Real-World Evidence to Support EU Regulatory Decision Making-Results From a Pilot of Regulatory Use Cases.

Studies using real-world data (RWD) can complement evidence from clinical trials and fill evidence gaps during different stages of a medicine's lifecycle. This review presents the experience resulting from the European Medicines Agency (EMA) pilot to generate RWE to support evaluations by EU regulators and down-stream decision makers from September 2021 to February 2023. A total of 61 research topics were identified for RWE generation during this period, covering a wide range of research questions, primarily generating evidence on medicines safety (22, 36%), followed by questions on the design and feasibility of clinical trials (11, 18%), drug utilization (10, 16%), clinical management (10, 16%), and disease epidemiology. A significant number of questions were related to the pediatric population and/or rare diseases. A total of 27 regulatory-led RWD studies have been conducted. Most studies were descriptive and aimed at estimating incidence and prevalence rates of clinical outcomes including adverse events or to evaluate medicines utilization. The review highlights key learnings to guide further efforts to enable the use and establish the value of real-world evidence (RWE) for regulatory decisions. For instance, there is a need to access additional fit-for-purpose and representative data, and to explore further means to provide timely evidence that meets regulatory timelines. The need for early interactions and close collaboration with study requesters, e.g., from the Agency's scientific Committees, to better understand the research question is equally important. Finally, the review provides our perspective on the way forward to maximize the potential of regulatory-led RWE generation.

Leveraging patient experience data to guide medicines development, regulation, access decisions and clinical care in the EU.

Patient experience data (PED), provided by patients/their carers without interpretation by clinicians, directly capture what matters more to patients on their medical condition, treatment and impact of healthcare. PED can be collected through different methodologies and these need to be robust and validated for its intended use. Medicine regulators are increasingly encouraging stakeholders to generate, collect and submit PED to support both scientific advice in development programs and regulatory decisions on the approval and use of these medicines. This article reviews the existing definitions and types of PED and demonstrate the potential for use in different settings of medicines' life cycle, focusing on Patient-Reported Outcomes (PRO) and Patient Preferences (PP). Furthermore, it addresses some challenges and opportunities, alluding to important regulatory guidance that has been published, methodological aspects and digitalization, highlighting the lack of guidance as a key hurdle to achieve more systematic inclusion of PED in regulatory submissions. In addition, the article discusses opportunities at European and global level that could be implemented to leverage PED use. New digital tools that allow patients to collect PED in real time could also contribute to these advances, but it is equally important not to overlook the challenges they entail. The numerous and relevant initiatives being developed by various stakeholders in this field, including regulators, show their confidence in PED's value and create an ideal moment to address challenges and consolidate PED use across medicines' life cycle.

COVID-19 pandemic and the consumption of self-care products for pediculosis capitis in Portugal: an interrupted time-series analysis.

This study aims to assess the effect of the COVID-19 pandemic on the consumption of self-care products for pediculosis capitis management, in Portugal. A segmented regression analysis of interrupted time series (March 2020) was performed from January 2017 to August 2023 to analyze the short- and long-term impact of the COVID-19 pandemic on the consumption of pediculicides and related products. Monthly rates of absolute consumption were estimated by community pharmacies' dispensing records. Portuguese municipalities were organized into quintiles according to their purchasing power index and percentage of youth, to study the association of these social and demographic variables on the sale of these products. COVID-19 pandemic significantly reduced the sales of products indicated for pediculosis. Since the start of the pandemic, an absolute decrease of 21.0 thousand packages was observed in the monthly average consumption (p < 0.0001) compared to the pre-pandemic period. After this reduction, the average monthly trend increased in the pandemic period in comparison with the previous period, although not significant (267.0 packages per month, p = 0.1102). Regions with higher disposable income and more young people were associated with higher sales of these products. The outbreak of the COVID-19 pandemic has had a notable impact on the sales of self-care products for pediculosis capitis in Portugal, in the short term. The lockdowns and other isolation measures implemented to control the spread of the virus may have led to a decrease in the number of head lice cases, consequently resulting in a reduction in sales of products.

Medicines for an aging population: The EMA perspective and policies.

