Use of a maturity model for facilitating the introduction of CAR T-cell therapy—Results of the START CAR-T project

Introduction: Chimeric antigen receptor (CAR) T-cell therapies are novel immunotherapies for the treatment of hematologic malignancies. They are administered in specialized centers by a multidisciplinary team and require the careful coordination of all steps involved in manufacturing and using cellular therapies. The Maturity Model (MM) is a tool developed and used for assessing the effectiveness of a variety of activities. In healthcare, it may assist clinicians in the gradual improvement of patient management with CAR T-cell therapy and other complex treatments. Methods: The START CAR-T project was initiated to investigate the potential of a MM in the setting of CAR T-cell therapy. Four Italian clinics participated in the creation of a dedicated MM. Following the development and test of this MM, its validity and generalizability were further tested with a questionnaire submitted to 18 Italian centers. Results: The START CAR-T MM assessed the maturity level of clinical sites, with a focus on organization, process, and digital support. For each area, the model defined four maturity steps, and indicated the actions required to evolve from a basic to an advanced status. The application of the MM to 18 clinical sites provided a description of the maturity level of Italian centers with regard to the introduction of CAR T-cell therapy. Conclusion: The START CAR-T MM appears to be a useful and widely applicable tool. It may help centers optimize many aspects of CAR T-cell therapy and improve patient access to this novel treatment option.

Cost-utility analysis of evolocumab in patients with ASCVD in Italy

Objective: The aim of this work was to evaluate the cost-effectiveness of evolocumab in addition to standard statin therapy with or without ezetimibe in the treatment of patients with clinically evident atherosclerotic cardiovascular disease (ASCVD) with levels of LDL-C above 100 mg/dL. Method: A theoretical cohort of patients was forecast by a Markov model that includes 11 health states for a lifetime horizon. In the base-case, the standard therapy was characterized by statins with or without ezetimibe. Two sub-populations have been considered, Recent MI (Myocardial Infarction in the last year) and Multiple events (population with multiple MI). The results were also presented for a subset of the Multiple events populations consisting of patients who have experienced a myocardial infarction (MI) in the last year. Results: For the Recent MI and Multiple events populations, ICER values of € 39,547 and € 35,744 respectively were estimated. The value of ICER was lower for the Multiple events with MI < 1 year population (€ 29,949). Considering statins with ezetimibe as standard therapy, ICER values were found to be equal to € 39,781, € 35,986 and € 30,190 respectively for the populations Recent MI, Multiple events and Multiple events with MI < 1 year. Conclusions: The estimated ICER values for the Recent MI, Multiple events and Multiple events populations with MI < 1 year were below the cost-effectiveness threshold of € 40,000, suggesting therefore how the treatment with evolocumab in addition to the standard therapy can be a cost-effective treatment both compared to standard therapy with statins and standard therapy with statins + ezetimibe.

The budgetary impact of alemtuzumab in multiple sclerosis in Quito, Ecuador. Payer’s perspective

Introduction: Multiple sclerosis is a neurological condition that causes disabilities and is most common in young adults. It imposes high financial costs affecting the quality of life of patients, families, and society. It is critical to measure the budgetary impact of new technologies to treat this disease. Objective: The aim of the article is to estimate the budgetary impact of introducing alemtuzumab as an escalation therapy in patients diagnosed with Recurrent Remitting Multiple Sclerosis and treated in Quito, Ecuador. Materials and methods: A cohort of 85 patients receiving treatment with disease-modifying therapies was used, within a 5-year timeframe, between 2021 and 2025. The baseline scenario, including the percentages of administration of the different drugs, is compared with the alternative scenario, including alemtuzumab. The cost assessment included only direct medical resources. To obtain local resources for management of the disease, a neurologist and clinical expert who treats most of the patients in Quito was consulted. Results: Considering a cohort of 85 patients with active Recurrent Remitting Multiple Sclerosis, the average global budget impact in 5 years would be USD 10,603,230.00 in the base case and USD 9,995,817.00 in the alemtuzumab scenario. Conclusion: The inclusion of alemtuzumab as escalation therapy represents budgetary savings over the next 5 years (2021-2025).

