Therapeutic innovation & regulatory science最新文献

{"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":"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":"956-962"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446128/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: 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/s43441-025-00821-y","DOIUrl":"10.1007/s43441-025-00821-y","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"981"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294883","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":"Leveraging Artificial Intelligence for Advancements in Liquid Dosage Formulations in the Pharmaceutical Industry.","authors":"D Nithyanantham, Akhil Nair, Usha Y Nayak","doi":"10.1007/s43441-025-00823-w","DOIUrl":"10.1007/s43441-025-00823-w","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1004-1031"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485852","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":"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":"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":"963-970"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","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":"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":"971-980"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446131/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practice of Cryopreservation of Cellular Starting Materials from the Asia-Pacific Region: An Industrial Perspective.","authors":"Yun Hsiang Chang, Yuma Fujimori, Cheng Chieh Chen, Masayo Urabe, Taeko Karaki, Yusuke Izumi, Kaoru Kaneko, Kisaragi Mochiki","doi":"10.1007/s43441-025-00808-9","DOIUrl":"10.1007/s43441-025-00808-9","url":null,"abstract":"<p><p>Chimeric antigen receptor T-cell (CAR-T) therapy uses autologous T cells from patients to eliminate malignant targets. Cryopreservation of cellular starting materials, particularly fresh leukocytes, is an important step before production. While this promising specialized immune therapy is advancing, regulations have evolved, as specified in the US (21CFR1271) and Europe (EU Annex 1, 1394/2007). Cryopreservation is considered by this as minimal manipulation or is not considered as substantial manipulation unless there is alteration of relevant biological cell characteristics or cellular engineering. Similar consideration has been made by health authorities in Australia and South Korea. Conversely, the health authority in Japan determines if the starting material is applicable to Good Gene, Cellular, and Tissue-based Products Manufacturing Practice based on scientific data regarding the impact on product quality and safety. Whereas regulations have evolved in the US and EU, this is the first article to systemically review, from a manufacturer's perspective, the specific regulatory positions taken towards cryopreservation in Asia-Pacific (APAC) countries, i.e. Japan, Australia and South Korea. These positions generally consider that formulation and cryopreservation should be performed in a closed system, thus protecting cellular starting materials from contaminant exposure with a low-risk approach. Local and centralized cryopreservation logistics are discussed along with optimal implementation practices. The impact of geographic access on cryopreservation logistics, as well as the importance of careful evaluation of logistical and cost aspects for successful supply of CAR-T therapies in APAC, are also discussed.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1107-1116"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216947","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":"Electronic patient-reported outcome assessments: evaluating patient preference for the number of items per screen.","authors":"Jennifer Lord-Bessen, Danielle Rodriguez, Karin S Coyne, Spencer Schaff, Alexandra V Kalpadakis-Smith","doi":"10.1007/s43441-025-00811-0","DOIUrl":"10.1007/s43441-025-00811-0","url":null,"abstract":"<p><strong>Background: </strong>In clinical trials, the single-item-per-screen format is commonly used for electronic patient-reported outcomes (ePROs). However, participant preferences for this format over multiple items per screen have not been investigated. This study evaluated participant preferences for single-item-per-screen vs. multiple-items-per-screen ePRO formats, the effect on completion times, and the comparability of scores between formats.</p><p><strong>Methods: </strong>Participation in this randomized, crossover, observational study involved ePRO completion in both single-item-per-screen and multiple-items-per-screen formats on an electronic tablet device during two study visits. A paper-based preference questionnaire was completed at each visit.</p><p><strong>Results: </strong>Thirty-seven adults (mean [SD] age = 49.6 [15.4] years; 51.4% female; 54.1% White) enrolled and 36 participants completed both visits. Twelve participants (33.3%) preferred the multiple-item format, 12 (33.3%) preferred the single-item format, 10 (27.8%) had no preference, and 2 (5.6%) did not notice a difference. Seventeen participants (47.2%) preferred the single-item format when participating in a clinical trial, and most (n = 20; 55.6%) believed that others would prefer this format in a clinical trial. The ePRO completion time (minutes:seconds) was longer for the single-item format than the multiple-item format (mean [SD], 6:42 [2:24] vs. 6:21 [2:22]; p = 0.1540). The ePRO scores were similar across both formats.