Cost of implementing CAR-T activity and managing CAR-T patients: an exploratory study.

BACKGROUND: Chimeric antigen receptor T cells (CAR-T) represent an innovation but raise issues for healthcare payers because of the uncertainty on impact at market launch, high cost and important organisational impact. The literature has focused on their assessment, appraisal and market access solutions. No evidence on the costs sustained to implement CAR-T is available and a few studies reported the cost of the CAR-T clinical pathway, including the activities that are remunerated through inpatient or outpatient fee-for-service/episode. This paper aims at filling the information gap, assessing the cost of implementing CAR-T activity and the full cost of managing the CAR-T clinical pathway. METHODS: Cost analysis relied on the Activity Based Costing approach, which was applied to two Italian healthcare organisations, both CAR-T Centres authorized by the regional governments with a minimum of 20 patients treated with the first two CAR-T therapies launched on the market. RESULTS: The cost of implementing CAR-T was estimated at €1.31 million (calculated for one of the organizations with complete data). Most of these costs (77%) were generated by quality assurance activity. The mean cost per patient entering the CAR-T pathway (59 and 27) and surviving at follow-up (21 and 5) ranges from €48K to €57K and from €96K to €106K, respectively. Fees for hospitalization and infusion of gene therapy accounts for more than 70% of these costs. The actual hospitalisation cost varies greatly across patients and is in general lower than the fee-for-episode paid by the region to the hospital. CONCLUSIONS: Despite its limitations (exploratory nature; the time spent by staff on activities which are not remunerated through fees was estimated through interviews with the CAR-T coordinators; cost items are not fully comparable), this research highlighted the relevant organisational and economic impact of CAR-T and provided important insights for policy makers and healthcare managers: the necessity to invest resources in CAR-T implementation; the need for assessing activities which are not remunerated through fees for service / episode; the opportunity to shift from fee-for-episode / service to bundled payments for CAR-T clinical pathway.

Assessment of a SARS-CoV-2 population-wide rapid antigen testing in Italy: a modeling and economic analysis study.

BACKGROUND: This study aimed to compare the cost-effectiveness of coronavirus disease 2019 (COVID-19) mass testing, carried out in November 2020 in the Italian Bolzano/Südtirol province, to scenarios without mass testing in terms of hospitalizations averted and quality-adjusted life-year (QALYs) saved. METHODS: We applied branching processes to estimate the effective reproduction number (Rt) and model scenarios with and without mass testing, assuming Rt = 0.9 and Rt = 0.95. We applied a bottom-up approach to estimate the costs of mass testing, with a mixture of bottom-up and top-down methodologies to estimate hospitalizations averted and incremental costs in case of non-intervention. Lastly, we estimated the incremental cost-effectiveness ratio (ICER), denoted by screening and related social costs, and hospitalization costs averted per outcome derived, hospitalizations averted and QALYs saved. RESULTS: The ICERs per QALY were €24 249 under Rt = 0.9 and €4604 under Rt = 0.95, considering the official and estimated data on disease spread. The cost-effectiveness acceptability curves show that for the Rt = 0.9 scenario, at the maximum threshold willingness to pay the value of €40 000, mass testing has an 80% probability of being cost-effective compared to no mass testing. Under the worst scenario (Rt = 0.95), at the willingness to pay threshold, mass testing has an almost 100% probability of being cost-effective. CONCLUSIONS: We provide evidence on the cost-effectiveness and potential impact of mass COVID-19 testing on a local healthcare system and community. Although the intervention is shown to be cost-effective, we believe the initiative should be carried out when there is initial rapid local disease transmission with a high Rt, as shown in our model.

Geographical variation in the use of private health insurance in a predominantly publicly-funded system.

We provide evidence of geographical variations in the use of private health insurance (PHI) in Italy. Our study offers an original contribution, using a 2016 dataset on the use of PHI amongst a population of more than 200,000 employees of a major company. The average claim per enrolee was €925, representing approximately 50% of public health expenditure per capita, primarily for dental care (27.2%), specialist outpatient services (26.3%) and inpatient care (25.2%). Residents in northern regions and metropolitan areas respectively claimed reimbursements for €164 and €483 more than those in southern regions and in non-metropolitan areas. Both supply and demand factors can explain these large geographical differences. The study suggests the urgency for policymakers to address the considerable disparities in the Italian healthcare system, revealing the overall social, cultural and economic conditions that shape the demand for healthcare.

