Therapeutic innovation & regulatory science最新文献

{"title":"Recommendation Paper on Advancing the Use of Decentralised Elements in Clinical Trials.","authors":"Alison Bond, Tracey Robertson, Christine Fletcher, Elizabeth Theogaraj, Greg Jordinson, Scott Askin","doi":"10.1007/s43441-025-00796-w","DOIUrl":"https://doi.org/10.1007/s43441-025-00796-w","url":null,"abstract":"<p><p>The expansion of the use of decentralised elements in clinical trials in the European Union is driven by the opportunities they offer, including their potential to enhance trial access and improve research outcomes. Despite these potential benefits, several regulatory, operational, and technological challenges impede their widespread adoption. This paper, developed by members of the European Federation of Pharmaceutical Industries and Associations, proposes strategies and policy recommendations to overcome these barriers. Through harmonised regulatory frameworks, improved data validation methods, and increased stakeholder collaboration, the use of decentralised elements could become a standard practice in clinical research as part of the clinical trial toolbox to be deployed as appropriate, thereby enabling innovation and allowing for equitable access to clinical trials for diverse populations.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161112","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":"Review of Recent Pharmacoepidemiologic Post-Market Safety Studies Through the Lens of the Estimand Framework.","authors":"Yong Ma, Jonathan Haddad, Wei Liu, Ellen Snyder, Dimitri Bennett, Susan Mayo","doi":"10.1007/s43441-025-00780-4","DOIUrl":"10.1007/s43441-025-00780-4","url":null,"abstract":"<p><p>The ICH E9(R1) estimand framework provides a systematic approach to ensure alignment among clinical trial objectives, trial conduct, statistical analyses, and interpretation of results, however, whether it can be readily utilized for the pharmacoepidemiologic safety studies has not been established. We selected articles on drug safety published in the Journal Pharmacoepidemiology and Drug Safety (PDS), during 2020 to investigate whether estimand attributes were well defined in the study design and reporting. We found that among twenty-five articles selected, nineteen were cohort studies and six were nested case-control studies. All studies had well-defined exposure, outcome, target population, and population level summary. The term intercurrent event (ICE) was not mentioned in any of the studies; however, many cohort studies discussed drug discontinuation, treatment modification and terminal events, and strategies to handle them. All studies used methods to control for confounding: propensity score methods or covariate adjustment, or both for cohort studies; matching and covariate adjustment for the nested case-control studies. We conclude that while the estimand framework can serve to add clarity and precision to pharmacoepidemiologic safety studies, more detailed considerations are required for bias assessment to compensate for the lack of randomization and other shortcomings in observational studies. Recent pharmacoepidemiology frameworks, such as Target Trial Emulation, STaRT-RWE, HARPER could be combined with the complementary principals from the estimand framework to help achieve the study objectives.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161136","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":"https://doi.org/10.1007/s43441-025-00814-x","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-26","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":"The Path To Tarlatamab Approval: Leveraging Innovative Strategies and Global Regulatory Pathways.","authors":"Vandana Pathak, Claudia Arredondo Pimentel, Elli Cooney, Brian Abbott, Jacqueline M Kline","doi":"10.1007/s43441-025-00809-8","DOIUrl":"https://doi.org/10.1007/s43441-025-00809-8","url":null,"abstract":"<p><p>On May 16, 2024, tarlatamab-dlle (IMDELLTRA^®) received approval as the first FDA DLL3 targeting bispecific T-cell engager (BiTE^®) therapy indicated for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) who have experienced disease progression on or after platinum-based chemotherapy. This case study provides insights into the regulatory mechanisms, including global expedited pathways, special designations, and US FDA's Oncology Center of Excellence initiatives, which played a key role in the expedited development, review, and approval of the tarlatamab marketing authorization application (MAA) globally.