innovation and drugs price and reimbursement a comparison between italy and the other major eu countries

This paper aims at investigating (i) differences and commonalities of drugs Price and Reimbursement (P&R) criteria between Italy and the other major EU countries and (ii) comparative advantages, pi..

Management of patients eligible for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors: economic impact and reform proposals:

Background: PCSK9 inhibitors are indicated for primary hypercholesterolemia (heterozygous familial and non-familial) and for homozygous familial hypercholesterolemia (only evolocumab). They are subject to a drug registry for patient eligibility and follow-up. Patient access to PCSK9 inhibitors is still very limited and varies across regions. Aim: This paper aimed to investigate the cost of the PCSK9-treated patient pathway and main barriers to patient access to medicines and to suggest some changes to this pathway. Methods: The research was conducted through a literature review and an expert panel, which was surveyed through a Delphi approach. The panel included seven clinicians and five pharmacists. Results: If patients are exempt from co-payment, the Italian National Health Service spends €169.70 and €276.93 per year to manage the PCSK9-treated patient pathway, depending on registry coverage (six or three treatment months, respectively). Non-exempt patients pay €176,43 and €271.53 (for six and three months of coverage, respectively) per year. The referral process and the length of the pre-PCSK9 treatment period were considered the main barriers to access. The panelists suggested that the pre-PCSK9 treatment period be shortened to three months; they recommended six months of registry coverage, thereby decreasing the costs compared to three months' coverage; and they advised that outpatient specialists also be authorized to manage the follow-up. These actions may reduce pathway costs and enhance awareness of the disease. Discussion: The study shows that the pathway of patients eligible for PCSK9 inhibitors can be improved. The surveyed experts integrated pathway-specific recommendations with broader advice to increase awareness on hypercholesterolemia in both citizens and general practitioners

Patients' associations and HTA for medicines: actual and future role in Italy

Introduction: This paper aims at investigating the role of Patients' Associations in drugs assessment and appraisal in Italy. Methods: Information were gathered through a mostly structured (forced ranking) questionnaire. The questionnaire, once validated, was administered to two national HTA organisations (AIFA and ISS) and Therapeutic Committees / Departments of five regions (Lombardy, Veneto, Emilia Romagna, Latium, Sicily). The average rank and the Kendall rank correlation coefficient were calculated where respondents were forced ranking. Results: The interactions with Patients' Associations are very different across HTA organisations, with only three respondents declaring a systematic relationship with these Associations and a focus on therapeutic targets more affected by new drugs launches. Patients' Associations are perceived more expert on the organisation of the Italian health care system and drugs reimbursement process than on technical issues (e.g. PROs – Patient Reported Outcomes). Respondents declared that fragmentation of relationships, with many associations involved, is the most important barrier to a systematic interaction with Patients' Associations and advocated for a stronger integration among them. Discussion: The interaction between HTA organisations and Patients' Associations is expected to increase in the future. To make this interaction more useful, Patients' Associations should improve their knowledge on drugs assessment techniques - mainly PRO - and enhance their awareness on budget issues for payers: the former could create a virtuous cycle that may drive HTA organisations paying more attention to PROs; the latter may help Patients' Associations and payers agreeing on actions aimed at making drugs more sustainable

A model for coupled electro-hydro-mechanical processes in fine grained soils accounting for gas generation and transport

A theoretical and numerical model is developed for the quantitative analysis of coupled processes taking place in active waste containment systems, such as electrokinetic barriers or fences, in which alow intensity DC current is circulated across the clay barrier to move polar and non-polar contaminants. A novel feature of the proposed approach is the allowance for the presence of air in the pore space. Under unsaturated conditions, all transport coefficients involved in the electrokinetic process are strongly dependent on the degree of saturation of pore liquid. In order to assess the predictive capability of the proposed theory and to appreciate the impact of gas production at the electrodes, a series of numerical simulations of simple onedimensional electrokinetic tests have been performed. The results of the simulations compare reasonably well with data obtained from laboratory experiments performed on an illitic clayey silt. The numerical results indicate that the impact of gas production at the electrodes can be significant, even in low-intensity and short-duration treatments

Second-generation antipsychotic drugs for patients with schizophrenia: systematic literature review and meta-analysis of metabolic and cardiovascular side effects

