Healthcare Systems and Artificial Intelligence: Focus on Challenges and the International Regulatory Framework.

BACKGROUND: Nowadays, healthcare systems are coping with the challenge of countering the exponential growth of healthcare costs worldwide, to support sustainability and to guarantee access to treatment for all patients. METHODS: Artificial Intelligence (AI) is the technology able to perform human cognitive functions through the creation of algorithms. The value of AI in healthcare and its ability to address healthcare delivery issues has been a subject of discussion within the scientific community for several years. RESULTS: The aim of this work is to provide an overview of the primary uses of AI in the healthcare system, to discuss its desirable future uses while shedding light on the major issues related to implications within international regulatory processes. In this manuscript, it will be described the main applications of AI in various aspects of health care, from clinical studies to ethical implications, focusing on the international regulatory framework in countries in which AI is used, to discuss and compare strengthens and weaknesses. CONCLUSIONS: The challenges in regulatory processes to facilitate the integration of AI in healthcare are significant. However, overcoming them is essential to ensure that AI-based technologies are adopted safely and effectively.

The lack of head-to-head randomised trials and the consequences for patients and national health service: The case of non-small cell lung cancer.

INTRODUCTION: To introduce a drug to the market, it's not mandatory for it to be more effective and safer than the current treatment for the same condition. Consequently, head-to-head studies between the two best treatments for the same condition are not required, and this could result in a lack of information for patients, clinicians, and decision-makers. This study aims to evaluate the presence of head-to-head studies among the drugs used for the treatment of non-small cell lung cancer (NSCLC). METHODS: Taking into account the National Comprehensive Cancer Network (NCCN) guidelines updated to 2022, which list all available treatments for each NSCLC subtype, the search engine Pubmed and the platform clinicaltrials.gov were consulted to find all completed and ongoing head-to-head studies among various treatments for NSCLC. RESULTS: Among the anti-EGFR (epidermal growth factor receptor) drugs, 7 studies were found, with 6 completed and 5 registrational for drug commercialisation. No completed study to date has compared osimertinib and afatinib. For anti-ALK (anaplastic lymphoma kinase) drugs, 7 studies were found, with 5 completed. Alectinib, brigatinib, and lorlatinib have no completed comparison studies, but all were compared with crizotinib. Among various immunotherapy-based regimens, 5 studies were found, with only 1 completed. Therapeutic regimens based on pembrolizumab, atezolizumab, or the combination of nivolumab/ipilimumab have not been compared in studies published to date. CONCLUSION: There are few head-to-head studies comparing treatments for NSCLC; there are no such studies between the latest generation of drugs. Consequently, ambiguous areas exist due to the lack of comparative studies among the available evidence, preventing the clinician's choice of the most effective treatment and risking the patient receiving suboptimal therapy. Simultaneously, the price of the drug cannot be determined correctly, relying only on indirect evaluations from different trials. To dispel this uncertainty, it would be desirable to initiate a process that brings together the demands derived from clinical practice and clinical research to provide clinicians and patients with the best possible evidence.

Antidepressant deprescribing: State of the art and recommendations-A literature overview.

INTRODUCTION: In recent years, the consumption of antidepressants has arisen. However, deprescribing antidepressant therapy is very complicated. The aim of this study was to implement practical recommendations for the development of guidelines to be used for antidepressant deprescription in clinical practice. MATERIALS AND METHODS: The literature search has been conducted on March 13, 2023, using Scopus and PubMed databases. The following search string has been used: "antidepressants AND (deprescribing OR deprescription)". All studies reporting a deprescribing intervention for antidepressant medication, regardless of the study design, have been included. Studies that did not report antidepressant drug deprescription interventions and non-English-language papers have been excluded. RESULTS: From the literature search, a total of 230 articles have been extracted. Applying the exclusion criteria, 26 articles have been considered eligible. Most of the analyzed studies (16, 61%) have been carried out in the real world, 3 (11%) were RCTs, 5 (19%) were qualitative studies, in particular expert opinions, 1 (4%) was a literature review, and 1 (4%) was a post-trial observational follow-up of an RCT. In 8 out of 26 studies (31%), the analyzed antidepressants have been specified: 2 (8%) focused on anticholinergics, 2 (8%) on SSRIs, 3 (11%) on tricyclic antidepressants, and 1 (4%) on esketamine. Nineteen out of 26 studies (73%) did not stratify antidepressants by therapeutic class. The sample sizes analyzed in the studies ranged from a minimum of 4 patients to a maximum of 113,909, and 12 studies included geriatric age as an inclusion criterion. A patient's therapy review has been the main deprescribing intervention, and it has been identified in 14 (54%) articles. Interventions have been carried out by clinicians in 4 (15%) studies, general practitioners in 5 (19%) studies, nurses in 2 (8%) studies, pharmacists in 4 (15%) studies, multidisciplinary teams in 10 (38%) studies, and patients in 1 (4%) study. CONCLUSIONS: From the literature review, it emerged that there is no clear evidence useful to support clinicians in antidepressant deprescribing interventions.

