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Pharmacovigilance in no profit clinical research. Requirements and challenges

Celeste Cagnazzo — 2024-08-01

The goals of Pharmacovigilance (PV) include early detection of new adverse reactions, broadening information on known reactions, identifying risk factors, comparing drug safety profiles, and effectively communicating safety information to healthcare professionals. In non-profit clinical research, PV activities often face challenges due to limited resources and training. An exploratory survey by the Italian Data Manager Group in 2022 highlighted critical issues in non-profit clinical trials, such as the lack of multidisciplinary support and insufficient training in PV. To strengthen PV in non-profit studies, continuous professional development and adequate resources are essential. Ensuring the presence of dedicated, well-trained professionals and promoting the use of updated tools and processes can significantly improve the management of PV activities, ultimately safeguarding patient health and maintaining high-quality research standards.

Innovation in the management of the breast cancer patient pathway: from correct identification to target therapies. Perspectives, opportunities and insights

Vincenzo Adamo — 2024-06-14

Considering the current and future therapeutic options that are or will be available in the adjuvant treatment of breast cancer, this document reports on the insights from two multi-regional expert meetings aimed at investigating possible problems of access to the treatment pathway involving the BRCA (BReast CAncer) test.

The experts stated that the update of the AIOM guidelines (diagnostic and therapeutic innovations) will require a correction of clinicians’ behaviors and a partial reorganization of the current Integrated Care Pathways (ICPs).

From this point of view, the update of the AIOM GLs could supply to Regions and, above all, to all cancer networks a valid rationale for starting a process of harmonization of ICPs aimed at guaranteeing the rapid access to treatments by improving the quality of the service provided by the National Health Service (SSN).

To ensure to breast cancer patients a rapid access to the latest approved treatments, experts believe that it will be necessary to update the access pathway to genetic tests. This could lead to an increase in the use of genetic tests, creating one of the main organizational and economic challenge that regions and cancer networks will have to face.

Follow-up of breast cancer: why is it necessary to start a Consensus in 2024?

Stefania Gori — 2024-02-23

In Italy, breast cancer is the most frequently diagnosed cancer in women, with 55,900 new cases in 2023 (over 90% in the early stages). Due to the screening, early diagnosis and adjuvant treatment, these patients have a 5-years survival rate of 87% after the diagnosis.

There are 834,154 women in Italy with a previous diagnosis of breast cancer: most of these women require a follow-up.

The AIOM, ESMO and ASCO Guidelines recommend for early breast cancer (EBC) a clinical follow-up with only physical examination (and eliciting of symptoms) and an annual X-ray mammography, on the basis of the results of two randomized trials published in 1994 that showed no benefit in overall survival with intensive follow-up.

However, an Italian survey reported the application by 80% of oncologists of an intensive follow-up based on the individual patient’s risk of recurrence. In fact, the oncologists believe that an early diagnosis of locoregional or distant recurrence may allow an early start of very effective therapies.

In this lack of up-to-date scientific data, many questions about follow-up remain unanswered and the few ongoing studies will provide results in several years.

Non-compliance with guideline recommendations leads to increased costs for the healthcare system. Furthermore, management varies widely from centre to centre with regard to guideline recommendations, resulting in inequalities between patients. For these reasons, the follow-up of breast cancer should be reconsidered.

In the absence of recent scientific evidence, a multidisciplinary group of breast cancer experts has initiated a Consensus on the follow-up of EBC according to the mini-Delphi methodology. The project will be completed by the end of 2024.

After 100 years of life, is there an insulin crisis? The problem of insulin costs and the opportunity of biosimilar insulins

Domenico Cucinotta — 2023-02-09

Considering other pharmacological approaches, also in the field of insulin therapy, the use of biosimilar drugs instead of originators could help to reduce the worldwide increasing costs of its related disease, that is, diabetes mellitus (DM), and the subsequent risk of insulin underutilization. Available evidences clearly demonstrate that biosimilar efficacy and safety are superimposable to those of the originator insulin with lower expenditure; despite this, however, their underutilization persists both in Eastern and in Western countries. Specific, regional activities are needed in order to improve biosimilar insulin use and to contribute to a substantial reduction of the costs of DM.