Background and Objectives: Second-Generation Antipsychotics (SGAs) for schizophrenia show different risk profiles, whose evidence has been evaluated through comparative reviews on RCTs and observational studies. Methods: We performed a systematic review and meta-analysis of weight gains, metabolic and cardiovascular side-effects of SGAs, relying on both RCTs and observational studies, by comparing variations between the start of treatment and the end of follow-up. The systematic review refers to papers published from June 2009 to November 2020. PRISMA criteria were followed. No restrictions on heterogeneity level have considered for meta-analysis. A test for the summary effect measure and heterogeneity (I2 metric) was used. Results: Seventy-nine papers were selected from 3,076 studies (61% RCTs, 39% observational studies). Olanzapine and risperidone reported the greatest weight gain and olanzapine the largest BMI increase. Paliperidone showed the highest increase in total cholesterol, but is the only drug reporting an increase in the HDL cholesterol. Quetiapine XR shows the highest decrease in fasting glucose. Lurasidone shows the lowest increase in body weight and a reduction in BMI and was also the only treatment reporting a decrease in total cholesterol and triglycerides. The highest increase in systolic and diastolic blood pressure was reported by quetiapine XR. Conclusions: Despite some limitations (differences in the mean dosages per patient and other side effects not included) this paper provides the first complete meta-analysis on SGAs in variations on metabolic risk profile between start of treatment and end of follow-up, with useful results for clinical practice and possibly for future economic evaluation studies

The assessment of new drugs for asthma and COPD: a Delphi study examining the perspectives of Italian payers and clinicians

Background: Asthma and chronic obstructive pulmonary disease (COPD) are disorders of the lungs characterized by airflow obstruction, inflammation and tissue remodeling. Management of patients with these diseases is complex and the improvement of diagnostic-therapeutic strategies represents a critical challenge for the healthcare system. In this context, investigating the criteria and information needed for an appropriate and effective evaluation of incoming treatment options is crucial to ensure that clinicians and policy-makers are provided with the best available evidence to make decisions aimed at improving patient outcomes. Therefore, the objective of this study was to investigate the degree of agreement among Health Technology Assessment (HTA) experts on issues crucial to the evaluation of new drugs for asthma and COPD and to appropriately manage the clinical pathway for patients. Method: This research was conducted using an e-Delphi technique organized in three subsequent rounds and involving a panel of ten experts (six regional and local payers and four clinicians). Panelists were asked to comment in written form on a set of statements, explaining qualitatively the extent to which they agreed or disagreed with the assertions. Statements were subsequently modified and resubmitted for assessment. Results: Panelists expressed their opinions during each round and, after round III, a consensus document was finalized. The degree of consensus was high among experts and concerned five main topics: (a) the need to address current unmet needs of patients with asthma or COPD, (b) the importance of further studies and real-life information in the evaluation of treatments, (c) existing evidence and evidence needed to assess drugs, (d) critical issues in obtaining a positive evaluation from regional and local authorities for new treatments to be included in regional formularies and to have an important place in therapeutic categories, and (e) the major obstacles to the appropriate administration of drugs and management of patients. Conclusion: The final document highlights that no proof of difference among drugs exists, that evidence on final endpoints (and particularly on mortality) should be strengthened and that actions regarding risk factors, appropriate diagnosis, patient staging and adherence to therapy are particularly important for a better clinical management

Corrigendum: The Economic Impact of a Switch From Prescription-Only to Non-prescription Drugs in Italy

The paper analyses the potential economic impact of switching drugs from prescription-only to over the counter status, using Italy as a case-study. The study assumes a societal perspective, investigating the effects of switches (and consequent delisting) on drugs spending, avoided visits by GPs (General Practitioners) and avoided time spent by patients for these visits. It overcomes the main pitfalls of previous studies, providing a rational for listing switchable products and applying both a static (no impact of switch on prices and volumes consumed) and a dynamic approach (impact on pricing policies and volumes depending on price-elasticity). Different scenarios were assumed including shorter/longer time spent for visits and inclusion/exclusion of the economic value of time of retiree patients. Results show that switching policy provides with societal savings ranging from 1 to 2.1 1 billion Euro. The economic impact on patients is less straightforward and depends on the scenarios used. If a longer time is spent on visits, the economic value of this time will compensate the cost of the switch to patients due to delisting. Despite the net economic benefit should be carefully interpreted, the results demonstrate how switching can contribute to the sustainability of the health care system in the middle-long run thanks to the more rational use of resources, combined with an increased awareness and responsibility of the involved stakeholders

The Economic Impact of a Switch From Prescription-Only to Non-prescription Drugs in Italy