Real-world data: how they can help to improve quality of care

The current COVID pandemic crisis made it even clearer that the solutions to several questions that public health must face require the access to good quality data. Several issues of the value and potential of health data and the current critical issues that hinder access are discussed in this paper. In particular, the paper (i) focuses on “real-world data” definition; (ii) proposes a review of the real-world data availability in our country; (iii) discusses its potential, with particular focus on the possibility of improving knowledge on the quality of care provided by the health system; (iv) emphasizes that the availability of data alone is not sufficient to increase our knowledge, underlining the need that innovative analysis methods (e.g., artificial intelligence techniques) must be framed in the paradigm of clinical research; and (v) addresses some ethical issues related to their use. The proposal is to realize an alliance between organizations interested in promoting research aimed at collecting scientifically solid evidence to support the clinical governance of public health.

New drug pricing criteria in Italy: considerations and proposals to support value and innovation

The definition of criteria and processes for the submission of price and reimbursement requests (P&R) of a drug in Italy cannot be separated from the definition of an overall “Pharmaceutical Policy” that includes, in an organic vision: (i) the governance related to the research, marketing and monitoring of drugs in the Italian market; (ii) the availability of drugs on the national territory as an element included in the essential levels of care (LEA) and the related conditions in terms of timing and equity of access between different regions, as well as towards other European countries; (iii) the assessment criteria used. The decree published in the Italian Official Journal in the summer of 2020, which defines the new criteria for the regulation of P&R of medicines in Italy, focuses on the final part of the process, i.e. the price negotiation. It would be necessary to frame this last step within a broader and more organic structure of drug policies aimed at: 1. optimising healthcare funding by encouraging competition between healthcare technologies; 2. reducing assessment time by simplifying processes; 3. improving early access to drugs for unmet need; 4. increasing the quality of P&R dossiers by improving interaction with the companies; 5. encouraging innovative agreements and complementary elements to the price; 6. encouraging the reproducibility of assessment methodologies in a value-based pricing system; 7. considering cost-benefit analyses as tools for the definition of price and conditions of reimbursability; 8. creating a place for discussion on drug policies.

Cost per responder for risankizumab vs secukinumab in patients with moderate-to-severe plaque psoriasis in Italy

Purpose: The objective of this analysis was to compare the cost per responder between risankizumab and secukinumab among patients with moderate-to-severe plaque psoriasis in Italy. Methods: The clinical efficacy was assessed based on IMMerge study of published efficacy data as measured by Psoriasis Area and Severity Index response (PASI 90 and PASI 100) for risankizumab and secukinumab. The treatment cost was based on the number of administrations dispensed in the first (induction plus maintenance period) and the second (maintenance period only) year of treatment and the ex-factory price of each treatment. The cost per responder was adopted as a cost-effectiveness indicator. Results: Independently of the PASI response (PASI 90 and PASI 100) used and the year of treatment considered, the cost per responder was consistently lower for risankizumab compared to secukinumab in all clinical measures. For example, considering the first-year costs and PASI 100, the cost per responder for risankizumab was € 24,506.83 compared to € 38,000.00 for secukinumab. The differences in the cost per responder between risankizumab and secukinumab increased when higher PASI response levels were considered. Conclusion: This economic evaluation suggested that the cost per responder is consistently lower for risankizumab compared to secukinumab from the perspective of the Italian National Health Service in the treatment of moderate-to-severe plaque psoriasis.

Price and reimbursement for orphan medicines and managed entry agreements: does Italy need a framework?

This article illustrates a consensus opinion of an expert panel on the need and usefulness of a framework for price and reimbursement (P&R) process and managed entry agreements (MEAs) for orphan medicines in Italy. This opinion was gathered in three rounds: an introductory document was sent to the panel and discussed during a recorded online meeting. A second document was sent to the panel for their review. In the third step the final document was validated. Members of the expert panel are the authors of the article. The panel agreed that Italy does not need a specific value framework for orphan medicines, driving the P&R process. Rather, a more structured value framework for all medicines tailored to the specific drugs can be useful. For orphan drugs, the panel advocated for a multidisciplinary approach and the contribution of different stakeholders to value assessment, and acknowledged the importance of addressing, more than for other drugs, unmet needs, equity issues and societal value. The panel raised the need of increasing the importance of patient-reported outcomes. Experts, acknowledging the growing criticisms in implementation of outcome-based agreements in Italy, expressed their position against their abandonment in favour of discounts only and supported orphan medicines as natural candidates for these agreements. Finally, the panel made some recommendations on the appraisal process for orphan medicines, including an early discussion on the uncertainty of the evidence generated and the adoption of a structured approach to identify the agreement, which better responds to the uncertainty.