Enhancing regulatory affairs in the market placing of new medical devices: how LLMs like ChatGPT may support and simplify processes

Fabio Di Bello — 2024-09-27

The market placing of a medical device in compliance with the requirements of EU Regulation 2017/745 (Medical Device Regulation) demands advanced regulatory expertise and a high level of detail and depth, inevitably leading to significant human and time resources. In an era where Artificial Intelligence (AI) is already present in various aspects of daily life, the potential and opportunity to use AI tools in the scientific field, such as the CE marking process of medical devices, are being explored. This process consists of several phases and related activities, some of which have been chosen as significant examples to evaluate how and to what extent AI can add value in achieving their compliance.

The article presents the overall results in terms of performance and reliability derived from generative AI tests using Large Language Models, such as ChatGPT, applied to some of the processes necessary for the market placing of a medical device. The method used focuses on the relationship between prompt quality and output quality, demonstrating the importance of prompt engineering in using these tools effectively alongside regulatory processes. It also emphasizes the need for end-users to have education, training, and understanding of the mechanisms of generative AI to optimize performance.

First experiences of using the Dexcom ONE CGM system: results from a national survey on the perception of early adopters

Andrea Boaretto — 2024-09-23

Introduction: The availability of increasingly accurate and high-performing Continuous Glucose Monitoring (CGM) systems today allows for the adoption of selection criteria based not only on clinical profiles but also on the preferences of people with diabetes.

Methods: The “Dexcom ONE Experience” study aimed to investigate the initial user experiences with the Dexcom ONE CGM system in the real lives of people with diabetes undergoing insulin therapy, specifically early adopters (i.e., patients who first in Italy adopted Dexcom ONE CGM who have used the device for at least 30 days). Empirical evidence was collected, focusing primarily on usability, satisfaction, and impact on quality of life (QoL) of the system, through an online survey. All survey participants were insulin-treated patients, as indicated by CGM device recommendations.

Results: Analysis was conducted on 300 completed surveys. 93% of respondents consider the device useful for diabetes management; 91% find it helps in more effectively managing therapy, while 88% report an improvement in health. 86% find it easy to learn how to use, and 93% plan to continue using it in the coming months. 74% believe the system to be highly reliable. The most recognized and utilized functions are data visibility on smartphones/receivers and glycaemic trend visibility. 70% of respondents express being “very or extremely satisfied” with the Dexcom ONE device experience (scoring 4/5), and 90% note a “positive or extremely positive” impact on their QoL from using the device.

Conclusions: In conclusion, usability and satisfaction levels have proven to be high among early adopters of the Dexcom ONE CGM system.

Training needs and educational sources of European musculoskeletal specialists: learning outcomes of the IBSA International Academy – MSK Modules

Stefano Guerrasio — 2024-07-01

Background: Building a meaningful training program for musculoskeletal (MSK) specialists is a major undertaking to improve the clinicians’ skills and ultimately patients’ outcome. The purpose of this study was to gather direct information from attendants of a training program called IBSA International Academy – MSK Modules on the perceived benefit of such initiative.

Methods: The IBSA International Academy has been developed during 2021 by IBSA’s Global Medical Affairs department with the involvement and support of an international faculty composed by experts in the field that has become the scientific Board of the Academy. More than 100 specialists from several European countries attended one or more modules focused on ultrasound (US) and US-guided infiltration and were asked to answer (a) a short survey just after the modules were completed and (b) a more detailed survey several weeks after their return to daily practice.

Results: A total of 114 specialists from 12 European countries attended the academy. The post-module evaluation form was completed by 94 (82.4%) and the follow-up survey by 30 (26.3%) participants. Response rate was highest for specialists from Nordic countries (50.0%) and lowest from Balkan countries (11.1%). The overall feedback of the participants to the academy was overwhelmingly positive both immediately and medium–long term after return to daily practice. About 57% of responders indicated mastering US and 30% indicated a better understanding of the anatomy as a key learning outcome of the academy. The added value of networking between peers and of direct contact with the experts in the faculty was mentioned by 77% and 53% respectively.

Budget impact analysis of natalizumab biosimilar on pharmaceutical expenditure for the treatment of relapsing-remitting multiple sclerosis in Italy

Roberto Bergamaschi — 2024-06-17

Background: The availability of high-efficacy disease-modifying therapy (DMT), including natalizumab, improved treatment efficacy in adults with highly-active relapsing-remitting multiple sclerosis (RRMS). Natalizumab patent protection has expired, and the natalizumab biosimilar (Tyruko®) has been recently reimbursed by AIFA. As the price of natalizumab biosimilar is expected to be lower as compared with natalizumab originator’s price, a budget impact analysis was conducted to assess the economic impact associated to the introduction of natalizumab biosimilar for patients with highly-active RRMS.