The European Medicines Agency adopted their Geriatric Medicines Strategy more than a decade ago. The strategy aims at elucidating the evidence basis for marketing authorization of new medicines which will be used in the older population, and at ensuring the appropriate communication of findings to the patient and healthcare provider. During the past decade new tools and data sources have emerged to support the strategy goals, and their use should be considered. Possible concrete actions are presented to improve the design of clinical trials, the data collection both pre- and post-approval, the assessment of the findings, and the communication to assist informed prescription and safe medicine taking. Implementation and prioritization of these actions should be done from the perspective of addressing the needs of patients while maximizing efficient use of resources, with the aim of integrating geriatric aspects into routine medicines development and assessment.

Tumor mutational burden in colorectal cancer: Implications for treatment.

Although immune checkpoint inhibitors have revolutionized the treatment of several advanced solid cancers, in colorectal cancer, the transformative benefit of these innovative medicines is currently limited to those with deficient mismatch repair or high microsatellite instability. Tumor mutational burden (TMB) has emerged as a potential predictor of immunotherapy benefit, but the lack of standardization in its assessment and reporting has hindered the introduction of this biomarker in routine clinical practice. Here, we compiled 45 colorectal cancer studies utilizing numerical thresholds for high-TMB. In this group of studies, TMB cut-offs ranged from 6.88 to 41 mut/Mb and were most often set at 10, 17, or 20 mut/Mb. Additionally, we observed divergent TMB definitions and inconsistent disclosure of specific methodological details, which collectively emphasize the substantial lack of harmonization within the field. Ongoing efforts to harmonize TMB assessment will be critical to validate TMB as a predictive marker of immunotherapy response.

Trends in orphan medicinal products approvals in the European Union between 2010-2022.

BACKGROUND: Over the last twenty years of orphan drug regulation in Europe, the regulatory framework has increased its complexity, with different regulatory paths and tools engineered to facilitate the innovation and accelerate approvals. Recently, the proposal of the new Pharmaceutical Legislation for the European Union, which will replace at least three Regulations and one Directive, was released and its new framework is raising many questions. The aim of this study was to present a characterisation of the Orphan Medicinal Products (OMPs) authorised by the European Commission (EC), between 2010 and 2022, looking into eighteen variables, contributing to the ongoing discussion on the proposal and implementation of the new Pharmaceutical Legislation proposed. METHODS: Data of the OMPs identified and approved between 2010 and 2022 were extracted from the European Public Assessment Reports (EPARs) produced by the European Medicines Agency. Information regarding legal basis of the application, applicant, protocol assistance received, type of authorization, registration status, type of molecule, ATC code, therapeutic area, target age, disease prevalence, number of pivotal clinical trials supporting the application, clinical trial designs, respective efficacy endpoints and number of patients enrolled in the pivotal clinical trials were extracted. A descriptive statistical analysis was applied. RESULTS: We identified 192 OMPs approved in the period between 2010 and 2022. 89% of the OMPs have legal basis of "full application". 86% of the sponsors received protocol assistance whereas 64% of the MAA benefited from the accelerated assessment. 53% of the active substances are small molecules; about 1 in 5 molecules are repurposed. 40% of the OMPs have oncological therapeutic indications and 56% of the OMPs are intended to treat only adults. 71% of the products were approved based on a single pivotal trial. CONCLUSIONS: This analysis of OMPs approved between 2010 and 2022 shows that a shift has occurred in the rare disease medicine development space. Through the period studied we observe an increase of non-small molecules approved, accelerated assessment received and non-standard MA's granted.

Inclusion of functional measures and frailty in the development and evaluation of medicines for older adults.

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E7, the guidance for the conduct of clinical trials in people older than age 65 years, dates from 1994. Since then, the inclusion of older people in clinical trials has hardly improved, particularly for the oldest old age group (individuals older than age 75 years), which is the fastest growing demographic bracket in the EU. Even though most medications are taken by this group, relevant endpoints and safety outcomes for this cohort are rarely included and reported, both in clinical trials and regulatory approval documents. To improve the critical appraisal and the regulatory review of medicines taken by frail older adults, eight recommendations are presented and discussed in this Health Policy. These recommendations are brought together from different perspectives and experience of the treatment of older patients. On one side, the perspective of medical practitioners from various clinical disciplines, with their direct experience of clinical decision making; on the other, the perspective of regulators assessing the data submitted in medicine registration dossiers, their relevance to the risk-benefit balance for older patients, and the communication of the findings in the product information. Efforts to improve the participation of older people in clinical trials have been in place for more than a decade, with little success. The recommendations presented here are relevant for stakeholders, authorities, pharmaceutical companies, and researchers alike, as the implementation of these measures is not under the capacity of a single entity. Improving the inclusion of frail older adults requires awareness, focus, and action on the part of those who can effect a much needed change.

