Search Results (35)

The discovery and development of new drugs is a lengthy, complex, and costly process, often requiring 10–20 years to progress from initial concept to market approval, with clinical trials representing the most resource-intensive stage. In recent years, Artificial Intelligence (AI) has emerged as a transformative technology capable of reshaping the entire pharmaceutical research and development (R&D) pipeline. The purpose of this narrative review is to examine the role of AI in drug discovery and development, highlighting its contributions, challenges, and future implications for pharmaceutical sciences and global public health. A comprehensive review of the scientific literature was conducted, focusing on published studies, reviews, and reports addressing the application of AI across the stages of drug discovery, preclinical development, clinical trials, and post-marketing surveillance. Key themes were identified, including AI-driven target identification, molecular screening, de novo drug design, predictive toxicity modelling, and clinical monitoring. The reviewed evidence indicates that AI has significantly accelerated drug discovery and development by reducing timeframes, costs, and failure rates. AI-based approaches have enhanced the efficiency of target identification, optimized lead compound selection, improved safety predictions, and supported adaptive clinical trial designs. Collectively, these advances position AI as a catalyst for innovation, particularly in promoting accessible, efficient, and sustainable healthcare solutions. However, substantial challenges remain, including reliance on high-quality and representative biomedical data, limited algorithmic transparency, high implementation costs, regulatory uncertainty, and ethical and legal concerns related to data privacy, bias, and equitable access. In conclusion, AI represents a paradigm shift in pharmaceutical research and drug development, offering unprecedented opportunities to improve efficiency and innovation. Addressing its technical, ethical, and regulatory limitations will be essential to fully realize its potential as a sustainable and globally impactful tool for therapeutic innovation. Full article

Background/Objectives: Type 2 diabetes and obesity present escalating global health and economic challenges, highlighting the need for therapies that can effectively manage glycemic levels and reduce excess adiposity. Semaglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist available in subcutaneous or oral formulation, has quickly evolved from a theoretical concept to a crucial component of modern metabolic care. This review explores the comprehensive development journey of semaglutide, drawing on evidence from medicinal chemistry, animal studies, initial human trials, the pivotal SUSTAIN and STEP programs, and real-world post-marketing surveillance. Methods: We conducted a detailed analysis of preclinical data sets, Phase I–III clinical trials, regulatory documents, and pharmaco-epidemiological studies published between 2008 and 2025. Results: Through strategic molecular modifications, such as specific amino-acid substitutions and the addition of a C18 fatty-diacid side chain to enhance albumin binding, the half-life of the peptide was extended to approximately 160 h, allowing for weekly dosing. Studies in rodents and non-human primates showed that semaglutide effectively lowered blood glucose levels, reduced body weight, and preserved β-cells while maintaining a favorable safety profile. Phase I trials confirmed consistent pharmacokinetics and tolerability, while Phase II trials identified 0.5 mg and 1.0 mg once weekly as the most effective doses. The extensive SUSTAIN program validated significant reductions in HbA1c levels and weight loss compared to other treatments, as well as a 26% decrease in the relative risk of major adverse cardiovascular events (SUSTAIN-6). Subsequent STEP trials expanded the use of semaglutide to chronic weight management, revealing that nearly two-thirds of patients experienced a body weight reduction of at least 15%. Regulatory approvals from the FDA, EMA, and other regulatory agencies were obtained between 2017 and 2021, with ongoing research focusing on metabolic dysfunction-associated steatohepatitis, cardiovascular events, and chronic kidney disease. Conclusions: The trajectory of semaglutide exemplifies how intentional peptide design, iterative translational research, and outcome-driven clinical trial design can lead to groundbreaking therapies for complex metabolic disorders. Full article

