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Innovation is increasingly important in the delivery of efficient healthcare; however, the pathways through which medical innovation reach clinical practice are fraught with uncertainty. Further scientific investigation and technological development are normal in medical innovation even when drugs, diagnostics or medical procedures are already adopted. Diffusion studies rarely admit such possibilities as a fundamental element of their conceptual frameworks. This paper explores the diffusion process of an antiretroviral drug (Abacavir) and the introduction of its companion pharmacogenetic test into clinical practice in Italy. This is a landmark case of translational medicine where the principles of pharmacogenetics made an important - applied - contribution to medical innovation shifting the focus away from the diffusion of a complete technology (the drug) towards that of a dynamic technology (Abacavir + developing companion diagnostics). We adopt the historical method to analyse the sequence of events. Key findings show that the diffusion process of a dynamic technology does not fit in the widely accepted S-shaped model for a complete technology. The diffusion phase presents complex interactions amongst the stakeholders involved, each operating on the basis of their own competences within the environment and the regulatory system; the analysis of the diffusion process should proceed through the correct identification of the dynamic technology – the therapy – and cannot be de-coupled from scientific discovery and technological development. [ABSTRACT FROM AUTHOR]

Aims: Using a database from two pharmaceutical companies that managed several compassionate use programs in the last few years in Italy, we have previously analyzed the data by the number of patients and centers in each region and province, showing that the use of compassionate drugs is largely diffused in the country, in a manner directly related to the size of population of each region. In the present study we used the same database to expand the analysis to single-center level, aiming to test the hypothesis whether, despite a good diffusion of compassionate drug uses in each region, the majority of them concentrates within a relatively low number of centers., Methods: Data from different programs were grouped per center, and the centers were ordered per the number of compassionate uses dispensed, and per region. Two cutoff levels, at 75% and 90%, were drawn to look at the number of centers accounting for such percentages of compassionate uses in each region., Results: Out of 343 centers throughout Italy, 93 and 156 centers (i.e., 27.11% and 45.48% of the total) account for about 75% and 90% of all compassionate drugs dispensed in Italy. In 6 regions out of 20 (Valle d'Aosta, Liguria, Umbria, Lazio, Molise and Campania) the centers accounting for 75% of all compassionate drugs dispensed are located in a single town. Forty and 20 out of the 93 centers dispensing 75% of all compassionate drugs are academic hospitals and research hospitals (Istituti di Ricovero e Cura a Carattere Scientifico, IRCCS), respectively., Conclusions: In this study we have demonstrated that, in spite of widespread diffusion of compassionate drug uses in all Italian regions, their management is restricted to a relatively low number of dispensing centers in each region.

Aims: Compassionate drugs are provided to patients with a specific disease and no further treatment option, most frequently via Early (or Expanded) Access Programs. In Italy, it often occurs that compassionate uses concern medicines whose price has not been negotiated yet (and therefore unavailable on the market), although their use has been approved in Europe. Thus, compassionate drug uses turn out to be a way to expedite the access to new innovative drugs with demonstrated efficacy. This study aims to investigate how widespread is the use of compassionate drugs throughout the Country., Methods: We analyzed data from 20 early access programs implemented by 2 pharmaceutical companies in the last few years. Data were analyzed by the number of patients and centers in each Region and province, and a correlation was established between patients and centers in each Region and the resident population. A further analysis was carried out with the same criteria on the subpopulation of oncology patients, including more than 80% of total study population., Results: In our sample, 7529 patients received compassionate drug treatments in 348 centers throughout Italy. A significant correlation exists between the resident population in each Region and the number of requesting centers (r2=0.877) and patients treated (r2=0.844) in the Region. Taking the value of the linear regression slope as the expected one, certain Regions show a better "performance", in terms of more patients treated than expected, namely Umbria, Emilia-Romagna, Lazio, Lombardy, Tuscany, Liguria and Friuli Venezia-Giulia., Conclusions: In this study we showed that the use of compassionate drugs in Italy is diffused in a manner closely related to the population of each Region. A number of Regions - mostly but not exclusively from the South and Island areas - show a performance below the expectations, in terms of patients treated.

Despite several attempts to provide a definite pattern regarding the effects of personality traits on performance in higher education, the debate over the nature of the relationship is far from being conclusive. The use of different subject pools and sample sizes, as well as the use of identification strategies that either do not adequately account for selection bias or are unable to establish causality between measures of academic performance and noncognitive skills, are possible sources of heterogeneity. This paper investigates the impact of the Big Five traits, as measured before the beginning of the academic year, on the grade point average achieved in the first year after the enrolment, taking advantage of a unique and large dataset from a cohort of Italian students in all undergraduate programs containing detailed information on student and parental characteristics. Relying on a robust strategy to credibly satisfy the conditional independence assumption, we find that higher levels of conscientiousness and openness to experience positively affect student score., Competing Interests: The authors have declared that no competing interests exist.

Objective: Compassionate Drug Use (CDU) allows patients with a specific disease and no further treatment option to access unauthorized treatments. In this study, we analyzed the requests of CDU approved by the Ethics Committee of Fondazione Policlinico Gemelli in the period January 1, 2018-June 30, 2021. We also estimated the economic impact of CUs., Materials and Methods: CDU requests were analyzed by year, by frequency and by regulatory status of the medicines requested. If an ex-factory price was available at the cutoff date of June 30, 2021, we estimated what would have been the costs for the National Health System (NHS) if the price was already negotiated at the time of CDU request., Results: In the study period, 463 CDU requests were processed by the Ethics Committee. The number of requests increase linearly from 45 in 2018 to an estimated number of 260 in 2021. The requests included 68 medicines or combinations of medicines; 16 products out of 68 accounted for 75% of all requests. For 7 of these 16 highly requested treatments, accounting for 110 requests out of 463, it was possible to estimate the costs of therapies according to their ex-factory prices. If these products were to be purchased by the NHS, the estimated cost was € 5.472.225., Conclusions: The access to unauthorized drugs through CDUs is undergoing a huge increase in the last few years. Such increase meets the ethical need to provide patients with the most recent, often innovative, therapeutic options.

