Global and Regional Health Technology Assessment

The role and impact of health economics in the optimization of patient care in osteoarthritis: insights from a practical example

Mickaël Hiligsmann — 2024-04-03

Osteoarthritis (OA) is a degenerative joint disease with a substantial global burden, causing chronic pain and reduced quality of life. Managing OA efficiently while maximizing healthcare resources is crucial. Health economics and health technology assessment (HTA) are central tools providing a framework to evaluate the clinical, economic, and ethical aspects of healthcare technologies and interventions. This article presents some insights into the role of health economics and the HTA process in OA management. It also illustrates an example of cost-effectiveness analysis in a specific healthcare context, on the basis of a recent clinical trial involving hyaluronic acid treatment for knee OA. While HTA offers valuable insights, it faces challenges like data availability and resource constraints. Integrating health economics into decision-making can enhance patient care and allocate resources effectively in OA and other healthcare domains.

HTA regulation: how is Italy moving?

Francesca Patarnello — 2024-03-05

Within the European evolutionary framework concerning citizens’ health, the focus shifts to the new HTA regulation, set to alter processes and influence decision-making at the individual country level regarding reimbursement and pricing. The ambitious goal of achieving faster and more uniform access will significantly reshape the evaluative model stabilized over the years, characterized by the creation of different rules and processes among member states and diverse output timelines across the countries.

The imminent adoption of a more collaborative process necessitates member countries and companies to address several steps to ensure a smooth transition without penalizing the unique aspects of individual countries or impeding real access. Italy, actively participating in European preparatory activities with AIFA, faces challenges in adapting its formal process due to AIFA’s ongoing reform since November 2022, which is not yet materialized.

National-level companies heavily depend on leadership and involvement rules from their HTA agencies, with the risk that agencies with more established engagement models with external stakeholders may present themselves on January 12, 2025, the start date of the new process for oncological and ATMP drugs, better prepared and may excel in designing scoping meetings and in formulating PICO.

Therefore, the activation of a country culture of HTA and a robust and extended “readiness” phase involving all stakeholders are desirable, along with the establishment of collaboration networks with universities and scientific societies to make valuable knowledge and qualified resources more readily available, crucial element for the delicate transition from the old to the new evaluative system.

The future of drugs distribution in the National Health System

Massimo Medaglia — 2024-01-15

The distribution of drugs reimbursed by the NHS in Italy can be summarized in three forms: direct (DD), on behalf of (DPC) and affiliated. The following document presents the results of the discussion of a multidisciplinary experts’ panel, from different professional realities in the healthcare system, on alternative methods of drugs’ distribution. It was highlighted how regional autonomy has led to extremely innovative experiences but also to a lack of homogeneity regarding the access to pharmaceutical assistance across Italy. The main recommendations developed by the experts can be summarized as follows:

To ensure decisions regarding prescription and classification, with respect to the healthcare delivery settings, with the consequent distribution model and purchasing processes, is AIFA’s responsibility.
To evaluate the reclassification of drugs from class H to class A-PHT for drugs intended to be taken at patient’s home, in cases where close monitoring by specialistic structures is not necessary.
To limit the inclusion of a drug in PHT to conditions of differential diagnostic complexity, need for recurrent patient’s referral to the healthcare facility, presence of AIFA monitoring register, settings of drugs’ administration (home hospitalization and home care).
In the field of PHT drugs, AIFA should, with the support of a multidisciplinary technical table:

Update the list periodically.
Identify the drugs on the list for which DD is preferential, leaving the others in DPC.
Evaluate the conditions to transfer some drugs to distribution under an agreement.

Regional administrative data and their role in planning, programming and controlling at regional level

Irene Marzona — 2024-04-25

Regional administrative data may help public administrations in organizing their information, identifying problems, defining solutions and verifying results of the actions taken.

The objective of this work is to present the discussion output of the working group (GDL) “The use of regional pharmaceutical data to facilitate health planning and outcome monitoring” which was held during the Regional Pharmaceutical Policy Forum of 2023.

The GDL focused on identifying a model for planning, programming and monitoring health resources based on the data-driven approach and on the use of already existing regional administrative data, defining some gaps and developing proposals to implement this strategy. In particular, were highlighted the needs to adopt a broader perspective that considers healthcare costs as a whole (and not, specifically, oriented towards the governance of pharmaceutical assistance), to create ad-hoc training courses focused on the use of real-world data, and, similarly to some European Countries, to move towards an open access policy (accessible data) that can be useful to improve citizens’ health protection services, in compliance with the GDPR.

