Federico Villa

Pharmaceutical industry investments in Italy must be supported with a reform process that promotes simplifications to generate an attractive ecosystem that can enhance innovation. Key actions include facilitating the start-up of clinical trials, promoting public-private partnerships to support technology transfer, integrating data infrastructures to overcome the logic of silos, expanding programs for prevention and early identification of diseases, simultaneous reimbursement for therapy and… Visualizza altro

Pharmaceutical industry investments in Italy must be supported with a reform process that promotes simplifications to generate an attractive ecosystem that can enhance innovation. Key actions include facilitating the start-up of clinical trials, promoting public-private partnerships to support technology transfer, integrating data infrastructures to overcome the logic of silos, expanding programs for prevention and early identification of diseases, simultaneous reimbursement for therapy and diagnostic testing, and launching a structural program for early access to therapies.

The total contribution of the sector in the last 10 years to the Italian economy was € 315 bn. Looking at employment (67 thousand people employed in the sector in 2020), it is possible to estimate about 280 thousand jobs activated in Italy just in 2020.

An Altems study quantified a leverage effect of 2.77 in terms of benefits to the Italian NHS from direct investment in clinical research, which means that for every € 1 invested by companies in clinical trials, € 1.77 of additional savings were generated for the NHS. Applying the multiplier on R&D investments of the entire pharmaceutical sector in 2020 (€ 1.6 bn), we could estimate approximately € 4.4 bn in benefits for the NHS. In addition to these benefits there are the noneconomic benefits of clinical research, including early access for patients to innovative therapies, resulting in improved clinical outcomes and quality of life for patients and caregivers in general. Meno dettagli

Introduction: It is well acknowledged that the price of orphan drugs is normally higher than that resulting from the value-based pricing. A correlation between the cost of therapy for orphan drugs and the epidemiology (prevalence and incidence) of the related rare disease can be hypothesized.
Methods: This analysis includes all approved orphan drugs by European Medicines Agency whose reimbursement was granted for the first therapeutic indication in the years 2014–2019 in Italy. Regression… Visualizza altro

Introduction: It is well acknowledged that the price of orphan drugs is normally higher than that resulting from the value-based pricing. A correlation between the cost of therapy for orphan drugs and the epidemiology (prevalence and incidence) of the related rare disease can be hypothesized.
Methods: This analysis includes all approved orphan drugs by European Medicines Agency whose reimbursement was granted for the first therapeutic indication in the years 2014–2019 in Italy. Regression and correlation analyses were performed to analyze the possible correlations between the logarithm of the annual therapy cost and the epidemiology of the rare diseases, between orphan drugs consumption and epidemiology of related rare disease and between therapy cost and the consumption.
Results: The regression analysis between the annual cost of therapy estimated on the published ex-factory price and the prevalence showed a slightly decreasing, not statistically significant, trend (coefficient: −0.10, p-value: 0.41). The results were similar when using the price resulting from the application of Managed Entry Agreements (coefficient: −0.11, p-value: 0.40). The regression analysis between sales volume and prevalence showed a positive slope without an acceptable level of significance (p-value: 0.04). The correlation analysis between the therapy cost and the sales volume highlighted again an absence of significant association, similarly if considering only ATC L orphan drugs, or the incidence.
Discussion: The definition of the price of an orphan drug seems not to depend on the rarity of the disease, and sales volumes do not correlate with the epidemiology of the rare disease and with the annual cost of therapy. Meno dettagli

Introduzione. L’accesso anticipato ai farmaci avviene in un contesto di incertezza informativa maggiore rispetto al momento della negoziazione di prezzo e rimborso. Scopo del contributo è analizzare la possibile applicazione dei managed entry agreement (MEA) negli early access program (EAP) in Italia. Metodo. La discussione è avvenuta con Focus Group, cui hanno partecipato clinici ed esperti provenienti da soggetti regolatori, servizi farmaceutici regionali e aziendali, imprese farmaceutiche… Visualizza altro

Introduzione. L’accesso anticipato ai farmaci avviene in un contesto di incertezza informativa maggiore rispetto al momento della negoziazione di prezzo e rimborso. Scopo del contributo è analizzare la possibile applicazione dei managed entry agreement (MEA) negli early access program (EAP) in Italia. Metodo. La discussione è avvenuta con Focus Group, cui hanno partecipato clinici ed esperti provenienti da soggetti regolatori, servizi farmaceutici regionali e aziendali, imprese farmaceutiche, associazioni di tutela dei diritti dei cittadini. Risultati. Il Focus Group ha sottolineato l’esigenza di discutere il tema dei MEA applicati agli EAP in un contesto più generale di revisione critica degli EAP, con una Lista 648 in cui sono presenti in prevalenza farmaci “maturi” e indicazioni per le quali solo in alcuni casi viene richiesta successivamente la negoziazione di prezzo e rimborso e un Fondo 5% caratterizzato da richieste complesse e imprevedibilità dei tempi di rimborso. Conclusioni. A partire dalla discussione su EAP e MEA, il Focus Group ha prodotto raccomandazioni rappresentate da un percorso normativo ad hoc per la riforma degli EAP, da un accesso precoce che riguardi categorie specifiche di farmaci, da MEA a supporto dell’accesso precoce di natura outcome-based e population-based, integrati poi nei processi decisionali di prezzo e rimborso. Meno dettagli