Factors Associated with Underreporting of Adverse Drug Reactions by Health Care Professionals: A Systematic Review Update.

INTRODUCTION: Underreporting is a major limitation of the voluntary reporting system of adverse drug reactions (ADRs). A 2009 systematic review showed the knowledge and attitudes of health professionals were strongly related with underreporting of ADRs. OBJECTIVE: Our aim was to update our previous systematic review to determine factors (sociodemographic, knowledge and attitudes) associated with the underreporting of ADRs by healthcare professionals. METHODS: We searched the MEDLINE and EMBASE databases for studies published between 2007 and 2021 that met the following inclusion criteria: (1) published in English, French, Portuguese or Spanish; (2) involving health professionals; and (3) the goal was to evaluate factors associated with underreporting of ADRs through spontaneous reporting. RESULTS: Overall, 65 papers were included. While health professional sociodemographic characteristics did not influence underreporting, knowledge and attitudes continue to show a significant effect: (1) ignorance (only serious ADRs need to be reported) in 86.2%; (2) lethargy (procrastination, lack of interest, and other excuses) in 84.6%; (3) complacency (the belief that only well tolerated drugs are allowed on the market) in 46.2%; (4) diffidence (fear of appearing ridiculous for reporting merely suspected ADRs) in 44.6%; and (5) insecurity (it is nearly impossible to determine whether or not a drug is responsible for a specific adverse reaction) in 33.8%, and the absence of feedback in 9.2%. In this review, the non-obligation to reporting and confidentiality emerge as new reasons for underreporting. CONCLUSIONS: Attitudes regarding the reporting of adverse reactions continue to be the main determinants of underreporting. Even though these are potentially modifiable factors through educational interventions, minimal changes have been observed since 2009. CLINICAL TRIALS REGISTRATION: PROSPERO registration number CRD42021227944.

COVID-19 pandemic and the quality of antibiotic use in primary care: an interrupted time-series study.

The coronavirus disease-19 pandemic and the related public health mitigation measures have impacted the transmission of infectious diseases; however, their impact on the use of antibacterials has not yet been extensively evaluated. This study evaluated the impact of the pandemic on the consumption patterns of antibacterials for systemic use in primary care in Portugal. An interrupted time-series analysis was performed using the autoregressive integrated moving average model of the antibacterials dispensed in the community pharmacies in Portugal from 1 January 2016 to 30 June 2022. Monthly rates of absolute consumption (all antibacterials for systemic use, and specifically penicillins; cephalosporins; macrolides, lincosamides, and streptogramins; and quinolones) and the relative consumption of antibacterials (penicillins sensitive to ß-lactamase, penicillin combinations including ß-lactamase inhibitors, third- and fourth-generation cephalosporins, fluoroquinolones, and the ratio of broad- to narrow-spectrum antibacterials) were estimated. Antibiotic consumption was expressed in defined daily doses per 1000 inhabitants per day (DID). In Portugal, the consumption of antibacterials (J01) declined sharply immediately after the beginning of the pandemic, having a significant reduction of >5 DID (P < .0001). A similar, short-term impact was found for penicillins (-2.920 DID; P < .0001); cephalosporins (-0.428 DID; P < .0001); macrolides, lincosamides, and streptogramins (-0.681 DID; P = .0021); and quinolones (-0.320 DID; P < .0001). A long-term increase was found for cephalosporins (+0.019 DID per month; P < .0001). Relative consumption changes were only found for third- and fourth-generation cephalosporins (0.0734%). Our study suggests that the coronavirus disease-19 pandemic may have resulted in a decrease in antibiotic use, with no significant changes in the relative dispense. Uncertainties regarding the long-term effects of the pandemic and its impact on the rates of resistance remain.

Factors associated with underreporting of adverse drug reactions by patients: a systematic review.