Heart failure and economic impact: an analysis in real clinical practice in Italy

Melania Dovizio — 2024-04-22

Introduction: Heart failure (HF) affects 1% of subjects aged 45-55 and over 10% of subjects aged ≥ 80 and in Italy represents the third leading cause of hospitalization.

Objective: To analyse the clinical and economic burden of HF in the Italian real clinical practice.

Methods: A retrospective analysis was conducted on the administrative databases of healthcare institutions for 4.2 million health-assisted residents. Between January 2012 and March 2021, patients with a hospital discharge diagnosis for HF were included. Among healthcare utilization and costs, treatments, hospitalizations, and specialist services were evaluated. The HF group was compared with a population without HF (no-HF) similar for age, sex distribution, and cardiovascular risk factors.

Results: The same number of patients with (N = 74,085) and without HF (N = 74,085) was included. A profile of cardiovascular comorbidities emerged in the HF group, mainly hypertension (88.6%), cardiovascular disease (61.3%) and diabetes (32.1%). Hospitalizations from any cause were 635.6 vs 429.8/1,000 person-year in the HF vs no-HF group. At one-year follow-up, all-cause mortality was 24.9% in HF patients and 8.4% in no-HF. Resource utilization/patient was respectively 26.8 ± 15.9 vs 17.1 ± 12.5 for medications, 0.8 ± 1.2 vs 0.3 ± 0.8 for hospitalizations, and 9.4 ± 12.6 vs 6.5 ± 9.8 for specialist services. This resource utilization resulted in significantly higher total healthcare costs in the HF group vs no-HF group (€ 5,910 vs € 3,574, p < 0.001), mainly related to hospitalizations (€ 3,702 vs € 1,958).

Conclusions: HF patients show a significantly higher clinical and economic burden than no-HF, with total healthcare costs being about 1.7 times the costs of the no-HF group.

Keywords: Cardiovascular comorbidities, Healthcare costs, Heart failure, Hospitalizations

The socioeconomic burden of adult attention-deficit/hyperactivity disorder in Spain

Maria Merino — 2024-04-05

Introduction: The symptoms of attention-deficit/hyperactivity disorder (ADHD) in adults highly interfere with function in multiple dimensions, increasing the economic burden associated with ADHD. The aim of this study was to explore the impact of ADHD in Spanish adults and estimate the associated economic burden within the healthcare, social, economic, and legal domains.

Methods: An economic model was developed from a social perspective using a bottom-up approach, based on the scientific literature and a multidisciplinary expert group.

Results: The cost incurred per diagnosed adult patient with ADHD included an annual cost of €15,652 and a one-time cost of €7,893 (3,035 M€ and 1,531 M€ for Spain, respectively). Regarding the annual cost, 50% was attributed to costs within the economic domain, of which 53% were work-absenteeism-related. Moreover, 28% was attributed to costs within the social domain, of which 74% were substance-abuse-related. Regarding the one-time cost, 52% was attributed to costs within the healthcare domain, of which approximately 50% were hospitalization-related costs. Moreover, 42% was attributed to costs within the legal domain, of which 62% were imprisonment-related costs.

Conclusions: This is the first report on the socioeconomic burden of ADHD in Spanish adults, shedding light on the large burden that adult ADHD poses on the healthcare system and society at large, as symptoms have been shown to impact almost every aspect of life. This is particularly important for undiagnosed/untreated patients with ADHD in Spain, as appropriate treatments have shown positive results in these areas and may reduce its associated socioeconomic burden.

Regional Formularies in Italy: current state and future perspectives

Alberto Bortolami — 2024-03-08

Regional Formularies (RF) are considered part of pharmaceutical policies implemented by regions to govern access of medicines to regional market. However, they have been actually challenged, because of their presumed impact on differences of patient’s access across the regions. The paper aimed at investigating the current status of RF and Regional Therapeutic Committees (CTR) and at suggesting/recommending possible reforms.

The current status was investigated through a questionnaire administered to the regional pharmaceutical departments. Recommendations were retrieved from a multi-stakeholder work group carried out on 30-31 March 2023, embedded into a Forum focused on the regional pharmaceutical policies.

Nineteen out of twenty-one regions responded to the survey: 12 use RF, mainly managed by the CTR; the RF frequency of update and the time needed for drugs listing greatly vary across regions; pharmacists, specialists and general practitioners are always represented in CTR, whereas other healthcare professionals and experts are more rarely involved; in 3 regions the CTR does not publish any RF update; the CTR mainly rely, to take decisions, on the dimension of the target population, the cost of therapy compared to alternative treatments and the impact on pharmaceutical expenditure.