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151897","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":"Letter to the Editor - Reply to \"Advancing AI Ethics Frameworks in Drug Development: Global Applicability, Practical Challenges, and Dynamic Governance\".","authors":"Timothé Ménard, Katrina A Bramstedt","doi":"10.1007/s43441-025-00813-y","DOIUrl":"https://doi.org/10.1007/s43441-025-00813-y","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151877","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":"Keeping the End in Mind: Reviewing U.S. FDA Inspections of Submissions including Real-World Data.","authors":"Cheryl Grandinetti, Donna R Rivera, Lee Pai-Scherf, Anna Choe, Paul G Kluetz, Stefanie Kraus, Gabriel K Innes, Kassa Ayalew","doi":"10.1007/s43441-025-00791-1","DOIUrl":"https://doi.org/10.1007/s43441-025-00791-1","url":null,"abstract":"<p><p>The increasing use of real-world data (RWD) to generate real-world evidence (RWE) presents unique opportunities and challenges for drug development and regulatory decision-making, particularly in the area of good clinical practice inspections. FDA typically focuses their application review-based inspections on pivotal studies that generate evidence submitted to support new drug and biological product applications. This focus applies regardless of the data sources used in those studies. In this article, we discuss the fundamental role of good clinical practice inspections in verifying the quality, integrity, and reliability of RWD used in regulatory submissions. Through case examples, we highlight specific challenges related to accessing RWD source records, assessing data quality, and evaluating processes for data curation, transformation, and analysis. Our experience underscores the importance of early engagement with regulatory agencies as well as the implementation of robust quality management practices throughout the study lifecycle. As RWD continues to shape the regulatory landscape, these case examples provide insights in navigating the complexities associated with submissions utilizing RWE for drug approval.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143714","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":"Cancer Clinical Trial Patients' Perceptions of Reporting Adverse Events Via an Electronic Platform.","authors":"Minna Grahvendy, Bena Brown, Laurelie R Wishart","doi":"10.1007/s43441-025-00804-z","DOIUrl":"https://doi.org/10.1007/s43441-025-00804-z","url":null,"abstract":"<p><strong>Background: </strong>Accurate adverse event (AE) reporting is critical to the success of clinical trials; over the last 10 years, momentum has been building to collect AE data directly from the patient. In this study, we investigated the use of an electronic, web-based platform by which cancer clinical trial patients self-reported AE data. In this report, we explored the perceptions and experiences of participants using the platform during participation in an interventional clinical trial.</p><p><strong>Methodology: </strong>Patients consenting to an interventional clinical trial run by a cancer clinical trial unit at a tertiary hospital in Australia were eligible for enrolment. Participants used an online platform to report symptomatic data weekly over 26 weeks. Participant feedback on the platform was collected via an implementation survey at baseline, week 12, and week 26 and a qualitative interview at week 26.</p><p><strong>Results: </strong>Participants agreed that the platform was acceptable, appropriate, and feasible in its purpose. This agreement remained throughout their participation on the study. Qualitative analysis of interview data revealed three major themes: accessibility and useability, platform functionality, and personal attributes and benefits/burdens. Participants reported areas for improvement, primarily around platform functionality and consideration of symptom burden limiting participant capacity to engage with the platform.</p><p><strong>Conclusions: </strong>To our knowledge, this is the first study that investigates, in-depth, the participant experience of self-reporting cancer clinical trial AE data via an electronic platform. Our study lends evidence from the participant-perspective to previously-reported studies investigating the feasibility of collecting AE data directly from the patient. Participants agreed that the platform was feasible and would be of benefit to future cancer clinical trial participants.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128811","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":"Navigating the Trends in USFDA Authorized Generic Approvals (2019-2024): Enhancing Healthcare Accessibility and Affordability.","authors":"M Sowndharya, Ramesh Joga, Kajal Gandhi, Gadekar Kailas Vijay, Sonali Waikar, Sravani Yerram, Rajeev Singh Raghuvanshi, Saurabh Srivastava","doi":"10.1007/s43441-025-00806-x","DOIUrl":"https://doi.org/10.1007/s43441-025-00806-x","url":null,"abstract":"<p><strong>Objective: </strong>This study examines trends in USFDA's authorized generic (AG) approvals from January 2019 to August 2024, focusing on approval patterns, leading therapeutic areas, dominant dosage forms, and key companies. The research aims to highlight market dynamics and the role of AGs in enhancing healthcare accessibility and affordability with case studies.</p><p><strong>Methods: </strong>Data was collected from the FDA's list of authorized generic drugs and analyzed to identify trends in annual approvals, therapeutic areas, and dosage forms. A company-wise analysis was conducted to identify top performers, with a detailed evaluation of their approval trends and strategic focus areas across therapeutic categories. Recent case studies of AGs were included to explore their clinical and economic significance. The impact of the Inflation Reduction Act, Continuing Appropriations Act, of 2020, and Health Extenders Act of 2019 on the definition and pricing of AGs, as well as its implications for the pharmaceutical industry and Medicaid Drug Rebate Program, were examined.