BACKGROUND: Spontaneous reporting is the most used method to monitor post-marketing safety information. Although patient involvement in spontaneous reporting has increased overtime, little is known about factors associated with patients' adverse drug reaction (ADR) reporting. AIM: To identify and assess the sociodemographic characteristics, attitudes and knowledge that influence spontaneous reporting and the reasons associated with ADR underreporting by patients. METHOD: A systematic review was conducted according to PRISMA guidelines. A search on the MEDLINE and EMBASE scientific databases was performed to retrieve studies published between 1 January 2006 and 1 November 2022. Studies were included if they addressed knowledge and attitudes associated with ADR underreporting. RESULTS: A total of 2512 citations were identified, of which 13 studies were included. Sociodemographic characteristics were frequently identified with ADR reporting in 6 studies, being age (3/13) and level of education (3/13) the most often reported. Older age groups (2/13) and individuals with higher level of education (3/13) were more likely to report ADRs. Underreporting was shown to be motivated by reasons related to knowledge, attitudes, and excuses. Ignorance (10/13), complacency (6/13), and lethargy (6/13) were the most frequent reasons for not reporting. CONCLUSION: This study highlighted the scarcity of research conducted with the aim of assessing ADR underreporting by patients. Knowledge, attitudes, and excuses were commonly observed in the decision to report ADRs. These motives are characteristics that can be changed; hence strategies must be designed to raise awareness, continually educate, and empower this population to change the paradigm of underreporting.

Treatment Advances in Sepsis and Septic Shock: Modulating Pro- and Anti-Inflammatory Mechanisms.

Sepsis is currently defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, and it affects over 25 million people every year. Even more severe, septic shock is a subset of sepsis defined by persistent hypotension, and hospital mortality rates are higher than 40%. Although early sepsis mortality has greatly improved in the past few years, sepsis patients who survive the hyperinflammation and subsequent organ damage often die from long-term complications, such as secondary infection, and despite decades of clinical trials targeting this stage of the disease, currently, no sepsis-specific therapies exist. As new pathophysiological mechanisms have been uncovered, immunostimulatory therapy has emerged as a promising path forward. Highly investigated treatment strategies include cytokines and growth factors, immune checkpoint inhibitors, and even cellular therapies. There is much to be learned from related illnesses, and immunotherapy trials in oncology, as well as the recent COVID-19 pandemic, have greatly informed sepsis research. Although the journey ahead is a long one, the stratification of patients according to their immune status and the employment of combination therapies represent a hopeful way forward.

A cross-country utilization patterns comparison of high expenditure therapeutic groups between Portugal and six European countries: the two sides of the Portuguese coin.

BACKGROUND: Understanding variability in prescribing patterns through comparative drug utilization studies can contribute to improve an efficient, effective and safe use of medicines. OBJECTIVES: To perform a cross-country comparison of consumption patterns of ambulatory high expenditure therapeutic groups between Portugal and six European countries and simulate potential cost-saving scenarios through the adoption of the different prescribing patterns of studied countries. METHODS: Cross-country comparison of 2019 drug consumption patterns between Portugal, Denmark, England, Finland, the Netherlands, Norway, and Spain. Analysis comprised antihypertensive drugs, glucose lowering drugs (GLD), insulins, lipid lowering drugs (LLD) and oral anticoagulants. Cost-saving analysis were performed using the Portugal average annual cost/daily defined dose and the potential reduction in expenditure simulating other European countries consumption pattern scenarios. RESULTS: Portugal had the lowest consumption uptake of metformin and the highest consumption of GLD (30.1%) and LLD (8.5% vs <3%) fixed-dose combinations. Annual cost-savings scenarios showed that Portugal would have saved between 53 M€ and 305 M€ if it had the same prescribing patterns than Norway or the Netherlands, respectively. CONCLUSIONS: Different utilization patterns across countries were found. Although Portugal has the lowest gross domestic product per capita among the countries studied, it had the highest uptake of newly and costly drugs.

A review of patient-reported outcomes used for regulatory approval of oncology medicinal products in the European Union between 2017 and 2020.