Background: Randomized controlled trials (RCTs) are the foundation of evidence-based medicine. However, the rapid pace of technological innovation in cardiovascular surgery and interventional cardiology challenges the traditional RCT framework. Observational studies may hold renewed value in fields where device evolution outpaces the time required to validate clinical outcomes. Methods: This analysis evaluates 270 randomized and non-randomized studies in transcatheter aortic valve implantation (TAVI), one of the most rapidly evolving areas in cardiovascular medicine. The investigation follows two lines: first, mapping the timeline of major RCTs against the introduction of new prosthetic models; second, comparing the prevalence, duration, and role of randomized (R) versus non-randomized (NR) studies. Results: The timeline reveals a persistent misalignment between innovation and validation. New prosthetic models frequently enter the market while RCTs for prior generations are still ongoing. For example, the Sapien 3 valve was approved, while trials on Sapien XT were still enrolling. Similarly, newer Evolut and Acurate models were introduced during ongoing studies of earlier versions, often prompting new studies before existing ones concluded. This leapfrogging effect fragments the evidence base and delays definitive comparisons. In parallel, randomized trials have increased in number and tend to be shorter in duration, reflecting a maturing field. However, non-randomized studies remain crucial for early testing and post-market surveillance. Conclusions: In a field with rapid technological evolution a sort of Zeno’s paradox occurs: long-term validation cannot keep pace with fast innovation, resetting the evidence base with each new model. To overcome this paradox, a paradigm shift in evidence generation is desirable. Future strategies must augment adaptive trial designs, leverage real-world data and use higher-level, advanced analyses to incorporate subjective variables and phenotypic diversity, to reduce confounding factors and speed up data access. Higher-level, integrative evidence analytics could help Achilles walk alongside the tortoise. Full article

Background/Objectives: The Tron FX is a stent retriever thrombectomy device that underwent a clinical trial in Japan in 2016. Its key feature is the availability of a 2/15 mm model designed for medium-vessel occlusion (MeVO). This study reports the results of postmarketing surveillance (PMS) conducted from 2019 to 2020. Methods: The PMS included data from 240 patients in whom a Tron FX was used during the first pass at 24 Japanese institutions. Occluded vessels involving the M2 and M3 segments of the middle cerebral artery, anterior cerebral artery, and posterior cerebral artery were classified as MeVO. The recanalization rate, first pass effect (FPE) rate, symptomatic intracranial hemorrhage (sICH) rate, and favorable prognosis rate at 90 days were evaluated. Treatment outcomes were also analyzed for cases in which the device was used after the second pass, excluding those with tandem occlusion, atherothrombotic brain infarction (ATBI), or percutaneous transluminal angioplasty (evaluation-appropriate cases), stratified by MeVO and large vessel occlusion (LVO) and according to Tron FX device size. Results: A total of 244 cases were enrolled, of which 218 were evaluation-appropriate. Across all cases, the recanalization rate (modified Thrombolysis in Cerebral Infarction score ≥ 2b) was 70.9%, the FPE rate was 23.4%, the sICH rate was 3.8%, and the proportion of patients with a good prognosis (modified Rankin Scale score 0–2 at 90 days) was 53.1%. Among evaluation-appropriate cases, excluding those with tandem lesions or ATBI, the corresponding rates were 72.9%, 24.8%, 6.9%, and 45.5%, respectively. When analyzed by occluded vessel type, the rates for MeVO were 71.9%, 23.7%, 6.1%, and 45.7%, respectively, while those for LVO were 74.0%, 26.0%, 7.7%, and 45.1%. According to device size, the outcomes for the 2/15 mm Tron FX were 72.9%, 23.5%, 4.7%, and 50.0%, respectively, and those for the 4/20 mm device were 72.9%, 25.6%, 8.3%, and 42.5%. Conclusions: The PMS results for the Tron FX thrombectomy device were excellent, particularly for MeVO and the 2/15 mm model. These findings suggest that the Tron FX may help improve thrombectomy outcomes in MeVO. Full article