Methods: A budget impact model was developed, considering the INHS perspective and a 5-years time horizon. The number of patients treated with natalizumab was estimated based on historical natalizumab consumption data, disease prevalence rates and natalizumab market share. The budget impact population was divided into prevalent and incident patients. The model assumes that some patients in treatment with natalizumab originator will switch to natalizumab biosimilar and that some naïve patients will directly start treatment with natalizumab biosimilar. The ex-factory price of natalizumab originator (intravenous and subcutaneous) and biosimilar (intravenous) and the corresponding administration costs were included. All assumptions were validated by expert opinion.

Results: Eligible population was estimated at 7,552, 7,779, 8,090, 8,494 and 8,834 in years 1, 2, 3, 4 and 5 respectively. The introduction of natalizumab biosimilar, considering a progressive increase in market share from 9.6% (year 1) to 40.5% (year 5), would provide an overall savings (5-years time horizon) over € 47 million to the INHS. The scenario analysis highlights that the lower treatment cost of biosimilar natalizumab compared to originator natalizumab would offset the higher cost associated with intravenous versus subcutaneous administration.

Conclusion: Considering the results of this budget impact analysis, it is realistic to expect that the presence of biosimilar natalizumab will contribute to the sustainability of public pharmaceutical expenditure.

Using the Nephrology Referral Form in Italian primary care to improve the care pathway of patients with anemia or other complications related to chronic kidney disease: survey findings

Giuseppe Pompilio — 2024-05-15

Introduction: Anemia is a potentially reversible condition in early chronic kidney disease (CKD) that requires timely intervention. General practitioners (GPs) play a crucial role in recognizing CKD. A new Nephrology Referral Form (NRF) was developed and tested in the Italian setting.

Methods: This mixed-methods survey, conducted between 2021 and 2022, introduced the NRF through focus group discussions involving a scientific committee. The NRF was tested in a 6-month trial involving 24 GPs each from Lazio and Puglia regions. GPs provided feedback on the use of the NRF in clinical practice through a questionnaire sent via Microsoft Form. The data were analyzed descriptively.

Results: After 6 months, 41.67% of the GPs were using the NRF at least once a week. Diabetes mellitus and hypertension were common triggers for NRF assessments. GPs overwhelmingly agreed (96%) on the NRF’s utility in identifying CKD cases, with 92% citing its effectiveness in diagnosing well-defined cases. The NRF facilitated specialist referrals, with 83% of GPs reporting increased referrals compared to the prior 6 months. Feedback underscored the NRF’s positive impact, suggesting improvements such as additional referral centers, regional/national networks, enhanced GP training, and increased collaboration.

Conclusion: GPs regularly used the NRF to identify and diagnose cases of CKD, streamlining the referral process and increasing referrals to specialists. Feedback emphasized the NRF’s positive impact and highlighted its potential as a valuable tool for enhancing early CKD detection, interventions, and fostering multidisciplinary management in primary care for better patient outcomes.

Economic evaluation of two therapeutic sequences in the first-line treatment of moderate to severe active ulcerative rectocolitis in Italy

Patrizio Armeni — 2024-03-02

Background: Vedolizumab (VDZ) and infliximab are used to treat moderate to severe ulcerative colitis (UC). The choice of the drug to use at first-line is often based on a combination of clinical and economic factors. The cost of treatment pathway is rarely considered. Therefore, this cost-consequence analysis (CCA) investigated the overall costs of treatment pathway for vedolizumab followed by infliximab (VDZ → IFX) compared to infliximab followed by vedolizumab (IFX → VDZ).

Methods: We used a published cost-consequence model (CCM), based on a targeted literature search reporting the time-on-treatment data for vedolizumab or infliximab in UC in first and second-line of treatment. CCM time horizon was defined by the length of treatment sequences. Considering the Italian hospital perspective, the CCA evaluated the biologic drugs acquisition costs, drug administration costs, hospitalization costs, switch costs, colectomy costs and third-line treatment costs. Third-line options included colectomy, tofacitinib, ustekinumab or dose escalation of second-line biologic.

Results: Over the 5.2-year time horizon (duration of the longer VDZ → IFX pathway), the mean cost per patient of VDZ → IFX pathway was slightly lower than the mean cost per patient of IFX → VDZ pathway (€ 86,339 vs 89,636). The CCM predicted that using VDZ as first-line treatment delayed the time to costly third-line therapies compared to first-line using IFX (VDZ-first-line median time-on-treatment 3.6-years and IFX-second-line 1.6-years; IFX-first-line 1.4-years and VDZ-second-line 2.3-years and third-line 1.5-years).