Introduction: Cancer and corresponding available treatments are associated with substantial symptoms and functional limitations. In this context, collection of patient-reported outcomes (PRO) in clinical trials gained special interest and is recommended by regulatory authorities. Within clinical trials framework, PRO may provide evidence to support medicines approval, labeling and marketing claims. This study aims to analyze the existing evidence based on PRO as part of new oncology indications receiving positive opinions issued by the European Medicines Agency (EMA) between 2017 and 2020 and to identify PRO related label claims granted. Methodology: Oncology medicinal products and indications approved by the European Commission following a positive opinion from the EMA between 2017 and 2020 were identified. European Public Assessment Report (EPAR) and Summary of Product Characteristics (SmPC) were reviewed for each medicinal product to identify use of PRO and PRO label claims. Results: A total of 128 oncology indications, corresponding to 76 medicines, were approved; of those, 100 (78.1%) included PRO in the confirmatory clinical trials. Thirty-seven indications were supported by double-blind randomized trials and the remainder 63 by open-label trials. Out of the 104 confirmatory trials analyzed, PRO were defined as a secondary endpoint in 60 studies (57.7%), exploratory in 31 (29.8%) and as both in 13 (12.5%). In total, 54 different PRO measures (PROM) were used, of those 41 (75.9%) were disease-specific measures. Nevertheless, PROM selected relied on the EORTC (41.3%), FACIT (17.1%) and EQ-5D (29.2%) measures. A total of 76 indications (59.4%) had PRO reviewers comments included in the EPAR, however only 22 indications (17.8%) included label claims in the SmPC. The reasons identified in the EMA assessment supporting the exclusion of PRO claims were described for 34 indications (44.7%). Conclusions: Despite growing recognition of the value of PRO data for the development of improved cancer therapies, PRO implementation remains challenging. The main reasons identified in our study are related with study design, missing data, study conduct and PROM selection.

A review of the continuous professional development system for pharmacists.

BACKGROUND: The Portuguese Pharmaceutical Society (PPS) implemented a system of Continuous Professional Development (CPD) for pharmacists in 2004. This system has evolved throughout the years, and currently all active pharmacists in Portugal are required to participate in the CPD program. Each CPD cycle takes 5 years. In each cycle, pharmacists must collect 15 CPD points, through participation in educational activities. The PPS accreditation process is managed via an online platform, where education/training providers, as well as pharmacists themselves, can submit educational activities for accreditation. Pharmacists may access their CPD status and assess their development at any point. The objective of this study was to analyze and review the educational activities submitted by providers over a 11-year period (2009-2019). METHODS: Data from activities were retrieved from the PPS CPD online platform. All educational activities were labeled according to the area of pharmaceutical professional focus, type of promoter, and activity type. RESULTS: During the study 3685 activities were analyzed. Over the last decade, submitted activities for accreditation increased in 52.6%. A significantly high proportion (98.9%) of these activities has been accredited. Promoters of activities were mostly pharmacies sectoral associations (29.6%), consultancy/training companies (19.6%), the PPS (18.5%), pharmaceutical industry (17.7%) and wholesalers' consortia (9.0%). Academia represented only 2.3% of the total amount of educational activities. The most frequent topics were related to "pharmacology & pharmacotherapy" (9.9%), followed by "counselling" (9.8%) and "management & administration" (7.2%). The most accredited type of activities was face-to-face (68.9%) and e-learning trainings (13.1%). CONCLUSIONS: This study shows increasing interest in submitting CPD activities for accreditation between 2009 and 2019, but it also demonstrates that Academia could play a more interventive role in the lifelong learning education of Portuguese pharmacists.

Implementation and Access to Pre-exposure Prophylaxis for Human Immunodeficiency Virus by Men Who Have Sex With Men in Europe.

Pre-exposure prophylaxis (PrEP) is a significant public health intervention with proven efficacy and safety in the prevention of human immunodeficiency virus (HIV) infection, which has taken a considerable amount of time to reach Europe in relation to their transatlantic counterparts, namely, the United States of America (USA). There, it is perceived as being an essential prevention tool to be integrated within existing medical, behavioral and structural interventions in place for the management and containment of HIV infection in men who have sex with men (MSM). In a region such as Europe, with approximately double the USA population, it is estimated that not even 10% have proper access to PrEP, and given the lack of coordination with healthcare, taking PrEP has to be at their own expense. Here, we identify the reasons behind the 4-year lag in the approval of PrEP in the European Union/European Economic Area (and Europe in general) and explore the efficacy and effectiveness of PrEP needed to be confirmed with some implementation or demonstration studies conducted in the region. Independent of the data gathered, access of MSM to PrEP is far from ideal in Europe and much still needs to be done. The demonstration of the cost-effectiveness of PrEP alongside other social and behavioral factors needs to be addressed, while the clear populations within MSM that will benefit from this intervention are properly identified and make use of the latest recommendations of the World Health Organization that consider not only daily PrEP but also event-driven PrEP. The momentum for the proper implementation of PrEP in the EU is not lost, and with the existence of generics and even new formulations, there is a renewed opportunity for unleashing the public health benefits arising from this pharmacological tool with other interventions in place (e.g., condoms, testing, and counseling).