The working group recommended to overcome the RFs, if they are merely considered a list of available drugs at regional level, focusing CTR activities to ensure market access and to govern the prescribing behaviour, and strengthening/anticipating the flow of information from the Italian Medicines Agency (AIFA) to the regions, to enable a more efficient approach to local access to drugs.

Cost per Number Needed to Treat (NNT) for upadacitinib in the treatment of bio-exposed patients with moderately-severely active ulcerative rectocolitis

Flavio Caprioli — 2024-03-07

Background: Only limited information is available on cost efficacy of the advanced therapies for the treatment of ulcerative rectocolitis. We evaluated the efficacy and the treatment costs of these advanced therapies in the treatment of bio-exposed (primary failure to a biological agent) patients with moderately to severely active ulcerative rectocolitis.

Methods: Data from a previous network meta-analysis (NMA) in the treatment of bio-exposed patients with moderately to severely active ulcerative rectocolitis was used. The analysis involved three therapies approved in Italy for the treatment of moderately to severely active ulcerative rectocolitis: upadacitinib (UPA), ustekinumab (UST) and vedolizumab (VDZ). According to the NMA results, the analysis was conducted considering two different timepoints: induction and maintenance. The pharmacoeconomic comparison between advanced therapies was carried out to estimate the respective cost for the NNT (Number Needed to Treat) compared to placebo using the clinical response (CRes) for the induction and clinical remission (CRem) and endoscopic improvement (EI) for the maintenance. Only the ex-factory price of each advanced therapy was considered. The cost per NNT was adopted as a cost-effectiveness indicator.

Results: Independently of the timepoint considered (induction or maintenance) and the clinical (CRem and CRes) or endoscopic endpoint (EI) evaluated, UPA had always the lower cost per NNT than UST and VDZ. For example, considering the induction and the CRes, the cost per NNT for upadacitinib (45 mg) was € 7,862.07 compared to € 30,459.38 for ustekinumab (6 mg/kg) and to € 67,868.00 for vedolizumab.

Conclusion: Upadacitinib is a cost-effective therapeutic option compared to ustekinumab and vedolizumab in the treatment of bio-exposed patients with moderately to severely active ulcerative rectocolitis.

Cost per NNT for upadacitinib in the treatment of patients with moderate-severe atopic dermatitis in Italy

Andrea Chiricozzi — 2024-02-16

Background: Targeted systemic therapies, including abrocitinib, baricitinib, dupilumab, tralokinumab and upadacitinib, are new treatments for moderate to severe atopic dermatitis (AD). We evaluated the efficacy and the costs of these targeted systemic therapies in the treatment of adult patients with moderate to severe AD.

Methods: The clinical efficacy was assessed considering the results of a previous network meta-analysis (NMA). The analysis involved five therapies approved in Italy for the treatment of moderate to severe AD: abrocitinib (ABR), baricitinib (BAR), dupilumab (DUP), tralokinumab (TRA) and upadacitinib (UPA). According to the NMA, the cost of the treatment was based on the number of administrations dispensed at 16 weeks and the clinical efficacy was measured by the number needed to treat (NNT) compared to placebo using the improvement ≥ 75% (EASI-75) or ≥ 90 (EASI-90) from baseline of the eczema area and severity index (EASI). Only the ex-factory price of the targeted systemic therapies was considered. The cost per NNT was adopted as a cost-effectiveness indicator.

Results: At 16 weeks, the cost per NNT based on EASI-75 was lower for UPA 15 mg (€ 6,384.00) compared to BAR 4 mg (€ 11,619.73) and 2 mg (€ 14,524.66), ABR 100 mg (€ 16,265.22), DUP 300 mg (€ 16,115.04) and TRA 300 mg (€ 31,710.24). UPA 15 (€ 8,512.00) also showed the lower cost per NNT based on EASI-90 at 16 weeks compared to BAR 4 mg (€ 14,788.75) and 2 mg (€ 20,862.70), ABR 100 mg (€ 25,922.69), DUP 300 mg (€ 25,992.00) and TRA 300 mg (€ 41,067.36).

Conclusions: The findings show that upadacitinib is the most cost-effective option (cost per NNT) for the treatment of moderate to severe atopic dermatitis.