Background and aim:
Evidence on determinants of prices for orphan medicines is scarce and not available for Italy. The aim of this paper is to provide an evidence on variables affecting the annual treatment cost of orphan drugs in Italy, testing the hypothesis of a negative correlation with the dimension of the target population and a positive correlation with the added therapeutic value of the drug and the quality of the evidence of pivotal studies.

Methods:
Drugs with a European… Visualizza altro

Background and aim:
Evidence on determinants of prices for orphan medicines is scarce and not available for Italy. The aim of this paper is to provide an evidence on variables affecting the annual treatment cost of orphan drugs in Italy, testing the hypothesis of a negative correlation with the dimension of the target population and a positive correlation with the added therapeutic value of the drug and the quality of the evidence of pivotal studies.

Methods:
Drugs with a European orphan designation reimbursed in Italy in the last 6 years (2014–2019) were considered. Univariate, cluster analysis and multiple regression models were used to investigate the correlation between the annual treatment cost and, as explanatory variables, the dimension of the target population, the existence of Randomized Clinical Trials as a proxy of the quality of the pivotal studies, the added therapeutic value.

Results:
In the univariate analysis prevalence and added therapeutic value, as expected, have a negative and positive correlation with cost respectively. The correlation with RCT is not significant. In the multivariate model, coefficients for prevalence and added value are confirmed but for the latter are not significant anymore. We also found, through an interaction analysis, that the existence of an RCT has a positive impact on annual treatment cost when the target population is very small.

Conclusions:
Our results suggest that value arguments and sustainability (dimension of the target population and its impact on budget impact) issues are considered for orphan drugs pricing: the role played by sustainability is systematically supported by our results. A more transparent and reproducible price negotiation process for orphan drugs is needed in Italy. This paper has contributed to highlight the implicit drivers of this process. Meno dettagli

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… Visualizza altro

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 Euro-pean 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 health-care 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. Meno dettagli

Background: In Italy both the consumption of antibiotics and the prevalence of bacterial resistance are higher than in other European countries. In 2017, the first National Action Plan on Antimicrobial Resistance (PNCAR) was adopted in Italy. In response to the PNCAR two National Reports on Antibiotics’ use in the human setting have been published. The article’s aim is to describe the pattern of antibiotics consumption in the community setting in Italy from 2013 to 2018. Methods: In order to… Visualizza altro

Background: In Italy both the consumption of antibiotics and the prevalence of bacterial resistance are higher than in other European countries. In 2017, the first National Action Plan on Antimicrobial Resistance (PNCAR) was adopted in Italy. In response to the PNCAR two National Reports on Antibiotics’ use in the human setting have been published. The article’s aim is to describe the pattern of antibiotics consumption in the community setting in Italy from 2013 to 2018. Methods: In order to analyse the consumption for reimbursed antibiotics dispensed by community pharmacies different data sources were used. Consumption was measured in terms of Defined Daily Dose (DDD), prescriptions or prevalence of use. Results: In 2018, the consumption of antibiotics in Italy amounted to 16.1 DDD per 1,000 inhabitants per day. The rates of consumption by geographical area were: 12.7 DDD in the North, 16.9 in the Centre and 20.4 in the South. The use was greater in the extreme age groups than in the population aged from 20 to 64 years. The consumption was higher in winter season with high peaks in the incidence of flu syndromes. In the paediatric population, a utilization rate of 1,010 prescriptions per 1,000 children, with a prevalence of use of 40.8%, was found. Conclusion: The study provides useful information on geographical variability of antibiotics’ use in Italy to guide decision makers in the introduction of tailored interventions, as suggested by PNCAR, aimed at promoting a more rational use of antibiotics for humans and reducing antimicrobial resistance. Meno dettagli

L’Italia è stata utilizzata come caso studio per indagare i determinanti della differenza tra la proposta di prezzo presentata dall’industria e il prezzo finale negoziato di un nuovo farmaco (∆P). I dati sono stati raccolti attraverso i sistemi informativi utilizzati dall’Agenzia Italiana del Farmaco (AIFA) e il periodo di tempo considerato è quello compreso tra il 2013 e il 2017. I fattori che influenzano il ∆P sono stati esaminati attraverso un’analisi di regressione. Quarantaquattro farmaci… Visualizza altro