Conclusion: The CCA showed that a biologic treatment pathway that begins with first-line vedolizumab is not more expensive than one beginning with first-line infliximab and delayed the time to costly third-line.

An Activity-Based Costing model applied to the management process of patients with migraine at IRCCS Mondino Foundation

Luca Degli Esposti — 2024-07-17

Background and aim: The ageing of the general population, with the increase in chronic diseases, poses the need for using technological innovation to face the growing healthcare needs. The present analysis applied the Activity-Based Costing tool in migraine patients followed at the IRCCS Mondino of Pavia to formalize and quantify the costs of the whole patient’s management process and to estimate the overall economic burden of migraine from the perspective of the National Health Service (NHS).

Methods: A two-stage analysis was conducted. The first stage aimed at drawing patient’s pathway, defining all the possible activities and actors involved in the healthcare delivery and treatment for migraine at the IRCCS during year 2022. The second phase was the development of a model to estimate the costs of the entire process by pricing the individual activities.

Results: The described model yielded an estimated total annual cost for the overall management of migraine of € 1,222,392, corresponding to a direct cost for a therapy of approximately 6 months per single patient of € 814. The most impactive items on the estimated annual expenditures were hospitalizations, followed by diagnostic examinations after follow-up visits and drugs dispensed by Hospital Pharmacy for home-administration (monoclonal antibodies).

Conclusions: This analysis allowed detailing the single activities and resources used in migraine patient’s pathway and then estimating the direct costs sustained by the NHS. The model could be translated to other diseases for optimizing the diagnostic/therapeutic and economic management of assisted patients and improving healthcare resource allocation.

Environmental sustainability in ophthalmology

Vittorio Capuano — 2024-02-21

Fournier’s gangrene wounds successfully healed with High pbserum enzymes: a case report

Eugenia Paris — 2024-02-26

Fournier’s gangrene is an aggressive form of infective necrotizing fasciitis in the perianal and genital area. In this article we discuss the case of a 75-year-old male patient diagnosed with Fournier’s gangrene with the entire perianal region affected. Surgical washings were performed and debridement with multiple flaps were required for reconstruction. Complications in the suture wounds, cavities, and a seroma were observed after 5 weeks, and they were treated with dressings. Treatment with High pbserum recombinant enzymes was initiated after 3 weeks, to accelerate the closure of the wounds. The granulation tissue was irrigated by drip irrigation once every 3 weeks, ensuring good tissue impregnation. We observed that the epithelialization of the affected areas was achieved after the first week, and in 1 month, most of the wounds healed properly without signs of infection. High pbserum is an enzyme cocktail, composed of higher collagenase concentration, lipase, and liase. This study shows how High pbserum improves and accelerates wound healing in a patient with Fournier’s gangrene. Further investigations are needed to conclude treatment recommendations.

A case of exaggerated placental site treated with hysteroscopy

Stefano Calzolari — 2024-01-11

Exaggerated placental site (EPS) is a benign lesion that can occur in association with term pregnancy, ectopic pregnancy, molar pregnancy, intrauterine fetal death or miscarriage. The characteristics of EPS are described in several case reports and have been reported after major surgery such as hysterectomy. We describe the hysteroscopic characteristic of EPS associated with a spontaneous miscarriage. Hysteroscopic inspection of the uterine cavity revealed copious tissue with increased vascularization without signs of invasion. No cleavage was visualized between material and myometrium could be established during the resection procedure. 40 days after hysteroscopy the patient became pregnant. The pregnancy proceeded without complications and during the cesarean section no residual placenta-related abnormal site appearance was noted on inspection of the uterine wall. The hysteroscopic treatment could be considered feasible to preserve future fertility in young women in cases of suspect non-malignant trophoblastic disease.

Vitreoretinal interface disorders

Marco Pastore — 2024-04-12

This article is designed to bridge the knowledge gap for Doctors, shedding light on retinal pathologies that have long dwelled in the shadows of ultra-specialization. It delves into the identification and management of atypical conditions affecting the vitreomacular interface, encompassing disorders like vitreomacular traction, epiretinal membrane, full thickness macular holes and lamellar holes. Optical coherence tomography emerges as a crucial diagnostic tool, significantly enhancing our capacity to recognize abnormalities at the vitreoretinal junction, offering clinical insights unattainable through conventional ophthalmic methods. While vitrectomy remains the predominant choice for treating these conditions, alternative approaches are being explored.