Therapeutic innovation & regulatory science最新文献

{"title":"Transforming Objective Participatory Patient Advocacy.","authors":"Pat Furlong, Timothy R Franson, Peter J Pitts","doi":"10.1007/s43441-025-00841-8","DOIUrl":"https://doi.org/10.1007/s43441-025-00841-8","url":null,"abstract":"<p><p>Objective Participatory Patient Advocacy (OPPA) is an important evolution from traditional patient advocacy to a strategic, data-driven approach that significantly impacts the patient voice vis-a-vis both drug development and the regulatory processes, particularly within the realm of rare diseases. Focusing on the exemplar of Parent Project Muscular Dystrophy (PPMD) and its work in Duchenne muscular dystrophy (DMD), this article highlights how OPPA leverages scientific rigor, collaborative partnerships, and a patient-centered perspective to accelerate the development and approval of effective therapies. The era of anecdote-driven advocacy is waning, making way for a new paradigm where patient advocacy organizations act as pivotal stakeholders in the drug development ecosystem. OPPA is characterized by its use of data-driven tools such as surveys, preference studies, and real-world evidence to inform research priorities, clinical trial designs, and regulatory decision-making. By adopting this objective approach, patient advocacy groups can contribute valuable insights into patient needs, preferences, and risk tolerance, which can then be integrated into the drug development process to ensure that therapies are both effective and aligned with patient values. These initiatives encompass a wide range of activities, including investing in cutting-edge research, advocating for legislative support for intramural research, and fostering collaborative partnerships with researchers, industry stakeholders, and regulatory agencies. PPMD's efforts to identify and validate biomarkers, map proteins, and develop industry guidance demonstrate its commitment to building a solid scientific foundation for DMD drug development. A key focus of the article is the collaborative effort between the FDA, PPMD, care-givers, healthcare providers, scientists, and regulatory experts to and the FDA, culminating in the creation of patient-initiated draft guidance for industry developing DMD therapies. This achievement signifies a shift in the regulatory landscape, with the FDA recognizing patient perspectives that has led to more flexible and patient-centered regulatory pathways and the approval of promising new therapies. Objective Participatory Patient Advocacy calls for continued collaboration between advocacy groups, regulators, industry, and researchers. These partnerships are essential to sustaining progress and ensuring meaningful outcomes. The lessons learned from PPMD's experience offer a roadmap for other rare disease communities to emulate, paving the way for a future where patient voices are central to the development of innovative therapies and the improvement of patient care.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675644","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 7-Year Analysis of the U.S. FDA Good Clinical Practice Inspection Outcomes for Marketing Applications.","authors":"Courtney McGuire, Jenn W Sellers, Laurie Muldowney","doi":"10.1007/s43441-025-00835-6","DOIUrl":"https://doi.org/10.1007/s43441-025-00835-6","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668570","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":"Hope is Not a Strategy: Using Robust Real-World Evidence to Make Better Clinical Development Decisions.","authors":"Nicolle M Gatto, Ulka B Campbell","doi":"10.1007/s43441-025-00822-x","DOIUrl":"https://doi.org/10.1007/s43441-025-00822-x","url":null,"abstract":"<p><p>Clinical development delays and failures do not serve public health. Reliance solely on expert opinion or historical patterns rather than evidence from representative, real-world point-of-care data about the indication results in suboptimal trial design, missed opportunities, and uninterpretable findings. Investment in real-world evidence (RWE) generation to build a deep, comprehensive, and current understanding of the characteristics, care, and outcomes of the indicated population is essential to improving clinical development decision making. Despite the recognized value of RWE, this evidence generation is not done systematically. Here we make integrated RWE generation more compelling and practicable by addressing concerns we have heard from biopharma leaders and, for emerging RWE leaders, providing a blueprint for designing real-world studies in a phased approach that aligns with clinical development investment. Our work is intended to facilitate more widespread adoption of integrated RWE generation, beginning early in development, so that robust RWE is in hand at the right time for evidence-based decision making by the sponsor, regulators, and payers.