Therapeutic innovation & regulatory science最新文献

{"title":"Application of Bayesian Borrowing Methods in Clinical Trials for Children with Type II Diabetes Mellitus.","authors":"Roberto Crackel, Yuanyuan Ji, Yoonhee Kim, James Travis, Wenda Tu, Yun Wang, Sunghee Kim, Pablo Bonangelino","doi":"10.1007/s43441-025-00874-z","DOIUrl":"https://doi.org/10.1007/s43441-025-00874-z","url":null,"abstract":"<p><p>Clinical trials for children with type II diabetes mellitus (T2DM) pose challenges often due to recruitment issues. The variability in the treatment effect for pediatrics with T2DM tends to be much larger than that for adults, therefore, a larger pediatric study is needed to independently detect a similar treatment effect. If leveraging adult information to a pediatric population can be appropriately justified, and scientific rational has been given for the relevancy of the adult information, then Bayesian borrowing methods can aid in reducing the number of patients needed for a pediatric study and therefore increase feasibility and efficiency. We introduce Bayesian borrowing methods to obtain scientifically sound and conclusive results with adequate study power in anti-diabetic products development for children with T2DM. To apply Bayesian borrowing methods, it is important to (1) identify the external data that can be leveraged, (2) pre-specify model parameters, (3) assess operating characteristics, and (4) pre-specify weights and the maximum amount of borrowing needed to achieve a study win. To protect against prior-data conflicts that may exist due to differences in T2DM between adults and pediatrics, we select a mixture prior to take an advantage that they adjust the degree of information borrowed based on the similarity between adults and pediatrics. We applied these methods to an anti-diabetic product. In conclusion, the outcomes of our step-by-step demonstration of the application of Bayesian borrowing methods provides a guide on how to pre-specify parameters and considerations that should be made when planning to implement said methods.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Review of Trials for Unsuccessful Pediatric Drug Development Programs Submitted to the US Food and Drug Administration 2015-2022.","authors":"Sherbet Samuels, Mark Seaton, Susan M Abdel-Rahman, Gilbert J Burckart","doi":"10.1007/s43441-025-00864-1","DOIUrl":"https://doi.org/10.1007/s43441-025-00864-1","url":null,"abstract":"<p><strong>Background: </strong>Legislative initiatives have spurred an increase in pediatric drug development programs. However, some drug products studied in the pediatric population have not received an approved pediatric indication, and efforts have been made to improve the outcomes of a greater percentage of pediatric trials.</p><p><strong>Objective: </strong>This analysis evaluated the rate of failure and the factors associated with those unsuccessful outcomes of recent pediatric drug development programs in comparison to earlier pediatric drug development programs.</p><p><strong>Methods: </strong>Publicly available information for non-oncology pediatric drug development programs submitted to the FDA between 2015 and 2022 were reviewed.</p><p><strong>Results: </strong>FDA reviews and drug product labeling for 211 drug products were examined. Of these, 32 (32/211, 15%) drug products for which pediatric trials were conducted did not receive an approved pediatric indication. The reasons for these unsuccessful outcomes were failure to demonstrate effectiveness only (18/32, 56%), failure to demonstrate safety only (7/32, 22%), or failure to demonstrate both effectiveness and safety (7/32, 22%). The psychiatry (8/32, 25%) and pain (5/32, 17%) therapeutic areas had the highest number of drug products that did not receive a pediatric indication.</p><p><strong>Conclusion: </strong>The findings from this review suggest that, although this represents an improvement from pre-2012 pediatric drug development programs, that basic problems are still encountered in pediatric trial designs and dose selection. The 15% failure rate may represent close to a best-case scenario for pediatric drug development presently, but an increased use of pediatric extrapolation could change that.