Time to treatment discontinuation in first-line non-small cell lung carcinoma: an overview.

OBJECTIVE: Time To Discontinuation (TTD) is defined as the time from the start of treatment to the end of treatment, usually occurring due to loss of efficacy or occurrence of adverse events. It has become an important surrogate efficacy endpoint especially in real-world studies due to its correlation with endpoints such as Progression Free Survival (PFS). The aim of the study is to conduct a literature review of all studies reporting TTD in first-line therapy of Non-Small Cell Lung Cancer (NSCLC). METHODS: All articles that reported TTD for any first-line treatment of NSCLC as of 30 June 2022 were extracted from the PubMed search engine. From these articles, the drugs, study type, and TTD values were extracted. A descriptive analysis of the studies was made, dividing the TTD by subgroup according to the type of treatment (traditional chemotherapy, target therapy, immunotherapy) and study design (clinical trials, real world studies). RESULTS: Fifty-five studies were considered for the analysis, of which 12 were published in 2021; 28 were clinical trials and 27 were real-world studies. Thirty of the studies considered involved conventional chemotherapy and expressed TTD values from 1.4 to 4.5 months, 5 of the studies considered involved immunotherapy with TTD values from 2.1 to 7.4 months and 18 of the studies considered target therapy, with TTD values from 4 to 31 months. The clinical trials reported TTD values from 1.4 to 16 months and the real-world studies from 2 to 31 months. CONCLUSION: Studies reporting TTD are increasing, most notably real-world studies. Given the increasing importance of TTD as an efficacy endpoint, it becomes critical to measure and monitor it in various therapeutic settings such as NSCLC. This is the first study to review all TTD values of drugs used in first-line NSCLC.

Medication adherence reporting in pivotal clinical trials: overview of oral oncological drugs.

OBJECTIVES: To assess how and to what extent adherence to medication is reported in pivotal clinical trials of oral cancer drugs. METHODS: All drugs authorised by the European Medicines Agency from 1 January 2014 to 31 December 2019 were considered for analysis. For each pivotal trial we extracted the journal of publication, phase of the study, posology, mention of adherence within the main text of the published article or additional material and the terms in which the adherence was reported. RESULTS: Thirty drugs were included in the analysis from 56 clinical trials. Eleven articles (19.6%) contained a mention of medication adherence in the main document, 26 (46.4%) in the supplementary material and 19 (33.9%) did not contain any reference to adherence. Seven studies reported medication adherence between the results, expressed as number of patients discontinuing treatment for non-compliance and mean or median percentage. CONCLUSIONS: Medication adherence in pivotal clinical trials of oral oncological drugs is poorly represented. There should be a greater level of reporting in the results and it should be included among the minimum set of recommendations in reporting health research.

Available information about paediatric use of onco-haematological drugs authorized by EMA since 2016.

BACKGROUND: The treatment options available to children with cancer are limited. This is why for more than 10 years, the European Medicine Agency (EMA) has stated that all drugs to be marketed must be tested on the paediatric population in accordance with the Paediatric Investigation Plan (PIP). The objective of this study is to make a cross sectional analysis of the information related to the use of cancer drugs authorised on the European market in the paediatric population. METHOD: The European Public Assessment Reports and PIPs have been considered. The following data were extracted for onco-haematological drugs approved since 2016: paediatric indications, information about the paediatric population in the Summary of Product Characteristics (SmPC) and presence and characteristics of PIPs. A descriptive analysis of the characteristics of the drugs was made from the point of view of the paediatric population. RESULTS: Forty-eight drugs with onco-haematological indications have been authorised for marketing since 2016, 7 (15%) of these have paediatric indications. Two (4%) drugs have no paediatric indication but have information related to the paediatric population within SmPC. Forty-one (85%) drugs have no reference to the paediatric population in SmPC. Seventeen (35%) drugs out of 48 do not have PIPs and 11 have been granted a waiver to present the results of paediatric studies. The other 19 active ingredients have a total of 28 PIPs. CONCLUSION AND RELEVANCE: Most of the onco-haematological drugs approved by EMA since 2016 have neither paediatric indications nor mentions about paediatric use in SmPC. PIPs represent an opportunity, but demand for the paediatric population is still huge.