L’Italia è stata utilizzata come caso studio per indagare i determinanti della differenza tra la proposta di prezzo presentata dall’industria e il prezzo finale negoziato di un nuovo farmaco (∆P). I dati sono stati raccolti attraverso i sistemi informativi utilizzati dall’Agenzia Italiana del Farmaco (AIFA) e il periodo di tempo considerato è quello compreso tra il 2013 e il 2017. I fattori che influenzano il ∆P sono stati esaminati attraverso un’analisi di regressione. Quarantaquattro farmaci orfani e 89 altre nuove entità hanno ottenuto la rimborsabilità nel periodo considerato. A seguito del processo di negoziazione, i prezzi proposti dai titolari di autorizzazione all’immissione in commercio (MAH) sono stati abbassati mediamente del 25,1% per i farmaci orfani e del 28,6% per gli altri prodotti. La riduzione di prezzo è stata maggiore per i farmaci innovativi (-32,2%). I fattori statisticamente significativi associati a una maggiore riduzione di prezzo sono stati: 1) l’implementazione di un registro di monitoraggio; 2) la negoziazione di un Managed Entry Agreement financial-based (MEA FB); 3) una popolazione target superiore a 20.000 pazienti; 4) una spesa prevista del Servizio Sanitario Nazionale superiore a 200 milioni di euro. L’influenza di alcune variabili sul ∆P era prevedibile (per es., per i farmaci con un impatto sul budget più elevato e una popolazione target più ampia), per altre meno (per es., una significativa riduzione di prezzo per i farmaci “innovativi”). L’attuazione degli accordi FB, che in molti casi sono confidenziali, è stato uno dei fattori determinanti con un maggiore impatto sul ∆P. Meno dettagli

Tale Rassegna, che raccoglie i principali dati presentati nel Rapporto Nazionale 2018 sull’uso degli antibiotici in Italia dell'Agenzia Italiana del Farmaco (AIFA), ha l’obiettivo di identificare le aree di potenziale inappropriatezza d’uso degli antibiotici.

In 2018 the overall Italian pharmaceutical expenditure (public and private) was 29.1 billion euro, almost the same as the previous year (-0.1%). The public outpatient expenditure amounted to 12.4 billion euro, a decrease of 4% compared to 2017, while the inpatient public expenditure grew markedly. The total private expenditure, including the cost-sharing and pharmaceuticals directly paid by patients increased by 3.8% compared to 2017 (amounting to 8.3 billion euro). In 2018 the total… Visualizza altro

In 2018 the overall Italian pharmaceutical expenditure (public and private) was 29.1 billion euro, almost the same as the previous year (-0.1%). The public outpatient expenditure amounted to 12.4 billion euro, a decrease of 4% compared to 2017, while the inpatient public expenditure grew markedly. The total private expenditure, including the cost-sharing and pharmaceuticals directly paid by patients increased by 3.8% compared to 2017 (amounting to 8.3 billion euro). In 2018 the total consumption, including INHS and private purchase, was 1,571.5 DDDs per every 1,000 inhabitants per day. Meno dettagli

Objectives: The aim of this paper is to investigate the determinants of the difference between the price proposal submitted by the industry and the final negotiated price. We used Italy as a case-study. Methods: Data were gathered through the information system used by Italian Medicines Agency. The time-frame for this analysis is 2013–2017. Factors influencing the delta price were analyzed through a regression analysis. Results: 44 orphan drugs and 89 new other molecular entities obtained… Visualizza altro

Objectives: The aim of this paper is to investigate the determinants of the difference between the price proposal submitted by the industry and the final negotiated price. We used Italy as a case-study. Methods: Data were gathered through the information system used by Italian Medicines Agency. The time-frame for this analysis is 2013–2017. Factors influencing the delta price were analyzed through a regression analysis. Results: 44 orphan drugs and 89 new other molecular entities obtained reimbursement in the last five years. Following the negotiation process, prices were lowered by 25.1% and 28.6% on average for orphan drugs and other molecules respectively. The price reduction was higher for innovative drugs (-32.2%). Statistically significant determinants associated to higher price reduction were: i) the implementation of a product specific monitoring registry, ii) the negotiation of a financial-based Managed Entry Agreement, iii) a target population larger than 20,000 patients, iv) an expected National Health Service expenditure larger than €200 million. Discussion: The impact of some variables on the delta price was predictable (e.g. for drugs with an expected higher budget impact and a larger population target), others were more surprising (e.g. a significant price reduction for “innovative” drugs). The implementation of financial-based agreements, which often rely on confidential arrangements, was one of the determinants with higher impact on price reduction. Meno dettagli

