULTS: HNC resulted in 9729 annual deaths and 157,328 YLL in Hungary, Poland, and Romania. PVFLP was estimated to be €449 million, (€87 million, €193 million, €169 million, in Hungary, Poland and Romania respectively) with a total PVFLP/HNC-death of €46,158. CONCLUSION: HNC leads to substantial societal costs in Hungary, Poland, and Romania. Given the number of premature deaths and associated productivity loss, reducing HNC burden should be a priority for policymakers. POLICY SUMMARY: Given the severe clinical and economic burden of HNC, a multidisciplinary approach is required to reduce this burden, including prevention policies and improved diagnostic techniques to promote early diagnosis. Improvements in preventative measures will not only decrease productivity losses relating to HNC but would also have a huge impact across other cancer indications (e.g., lung and cervical cancers) and other illnesses linked to these policy areas (e.g., heart disease and diabetes).

The cost-effectiveness of unilateral magnetic resonance-guided focused ultrasound in comparison with unilateral deep brain stimulation for the treatment of medically refractory essential tremor in England.

OBJECTIVES: This study aims to ascertain the cost-effectiveness of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of medically refractory Essential Tremor (mrET) in England. Essential Tremor (ET) is the most common movement disorder affecting approximately 1 million in the UK causing considerable societal impact affecting patients, carers and the wider healthservice. Medical treatment has mixed efficacy, with approximately 25-55% of ET medication refractory. Deep brain stimulation (DBS) is a proven neurosurgical treatment; however, the risks of surgery and anaesthesia mean some patients are ineligible. MRgFUS is an emerging noninvasive technique that causes tremor suppression by thermal ablation of tremor-sensitive brain tissue. Several international clinical trials have demonstrated MRgFUS is safe and clinically effective; however, to-date no cost-effectiveness study has been performed in Europe. METHODS: A Markov model was used to assess two subpopulations of mrET - those eligible and those ineligible for neurosurgery - in the context specific to England and its healthcare system. For those eligible for neurosurgery, MRgFUS was compared to DBS, the current standard treatment. For those ineligible for neurosurgery, MRgFUS was compared to treatment with medication alone. The model calculated the Incremental cost-effectiveness ratio (ICER) with appropriate sensitivity and scenario analyses. RESULTS: For those eligible for neurosurgery: In the model base case, the MRgFUS was economically dominant compared to DBS; MRgFUS was less costly (£19,779 vs £62,348) and more effective generating 0.03 additional quality-adjusted life-years (QALYs) per patient (3.71 vs 3.68) over the 5-year time horizon.For those ineligible for neurosurgery: In the model base case, MRgFUS cost over £16,000 per patient more than medication alone (£19,779 vs £62,348) but yielded 0.77 additional QALYs per patient(3.71 vs 2.95), producing an incremental cost-effectiveness ratio (ICER) of £20,851 per QALY. This ICER of £20,851 per QALY falls within the National Institute for Clinical Excellence's (NICE) willingness to pay threshold (WTP) of 20,000-30,000 demonstrating the cost-effectiveness profile of MRgFUS. CONCLUSION: This study demonstrates the favourable cost-effectiveness profile of MRgFUS for the treatment of mrET in England; in both patients suitable and not suitable for neurosurgery. ADVANCES IN KNOWLEDGE: The introduction of MRgFUS as a widely available ET treatment in UK is currently undergoing the necessary stages of regulatory approval. As the first European study, these favourable cost-effectiveness outcomes (notably the model base case ICER falling within NICE's WTP) can provide a basis for future commissioning of brain MRgFUS treatments in the UK, Europe and globally.

Health economic evaluation of an mRNA high-risk human papillomavirus (HR-HPV) assay versus a DNA HR-HPV assay for the proposed French cervical screening programme.

OBJECTIVE: Population screening programmes must make good use of resources for the health system and users. To evaluate impacts of the type of diagnostic test in the new French cervical screening programme, an messenger ribonucleic acid (mRNA) high-risk human papillomavirus assay was compared to a deoxyribonucleic acid (DNA) high-risk human papillomavirus assay for a hypothetical cohort of women aged 25 to 65 years. PERSPECTIVE: This evaluation takes the perspective of the French healthcare system. SETTING: France. METHODS: A decision tree model reflecting the French cervical screening algorithms was parametrised using French cost and population data and the Danish Horizon study. The outcomes were total costs, and number of colposcopies, HPV tests and cytology tests for the cohort. One-way and probabilistic sensitivity analyses and scenarios analyses were conducted to test the robustness of results to parameter and structural uncertainty. RESULTS: Adopting an mRNA versus DNA assay as part of national cervical screening in France is estimated to save €6.5 million (95% credibility intervals €-1.3 - €13.5 million) and prevent 47,795 (95% credibility intervals 35,309 - 60,139) unnecessary colposcopies, 38,666 unnecessary HPV tests and 121,670 cytology tests over two years for a cohort of 2,168,806 million women aged 25 to 65 years. Sensitivity analyses indicated robust results across a range of inputs. CONCLUSION: The choice of high-risk human papillomavirus assay makes a significant difference to resource use and costs and is important to consider when implementing cervical screening in France. Using an mRNA versus DNA assay can result in cost savings and reductions in unnecessary testing and procedures, which in turn benefits women and the health care system.