A multicentre study with real-world data of the use of palbociclib in the treatment of breast cancer: Treatment duration correlates with dose reductions.

OBJECTIVE: Palbociclib, a highly selective reversible CDK4-6 kinase inhibitor, is indicated in combination with an aromatase inhibitor or in combination with fulvestrant in women who had received prior endocrine treatment. Studies have demonstrated the efficacy of palbociclib in combination with fulvestrant in increasing progression-free survival in patients who relapsed or progressed on previous endocrine therapy, or in combination with aromatase inhibitor in patients who had not received previous treatments. We analysed the prescribing patterns of palbociclib in real practice correlating it with the evidence of treatment-related toxicity management and to time-to-treatment discontinuation and treatment adherence. METHODS: For the observational, retrospective study, data were collected from five Italian hospital centres that prescribed palbociclib between April 2017 and April 2020. Each centre provided data derived from an administrative database of adult patients treated with palbociclib for the two therapeutic indications.Treatment adherence was calculated using the proportion of days covered method while time-to-treatment discontinuation was defined as the difference between the first and last date treatment was administered plus the days ideally covered by the last date treatment was given. RESULTS: There were 375 patients enrolled during the study period, of whom 159 were treated with palbociclib and aromatase inhibitor and 216 were treated with palbociclib and fulvestrant. The time-to-treatment discontinuation was 8.9 months in the case of P + f (95% CI: 7.1-12.7) and 13.7 months in the case of P + ia (95% CI: 8.9-17.5). In both cohorts, treatments that received at least one dose reduction had a statistically higher time-to-treatment discontinuation than those without dose reduction (17.7 months vs. 9.2 and 16.6 vs. 7.4).The mean adherence in our study was 0.9 and remained high in treatments with one dose reduction (0.83) and this with two dose reductions (0.87). CONCLUSION: Based on these findings, it appears that the management of toxicities through reducing doses, as required by the Summary of Product Characteristics, results in a better outcome in terms of therapy duration, and therefore time to failure due to progression or toxicity.

Adherence, persistence and switching rates of apixaban, dabigatran and rivaroxaban in non-valvular atrial fibrillation: a multicentre real-life analysis at 3 years.

INTRODUCTION: Adherence to and persistence with long-term treatment with oral anticoagulants play a significant role in preventing adverse events and mortality in patients with cardiac conditions. The aim of this study was to evaluate the adherence, persistence and switching rate at 3 years in real-life patients with non-valvular atrial fibrillation receiving treatment with first-line new oral anticoagulants. METHODS: The study assessed all patients treated with drugs with the ATC codes B01AA, B01AE, B01AF and dispensed in pharmacies in the Lanciano-Vasto-Chieti and Pescara Local Health Units from 1 January 2011 to 30 September 2021. Adherence was calculated as the proportion of days covered; persistence was calculated as the difference in days between the start and end of treatment; and the switching rate was calculated as the difference in days between the start of treatment and the switch. RESULTS: A total of 4270 patients were analysed. The absolute adherence figure at 3 years was 0.85. The lowest adherence levels were found in patients treated with dabigatran with an absolute value of 0.72, while the highest levels were found in patients treated with rivaroxaban with an absolute value at 3 years of 0.88. The persistence curves at 3 years of treatment with dabigatran showed a statistically significant difference (p<0.0001) compared with those of rivaroxaban and apixaban. CONCLUSIONS: The data collected over a 3-year period showed that adherence and persistence levels and switch data were optimal and comparable in patients with non-valvular atrial fibrillation receiving treatment with either rivaroxaban or apixaban. In contrast, patients treated with dabigatran had worrying adherence and persistence levels.

The impact of COVID-19 on chronic therapies: the Pescara (ASL) local health authority experience in Italy.