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incretin Dominance and Emerging Mechanisms in Obesity Pharmacotherapy: Insights from 275 Registered Clinical Trials (2019-2024).","authors":"Lucas Antônio Dos Santos Barbosa, Bassel Almarie, Eduardo Luiz Gasnhar Moreira","doi":"10.1007/s43441-025-00875-y","DOIUrl":"https://doi.org/10.1007/s43441-025-00875-y","url":null,"abstract":"<p><p>Obesity remains a critical global health challenge, with rising prevalence and a substantial cardiometabolic and psychosocial burden. Recent therapeutic advances, particularly in incretin-based strategies, underscore the need for a comprehensive characterization of the evolving pharmacological landscape. We conducted a systematic review of clinical trials registered on ClinicalTrials.gov between October 2019 and October 2024, focusing on pharmacological interventions for obesity from early exploratory stages to Phase 3. A total of 275 eligible trials were identified and analyzed. Incretin pathway modulators predominated (69.8%), especially GLP-1 receptor agonists and dual or triple agonists targeting GLP-1, GIP, and glucagon receptors. Most trials were in Phase 2 (40.7%) or Phase 3 (31.3%), indicating a maturing pipeline, while early-stage innovation remained limited (3.3% of trials). Drug repurposing was common (22.2%), notably involving semaglutide and liraglutide, originally approved for type 2 diabetes. Industry-sponsored trials constituted the majority (75.3%), with limited academic (22.2%) and governmental (2.5%) participation. Geographically, trials were concentrated in the United States, China, and Denmark, with relatively few international multicenter studies. While the obesity drug pipeline is expanding rapidly, it remains heavily centered on incretin-based therapies. This dominance, despite strong clinical efficacy, raises concerns regarding long-term safety, accessibility, and mechanistic diversity. Greater investment in early-phase innovation and alternative pharmacological targets will be essential to diversify treatment options and address the unmet need for equitable and sustainable obesity management.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Preliminary Study Introducing Electronic Patient-Reported Outcome (ePRO) Using Bring Your Own Device (BYOD) in Post-marketing Surveillance in Japan.","authors":"Naomi Sugimoto, Mika Morimasa, Hidetoshi Misawa, Nobushige Matsuoka, Yurami Sato, Hiromi Yamaguchi, Tetsuya Hiraiwa, Natsuno Yamashita, Akira Hoshino, Masanori Kawai","doi":"10.1007/s43441-025-00873-0","DOIUrl":"https://doi.org/10.1007/s43441-025-00873-0","url":null,"abstract":"<p><strong>Background: </strong>The method of collecting electronic patient-reported outcome (ePRO) data using the bring your own device (BYOD) approach has become very common recently, especially in clinical trials. We conducted a preliminary study to evaluate the processes before introducing ePRO using BYOD in regulatory-required observational post-marketing surveillance (PMS) in Japan.</p><p><strong>Methods: </strong>We conducted a multicenter observational study using a two-period, two-sequence, cross-over design. Participants were allocated to Group 1 (starting with ePRO) or Group 2 (starting with paper PRO). The observation period was 14 days in total: seven days each for ePRO and paper PRO. We assessed the usability, implementation process, support system, and materials for ePRO through questionnaires.</p><p><strong>Results: </strong>All participants in Group 1 (n = 78) and Group 2 (n = 73) were included in the analysis set. The collection of information with ePRO was comparable to that with paper PRO. We found no remarkable difference in data entry status between ePRO and paper PRO based on sex and no trend toward a higher proportion of missing data in ePRO with age. More than half of the participants responded favorably to most of the questionnaire items about ePRO. Although the investigators considered the materials for the ePRO system useful, there is still room for improvement.</p><p><strong>Conclusion: </strong>Our two-week pilot indicates that ePRO can achieve data completeness comparable to paper in motivated clinics. The points to consider when using ePRO in actual PMS were confirmed. Further assessment in actual studies conducted in compliance with local regulations is needed.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Use of Unmanned Aerial Vehicles (UAV) on Delivering Biological Samples for COVID-19 and Tuberculosis Diagnosis: A Scoping Review.","authors":"Olga Maíra Machado Rodrigues, Izabela Gimenes Lopes, Mariah Eduarda Ferreira de Oliveira, Mônica Angélica Carreira Fragoso, Maria Regina Fernandes de Oliveira, Raquel Santos Silva, Glaura Regina de Castro E Caldo Lima, Amílcar Sabino Damazo, Wagner de Jesus Martins","doi":"10.1007/s43441-025-00865-0","DOIUrl":"https://doi.org/10.1007/s43441-025-00865-0","url":null,"abstract":"<p><strong>Purpose: </strong>To identify and review scientific evidence from experimental studies utilizing unmanned aerial vehicles (UAVs) to transport samples for the diagnosis of COVID-19 and tuberculosis (TB). This exploratory study aims to support the future development of UAVs for transporting biological samples within the Brazilian Unified Health System (SUS).