Overtreatment and undertreatment in a sample of elderly people with diabetes.

AIMS: In older adults with type 2 diabetes (T2D), overtreatment remains prevalent and undertreatment ignored. The main objective is to estimate the prevalence and examine factors associated with potential overtreatment and undertreatment. METHOD: Observational study conducted within an administrative database of older adults with T2D who registered in 2018 at the Portuguese Diabetes Association. Participants were categorized either as potentially overtreated (HbA1c ≤ 7.5%), appropriately on target (HbA1c ≥7.5 to ≤9%), or potentially undertreated (HbA1c > 9%). RESULTS: The study included 444 participants: potential overtreatment and undertreatment were found in 60.5% and 12.6% of the study population. Taking the patients on target as a comparator, the group of potentially overtreated showed to be more men (61.3% vs 52.2%), less-obese (34.1% vs 39.2), higher cardiovascular diseases (13.7% vs 11%), peripheral vascular diseases (16.7% vs 12.8%), diabetic foot (10% vs 4.5%), and severe kidney disease (5.2% vs 4.5%). Conversely, the potentially undertreated participants were more women (64.2% vs 47.7%), obese (49% vs 39.2%), had more dyslipidemia (69% vs 63.1%), peripheral vascular disease (14.2% vs 12.8%), diabetic foot (8.9% vs 4.5%), and infections (14.2% vs 11.9%). The odds of potential overtreatment were mostly decreased by 59% of women, 73.5% in those with retinopathy, and 86.3% in insulin, 65.4% sulfonylureas, and 66.8% in SGLT2 inhibitors users. Contrariwise, an increase in the odds of potential undertreatment was more than 4.8 times higher in insulin, and more than 3.1 times higher in sulfonylureas users. CONCLUSION: Potential overtreatment and undertreatment in older adults with T2D in routine clinical practice should guide the clinicians to balance the use of newer oral antidiabetic agents considering its safety profile regarding hypoglycemia.

Scientific Advances in Diabetes: The Impact of the Innovative Medicines Initiative.

Diabetes Mellitus is one of the World Health Organization's priority diseases under research by the first and second programmes of Innovative Medicines Initiative, with the acronyms IMI1 and IMI2, respectively. Up to October of 2019, 13 projects were funded by IMI for Diabetes & Metabolic disorders, namely SUMMIT, IMIDIA, DIRECT, StemBANCC, EMIF, EBiSC, INNODIA, RHAPSODY, BEAT-DKD, LITMUS, Hypo-RESOLVE, IM2PACT, and CARDIATEAM. In general, a total of €447 249 438 was spent by IMI in the area of Diabetes. In order to prompt a better integration of achievements between the different projects, we perform a literature review and used three data sources, namely the official project's websites, the contact with the project's coordinators and co-coordinator, and the CORDIS database. From the 662 citations identified, 185 were included. The data collected were integrated into the objectives proposed for the four IMI2 program research axes: (1) target and biomarker identification, (2) innovative clinical trials paradigms, (3) innovative medicines, and (4) patient-tailored adherence programmes. The IMI funded projects identified new biomarkers, medical and research tools, determinants of inter-individual variability, relevant pathways, clinical trial designs, clinical endpoints, therapeutic targets and concepts, pharmacologic agents, large-scale production strategies, and patient-centered predictive models for diabetes and its complications. Taking into account the scientific data produced, we provided a joint vision with strategies for integrating personalized medicine into healthcare practice. The major limitations of this article were the large gap of data in the libraries on the official project websites and even the Cordis database was not complete and up to date.

Ebola outbreaks: A stress test of the preparedness of medicines regulatory systems for public health crises.