INTRODUCTION: At this time in history fraught with restrictions and issues stemming from the COVID-19 pandemic, the care and management of chronic therapies is a major concern for society. The objective of the following study was to assess whether adherence and persistence in patients treated with hypoglycaemic drugs and statins during 2020 changed in comparison with pre-pandemic years. MATERIALS AND METHODS: A retrospective study was conducted, taking into account the drugs dispensed at pharmacies in the territory of the ASL (Local Health Authority) of Pescara from January 1, 2011 to December 2020 of all patients treated with ATC A10B (hypoglycaemic group) and ATC C10A (statin group). Adherence was calculated using the Proportion of days covered (PDC) method. Persistence to treatment was calculated as the difference in days between the start and end of therapy. RESULTS: A total of 12,030 patients treated with hypoglycaemic drugs and 19,699 with statins were analysed. Adherence data ranged from values of 0.79 and 0.75 in 2012 to 0.92 and 0.79 in 2020 for the hypoglycaemic group and statin group, respectively. Persistence curves stratified by year showed a statistically significant difference for both groups under analysis (p < .0001). CONCLUSIONS: The adherence figure did not change much, unlike the persistence figure. In fact, during 2020, the great impact that COVID-19 had on follow-up visits, on the availability of drugs, and on the difficulty of access to health facilities resulted in chronic patients abandoning therapy.

Randomized clinical trials and real life studies: Comparison of baseline characteristics of patients in oral target therapies for renal cell carcinoma.

INTRODUCTION: Pivotal Randomized Controlled Trials (RCTs) constitute scientific evidence in support of therapeutic choices when a drug is authorized in the market. In RCTs, patients are selected in a rigorous manner, in order to avoid bias that may influence efficacy assessments. Therefore, patients who take the drug in Real Life Studies (RLSs) are not the same as those participating in RCTs, which, in turn, leads to low data transferability from RCTs to RLS. The objective of this study was to evaluate the differences between RCTs and RLS, in terms of patient baseline characteristics. MATERIALS AND METHODS: Our study includes all oral target therapies for RCC (Renal Cell Carcinoma) marketed in Europe before March 31, 2019. For each treatment, we considered both RCTs and RLSs, the former gathered from Summary of Product Characteristics published on the European Medicine Agency (EMA) website, and the latter yielded by our search in relevant literature. For each drug considered, we then compared the baseline characteristics of patients included in the RCT samples with those of the samples included in the RLSs using the Chi-squared and Mann-Whitney tests. RESULTS: We considered six medicines, for a total of 9 pivotal RCTs and 31 RLSs. RCTs reported the same type of patient baseline characteristics, whereas RLSs are more varied in reporting. Some patient baseline characteristics (metastases, previous treatments, etc.) were significantly different between RCTs and RLs. Other characteristics, such as ECOG Performance Status, brain metastases, and comorbidities, liver and kidney failure, are comprised in exclusion criteria of RCTs, though are included in RLS.Discussion and Conclusion: While evaluating equal treatments for the same indications, RCTs and RLSs do not always assess patients with the same characteristics. It would be necessary to produce evidence from RLSs so as to have an idea of treatment effectiveness in patients groups that are not eligible or underrepresented in RCTs.

Adherence and persistence in the use of statins and ezetimibe over 8 years in a real-life study.

BACKGROUND: Adherence and persistence to treatment are crucial in statin therapy as they are synonymous with efficacy and quality of care. The aim of this study was the real-life assessment of adherence and persistence over eight years in treatment-naive patients receiving atorvastatin, lovastatin, simvastatin, pravastatin, ezetimibe. METHODS: Adherence to treatment was calculated using the 'proportion of days covered' method and persistence as the difference between the start and end of the therapy under study. RESULTS: Treatment adherence was consistently above 85% for all drugs under study in each year. Treatment persistence was shown to half halved already from the first year. CONCLUSION: Adherent patients had a higher persistence than non-adherent patients.

Drug utilisation pattern over 3 years in the real-world treatment of type II diabetes.