</p><p><strong>Methods: </strong>This scoping review defined its eligibility criteria using the PECO acronym, focusing on: Population: biological samples for diagnosing COVID-19 or TB; Exposure: UAV transportation; Comparator: land transportation; Outcomes: Cost, effectiveness, methods for sample preservation, flight parameters (time, altitude, speed, distance), and quality of transported samples. Eligible studies were identified through searches in Medline via PubMed, Scopus, Embase, and Web of Science. Grey literature was explored via Google Scholar.</p><p><strong>Results: </strong>Of the 2,052 articles initially found, 797 were duplicates, 1,247 were screened by title and abstract and excluded, eight were retrieved (and fully read) of which five met the eligibility criteria and were included in the review. These studies provided diverse evidence regarding cost, operational performance, safety, and sample integrity.</p><p><strong>Conclusion: </strong>The reviewed studies demonstrate promising applications of UAVs in healthcare logistics. However, regulatory and legal frameworks require adaptation to ensure operational safety. Further experimental studies are necessary, particularly involving beyond visual line of sight (BVLOS) operations, to evaluate scalability and potential cost reductions.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Future-Proofing European Pharmaceutical Regulatory and Market Access Practices Based on EU Learnings from the COVID-19 Pandemic: Insights from Multi-Stakeholder Interviews.","authors":"Zilke Claessens, Grace Beirne, Catherine Decouttere, Nico Vandaele, Liese Barbier, Isabelle Huys","doi":"10.1007/s43441-025-00855-2","DOIUrl":"https://doi.org/10.1007/s43441-025-00855-2","url":null,"abstract":"<p><strong>Introduction: </strong>During the COVID-19 pandemic, regulatory and market access actions were taken to expedite the market entry of COVID-19 medicines. This study aims to (i) capture multi-stakeholder views on these actions, and (ii) provide recommendations for future-proofing routine and health-emergency frameworks.</p><p><strong>Methods: </strong>Semi-structured interviews were conducted with policy makers/advisors (i.e. regulators, HTA assessors, and payers), and pharmaceutical industry representatives across Europe to elicit their perspectives on marketing authorisation and market access practices during the COVID-19 pandemic. Interviews were transcribed ad verbatim and transcripts analysed via the thematic framework method.</p><p><strong>Results: </strong>The interviews (n = 16) resulted in an overview of stakeholder-perceived benefits and limitations for four key regulatory advice or authorisation procedures (i.e. emergency task force, rapid scientific advice, rolling review, conditional marketing authorisation) and one market access procedure (i.e. joint procurement) applied during the COVID-19 pandemic. Highlighted benefits of the procedures relate to a reduction in timelines, enhanced collaboration and alignment, procedural flexibilities, and often a combination of these. Challenges are linked to inefficient allocation of time and resources for both industry representatives and policymakers/advisors and decreased transparency in certain procedures. In addition, several recommendations for the optimisation of both the routine and health-emergency healthcare framework were proposed. Emphasis is placed on the need for enhanced interaction and alignment between industry representatives and policymakers/advisors but also within stakeholder groups, development of more pragmatic and flexible procedures, and application of clear and transparent eligibility criteria for facilitating actions.</p><p><strong>Conclusion: </strong>This study provides an overview of the perceptions from regulatory, and market access practices during COVID-19, highlighting how these experiences can inform regulatory and market access practices both in routine times and during health emergencies. Taking stock of stakeholder reflections and lessons learned are valuable for improving preparedness and responsiveness in future health crises.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reliance into Action : Understanding EMA Documents to Streamline Reliance for Marketing Authorization Applications.","authors":"Isabelle Colmagne Poulard, Susanne Ausborn, Martin Harvey Allchurch, Victoria Palmi, Alberto Ganan, Angelika Joos, Andrew Deavin, Corentin Beauchesne, Priti Shah, Jyothsna Krishnan, Chaima Askri","doi":"10.1007/s43441-025-00824-9","DOIUrl":"10.1007/s43441-025-00824-9","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1032-1041"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficiency of Lifecycle Management for Medicinal Products in the EU: Industry Experience with Variations to Implement a New European Pharmacopoeia Active Substance Monograph for a Generic Eye Drops Solution - A Case Study.","authors":"Fabian P Schwarb, Betty Lämmel, Beatrice A Harder Engelhard","doi":"10.1007/s43441-025-00802-1","DOIUrl":"10.1007/s43441-025-00802-1","url":null,"abstract":"<p><strong>Background: </strong>While numerous efforts were taken by the regulators globally to have more streamlined and predictable post-approval CMC variation procedures, there are still areas where cumbersome and parallel assessments of variations may delay implementation of important CMC changes and bind resources in industry and regulatory authorities.