The economic impact of compassionate use of medicines.

BACKGROUND: Compassionate use programs (CUP) for medicines respond to the ethical imperative of providing access to medicines before marketing approval to patients not recruited in trials. The economic impact of clinical trials has previously been investigated. No evidence on the net economic benefit of CUP exists. This research aims to address this information gap by estimating the economic consequences of 11 CUP in Italy conducted between March 2015 and December 2020 from the perspective of public health care system in Italy (National Health Service). Eight programs concern cancer treatments, two refer to spinal muscular atrophy, and one is indicated for multiple sclerosis. METHODS: Since CUP medicines are covered by the industry, the net economic benefit includes: (i) avoided costs of the Standard of Care (SoC) the patients would have received had they not joined the CUP, (ii) costs not covered by the pharmaceutical industry sponsor, but instead sustained by payers, such as those associated with adverse events (only severe side effects resulting in hospitalisation and attributable to CUP medicines), and (iii) costs for combination therapies and diagnostic procedures not used with the SoC. The SoC costing relied on publicly available data. Information on adverse events and diagnostic procedures was retrieved from the CUP and monetized using the relevant fee for episode or service. One CUP was excluded since a SoC was not identified. RESULTS: 2,713 patients were treated in the 11 CUP where a SoC was identified. The SoC mean cost per patient ranged from €11,415 to €20,299. The total cost of the SoC ranged between €31.0 and €55.1 million. The mean cost per patient covered by hospitals hosting CUP was equal to €1,646, with a total cost of €4.5 million. The net economic benefit ranged €26.5 million - €50.6 million. CONCLUSIONS: Despite research limitations, this paper illustrates for the first time the net economic impact of CUP from a public payer perspective. It is important to integrate these estimates with the prospective effects of CUP implementation, i.e., the economic value of the comparative benefit profile of medicines used in CUP versus the SoC, including effects from a societal perspective.

Reflections on the Importance of Cost of Illness Analysis in Rare Diseases: A Proposal.

In the field of rare diseases (RDs), the evidence standard is often lower than that required by health technology assessment (HTA) and payer authorities. In this commentary, we propose that appropriate economic evaluation for rare disease treatments should be initially informed by cost-of-illness (COI) studies conducted using a societal perspective. Such an approach contributes to improving countries' understanding of RDs in their entirety as societal and not merely clinical, or product-specific issues. In order to exemplify how the disease burden's distribution has changed over the last fifteen years, key COI studies for Hemophilia, Fragile X Syndrome, Cystic Fibrosis, and Juvenile Idiopathic Arthritis are examined. Evidence shows that, besides methodological variability and cross-country differences, the disease burden's share represented by direct costs generally grows over time as novel treatments become available. Hence, to support effective decision-making processes, it seems necessary to assess the re-allocation of the burden produced by new medicinal products, and this approach requires identifying cost drivers through COI studies with robust design and standardized methodology.

Social Economic Costs, Health-Related Quality of Life and Disability in Patients with Cri Du Chat Syndrome.

Background: Cri du Chat syndrome (CdC) is a rare disease caused by the deletion on the short arm of the chromosome 5, with an incidence of 1:15,000 to 1:50,000 live-born infants. No study at international level has assessed the costs, Quality of Life (QoL) and Disability through standardized quantitative tools. The aim is to estimate economic costs related to CdC from a societal perspective, to assess the QoL and Disability in patients with CdC along with their caregivers in Italy. Methods: A cross-sectional study of patients with Cri du Chat in Italy was carried out. A cost of illness approach from a societal perspective was used to estimate cost, and a micro-costing method was adopted. The QoL was measured with EuroQol 5-domain (EQ-5D) questionnaire and Disability by using World Health Organization Disability Assessment Schedule 36 item (WHODAS 2.0). Results: A total of 76 questionnaires were collected from caregivers taking care of 40 adult patients and 36 minor patients. All patients need a carer and the principal caregiver is commonly informal carer or a family member (93%). The EQ-5D VAS score for patients is 65.5 (SD = 22.4) out of 100; while the most important compromised areas of QoL are usual activities and self-care. The overall WHODAS 2.0 score is 65% (0 = no disability; 100 = full disability). The average annual cost of a patient with Cri du Chat in our population is €87,856.24; the main cost item of patients with Cri du Chat syndrome is informal care (i.e., €76,981.69 yearly) since it constitutes the 87% of total costs. Results highlight the burden of CdC in terms of its impact on QoL and Disability for patients and caregivers in Italy, with a score much lower than that of general population. The disease is associated with considerable costs of informal care. Conclusions: Cri du Chat syndrome was found to be linked with a significant socioeconomic impact which is dominated by direct non-healthcare informal costs.