INTRODUCTION: Non-adherence to therapy is very common in patients with type II diabetes, leading to an increase in morbidity and mortality. The development of new oral therapies following metformin has increased the possibilities of treatment but little has been done in terms of improving medication adherence. The goal of the following study is to evaluate adherence and persistence over a period of 3 years in real-world diabetic patients and describe the comorbidities found in the group of patients studied. MATERIAL AND METHODOLOGY: A non-interventional pharmacological observational study was conducted by examining all therapies from 2011 to 2019 at a local health centre in Pescara (ASL). The medication adherence and persistence over a 3-year period were calculated using the pharmacy-refill method. The identification of the comorbidities was carried out in accordance with the Anatomical Therapeutic Chemical (ATC) Classification system at the fourth level. RESULTS: A total of 19 600 patients undergoing treatment for type II diabetes from January 2011 to December 2019 were analysed. The absolute adherence value at 3 years was 0.68 ± 0.23. The 3-year persistence curves showed a statistically significant difference (P < .0001). The ATCs with highest figures in the entire study group were: A02BC, B01AC and C10AA with 14 220, 13 934 and 10 858 patients, respectively. CONCLUSIONS: Adherence to therapy was suboptimal, while persistence curves showed a statistically significant difference, with patients treated with metformin showing better results. Comorbidities analysed showed a greater relevance of heart disease.

Adherence and persistence analysis in patients treated with double antiplatelet therapy (DAPT) at two years in real life.

INTRODUCTION: Double antiplatelet therapy (DAPT) is indicated for the treatment of coronary artery diseases (CAD). The optimal duration of therapy with DAPT continues to be a subject of debate in the scientific community. To improve adherence to DAPT, the FDC (fixed dose combination) of Acetylsalicylic acid (ASA) and clopidogrel was developed into a single pill instead of two separate pills thus facilitating the dosage and administration of the therapy and increasing compliance. The aim of this study was to assess adherence and persistence over a period of two years in patients treated with DAPT composed of: ASA/clopidogrel, ASA/prasugrel, ASA/ticagrelor and FDC with ASA and clopidogrel in real life and to assess whether the use of ASA and clopidogrel FDC is associated with improved adherence. MATERIALS AND METHODS: In the following retrospective pharmacological-observational non-interventional study, all patients treated with DAPT in the Hospital of Pescara from January 2010 to October 2019 were considered. Persistence to treatment is defined as the duration of time from initiation to discontinuation of treatment. Adherence was calculated as the ratio between Received Daily Dose (RDD) and Prescribed Daily Dose (PDD). RESULTS: 277 patients treated with ASA/clopidogrel, 77 patients treated with ASA/prasugrel, 57 patients treated with ASA/ticagrelor and 108 patients treated with FDC of ASA/clopidogrel were analysed. Persistence curves at two years showed a statistically significant difference (p < 0.001). Adherence to therapy was optimal with an absolute value at two years of 0.96. Adherence was better in patients treated with ASA/prasugrel with a value of 0.98 and with 97 % of patients with an adherence value greater than or equal to 0.8, while, it was worse in patients treated with FDC ASA/clopidogrel with an absolute value of 0.94 and with 88 % of patients with an optimal adherence value. No statistically significant difference was found between the ASA/clopidogrel FDC in comparison to each component taken as a separate pill (p = 0.0752). CONCLUSION: DAPT along with ASA/clopidogrel showed a statistically significant better persistence than ASA/ticagrelor and ASA/prasugrel. Whereas, to our knowledge and as per the current literature no statistically significant differences were found, in terms of adherence in real life, between the use of ASA/Clopidogrel FDC and the use of two different pills.

Long-acting Injectable vs. Oral Antipsychotics: Adherence, Persistence and Switching over three Years of Real-life Analysis.

BACKGROUND: Persistence and adherence to treatment are considered efficacy outcomes in psychiatric disorders. One of the best ways to improve these values in patients with psychiatric disorders is to prefer Long-Acting Injectable (LAI) drugs to oral AP. OBJECTIVE: The objective of this study is to evaluate adherence, persistence and switching of antipsychotics and compare in real life long-acting with oral formulations. MATERIALS AND METHODS: This pharmacological, observational, retrospective and non-interventional study involved all patients of the ASL of Pescara treated in the front-line with AP in the period between January 2011 and February 2019. Adherence was measured using the ratio between the received daily dose and prescribed daily dose. Persistence to treatment with antipsychotics was calculated as the daily difference between the beginning and end of treatment. RESULTS: We examined 840 patients treated with aripiprazole, 130 patients treated with paliperidone and 925 patients treated with risperidone. Adherence was significantly better in long-acting formulations with values of 0.89 (aripiprazole) and 0.82 (paliperidone and risperidone) than in oral formulations with values of 0.78, 0.70 and 0.58, respectively (p> 0.999, p= 0.0091, p=< 0.0001). Threeyear persistence curves relating to three study drugs did not show a statistically significant difference (p = 0.3314). Persistence curves based on formulation have not shown a statistically significant difference (p= 0, 4658, p=0, 4794, p=0, 2199 for ariprazolo, paliperidone and risperidone, respectively). 7% of patients were treated with aripiprazole, 12% of patients were treated with risperidone and 28% of patients were treated with paliperidone switched therapy. CONCLUSION: In all the drugs of present study, adherence values were better in LAI than in OA, whereas no statistically significant difference was found in persistence values.