</p><p><strong>Results: </strong>AG approvals peaked in 2019 (31%) and 2020 (33%), then declined. Leading therapeutic areas were cardiovascular (18%), neurology (14%), and endocrinology (13%). Tablets comprised 35% of approvals, followed by capsules (23%) and solutions (9%). GlaxoSmithKline led with 7% of approvals, primarily in pulmonology and migraine, while Bausch Health (6.25%) focused on dermatology and endocrinology. IBSA Pharma (5.47%) excelled in endocrinology and pain management. Pfizer and Cediprof each had 4.69%, with Pfizer focusing on cardiovascular and infectious diseases, and Cediprof specializing in endocrinology. Recent case studies of AGs provided an affordable, effective alternative for diabetes and cardiovascular care.</p><p><strong>Conclusion: </strong>AGs effectively bridge the transition from branded to generic drugs, supporting broader access to treatment, cost efficiency, and ongoing innovation in the pharmaceutical sector. The analysis highlights AGs' significant role in addressing healthcare needs while underscoring challenges like exclusivity agreements and profit constraints for traditional generics. These findings affirm AGs as pivotal in advancing pharmaceutical market dynamics and healthcare affordability.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120925","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 Oncology Drug Development in the US: The Interplay between Innovations and Regulatory Science.","authors":"Yannan Nancy Dou, Jian Wang","doi":"10.1007/s43441-025-00800-3","DOIUrl":"https://doi.org/10.1007/s43441-025-00800-3","url":null,"abstract":"<p><p>The landscape of drug development has evolved with the adoption of new therapeutic modalities, cutting-edge technology platforms, emerging scientific insights, and modern patient-centric clinical trial designs. In this review, we investigate the interplay between innovation and regulatory science in cancer drug development in the United States. As new innovations emerge, regulatory science adapts to integrate new discoveries and technologies, ensuring alignment with established regulations and safety standards. This fuels additional innovations through data and evidence generation, potentially expediting the development of revolutionary treatments and advancing patient access to novel, promising therapies. Early and frequent engagement with regulators is vital for drug developers aiming to successfully apply innovative approaches.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128810","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":"Genome Editing in Gynecological Oncology: The Emerging Role of CRISPR/Cas9 in Precision Cancer Therapy.","authors":"Naina Kumar","doi":"10.1007/s43441-025-00807-w","DOIUrl":"https://doi.org/10.1007/s43441-025-00807-w","url":null,"abstract":"<p><strong>Introduction: </strong>Gynecological cancers, including cervical, ovarian, and endometrial cancers, represent a significant global health challenge due to their high prevalence and profound impact on mortality and quality of life. This narrative review explores the transformative capability of genome editing, specifically clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) technology, in advancing the management of these cancers. Genome editing offers great opportunities to develop targeted therapies by enabling precise modifications of genes involved in cancer initiation, progression, and chemoresistance.</p><p><strong>Methodology: </strong>A comprehensive literature search was conducted from October 2004 to October 2024. Only peer-reviewed relevant English articles with substantial insights into the impact of genome editing on cancer therapies were considered using keywords such as \"CRISPR/Cas9,\" \"genome editing,\" \"gynecological cancers,\" and specific cancer types like \"cervical cancer,\" \"ovarian cancer,\" and \"endometrial cancer.\"</p><p><strong>Conclusion: </strong>Genome editing, particularly CRISPR/Cas9, holds substantial capacity for revolutionizing the treatment landscape of gynecological cancers by enabling highly specific, gene-targeted therapies that can overcome conventional treatment limitations such as chemoresistance and tumor recurrence. Emerging preclinical studies demonstrate the feasibility of correcting oncogenic mutations and enhancing the sensitivity of tumors to existing therapies. However, before clinical translation can be realized, critical challenges-including off-target effects, delivery system optimization, and immune responses-must be systematically addressed through rigorous research and clinical trials. Advancing these solutions will be essential for safely integrating CRISPR-based interventions into personalized medicine approaches for gynecological malignancies.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111996","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}