Clinical trial (CT) safety surveillance is critical to protecting participants and ensuring reliable evidence on the safety and efficacy of new medical products. This is especially relevant in Africa, where CT activity remains limited, regulatory maturity varies, and drug safety surveillance systems are under-resourced despite considerable demographic advantages and genetic and cultural diversity. Pre-licensure safety monitoring is a vital yet underdeveloped element of the research ecosystem, and the absence of a regional repository for safety data constrains early detection of risks, particularly in multi-country trials. To assess the current state of CT safety surveillance in Africa, a landscape analysis of the systems for clinical trial safety data reporting, collation, and analysis was conducted. Expert perspectives were synthesized to describe existing practices, identify key gaps, and propose opportunities for strengthening systems. Findings revealed limited regulatory capacity, limited drug safety monitoring expertise, and inadequate resources for causality assessment and aggregate data analysis. Despite these challenges, opportunities exist to strengthen CT safety surveillance through digitization of reporting systems, harmonization of serious adverse event forms, regional collaboration, and capacity building for strengthening the ecosystem. Experts emphasized the need for collaboration among regulators of member states, availability of electronic CT management platform in member states and a regional pre-licensure safety data repository to enable timely evidence generation, support member states, and ensure appropriate linkages between pre-licensure and post-market surveillance. Strengthening CT safety surveillance is critical for safeguarding participants, promoting ethical research, and enhancing Africa’s role in global clinical research. The results of this landscape analysis provide a roadmap for building a coordinated model for pre-licensure safety monitoring across the continent. Full article

Background: Medication safety in pregnancy, puerperium, and perinatal periods is underexplored because these populations are excluded from clinical trials. EudraVigilance offers post-marketing evidence, but disproportionality analyses focus on isolated drug event pairs and may miss syndromic patterns. We applied a network- and cluster-based framework to EudraVigilance reports on antiviral use in pregnancy to improve surveillance and identify meaningful constellations. Methods: We retrieved all individual case safety reports (ICSRs) from January 2015 to June 2025, including pregnancy, puerperium, or perinatal terms, focusing on suspect antivirals. After parsing terms, disproportionality metrics were computed as a benchmark. A bipartite drug–event network was built and projected to event–event co-occurrence networks; Louvain community detection identified clusters. Clusters were characterized by size, drug mix, seriousness, overlap with disproportionality signals, and stratification across periods. Results: The dataset comprised 106,924 ICSRs and 232,067 unique pairs. Disproportionality yielded 6142 signals, mainly involving antiretrovirals (ritonavir, lamivudine, zidovudine, emtricitabine/tenofovir). Network analysis revealed clusters grouping maternal and fetal/neonatal outcomes (e.g., fetal death, low birth weight), and transplacental transfer, highlighting structures not visible in pairwise analyses. Several clusters combined high-frequency exposures with clinically relevant outcomes, suggesting early-warning potential. Conclusions: Combining disproportionality with network- and cluster-based pharmacovigilance adds value for monitoring pregnancy medication safety. Beyond individual signals, this approach reveals meaningful clusters and “bridge” reactions connecting adverse-event domains, offering a richer framework for perinatal surveillance. Despite spontaneous-reporting limits, findings generate hypotheses for mechanistic and pharmacoepidemiologic follow-up and support network methods as complements to traditional pharmacovigilance. Full article

Background: Stomatitis is a common adverse event associated with targeted therapies for hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer, particularly those inhibiting the PI3K/AKT/mTOR pathway. While mTOR-inhibitor-associated stomatitis is well established, less is known about its occurrence with other kinase inhibitors in real-world settings. We performed a pharmacovigilance disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) to evaluate stomatitis reports for alpelisib, capivasertib, everolimus, and palbociclib. Methods: Events were identified using four term sets—Stomatitis, Original Trial Terms (OTT), Comprehensive Trial Terms (CTT), and Stomatitis-Associated Main Terms (SAMT)—which reflect varying definitions and medical terminologies. Disproportionality analyses using reporting odds ratio (ROR), proportional reporting ratio (PRR), and Information Component (IC) were calculated with 95% confidence intervals. Results: All agents showed ROR and PRR >1, indicating higher odds and reporting proportions of stomatitis compared with other drugs. These findings were confirmed by IC analysis. Everolimus demonstrated the strongest association (ROR: 30.72 [29.61–31.88]), followed by alpelisib (ROR: 13.11 [11.79–14.58]) and palbociclib (ROR: 11.73 [11.35–12.11]). Capivasertib had the lowest reporting odds (ROR: 3.14 [1.81–5.43]), though limited by fewer reports. Differences between CTT and SAMT were minimal (~2%). Conclusions: These results support the use of the SAMT as an efficient screening tool. Furthermore, these findings underscore the need for optimized stomatitis detection and continued monitoring, particularly for PI3K and mTOR inhibitors, in both clinical trials and postmarketing surveillance. Full article