Given the extensive development of new molecules over the last 10 years, regulatory authorities (RAs) have been intensively working on evaluating how to identify and manage “innovative” drugs. The purpose of this article is to analyze whether RAs have procedures capable of ensuring access to innovative drug therapies and to understand what criteria RAs around the world (Europe, USA, Canada, Australia, and Japan) use to identify innovative drugs, comparing the different strategies and tools used… Visualizza altro

Given the extensive development of new molecules over the last 10 years, regulatory authorities (RAs) have been intensively working on evaluating how to identify and manage “innovative” drugs. The purpose of this article is to analyze whether RAs have procedures capable of ensuring access to innovative drug therapies and to understand what criteria RAs around the world (Europe, USA, Canada, Australia, and Japan) use to identify innovative drugs, comparing the different strategies and tools used to prioritize the assessment of the most promising drugs. All the RAs under review consistently use two elements to speed up drug access: (1) the handling (shortening) of approval times and the (2) management of the (limited) evidence available. No international RA utilizes any state-of-the-art method to evaluate the innovativeness of medicinal products. Harmonizing a definition and the criteria used to define pharmaceutical innovation would allow faster access to patients. Meno dettagli

EMA has adopted assessment systems and drug registration procedures to respond to the needs for rapid patient access to therapies, such as CMA and UEC. AIFA has introduced tools for governing prescriptive behaviour in order to promote appropriateness and correct use of drugs and to manage the uncertainty of financial impact, including MEAs. The MEAs are conditional access agreements to the market for new drugs aimed at managing the uncertainty on the clinical and economic effects of the drugs… Visualizza altro

EMA has adopted assessment systems and drug registration procedures to respond to the needs for rapid patient access to therapies, such as CMA and UEC. AIFA has introduced tools for governing prescriptive behaviour in order to promote appropriateness and correct use of drugs and to manage the uncertainty of financial impact, including MEAs. The MEAs are conditional access agreements to the market for new drugs aimed at managing the uncertainty on the clinical and economic effects of the drugs themselves. The aim of this study is to analyse, through the use of the information systems of the AIFA and the institutional website of the EMA, how the drugs authorised by EMA with CMA or UEC have been managed on the access side to the Italian NHS. This in order to understand how the uncertainty deriving from the authorisation processes was subsequently reflected on the reimbursement processes to be borne by the NHS. From the analyses carried out, it emerges that 64% of the drugs approved with CMA were admitted to reimbursement and 68% of those approved with the UEC procedure. Furthermore, it can be noted that approval with CMA is predictive for the application of a financial-based or outcome-based MEA (61%), with the application of a monitoring register, unlike the drugs approved UEC for which no conditional reimbursement arrangements have been applied at the patient level. Furthermore, by carrying out a comparative analysis of the time of access to market following negotiation, from the positive opinion of the CHMP to the decision published in the Official Italian Gazette, it emerged that the drugs approved by the UEC procedure take on average more time (897 days) to arrive at the price and reimbursement (P&R) compared to CMA drugs (636 days). Considering instead only the period from the request for P&R to the determination of P&R for the same group of drugs, the process seems to be on average faster for the drugs classified as UEC than for those with CMA (329 vs. 510 days) Meno dettagli

(...) Se da un lato la crescente consapevolezza della necessità di terapie per le malattie rare ha spinto sia gli Stati Uniti sia l’Unione Europea ad approvare delle legislazioni finalizzate a incentivare lo sviluppo di questi medicinali e ad accelerare le procedure di autorizzazione, dall’altro l’ingresso sempre maggiore di prodotti sul mercato per la cura di malattie rare ad alto costo, supportati da studi registrativi basati su popolazioni molto ristrette, pongono alcuni interrogativi… Visualizza altro

(...) Se da un lato la crescente consapevolezza della necessità di terapie per le malattie rare ha spinto sia gli Stati Uniti sia l’Unione Europea ad approvare delle legislazioni finalizzate a incentivare lo sviluppo di questi medicinali e ad accelerare le procedure di autorizzazione, dall’altro l’ingresso sempre maggiore di prodotti sul mercato per la cura di malattie rare ad alto costo, supportati da studi registrativi basati su popolazioni molto ristrette, pongono alcuni interrogativi riguardo alla sostenibilità futura. L’impegno
delle aziende a rendere etico il prezzo dei farmaci, unitamente alla capacità del servizio sanitario di trovare strumenti adatti a contenere la spesa, continuerà a consentire l’accesso a farmaci per malattie rare e ultra rare. Meno dettagli