</p><p><strong>Methods: </strong>In this case study a switch from an ASMF (Active Substance Master File) to the CEP (Certification of Suitability to the monographs of the European Pharmacopoeia) for an already approved manufacturer used for a generic ophthalmic formulation with 38 licenses (Marketing Authorisations, MAs) in the EEA was selected to investigate time needed for generation, submission and approval of variations as well as consistency of variation classification by experienced regulatory professionals and Competent Authorities (CAs), respectively.</p><p><strong>Results: </strong>Overall, four variations were needed for the change from an ASMF to the CEP to cover the concomitant changes that were required to fully align with the European Pharmacopoeia (Ph. Eur.) requirements for the active substance and consequentially for drug product. In one case the CA requested a 5th variation to cover the switch from in-house to Ph. Eur.</p><p><strong>Requirements: </strong>While average CAs approval time was 4.6 (± 2.1) months (range 2-8 months), overall it took 15.2 (± 2.8) months (range 11-20 months) from data collection and variation generation by the CDMO (Contract Development and Manufacturing Organization) until approval by the respective CA. Good alignment was achieved for most of the aspects, however, when implementation of Ph. Eur. requirements included removal or widening of acceptance criteria, there were quite diverse opinions on the classification by regulatory professionals and CAs, resulting in the same change to be approved as Type IA, Type IB, and Type II variations, respectively, in the different EEA countries.</p><p><strong>Conclusions: </strong>The long lead times and inconsistent variation classifications hamper switching to a new CEP or adding a new active substance supplier. More efficiency in variation regulations would be beneficial to allow for faster implementation of changes to assure the supply chain.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1042-1052"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing AI Ethics Frameworks in Drug Development: Global Applicability, Practical Challenges, and Dynamic Governance.","authors":"Kai Chen, Zekai Yu","doi":"10.1007/s43441-025-00814-x","DOIUrl":"10.1007/s43441-025-00814-x","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"933-934"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Phase I Clinical Trial Design of Anti-Cancer Agents.","authors":"Juhee Cho, Haesook Bok, Taeyoun Jo, Sohyun Ahn","doi":"10.1007/s43441-025-00830-x","DOIUrl":"10.1007/s43441-025-00830-x","url":null,"abstract":"<p><p>Since 2000, there have been cancer research and regulatory changes in the development of anti-cancer therapies. The broadening understanding of cancer biology, coupled with advances in molecular biology and technology, has led to the development of new cancer drugs with diverse mechanisms of action. This study aims to analyze the trends and major features of Phase 1 clinical trial designs for anti-cancer agents approved by the U.S. FDA between 2013 and 2024. Out of the 143 anticancer drugs approved between 2013 and 2024, targeted therapies were the most common drug class, accounting for 86 approvals. Notably, there has been a recent increase in the approval of bi-specific T-cell engagers. Lung cancer and leukemia each had the highest number of initial indications, with 24 and 21 drugs for each. It was considered that the primary objective of phase I study was to determine DLT (Dose-Limiting Toxicity), MTD (Maximum Tolerated Dose), and RP2D (Recommended Phase 2 Dose), with secondary objectives focusing on observing antitumor responses, regardless of drug class. The overall design features of Phase I clinical trials for anticancer drugs can be described as 'non-randomized,' 'open,' 'without comparison,' and 'seamless dose expansion'. During the research period from 2013 to 2024, the 3 + 3 dose escalation design has seemed remained the most commonly used approach.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"909-918"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}