Background/Objectives: Ιnflammatory bowel disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), is increasingly associated with cardiovascular (CV) complications, such as heart failure (HF), arrhythmias, and acute coronary syndromes (ACSs). As the therapeutic landscape of IBD evolves, with the introduction of newer biologics and small molecules, their CV safety warrants critical evaluation. The objective of this review is to provide an update on the current evidence of CV risks associated with IBD treatments. Methods: A comprehensive literature search from inception to April 2025 was conducted using PubMed and Medline to identify randomized controlled trials, observational studies, systematic reviews, as well as pharmacovigilance data reporting CV safety outcomes of biologic and small-molecule drugs approved for IBD. Additionally, analysis of the European Summary of Product Characteristics for each agent was also performed. Results: Anti-TNF agents, particularly infliximab, have been associated with increased reporting of HF and arrhythmias, particularly in patients with pre-existing cardiac disease. Ustekinumab and vedolizumab show consistently favorable CV safety profiles across trials and real-world studies. IL-23p19 inhibitors demonstrate low CV event rates overall, although signals for atrial fibrillation have emerged with risankizumab. Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators carry class-specific CV warnings, due to signals mainly on non-IBD populations, and require careful use in high-risk individuals. Conclusions: Although most IBD therapies are generally safe from a CV perspective, certain agents may pose risks in vulnerable patients. Individualized CV risk assessment and ongoing post-marketing surveillance are essential to guide therapeutic choices and ensure patient safety. Full article

Background/Objectives: This post-marketing surveillance study was conducted to evaluate the safety and effectiveness of [¹⁷⁷Lu]Lu-DOTA-TATE in patients with GEP-NETs in real-world practice in South Korea. Methods: From July 2020 to July 2024, a total of 89 patients from 6 institutions diagnosed with GEP-NETs, as outlined in the approved indication for [¹⁷⁷Lu]Lu-DOTA-TATE, were enrolled. Safety was the primary objective, whereas effectiveness was a secondary objective. In this article, findings were analyzed and compared with the NETTER-1 and NETTER-2 trials. Results: Baseline characteristics were comparable to NETTER-1 and NETTER-2 except for the notably high proportion of G2 (77.1%) among participants. Less than half of patients (41.0%) completed four cycles of [¹⁷⁷Lu]Lu-DOTA-TATE treatment, presenting a lower portion of completion rate compared to 75.7% in NETTER-1 and 87.8% in NETTER-2. Among the 83 patients, 60 patients (72.3%, 239 cases) had at least 1 AE, with 6 patients (7.2%, 8 cases) experiencing SAEs. The most common AE was nausea (34.9%, 46 cases), and most AEs were mild in severity (94.6%, 226 cases). Overall, the safety profile in this study presented minimal differences from NETTER-1 and NETTER-2. This study reports 37.7% of ORR which was between 14.7% in NETTER-1 and 43.0% in NETTER-2. Conclusions: This nationwide post-marketing surveillance study complemented the safety and effectiveness of [¹⁷⁷Lu]Lu-DOTA-TATE among Koreans, which was not probed in two pivotal trials. The data would support the clinical implication of [¹⁷⁷Lu]Lu-DOTA-TATE for the GEP-NETs treatment. Full article