The paper analyses the potential economic impact of switching drugs from prescription-only to over the counter status, using Italy as a case-study. The study assumes a societal perspective, investigating the effects of switches (and consequent delisting) on drugs spending, avoided visits by GPs (General Practitioners) and avoided time spent by patients for these visits. It overcomes the main pitfalls of previous studies, providing a rational for listing switchable products and applying both a static (no impact of switch on prices and volumes consumed) and a dynamic approach (impact on pricing policies and volumes depending on price-elasticity). Different scenarios were assumed including shorter/longer time spent for visits and inclusion/exclusion of the economic value of time of retiree patients. Results show that switching policy provides with societal savings ranging from 1 to 2.1 1 billion Euro. The economic impact on patients is less straightforward and depends on the scenarios used. If a longer time is spent on visits, the economic value of this time will compensate the cost of the switch to patients due to delisting. Despite the net economic benefit should be carefully interpreted, the results demonstrate how switching can contribute to the sustainability of the health care system in the middle-long run thanks to the more rational use of resources, combined with an increased awareness and responsibility of the involved stakeholders

The value of obinutuzumab for untreated advanced Follicular Lymphoma: an assessment based on Multicriteria Decision Analysis (MCDA)

Introduction: Multicriteria Decision Analysis (MCDA) provides a framework that enhances transparency and repeatability of decisions taken on a multicriteria basis. Objective: This analysis aims at assessing obinutuzumab compared to rituximab used as a first-line treatment for Follicular Lymphoma (FL) in the Italian health care system, using an MCDA approach. Materials and Methods: We used the EVIDEM V10 MCDA framework and a Delphi approach to scrutinize the views of a panel of physicians, payers and patients on value domains and their application to our research target. Results: All stakeholders attached medium-high scores to FL severity (patients at higher risk of relapsing), unmet needs, obinutuzumab clinical benefit and evidence quality, and lower scores to organizational impact and, except for payers, to costs. The comparative analysis highlighted positive scores for the domains "incremental efficacy" (2.6: range −5/+5) and "incremental patient benefit" (1.5: range −5/+5) of obinutuzumab compared to rituximab. A slight increase of severe adverse events (≥3) for obinutuzumab was estimated by the panellists. Obinutuzumab compared to rituximab received a neutral evaluation for costs and for organizational impact. Conclusion: This study reveals that MCDA could be a useful framework for evaluating a drug and it can be used to elicit the views of different stakeholder groups (as patients). The key criteria driving the value of obinutuzuma

From Indication-Based Pricing to Blended Approach: Evidence on the Price and Reimbursement Negotiation in Italy

BackgroundNew indications for existing medicines are increasing over time. In most countries, drug pricing and reimbursement conditions are renegotiated every time a new indication is approved. There is a growing interest in the price negotiation model for new indications, specifically comparing an indication-based versus blended approach. However, little evidence currently exists regarding the complexity of these negotiations and their impact on actual prices. Italy has recently transitioned from an indication-based approach to a blended price model. This study aims to measure the impact of price and reimbursement negotiation of new indications on discounts (i.e. actual prices) and on the negotiation duration, used as a proxy of its complexity.MethodsWe considered new indications approved through a European centralized procedure from January 2013 to March 2022 for which the price and reimbursement status was approved in Italy between January 2015 and March 2022, amounting to 52 new indications. Data on the timeframe of the Italian price and reimbursement process and its phases were obtained from publicly available sources. Discounts for the first indication and their subsequent increases for new indications were estimated by comparing ex-factory prices and tendered prices. To calculate p-values, we employed the Mann-Whitney test, and multiple regression models were utilized to examine correlations between negotiation time and the characteristics of the medicines.ResultsThe mean time to reimbursement was 603 days, in contrast to 583 days for the first launch. Price negotiation took longer for rare diseases, cancer drugs, and in case of therapies with minor added therapeutic value. On average, the additional discount (on top of discounts for prior indications) was 13%, significantly lower than the mean discount for the first indications approved (24.9%). The discounts increment was lower, but negotiation took longer if a Managed Entry Agreement accompanied the final agreement. Additionally, discounts have increased over the years.ConclusionThe negotiation for new indications takes longer than the first one, and provides, on average, an additional discount of 13%. While our findings bear the potential for significant policy implications, they necessitate prudent interpretation due to a limited number of observations. The increasing trend in additional discounts over time applied to all indications in recent negotiations, may suggest a descending trend of value for new indications and a shift from an indication-based pricing approach to a blended model. Otherwise, budget impact considerations might have outweighed a value-based approach in the recent negotiations. If so, two potential options for restoring a value-based approach are returning to an indication-based pricing or giving explicit and higher weight to value within a blended model