Factors influencing adherence to adjuvant endocrine therapy in breast cancer-treated women: using real-world data to inform a switch from acute to chronic disease management.

PURPOSE: Adjuvant endocrine therapy (AET) for ≥ 5 years is generally recommended for women with hormone receptor-positive breast cancer to reduce cancer recurrence/mortality; however, adherence can be suboptimal. We tested determinants of AET adherence using patient characteristics, treatment pathways, AET initiation timing, and multiple healthcare facility use. An underlying objective was to explore how oncological pathways mirror chronic disease management to monitor adherence and target improvement interventions using administrative datasets. METHODS: Using patient-linked administrative health data from the Italian Lombardy Region, we identified 33.291 surviving patients starting AET in 2010-2016, with two (22.939 patients) or five years (8400 patients) follow-up, using a ≥ 80% prescription refill approach to measure adherence and logistic regression to test determinants of adherence. RESULTS: AET crude adherence falls significantly during follow-up, from 94% at 1 Year to 58% at 5 Years. At 5 Years, patients who were older (>70), prescribed tamoxifen-only (OR 0.69; 95% CI 0.57-0.83; p = 0.0001) vs. aromatase inhibitors-only or therapy switches, treated for depression (OR 0.68; 95% CI 0.60-0.78; p < 0.0001), with surgery performed in high-volume hospitals (OR 0.85; 95% CI 0.75-0.97; p = 0.0116) showed lower adherence. Loyalty, or continued care in the surgical hospital (OR 1.73; 95% CI 1.51-2.00; p < 0.0001), undergoing chemotherapy before AET (OR 2.65; 95% CI 2.02-3.48; p < 0.0001), and earlier AET initiation, positively influenced adherence. CONCLUSIONS: Chronic disease monitoring using administrative data can help oncologists focus efforts to ensure AET adherence. Results suggest addressing mental health, age, disease severity patient perceptions, timely AET initiation and therapy switches, and encouraging continued follow-up in the same hospital or better care coordination with outside follow-up specialists.

Patient access to oral nutritional supplements: Which policies count?

OBJECTIVES: Oral nutritional supplements (ONS) represent a cost-effective method for treating malnutrition. The aim of this study was to investigate the effects of public policies on patient access to ONS, using the Italian regionalized health care system as a case study, subsequently compared with the centralized British National Health Service. METHODS: Regional policies in the nine largest Italian regions and British policies were gathered through a literature review; interviews with officers responsible for clinical nutrition policies at the regional level in Italy were also conducted. Total ONS regional sales in Italy were gathered from industry sources. RESULTS: Regulation by Italian regions focused on patient access and local prescribing issues (facilities and specialists allowed to prescribe reimbursed ONS, clinical pathways for malnutrition or disease-related malnutrition, length of prescriptions, and distribution of ONS). British policies focused on organizational issues (clinical governance through multidisciplinary Nutrition Support Teams, Nutrition Steering Committees and Clinical Commissioning Groups), education and referral by health care professionals. Neither per capita reimbursed ONS expenditure nor the proportion covered by public funds seem dependent on policies implemented at the regional level in Italy. There is no cutting-edge evidence that British policies produced broader diffusion of ONS, but they appear to have standardized their use within a more homogenous framework. CONCLUSION: As no clear relation between regional policies and variation in patient access to ONS emerges in Italy, national policies should be encouraged to enhance awareness of malnutrition among health care professionals and encourage the diffusion of multidisciplinary nutrition teams in health care organizations.