Objective: The adalimumab originator Humira® introduced a new citrate-free formulation in 2016, before the patent expiry that occurred in the European Union in October 2018. Some of the adalimumab biosimilars that were subsequently marketed are citrate-free, while others are not. Since citrate as an excipient is associated with pain at the injection site, recent anecdotical reporting in Italy raised the issue of possible prescription biases related to the differences in formulation existing among the various adalimumab products. In this study, we analyzed the data obtained from the 'Rete Nazionale di Farmacovigilanza' (Pharmacovigilance National Network) to investigate whether, and to what extent, the differences in the formulation of the various adalimumab versions had an impact on the rate of injection site reactions reported in Italy in the period 2016-2019., Materials and Methods: A search was conducted based on 3 search criteria: (1) time frame; (2) suspected drugs, and (3) adverse reaction type. Reports classified in the System Organ Class "Administration site conditions" were analyzed by year, product, and type of adverse event (whether including or not 'pain'). Data were reported both as absolute numbers, as well as signaling rates, considering the consumption data expressed as defined daily doses (DDD)., Results: We found that: (1) The change in Humira® formulation introduced in august 2016 was followed by a decrease in the reports of injection site reactions (from 45 in 2016 to 12, 12 and 8 in 2017, 2018, and 2019, respectively); (2) after the introduction of biosimilars during 2018, in 2019 a marked shift in reporting toward biosimilars was observed (52 out of 60; 87%)., Conclusions: While the decrease in Humira® reports is consistent with the improved tolerability of the new formulation, the huge increase in biosimilar reporting may be only in part explained by the differences in formulation and cannot be accounted for by a parallel increase in exposure, since 58.3% of total DDDs provided in 2019 were still attributed to Humira®.

Background: Statins are among the most commonly prescribed drugs worldwide in the prevention of cardiovascular diseases and their effectiveness is largely acknowledged. The consumption of statins increased four-fold during the 2000-2010 decade in Italy and national and regional control policies were developed. Restrictions to reimbursement were fixed at the national level, whereas co-payment was introduced in some, but not all, regions. The aim of the present study is to assess the impact of such policies on the consumption of statins in Italy between 2001-2007 among outpatients., Methods: The statin use was measured in terms of defined daily doses per 1,000 inhabitants per day (DDD/1000 inh. day) from May 2001 to December 2007. The study was conducted in 17 out of 21 regions, nine of which had implemented a co-payment policy. Time trends in consumption before and after the introduction of co-payment policies and reimbursement criteria were examined using segmented regression analysis of interrupted time-series, adjusting for seasonal components., Results: The consumption of statins increased by 22.9 DDD/1000 inh. day in May 2001 to 54.7 DDD/1000 inh. day in December 2007. On average, there was a 1.7% increase in statin use each month before the national guideline changed while the increase was about 0.5% afterwards. The revision of the reimbursement criteria was associated with a significant decrease in level (coefficient = -2.80, 95% CI -3.70 to -1.90 p-value <0.001) and trend (coefficient = -0.33, 95% CI -0.37 to -0.29 p-value <0.001). The introduction of co-payment was associated with a significant change in trend of consumption so that the overall use of the drug increased by 0.04 (95% CI 0.02 to 0.07, p-value < 0.001) DDD/1000 inh. day per month in the post-intervention period, but there was no evidence of a change in level of consumption (p-value = 0.163)., Conclusions: Consumption of statins in Italy increased almost three-fold during the study period. The restriction to reimbursement Interventions was associated with an immediate drop and a decrease in trend of statin use, while the regional copayment was associated with a small increase in trend of statin use.

Purpose: The continuous growth of antidepressant consumption and expenditure, especially for selective serotonin reuptake inhibitors (SSRIs), has led to the adoption of several policy measures directed toward cost control in Western countries. In Italy, copayment policies have been heterogeneously introduced at a regional level as part of a strategy designed to reduce drug consumption. The aim of our study was to evaluate whether regional copayment policies have affected trends in the consumption of and expenditure for SSRIs from 2001 to 2007., Methods: The consumption of SSRIs was measured in terms of defined daily doses per 1,000 inhabitants (DDD/1000) per day from May 2001 to December 2007. Time trends in consumption and expenditure before and after the introduction of copayment policies were examined using segmented regression analysis of interrupted time-series, adjusting for seasonal components. The study was conducted for 17 regions, nine of which had implemented a copayment policy., Results: The overall consumption of SSRIs in Italy increased during the study period, from a monthly consumption of 12.85 DDD/1000 per day in May 2001 to 23.40 DDD/1000 per day in December 2007. The average monthly increase in SSRI use was 0.82 % in regions with a copayment policy versus 0.77 % in regions without a copayment policy (P = 0.329). According to the multivariable analysis, copayment was associated with a 1 % reduction in the monthly growth rate of SSRI consumption (P  = 0.01). The impact of copayment on expenditure was statistically significant (P  < 0.005) on both the level and the trend, even though the estimate of the effect was negligible., Conclusions: The implementation of copayment policies in Italy affected both the use and expenditure of SSRIs between 2001 and 2007 to only to a minor extent.