In a globalized world, infectious diseases of international concern are inevitable. When they (re-)emerge, the regulatory system works towards mitigating their impact. Ebola outbreaks marked a turning point in regulatory preparedness and efforts led to the accelerated development of therapeutic agents, in a catastrophic environment. However, only one clinical trial determined a vaccine's efficacy. Key lessons were considered and applied thereafter. The collaborative work resulted in the approval of the first therapeutic options against Ebola, a milestone in public health preparedness. The response demonstrated the successful implementation of regulatory mechanisms fostering development, early access and assessment of therapeutic agents, and the flexibility to embrace innovative regulatory solutions. The current system is robust to address health crises and protect global health.

Drug-drug interactions and inappropriate medicines impact on glycemic control and kidney function in older adults with diabetes-attending specialty care institution.

PURPOSE: To describe and assess the impact of polypharmacy, and its potential adverse reactions; serious clinically relevant drug-drug interactions (DDIs) and inappropriate medicines (PIMs) on glycemic target, and kidney function in a sample of older adults with type 2 diabetes (T2D). METHODS: Cross-sectional study was performed in a real-world database including 444 elderly people with T2D from the Portuguese Diabetes Association, aged ≥ 65 years, and registered in 2018. DDIs were analyzed using Micromedex drug-interaction platform and PIMs identified using STOPP criteria version-2. RESULTS: Polypharmacy was identified in 43.6% of patients. This group of patients has shown to be more females (50 vs. 39.6%, P=0.0208), higher HbA1c targets (P=0.0275), longer diabetes duration (66.4 vs. 54.4%, P=0.0019), more hypertensive (87 vs. 62.9%, P<0.0001), using more insulin (38.1 vs. 26%, P=0.0062), sulfonylureas (37.1 vs. 15.6%, P<0.0001), GLP-1 receptor-agonists (9.7 vs. 3.6%, P=0.0077), metformin-DPP-4 inhibitors (41.2 vs. 29.2%, P=0.0081), and SGLT2 inhibitors (19 vs. 9.6%, P=0.0040). A total of 8.7% of patients had potentially serious clinically relevant DDIs, mainly due to interacting medicine pairs dexamethasone and fluoroquinolones. Furthermore, 23.4% had PIMs, and cardiovascular medicines accounted for largest therapeutic group associated. Polypharmacy found to be associated with twofold greater odds of having HbA1c ≤8%, whereas PIMs associated with 2.5-fold greater odds of having HbA1c ≤9%, and 5.5-folds greater odds of having severe kidney function. CONCLUSIONS: These findings suggested that there is a potential association between polypharmacy and PIMs and altered glycemic control, and PIMs with the deterioration of kidney function.

Burnout in the Pharmaceutical Activity: The Impact of COVID-19.

IMPORTANCE: Pharmacists are among the healthcare professionals involved in the response to the COVID-19 pandemic, maintaining essential services. In the context of restrictions and reorganization of human resources, as a result of policies recently applied to the health sector, following international guidelines, and given the scarcity of data on burnout in pharmaceutical activity, it was considered highly relevant to promote a nationwide survey aiming to collect more complete evidence on the burnout syndrome and to understand how pharmacists have viewed their work and the people they worked closely with. OBJECTIVES: The study aimed to assess the occurrence of pharmacist burnout and determine outcomes for each of its dimensions; identify potentially associated characteristics; and determine profiles and critical limits. DESIGN: A cross-sectional observational study conducted by a multidisciplinary panel from the Portuguese Pharmaceutical Society (PPS). Professionals from community and hospital pharmacies who were at the forefront of the COVID-19 response were involved in (i) confirming the need and pertinence for conducting this research, (ii) identifying the main factors leading to pharmaceutical emotional distress ("burnout"), and (iii) disseminating the survey. The questionnaire was designed for digital voluntary, confidential, and anonymous participation and divided into four segments of data collection: (i) demographics, (ii) employment and workplace characterization, (iii) pandemic impact on labor activity, and (iv) burnout assessment (as described ahead). SETTING: An electronic survey was addressed to all PPS members, and an account was created solely to manage the questionnaire data for the research team. The web-based and user-friendly platform Google Forms supported the data capture and provided an intuitive interface for validated data entry. PARTICIPANTS: In a population of 15,565 pharmacists (members of the PPS), the minimum recommended sample size (Epi Info software), with a 5% margin of error and a 99.9% confidence interval, should be 1,012 individuals. A total of 1,362 pharmacists participated in the study. Of these, 91.4% (n = 1,246) were involved in direct patient care activity and 7.7% (n = 106) in non-direct patient care activity.