Background/objectives: This was a post hoc analysis of safety data across the bivalent respiratory syncytial virus prefusion F (RSVpreF) vaccine clinical trial development program. Methods: Data from eight clinical trials in 46,913 immunocompetent adults who received RSVpreF or placebo were analyzed. Local reactions and systemic events were assessed among non-pregnant ≥18-year-olds (n = 9517); adverse events (AEs) among pregnant and non-pregnant 18–59-year-olds (n = 9238); and vaccine-related AEs among non-pregnant ≥18-year-olds (n = 39,314). Post-marketing data in non-pregnant adults were considered. Results: Local reactions and systemic events were reported more frequently in RSVpreF versus placebo recipients; injection site pain was the most common local reaction (RSVpreF, 18.9%; placebo, 7.4%), and fatigue (23.5%; 18.4%) and headache (19.5%; 15.0%) were the most common systemic events. Percentages of AEs within 1 month after vaccination were similar across groups (RSVpreF, 12.8%; placebo, 13.1%); severe AEs were reported in ≤1.5% of participants. Differences in percentages of individuals reporting vaccine-related AEs between the RSVpreF and placebo groups were <0.2% for all related AEs. Serious AEs throughout the study were reported in ≤14.0% (RSVpreF, 12.6%; placebo, 14.0%). No atrial fibrillation, Guillain-Barré syndrome, or acute polyneuropathy cases were reported. The AE data from post-marketing data sources were consistent with the safety profile from the clinical trial program, with no new safety concerns. Conclusions: Integrated data demonstrated that RSVpreF was well tolerated with a favorable safety profile in non-pregnant and pregnant adults. Ongoing surveillance through real-world use and clinical trial experience continue to support the safety profile of RSVpreF. ClinicalTrials.gov: NCT03529773/NCT04071158/NCT04785612/NCT05035212/NCT05096208/NCT05842967/NCT04032093/NCT04424316. Full article

Maternal vaginal and rectal colonization by Streptococcus agalactiae (group B streptococcus, GBS) is the main risk factor for the development of newborn early-onset GBS disease (GBS-EOD). Much effort is in place for its prevention, including the development of vaccines. Currently, both a hexavalent glycoconjugate GBS vaccine against the most prevalent serotypes and a protein subunit vaccine have completed phase two clinical trials. GBS surveillance in both maternal carriage and neonatal disease is therefore important in establishing the coverage of the potential vaccines and in setting up the basis for pre- and post-marketing surveillance. A single-site study was conducted in the years 2020–2021 on the characteristics of 325 GBS strains (serotype distribution; identification of the alpha-like protein family member; and resistance to macrolides, tetracycline, and high-level gentamicin) isolated from the vaginal/rectal site in women in late pregnancy as well as in seven cases of GBS-EOD and one case of GBS-related stillbirth occurring in the same location and time period. The study indicated that the coverage of the developing vaccines was excellent (97.2% for the hexavalent glycoconjugate vaccine and 98.7% for the alpha-like protein subunit vaccine). However, the detection of the serotypes VI, VII, and IX—not covered by current vaccine formulations—accounting for 3.0% of isolates, as well as of negative alpha-like GBS strains from maternal carriage (1.2%), should be closely monitored over time. The high rates of GBS resistance to erythromycin (33.5%) and to clindamycin (29.5% in maternal carriage and 57.1% in GBS-EOD) was mostly due to the ever-increasing spread of the multidrug-resistant ST-17 subclone of serotype III. This finding, along with the newly emerging high-level gentamicin resistance in carriers (4.0%), mainly in serotype IV strains, poses a threat for the continued effectiveness of antibiotic therapy in invasive disease. Full article

The regulation of clinical trials for medicinal products and medical devices has undergone numerous changes in recent years in the European Union, challenging manufacturers and national regulatory agencies as well. With the introduction of combined drug–device products, the regulatory landscape has been drastically changed to adapt to novel technological advancements and innovations. A comparative analysis has not yet been published highlighting the main differences and common elements of these two medicinal products, which took up almost all of the market in the pharmaceutical sector. Due to stricter regulations in the field of medical devices, the process from application up until post-market surveillance became more difficult, but a correlation between the regulation of drug trials can also be found. The main differences lie in the risk management systems, where, regardless of the background knowledge of a drug, it is always strict and mandatory structured progress, while in the case of medical devices, it is more flexible based on the risk category of the product. Generally, the utilization of e-health opportunities, transparency, and data accessibility have been improved in both fields. Via the adaptation of the mentioned regulation in the EU, the safety of patients and the efficacy of trials have been greatly increased. This manuscript aims to compare the specific regulations of these two types of medicinal products with a brief outlook on the non-EU sector as well. Full article