Clinical and economic burden of peristomal skin complications: Activity Based Costing analysis

Agostino Fortunato — 2024-01-23

Introduction: An ostomy is a procedure in which an opening is made in the abdominal wall to establish a communication between the intestinal or urinary system and the external environment. Peristomal skin complications pose a constant challenge for the majority of individuals with a stoma, as they represent the most common postoperative complication. The aim of this study was to develop an economic evaluation model for assessing the costs associated with peristomal skin complications.

Methods: In order to identify these costs, a survey was conducted in collaboration with the Coloplast Ostomy Forum group with the aim of mapping and documenting the timelines and all activities in the management of these complications. The data obtained from the survey were subsequently analyzed using the Activity Based Costing methodology.

Results: The results of this analysis clearly indicate that the expenditure for initial visits is higher compared to subsequent ones, and that severe peristomal skin complications impose a greater economic burden than less severe complications. Specifically, the average total cost for managing severe peristomal skin complications amounts to € 104.6.

Conclusion: This kind of analysis could provide support to decision-makers in dealing with a more accurate estimate of costs related to healthcare processes, aiming to implement rates able to “cover” the overall cost of certain healthcare activities. Specifically, there is currently no specific rate aimed at defining the value associated with the care and management of this type of complication, so this study confirms that this is an economic challenge that the National Health Service must address.

Italian healthcare resource consumption for patients on hemodialysis treated for chronic kidney disease-associated pruritus (CKD-aP)

Silvia Calabria — 2024-01-15

Background: Chronic kidney disease-associated pruritus (CKD-aP) affects patients on hemodialysis. This study identified hemodialysis patients presumably affected or not affected by CKD-aP and integrated healthcare costs, from the perspective of the Italian administrative healthcare data.

Methods: Through cross-linkage of Italian administrative healthcare data collected between 2015 and 2017 (accrual period) in the database of Fondazione ReS (Ricerca e Salute), patients undergoing in-hospital/outpatient hemodialysis were selected. Cohorts with and without CKD-aP were created based on the presence/absence of CKD-aP-related treatment (according to common clinical practice and guidelines) supplies and assessed in terms of CKD-aP-related treatments and mean healthcare costs per capita paid by the Italian National Health Service (INHS).

Results: Of 1,239 people on hemodialysis for ≥2 years, CKD-aP affected 218 patients. Patients with CKD-aP were older and with more comorbidities. During the follow-up year, on average, the INHS spent €37,065 per case, €31,286 per control and € 35,988 per non-CKD-aP subject. High-efficiency dialytic therapies performed to people on hemodialysis with CKD-aP largely weighed on the overall mean annual cost.

Conclusions: This real-world study identified patients on chronic hemodialysis potentially treated for CKD-aP. Interestingly, high-efficiency dialysis seems the most frequent and expensive choice for the treatment of CKD-aP. The discovery of appropriate and effective treatments for this condition might offer cost offsets.

A pharmacoeconomic analysis from Italian guidelines for the management of prolactinomas

Michele Basile — 2024-01-09

Background: Prolactinoma, the most common pituitary adenoma, is usually treated with dopamine agonist (DA) therapy like cabergoline. Surgery is second-line therapy, and radiotherapy is used if surgical treatment fails or in relapsing macroprolactinoma.

Objective: This study aimed to provide economic evidence for the management of prolactinoma in Italy, using a cost-of-illness and cost-utility analysis that considered various treatment options, including cabergoline, bromocriptine, temozolomide, radiation therapy, and surgical strategies.

Methods: The researchers conducted a systematic literature review for each research question on scientific databases and surveyed a panel of experts for each therapeutic procedure’s specific drivers that contributed to its total cost.

Results: The average cost of the first year of treatment was €2,558.91 and €3,287.40 for subjects with microprolactinoma and macroprolactinoma, respectively. Follow-up costs from the second to the fifth year after initial treatment were €798.13 and €1,084.59 per year in both groups. Cabergoline had an adequate cost-utility profile, with an incremental cost-effectiveness ratio (ICER) of €3,201.15 compared to bromocriptine, based on a willingness-to-pay of €40,000 per quality-adjusted life year (QALY) in the reference economy. Endoscopic surgery was more cost-effective than cabergoline, with an ICER of €44,846.64. Considering a willingness-to-pay of €40,000/QALY, the baseline findings show cabergoline to have high cost utility and endoscopic surgery just a tad above that.

Conclusions: Due to the favorable cost-utility profile and safety of surgical treatment, pituitary surgery should be considered more frequently as the initial therapeutic approach. This management choice could lead to better outcomes and an appropriate allocation of healthcare resources.