Medical and health informatics services during and after the COVID-19 pandemic should be virtual, tailored, responsive and interactive: a case study in Belgium.

This is part of a new series in this regular feature regarding trends in the provision of information by health science libraries. By sharing expertise and drawing together relevant trends the series intends to serve as a road map for both health science librarians and health informatics professionals. This article shows how a medical and biomedical research library changed practices, and reassessed user needs for the COVID-19 emergency. Discusses changes to online education (and collaborative working) to provide user-friendly services, researcher support tailored to need and re-visioning library space. J.M.

Real-life adherence in capecitabine therapy using two analysis methods and persistence after 6 months of treatment.

Medication adherence in the field of Oncology is crucial in therapy management and can influence the probability of achieving and maintaining efficacy over time. We conducted a cross-sectional study to evaluate adherence and persistence to oral therapy with Capecitabine, using two different calculation methods: therapy diary and indirect prescription refilling patterns. The main objective of the study was to compare the two methods of analysis and to propose a reliable adherence datum, yielded by the application of two complementary methodologies. We consequently set out to verify if data collected from therapy diaries can be superimposed to those gathered from prescription refilling patterns. Furthermore, we included data on patient-perceived quality in relation to Capecitabine therapy, as well as adverse reactions and their duration. Of 594 patients who used the study drug as of January 1, 2012, 45 completed their therapy diary. Adherence to treatment was 0.93 ± 0.10 and 0.84 ± 0.15, calculated using therapy diaries and pharmacy refill data, respectively. In terms of persistence, 53% of patients continued with treatment after six months of therapy. On a 1 to 5 scale, perceived quality was 3.31. In conclusion, when it comes to calculating adherence, it is important to preserve the objectivity of the method, which must be unencumbered by any conditioning. Regardless of the method, also considering what has already been discussed in the available literature, adherence in patients under treatment with Capecitabine, unlike persistence, is good.

Adherence and persistence analysis after three years in real-life of inhalation therapies used in the treatment of COPD.

INTRODUCTION: Low adherence and persistence values, which indicate real-life efficiency, have been widely reported in patients suffering from COPD (Chronic Obstructive Pulmonary Disease). Poor adherence may be related to treatment dosage, thus, simplifying the dosing regimen might improve adherence. The objective of the present study was either to evaluate adherence and persistence in primary drugs used in COPD treatment after 3 years in real life and assess whether the different dosing regimen affects adherence levels to therapy. MATERIALS AND METHODS: A pharmacological, observational, non-interventional, retrospective study was carried out by taking into consideration the drugs dispensed between 1 January 2011 and 31 December 2018 at the hospital pharmacy of Pescara. Adherence was reckoned as the ratio between Received Daily Dose (RDD) and Prescribed Daily Dose (PDD). Treatment persistence was reckoned as the time from the start of treatment until its discontinuation. The evaluation of the two drug used indices was carried out by using three different dose regimens: Defined Daily Dose (DDD), minimum daily dose, maximum daily dose. RESULTS: During the study period, 52,374 patients met the inclusion criteria, and after applying the exclusion criteria, 3432, 3608, and 3594 were eligible for analysis by maximum daily, dose, DDD, and minimum daily dose, respectively. For the majority of active ingredients, adherence data was less than 0.8, that is the cut-off universally accepted as ideal value for adherence. In terms of adherence, a statistically significant difference has been highlighted in active ingredients requiring a single daily inhalation, with respect to active ingredients requiring multiple inhalations. Persistence curves have shown no statistically significant difference. CONCLUSIONS: It would be appropriate to promote the use of drugs which require a single daily dose in order to improve adherence in these patients.

Cancer drugs for solid tumors approved by the EMA since 2014: an overview of pivotal clinical trials.