</p><p><strong>Conclusion: </strong>This study provided evidence that both single-item and multiple-items-per-screen presented on an electronic tablet device are acceptable to users and that format preference may be specific to each individual. Thus, clinical programs need to consider the targeted study population, the purpose of use, and the overall trial design when designing ePRO solutions.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1138-1147"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267284","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":"10.1007/s43441-025-00813-y","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"932"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","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":"Diverse Roles and Characteristics of Academic Research Organizations in Japan: Results of A Questionnaire-Based Study.","authors":"Reo Tanoshima, Riki Tanaka, Koji Hara, Hironori Fukuoka, Tatsuya Haze, Naoko Inagaki, Akifumi Ijuin, Manabu Nitta, Yusuke Kobayashi, Kozo Okada, Akito Nozaki, Etsuko Miyagi, Tetsuya Yamamoto, Takahisa Goto","doi":"10.1007/s43441-025-00797-9","DOIUrl":"10.1007/s43441-025-00797-9","url":null,"abstract":"<p><strong>Background: </strong>Clinical trials in Japan are governed by three regulations: Japanese Good Clinical Practice (J-GCP), the Clinical Trials Act, and the Ethical Guidelines for Medical and Biological Research Involving Human Subjects. Academic research organizations (AROs) are non-profit entities established to support clinician-scientists in conducting rigorous and high-quality clinical trials. However, Japan's unique decentralized clinical trial system has resulted in relatively small AROs with diverse roles. Additionally, work style reforms among Japanese physicians pose challenges for allocating time to research. This study aimed to assess the demographics, activities, and roles of AROs in Japan.</p><p><strong>Methods: </strong>We distributed a questionnaire survey to 31 AROs in Japan between October and December 2023. The survey collected data on organizational mission, vision, annual planning, clinical trial support, the number of supported studies, financial independence, and management of researchers' working hours.</p><p><strong>Results: </strong>Responses were received from 20 AROs (64.5%), including five public university hospitals and two clinical research core hospitals. The median staff size was 26.7 (range: 2-80), with public university hospitals reporting a median of 22.6 (range: 1449). Y-NEXT had a larger staff size (53.4) compared with other public university hospitals but fewer than clinical research core hospitals (median: 78.5). Thirteen AROs (65.0%) reported having organizational missions, and 25.0% were financially independent. Effort allocation for staff varied among institutions, and six AROs (30.0%) managed researchers' working hours.</p><p><strong>Conclusion: </strong>The roles and ultimate goals of AROs vary across institutions, highlighting the need for alignment with each institution's clinical research priorities and principles.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1098-1106"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187980","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":"Exploring Diabetes Clinical Trial Participation: A Diverse Group Interview Study.","authors":"Deborah A Taira, Kauilaonālani Tengan, Julia Takata, Cody Porter, Mona Shing Ranken, Tetine L Sentell, Todd B Seto","doi":"10.1007/s43441-025-00867-y","DOIUrl":"https://doi.org/10.1007/s43441-025-00867-y","url":null,"abstract":"<p><strong>Background: </strong>Clinical trial participation is critical for ensuring new medical treatments are safe and effective for all populations. Native Hawaiian (NH), Pacific Islander (PI), and Filipino individuals experience a disproportionate burden of type 2 diabetes yet remain underrepresented in clinical trials. The primary objective was to generate insights into the motivations, barriers, and communication preferences around clinical trial participation among hospitalized patients from diverse racial/ethnic backgrounds, particularly groups that have been historically underrepresented in research.</p><p><strong>Methods: </strong>We conducted in-person, semi-structured interviews with 56 hospitalized patients at a medical center in Hawai'i. Participants ranked reasons for joining or not joining a clinical trial and responded to open-ended questions. Quantitative data were summarized descriptively. Qualitative responses were analyzed using Rapid Qualitative Analysis and organized by race/ethnicity.</p><p><strong>Results: </strong>While 84% expressed willingness to join a trial, most had never been asked. NH participants prioritized helping their community and accessing new treatments. PI participants emphasized helping their doctor and advancing science. Filipino participants valued new treatments and contributing to science. White participants ranked financial incentives and community benefit. Major barriers included concerns about unknown medication risks, lack of understanding, and mistrust-particularly among PI and Filipino participants. Many NH and PI participants noted that helping family members was a key motivator. Across all groups, preferred communication strategies included physician referrals, text messaging, and physical mail.</p><p><strong>Conclusion: </strong>Tailored recruitment strategies emphasizing family and community benefits, involvement of trusted local providers, and culturally relevant communication may enhance clinical trial participation among underrepresented populations with type 2 diabetes.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970096","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}