Qualitative Validation of COPD Evidenced Care Pathways in Japan, Canada, England, and Germany: Common Barriers to Optimal COPD Care.

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. A comprehensive and detailed understanding of COPD care pathways from pre-diagnosis to acute care is required to understand the common barriers to optimal COPD care across diverse health systems. Methods: Country-specific COPD care pathways were created for four high-income countries using international recommendations and country-specific guidelines, then populated with published epidemiological, clinical, and economic data. To refine and validate the pathways, semi-structured interviews using pre-prepared discussion guides and country-specific pathway maps were held with twenty-four primary and secondary care respiratory healthcare professionals. Thematic analysis was then performed on the interview transcripts. Results: The COPD care pathway showed broad consistency across the countries. Three key themes relating to barriers in optimal COPD management were identified across the countries: journey to diagnosis, treatment, and the impact of COVID-19. Common barriers included presentation to healthcare with advanced COPD, low COPD consideration, and sub-optimal acute and chronic disease management. COVID-19 has negatively impacted disease management across the pathway but presents opportunities to retain virtual consultations. Structural factors such as insurance and short duration of appointments also impacted the diagnosis and management of COPD. Conclusion: COPD is an important public health issue that needs urgent prioritization. The use of Evidenced Care Pathways with decision-makers can facilitate evidence-based decision making on interventions and policies to improve care and outcomes for patients and reduce unnecessary resource use and associated costs for the healthcare provider/payer.

Assessing the clinical impact and resource use of a 30-minute chlamydia and gonorrhoea point-of-care test at three sexual health services.

OBJECTIVES: To assess clinical metrics and resource use of a 30-minute point-of-care test (POCT) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) compared to laboratory-based testing. METHODS: Three English sexual health services (SHSs) were recruited as part of a study. Existing processes for CT/NG testing and treatment were assessed, and adaptions to incorporate the CT/NG POCT were developed during semi-structured interviews. Staff time and consumables data were collected by clinic staff prior to and following introduction of the POCT. RESULTS: SHSs selected patient groups for whom the CT/NG POCT would be used. Testing and treatment process data were collected for 225 patients (n = 118 POC; n = 107 standard). The percentage of patients receiving unnecessary CT treatment was 5% (5/95) and 13% (12/93) for POC and standard care respectively. The average CT/NG pathway cost varied and was on average £61.55 for POC and £50.88 for standard care. For the two SHSs where the POCT was used during a patient's visit, for standard and POC respectively, the average time to CT treatment was 10.0 and 0.0 days and to NG treatment, 0.3 and 0.0 days. CONCLUSION: Use of a 30-minute POCT at three SHSs yielded clinical benefits by reducing time to treatment and unnecessary CT treatment.

A health economic model to estimate the costs and benefits of an mRNA vs DNA high-risk HPV assay in a hypothetical HPV primary screening algorithm in Ontario, Canada.

This study models the impact of using two different types of high-risk (HR) human papillomavirus (HPV) tests: mRNA (Aptima) and DNA (Hybrid Capture 2) as part of a hypothetical primary HPV screening program in Ontario, Canada. Outcomes were the costs of the screening program, and number of colposcopies, HPV tests and cytology tests. Results were estimated for one cohort going through the screening algorithm. A decision tree model was adapted from a published UK study, with inputs drawn from published Canadian data for the probabilities through the model, costs, demographic, and screening data from Ontario. Sensitivity and scenario analyses explored uncertainty in the model inputs and assumptions. Results indicated that screening using an mRNA test could yield cost savings of CAD $4,007,266 (95% credibility interval [CI]: -7,866,251 - 8,035) compared to using a DNA test, with 10,639 (95% CI: 10,170 - 11,094) fewer women undergoing unnecessary colposcopies, and reductions in unnecessary HR-HPV and cytology tests. The HR-HPV test comprised the largest percentage of the costs saved, and the probability of being HPV positive in the first year had the biggest impact on results. These results indicate that the choice of HR-HPV test is important when implementing a primary HPV screening program to avoid unnecessary resource use and cost, which will benefit both women and healthcare providers.

Antimicrobial resistance point-of-care testing for gonorrhoea treatment regimens: cost-effectiveness and impact on ceftriaxone use of five hypothetical strategies compared with standard care in England sexual health clinics.