INTRODUCTION: The European Medicine Agency (EMA) authorizes the marketing of drugs, with the authorization being full, conditional or issued under exceptional circumstances. Usually the efficacy and safety of drugs must be demonstrated in at least 2 well-controlled trials, but this rule is not always observed. The objective of the trial is to provide an overview of the pivotal trials of cancer drugs authorized for marketing in Europe since 2014. MATERIALS AND METHODS: From the technical data sheets of each drug authorized by the EMA between January 1, 2014 and May 31, 2019, we evaluated the relative pivotal trial(s) in terms of the following characteristics: number of patients, masking, trial phase, number of arms, primary endpoint(s), presence of subgroup analysis, quality of life as endpoint, and value of statistical p. The results provided us with the total number of trials, which we then divided into trials for orphan and non-orphan drugs. RESULTS: We considered 38 medicines, 6 of which were classified as orphans, for a total of 96 pivotal trials. Four drugs had conditional authorization, 1 was authorized under exceptional circumstances. Seventeen drugs underwent only 1 pivotal trial to support marketing authorization. Most of the trials were phase 3 and open-label, with 2 arms. Most trials considered the progression-free survival (PFS) as the primary endpoint, less than 30% of trials consider OS as a primary endpoint, and less than 40% of trials reported quality of life. The p values, with very few exceptions, were below 0.05. CONCLUSIONS: The rule of 2 well-controlled trials was complied with in just over 50% of the authorized drugs, and even when there was only 1 pivotal trial supporting the authorization, the trial itself may not have been necessarily well-controlled; the authorization was revoked for a drug because the trial did not confirm the benefits expected from confirmatory trials; while for 2 drugs, the evidence of efficacy yielded by the trials was not considered exhaustive. Considering that sometimes clinical authorization trials do not provide complete data on safety and efficacy, it would be perhaps appropriate to gather more pre-marketing evidence or leverage post-marketing data to complete the available information and have greater certainty.

Adalimumab and etanercept adherence, persistence and switch in the treatment of psoriatic arthritis: 10-year real-life analysis.

Objectives: The objective of this study was to calculate adherence, persistence and 10-year switches in patients with PsA, by comparing adalimumab and etanercept in real life.Methods: The authors conducted a retrospective, observational, pharmacological and non-interventional study taking into consideration the dispensations of the study drugs at the Hospital Pharmacy, from 1 January 2007 to 31 December 2018. In the study, the authors considered adalimumab and etanercept. The authors calculated adherence to treatment through the relationship between received daily dose (RDD) and prescribed daily dose (PDD), and calculated persistence to treatment as the difference in days between the first and last dispensation.Results: The authors enrolled 113 patients, 60 treated with adalimumab and 53 with etanercept. Adherence levels were 0.83 for adalimumab and 0.84 for etanercept. Switches occurred in 42% of adalimumab and in 47% of etanercept prescriptions.Conclusion: In the treatment of PsA, persistence and switches are a problem for patients who cannot follow a consistent therapy over time, for clinicians who have to manage therapy suspension and changes, and for the National Health System that must procure and pay for a high number of drugs without information on their real value in terms of efficacy and safety of use.

Dosage adjustments in pivotal clinical trials with oral targeted therapies in solid tumors conducted in Europe.

PURPOSE: The aim of this study was to evaluate in what measure is dosage adjustment particularly prevalent in pivotal clinical trials of oral targeted therapy drugs approved by the European Medicine Agency as of July 31, 2018, for the treatment of solid tumors. METHODS: We performed a search on the official EMA site on human medicines, using as Keyword Search the ATC Code L01X (other antineoplastic agents); from the list of drugs results, we subsequently excluded antineoplastic drugs for hematological diseases, as well as refused and withdrawn drugs. For all analyzed drugs, we recorded full dosages, dose adjustments with relative reduction percentage, reason for the adjustments, number of patients included in the trial, percentage of patients who reduced their dosage or temporarily discontinued therapy, cause of dose reduction, and presence or absence of reference to a clinical outcome in patients who reduced their dose or discontinued therapy. RESULTS: We considered 74 pivotal trials on 29 target therapies, of which 56 (76%) provide information on dosage reduction, 41 (55%) on therapy suspension, and 29 (39%) on the dose taken by the sample. Trials that provide information on dosage adjustment include reduction and suspension data widely used to manage side effects; they concern, respectively, 32 and 44% of the samples considered. No trial results take account of the possible role of adjustment in clinical outcomes. CONCLUSION: It would be advisable for pivotal clinical trials to give more relevance to dose management, which is a widely used tool for the management of adverse events in clinical practice. To date, such information is lacking.