Health care costs of influenza-related episodes in high income countries: A systematic review.

INTRODUCTION: This study systematically reviews costing studies of seasonal influenza-like illness (ILI) in high-income countries. Existing reviews on the economic impact of ILI do not report information on drug consumption and its costs, nor do they provide data on the overall cost per episode. METHODS: The PRISMA-P checklist was used to design the research protocol. Studies included were cost of illness analysis (COI) and modeling studies that estimated the cost of ILI episodes. Records were searched from January 2000 to December 2016 in electronic bibliographic databases including Medline, Embase, Science Direct, the Cochrane Library, the Centre for Reviews and Disseminations of the University of York, and Google scholar. References from the included studies were hand-searched for completion. Abstract screening, full-text analysis and data extraction were performed by two reviewers independently and discrepancies were resolved by discussion with a third reviewer. A standardized, pre-piloted form was used for data extraction. All costs were converted to 2015 US$ Purchasing Power Parities. RESULTS: The literature search identified 5,104 records. After abstract and title screening, 76 studies were analyzed full-text and 27 studies were finally included in the review. Full estimates of the cost per episode range from US$19 in Korea to US$323 in Germany. Particularly, the cost per episode of laboratory confirmed influenza cases was estimated between US$64 and US$73. Inpatient and outpatient services account for the majority of the costs. Differences in the estimates may reflect country-specific characteristics, as well as other study-specific features including study design, identification strategy of ILI cases, study populations and types of costs included in the analysis. Children usually register higher costs, whereas evidence for the elderly is less conclusive. Patients risk-profile, co-morbidities and complications are the other important cost-drivers. None of the papers considered appropriateness in resource use (e.g. abuse of antibiotics). Despite cost of illness studies have ultimately a descriptive role, evidence on (in)appropriateness is useful for policy-makers.

Social/economic costs and quality of life in patients with haemophilia in Europe.

OBJECTIVE: The aim of this study was to determine the economic burden from a societal perspective and the health-related quality of life (HRQOL) of patients with haemophilia in Europe. METHODS: We conducted a cross-sectional study of patients with haemophilia from Bulgaria, France, Germany, Hungary, Italy, Spain Sweden and the UK. Data on demographic characteristics, health resource utilisation, informal care, loss of labour productivity and HRQOL were collected from the questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D) questionnaire. The costs have been estimated from a societal perspective adopting a bottom-up approach. RESULTS: A total of 401 questionnaires were included in the study, of which 339 were collected from patients with haemophilia and 62 from caregivers. The lowest average annual cost per person was reported in Bulgaria (€6,660) and the highest in Germany (€194,490). Our results demonstrate both a large difference from country to country in the average annual cost per patient in 2012 and the driving role of drugs in costs. Drugs represent nearly 90 % of direct healthcare costs in a majority of the countries analysed (Hungary, Italy, Spain and Germany). In Bulgaria, France and Sweden, however, healthcare services (visits, tests and hospitalisations) prevail. Costs are also shown to differ between children and adults. The mean EQ-5D index score for adult patients was 0.69 and mean EQ-5D VAS was 66.6. The mean EQ-5D index score for carers was 0.87 and mean EQ-5D VAS was 75.5. In the disability score, 60 % showed no disability and measuring caregiver burden with the Zarit Index produced an overall mean score of 25.3. CONCLUSION: We have shown that haemophilia is associated with a substantial economic burden and impaired HRQOL. Studies on cost of illness and HRQOL are important for haemophilia as the future of this disease is likely to change with the development of new innovative treatments. The introduction of these treatments will most likely impact future costs related to haemophilia.

Social/economic costs and health-related quality of life in patients with Duchenne muscular dystrophy in Europe.