Cost-effectiveness and budget impact analysis for high dose quadrivalent influenza vaccine in the Italian elderly population

Introduction. Influenza is a widespread acute respiratory disease and represents a serious Public Health problem, both from the NHS and society perspectives. The High Dose quadrivalent influenza vaccine (QIV HD) is a flu vaccine containing 4 times the antigens of a Standard Dose vaccine, resulting in demonstrated superior protection in the population aged 65 years and over. Methods. The analysis has been conducted from the perspective of the NHS. The CEA focuses on the comparison between QIV HD and the QIV SD vaccine. The BIM aims to estimate the potential economic impact for the National Health Service (NHS) resulting from the use of QIV HD in clinical practice in subjects aged 65 or over, when considering its introduction in combination with currently used vaccines, QIV SD and adjuvanted TIV. Results. In a scenario which considers hospitalizations possibly related to influenza, so including cardio-respiratory events, a dominant cost-effectiveness profile emerges in the comparison with QIV SD. In terms of budget impact, overall savings obtained by comparing the two scenarios regarding hospitalizations are equal to 92,766,429 € over the three years’ time horizon considered in the analysis. Conclusions. Nowadays, also considering the state of emergency due to the spread of the SARS-CoV-2 virus, it is crucial to implement innovative health technologies that improve the efficiency and sustainability of the health system. Also, it is essential to protect the elderly population, helping to avoid overload and healthcare systems disruption due to the many COVID-19 hospitalizations.

Budget Impact Analysis of prolonged-release buprenorphine depot-formulation for the management of patients affected by opioid use disorder

Background: Opioid use disorder (OUD) is a disorder associated with significant rate of morbidity and mortality. Frequent clinic attendance for supervised consumption of sublingual buprenorphine is common. Prolonged-release buprenorphine (PRB) allows a management based on weekly or monthly subcutaneous injections, thus limiting the burdens of clinic attendance and the risks associated with sublingual formulations. Objective: To determine the price level of PRB that allows to obtain a neutral impact from the point of view of the economic resources absorbed, in comparison with the alternatives currently available in the Italian context for the management of patients suffering from OUD. Methods: The analysis assumes a daily PRB cost of €8.526 (neutral cost). The analysis aims to determine the economic impact associated with the introduction of PRB in the Italian context for the management of OUD patients. Results are expressed in terms of differential resourced absorbed in the alternative scenarios. A one-way sensitivity analysis was also carried out to test the robustness of the results. Results: The introduction of PRB implies an increase in the drug acquisition costs over the 5-year time horizon of €19.563.019,13: such costs are fully compensated by the other cost driver considered in the analysis (drug tests provided, health professionals’ time destined to the provision of the treatment, indirect costs, for savings equal to €6.167.026,94, €9.106.824,67 and €4.289.167,53 respectively) demonstrating its effectiveness in particular by an organizational point of view. Lower price levels for PRB would imply significant savings for the SSN. Conclusions: PRB resulted to be associated to a lower level of resources’ absorption in the Italian sector as compared with the available alternatives thus allowing to re-allocate health founds to other fields of the care sector ensuring greater safety for patients and a decreased misuse and diversion rate.

Place in therapy of innovative drugs in multiple myeloma in 2021 and 2023 according to an expert panel Delphi consensus

Introduction: The objective of this study was to understand the potential use of single agents and drug combinations in multiple myeloma (MM) across treatment lines in the years 2021 and 2023. Methods: The method used was Delphi Panel Method survey, administered to European Myeloma Network (EMN) Italy Working Group centres. Future treatments were identified assessing all available web-based information sources, including therapies (single drugs or combinations) with strong evidence of efficacy, likely to be on the Italian market in 2021 and 2023. Participants were asked to report on the likelihood of prescription for MM therapies, across treatment lines. Results: Across the 15 centres taking part in the survey, about 890 patients per year are forecasted to receive a new diagnosis of MM. In 2021, the Panel forecasted 66% of 1L-TE (transplant eligible) patients will be treated with bortezomib-thalidomide-dexamethasone (VTD) and 32% of patients with daratumumab-bortezomib-thalidomide-dexamethasone (DVTd), with a substantial decrease of VTD (15%) and a marked increase of DVTd (81%) forecasted for 2023. The 2L and 3L R(lenalidomide)-based combination treatments are expected to drop and will likely be substituted by a steep increase in P(pomalidomide)-based regimes (from 7% to 23%). On the contrary, in 3L treatment, all combination therapies (with the exception of IsaPd – isatuximab-pomalidomide-dexamethasone) are expected to lose market share in favour of the most recent new therapies. Conclusions: Expert Panel agrees that many different new drugs and combinations will be used in MM, with different mechanisms of action, both at diagnosis and in subsequent phases of the disease, with a corresponding decline of the drugs currently used.