Background/Objectives: Breast implants are widely used in reconstructive surgeries, as well as in cosmetic procedures, to enhance or restore breast shape and volume. With advances in techniques and materials, these devices have become safer and more effective over the years. Nevertheless, complications such as capsular contracture, rupture, infections, or other types of malignancies (BIA-SCC). This study evaluated the postmarketing safety and performance of implants via technovigilance data and a review of scientific studies. Methods: The research analyzed publications from the BVS, PubMed, Embase, and ClinicalTrials databases from between 2007 and 2023 (15 years), in addition to reports registered in the Notivisa system during the same period. Results: A total of 113 studies were identified, 15 of which were selected for the final analysis, which revealed that capsular contracture, seroma, infection, and rupture were the most common complications. In the Notivisa system, 786 reports were found, including 397 technical complaints and 389 adverse events, with pain, infections, and lymphoma among the most frequently reported issues. Conclusions: These findings highlight the importance of continuous surveillance to identify risks and promote improvements in the quality and safety of breast implants, ensuring patient well-being. As a practical contribution, a clinical decision-making algorithm was proposed to support healthcare professionals in the early identification and management of implant-related complications. Full article

Background: Respiratory syncytial virus (RSV) poses a significant health burden in children, being the major cause of lower respiratory tract infection (LRTI), including bronchiolitis. During the 2023–2024 RSV season, Spain introduced nirsevimab, a monoclonal antibody for universal RSV prophylaxis in infants. This study reviews the safety of nirsevimab through post-marketing surveillance. Material and Methods: A descriptive pharmacovigilance study was made based on spontaneous reporting data of suspected adverse events (SAEs) from the Spanish Pharmacovigilance System for Medicinal Products for Human Use (SEFV-H) and industry reports. SAEs reported between September 2023 and May 2024 were extracted from the Spanish Pharmacovigilance Adverse Reactions Data (FEDRA) database. Cases were analysed by sex, age, severity, and SAEs classification using the Preferred Terms (PT) level of the Medical Dictionary for Regulatory Activities (MedDRA). Reporting rates were estimated based on immunization coverage and birth data. Results: Sixty-seven cases reported 141 SAEs, yielding an overall rate of 23.1 cases per 100,000 doses. Common events included rash (8.51%), drug ineffectiveness (7.09%), and pyrexia (7.09%). Serious events constituted 53.70% of reports, including two fatalities (3.00%). No new safety signals or unexpected risks, such as antibody-dependent enhancement (ADE), were identified. Discussion: SAEs reported peaked early in the campaign, reflecting heightened reporting in new immunization programs. The safety profile aligns with clinical trial findings and regulatory expectations, confirming nirsevimab’s benefit–risk balance. Continued pharmacovigilance is critical for maintaining public trust in RSV prophylaxis. Nirsevimab demonstrated a favorable safety profile during Spain’s initial universal RSV immunization campaign in infants, supporting its continued use in reducing RSV-related morbidity. Full article

Pharmacovigilance plays a central role in safeguarding public health by continuously monitoring the safety of vaccines, being critical in a climate of vaccine hesitancy, where public trust is paramount. Pharmacovigilance strategies employed to gather information on adverse events following immunization (AEFIs) include pre-registration data, media reports, clinical trials, and societal reporting. Early detection of AEFIs during clinical trials is crucial for thorough safety analysis and preventing serious reactions once vaccines are deployed. This review highlights the importance of societal reporting, encompassing contributions from community members, healthcare workers, and pharmaceutical companies. Technological advancements such as quick response (QR) codes can facilitate prompt AEFI reporting. While vaccines are demonstrably safe, the possibility of adverse events necessitates continuous post-marketing surveillance. However, underreporting remains a challenge, underscoring the critical role of public engagement in pharmacovigilance. This narrative review comprehensively examines and synthesizes key aspects of virus vaccine pharmacovigilance, with special considerations for specific population groups. We explore applicable legislation, the spectrum of AEFIs associated with major vaccines, and the unique challenges and perspectives surrounding pharmacovigilance in this domain. Full article