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660306","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":"Estimand Endpoints for Longitudinal Measures of Continuous Disease Progression with an Alzheimer's Disease Example.","authors":"Haoyan Hu, Miroslaw Brys, Stephen J Ruberg, Yongming Qu","doi":"10.1007/s43441-025-00843-6","DOIUrl":"https://doi.org/10.1007/s43441-025-00843-6","url":null,"abstract":"<p><p>The ICH E9 (R1) Addendum provides a framework to define an estimand and perform sensitivity analysis. The clinical endpoint (i.e., variable, response, outcome) is one of the important estimand attributes. In our opinion, the selection of the endpoint in Alzheimer's disease requires more exploration beyond what is used currently. The change in a cognitive and functional assessment scale from baseline to a specific time point of interest is often used as a primary or key secondary endpoint in clinical trials. However, such a change from baseline to the time point of interest may not reflect the benefit of the treatment over the course of treatment duration and may be difficult to intuitively understand by patients and clinicians. For two patients with the same change from baseline, the patient with rapid disease progression in the beginning is considered to have overall worse quality of life compared to the other patient with slow disease progression in the beginning but rapid progression toward the end. We explore time-averaged measurement (TAM) as a new endpoint and propose using the relative change to quantify the treatment difference. Estimands under the ICH E9 (R1) Addendum were considered by using various strategies in handling intercurrent events and used corresponding methods for handling missing data. We illustrate the use of TAM and compare the results with other commonly used estimand endpoints (the change from baseline, the relative disease progression model, and the slope of disease progression) for different estimands and imputation methods from retrospective analyses of a historical study.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660305","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":"Identification and Description of Regulatory and Health Technology Assessment Agencies' Guidance Related to Patient Experience Data in North America, Europe, and Asia Pacific.","authors":"Laure Delbecque, Juergen Zschocke, Ding Ding, Jiat-Ling Poon, Carolina Alonzo, Nancy Gabriela Pérez, Shane Myrick, Jennifer N Hill","doi":"10.1007/s43441-025-00777-z","DOIUrl":"https://doi.org/10.1007/s43441-025-00777-z","url":null,"abstract":"<p><strong>Objectives: </strong>To identify and describe patient experience data (PED)-related guidance issued by regulatory and health technology assessment (HTA) agencies in North America, Europe, and Asia Pacific.</p><p><strong>Methods: </strong>National agency websites were manually searched (October 2021, updated October-December 2023) to identify standalone PED guidance, and general submission/clinical trial or disease-specific guidance in four therapy areas, including PED-related recommendations. Identified documents were reviewed for requirements/expectations on types of PED; concepts of interest and instruments/tools; validation, analysis, and interpretation; study design, and endpoint definitions.</p><p><strong>Results: </strong>A total of 34 regulatory and 21 HTA documents were reviewed across 7 and 11 agencies, respectively. Most regulatory agencies expected data collected via clinical outcome assessments; concepts of interest were similar; specific tools were not usually recommended, although the use of validated instruments was expected; and meaningful within-patient change was generally considered key to interpretation. HTA guidance on PED varied primarily based on country requirement for utility estimates to inform economic evaluation (little/no guidance beyond the concept of interest) versus interest in PED on signs, symptoms, or disease impact on functioning (generally more comprehensive details on PED expectations).</p><p><strong>Conclusion: </strong>Through PED, patient voice is an increasingly important factor in regulatory, access, and reimbursement decision-making. Regulatory and HTA agencies in North America, Europe, and Asia Pacific have varying expectations regarding PED. This misalignment can necessitate the collection of multiple types of PED to meet all requirements (resulting in complex clinical trial protocols and significant patient burden), and lead to differences in data interpretation or gaps in the expected data. Therefore, PED measurement standards should be harmonized globally, and the collection of required PED should be ensured early during drug development to ensure decisions can be made based on valid and reliable data.