BackgroundWidespread ceftriaxone antimicrobial resistance (AMR) threatens Neisseria gonorrhoeae (NG) treatment, with few alternatives available. AMR point-of-care tests (AMR POCT) may enable alternative treatments, including abandoned regimens, sparing ceftriaxone use. We assessed cost-effectiveness of five hypothetical AMR POCT strategies: A-C included a second antibiotic alongside ceftriaxone; and D and E consisted of a single antibiotic alternative, compared with standard care (SC: ceftriaxone and azithromycin).AimAssess costs and effectiveness of AMR POCT strategies that optimise NG treatment and reduce ceftriaxone use.MethodsThe five AMR POCT treatment strategies were compared using a decision tree model simulating 38,870 NG-diagnosed England sexual health clinic (SHC) attendees; A micro-costing approach, representing cost to the SHC (for 2015/16), was employed. Primary outcomes were: total costs; percentage of patients given optimal treatment (regimens curing NG, without AMR); percentage of patients given non-ceftriaxone optimal treatment; cost-effectiveness (cost per optimal treatment gained).ResultsAll strategies cost more than SC. Strategy B (azithromycin and ciprofloxacin (azithromycin preferred); dual therapy) avoided most suboptimal treatments (n = 48) but cost most to implement (GBP 4,093,844 (EUR 5,474,656)). Strategy D (azithromycin AMR POCT; monotherapy) was most cost-effective for both cost per optimal treatments gained (GBP 414.67 (EUR 554.53)) and per ceftriaxone-sparing treatment (GBP 11.29 (EUR 15.09)) but with treatment failures (n = 34) and suboptimal treatments (n = 706).ConclusionsAMR POCT may enable improved antibiotic stewardship, but require net health system investment. A small reduction in test cost would enable monotherapy AMR POCT strategies to be cost-saving.

Use of the Aptima mRNA high-risk human papillomavirus (HR-HPV) assay compared to a DNA HR-HPV assay in the English cervical screening programme: a decision tree model based economic evaluation.

OBJECTIVE: To estimate the impact of using the Aptima messenger RNA (mRNA) high-risk human papilloma virus (HR-HPV) assay versus a DNA HR-HPV assay in a primary HPV cervical screening programme. DESIGN: One hypothetical cohort followed for 3 years through HPV primary cervical screening. SETTING: England. PARTICIPANTS: A hypothetical cohort of women aged 25-65 years tested in the National Health Service (NHS) Cervical Screening Programme (CSP) for first call or routine recall testing. METHODS: A decision tree parameterised with data from the CSP (2017/18) and the HORIZON study. Uncertainty analyses were conducted using data from the FOCAL and GAST studies, other DNA HPV tests in addition to one-way and probabilistic sensitivity and scenarios analyses, to test the robustness of results. INTERVENTIONS: Aptima mRNA HR-HPV assay and a DNA HR-HPV assay (cobas 4800 HPV assay). MAIN OUTCOME MEASURES: Primary: total colposcopies and total costs for the cohort. Secondary: total HPV and cytology tests, number lost to follow-up. RESULTS: At baseline for a population of 2.25 million women, an estimated £15.4 million (95% credibility intervals (CI) £6.5 to 24.1 million) could be saved and 28 009 (95% CI 27 499 to 28 527) unnecessary colposcopies averted if Aptima mRNA assays are used instead of a DNA assay, with 90 605 fewer unnecessary HR-HPV and 253 477 cytology tests performed. These savings are due to a lower number of HPV positive samples in the mRNA arm. When data from other primary HPV screening trials were compared, results indicated that using the Aptima mRNA assay generated cost savings and reduced testing in every scenario. CONCLUSION: Using the Aptima mRNA assay versus a DNA assay would almost certainly yield cost savings and reduce unnecessary testing and procedures, benefiting the NHS and women in the CSP.

Repeat screening for syphilis in pregnancy as an alternative screening strategy in the UK: a cost-effectiveness analysis.

OBJECTIVES: To assess the cost-effectiveness of universal repeat screening for syphilis in late pregnancy, compared with the current strategy of single screening in early pregnancy with repeat screening offered only to high-risk women. DESIGN: A decision tree model was developed to assess the incremental costs and health benefits of the two screening strategies. The base case analysis considered short-term costs during the pregnancy and the initial weeks after delivery. Deterministic and probabilistic sensitivity analyses and scenario analyses were conducted to assess the robustness of the results. SETTING: UK antenatal screening programme. POPULATION: Hypothetical cohort of pregnant women who access antenatal care and receive a syphilis screen in 1 year. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the cost to avoid one case of congenital syphilis (CS). Secondary outcomes were the cost to avoid one case of intrauterine fetal demise (IUFD) or neonatal death and the number of women needing to be screened/treated to avoid one case of CS, IUFD or neonatal death. The cost per quality-adjusted life year gained was assessed in scenario analyses. RESULTS: Base case results indicated that for pregnant women in the UK (n=725 891), the repeat screening strategy would result in 5.5 fewer cases of CS (from 8.8 to 3.3), 0.1 fewer cases of neonatal death and 0.3 fewer cases of IUFD annually compared with the single screening strategy. This equates to an additional £1.8 million per case of CS prevented. When lifetime horizon was considered, the incremental cost-effectiveness ratio for the repeat screening strategy was £120 494. CONCLUSIONS: Universal repeat screening for syphilis in pregnancy is unlikely to be cost-effective in the current UK setting where syphilis prevalence is low. Repeat screening may be cost-effective in countries with a higher syphilis incidence in pregnancy, particularly if the cost per screen is low.