OBJECTIVE: The aim of this study was to determine the economic burden from a societal perspective and the health-related quality of life (HRQOL) of patients with Duchenne muscular dystrophy (DMD) in Europe. METHODS: We conducted a cross-sectional study of patients with DMD from Bulgaria, France, Germany, Hungary, Italy, Spain, Sweden, and the UK. Data on demographic characteristics, healthcare resource utilization, informal care, labor productivity losses, and HRQOL were collected from the questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D) questionnaire. Costs have been estimated from a societal perspective adopting a bottom-up approach. RESULTS: A total of 422 questionnaires were included in the study; 268 of which were collected from patients with DMD and 154 from caregivers. The average annual cost per person in 2012 ranged from €7657 in Hungary to €58,704 in France. Direct non-healthcare costs are the main component of whole costs and informal care is the main driver of non-healthcare costs. Costs are also shown to differ between children and adults. With regard to HRQOL of adult patients, the EQ-5D VAS score and EQ-5D index scores were 50.5 and 0.24, respectively. The corresponding EQ-5D VAS and EQ-5D index scores for caregivers were 74.7 and 0.71, respectively. CONCLUSIONS: We have estimated the average annual cost per patient with DMD in eight European countries adopting a social perspective, and to our knowledge this is the first study with such a wide perspective. The results on costs show a considerable gap between Eastern and Western European countries. Non-healthcare costs range from 64 to 89 % of overall costs and informal care is to a great extent the main driver of this cost category. The HRQOL of people with DMD is much lower than that of the general population.

The social burden and quality of life of patients with haemophilia in Italy.

BACKGROUND: In Italy, the project on the social burden and quality of life (QoL) of patients with haemophilia investigates costs from a society perspective and provides an overview of their quality of life. Moreover, as life expectancy increased in recent years along with new treatment strategies implemented in the last decades, it analyses trends of costs other than drugs simulating impacts during patient whole life. MATERIAL AND METHODS: We ran a web-based cross-sectional survey supported by the Italian Federation of Haemophilia Societies in recruiting patients with haemophilia and their caregivers. We developed a questionnaire to collect information on demographic characteristics, healthcare and social services consumption, formal and informal care utilisation, productivity loss and quality of life. In particular, quality of life was assessed through the EuroQoL tool. Last, we applied the illness cost method from a society perspective. RESULTS: On average, quality of life is worse in adult patients compared to child and caregivers: more than 75% of adult patients declare physical problems, 43% of adult patients and 54% of their parents have anxiety problems. Assuming a society perspective, the estimated mean annual total cost per patient in 2012 is 117,732 €. Drugs represent 92% of total costs. Focusing on costs other than drugs, each additional point of EuroQoL tool implies a costs' reduction of 279 €. The impact of age varies across age groups: each added year implies a total decrease of costs up to 46.6 years old. Afterwards, every additional year increases costs. DISCUSSION: Quality of life of patients with haemophilia and their caregivers improved and it influences positively on consumed resources and on their contribution to the social-economic system. Costs other than drugs for patients with haemophilia follow the same trends of general population.

Stakeholders involvement by HTA Organisations: why is so different?

OBJECTIVE: To investigate stakeholder involvement by Health Technology Assessment Organisations (HTAOs) in France, Spain, England and Wales, Germany, Sweden, and The Netherlands and to examine whether this involvement depends on (i) the administrative tradition and the relevant conception of the relationship between state and society (contractarian and corporative vs. organic), (ii) the general structure of the healthcare system (HCS) (Bismarckian vs. Beveridgian system), and (iii) the role of Health Technology Assessment (HTA) and HTAOs in the HCS. METHODS: Given the exploratory nature of the study, we considered interviews based on semi-structured questionnaires the most appropriate data-gathering technique. The interviews were administered to 16 key personnel in the HTAOs concerned. We have also carried out a literature review on HTAOs and stakeholders (1999-2011) using PubMed, Ebsco, JSTOR and Wiley Science. RESULTS: In contractarian and (to a lesser extent) Bismarckian models, stakeholders are more involved. The administrative tradition and the HCS appear less important when the HTA is binding and used for regulatory purposes. In such situations, stakeholders are more intensively involved because their participation provides an opportunity for HTAOs to achieve consensus and legitimacy in advance. CONCLUSIONS: Despite the limitations of the research (we did not conduct multiple interviews for each HTAO, and key informants were not always available) and its exploratory nature, we can conclude that models of stakeholders involvement cannot easily be transferred from one country to another due to the importance of national administrative traditions and the characteristics of HCSs.