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660307","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":"Characteristics of Multi-Regional Clinical Trials Conducted in Asia, Focusing on Japan's Participation and Small/Medium Companies-Sponsored Trials.","authors":"Akihito Kojima, Hideki Hanaoka, Yoshiaki Uyama","doi":"10.1007/s43441-025-00837-4","DOIUrl":"https://doi.org/10.1007/s43441-025-00837-4","url":null,"abstract":"<p><strong>Background: </strong>Less participation by Japan in multi-regional clinical trials (MRCTs) is one of concerns that leads to drug loss in Japan, but the characteristics of Japan's participation in MRCTs have not been well studied.</p><p><strong>Purpose: </strong>This study investigated Japan's situation in global drug development by characterizing its participation in MRCTs compared with East and South-East Asian countries/regions, with a focus on MRCTs sponsored by small-medium companies to discuss necessary measures in further promoting drug development in Japan.</p><p><strong>Methods: </strong>Data from MRCTs conducted in East and South-East Asia during the period from January 1, 2013 to December 31, 2022 were analyzed.</p><p><strong>Results: </strong>Japan's participation in MRCTs conducted in Asia (East Asia and South-East Asia) was limited. In particular, Japan participated in only 15-16% of MRCTs sponsored by Small/Medium-pharma (mainly US-based companies), with even less participation in Early Phase MRCTs. Japan's participation in MRCTs was markedly lower than other Asian countries/regions such as Singapore, South Korea, and Taiwan, although it was relatively higher in MRCTs that targeted neoplasms compared with other diseases.</p><p><strong>Conclusion: </strong>Results of this study raise significant concern about future potential drug loss in Japan. It is urgent to increase the participation of Japan in MRCTs in order to continuously provide new globally developed drugs to patients in Japan. For that purpose, an integrated approach that includes continuous improvement in pharmaceutical regulations and the clinical trial environment, as well as market attractiveness, will be necessary in parallel with strengthening of collaborations between Japan and other Asian countries/regions.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650586","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":"Impact of China's Drug Review and Approval System Reform on Pediatric Drugs: an Analysis Based on Registration Data from 2015 to 2024.","authors":"Tao Yang, Hao Zhang","doi":"10.1007/s43441-025-00842-7","DOIUrl":"https://doi.org/10.1007/s43441-025-00842-7","url":null,"abstract":"<p><p>This study systematically evaluated the impact of China's drug review system reform on pediatric drug approval efficiency using 310 pediatric drug registration records (2015-2024) from the CDE of China's NMPA supplemented with the YaoZhi Database, with comparative analysis of adult drug review patterns. Post-2019 amendments to the DAL significantly reduced pediatric review timelines from a median of 450 days (2015-2019) to 377 days (2020-2024; P < 0.0001), representing a 16.4% reduction versus adult drugs (451 days). The standard review pathway showed even greater pediatric acceleration (385 days vs. adult 497.5 days; 22.6% reduction, P < 0.0001), demonstrating targeted regulatory resource allocation. While biologics exhibited significant review advantages (342 days vs. chemical drugs' 403 days; P = 0.0085), structural imbalances persisted: high import dependency (73.9% imported vs. 26.1% domestic), inadequate child-appropriate formulations (< 10%), and critical therapeutic gaps (traditional Chinese medicines: 1.3%; rare disease drugs: < 5%). Efficiency gains were linked to expanded priority review adoption and optimized technical standards, yet unresolved deficits necessitate: establishing a dedicated pediatric review database with unified standards and conditional access; optimizing resource allocation for clinically urgent drugs; enhancing rare disease incentives; and accelerating age-appropriate formulation innovation-collectively enhancing regulatory science to address pediatric clinical needs.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643636","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":"Unlocking Generic Market Access: A Retrospective Analysis of USFDA Paragraph IV Filings (2020-2024).","authors":"Kajal Gandhi, Ramesh Joga, M Sowndharya, Gadekar Kailas Vijay, Sonali Waiker, Sravani Yerram, Rajeev Singh Raghuvanshi, Saurabh Srivastava","doi":"10.1007/s43441-025-00831-w","DOIUrl":"https://doi.org/10.1007/s43441-025-00831-w","url":null,"abstract":"<p><strong>Purpose: </strong>This article aims to explore the implications of Paragraph IV certification on generic drug market entry while innovators' patents are still active. It also examines the challenges posed by patent settlements, the BLOCKING Act, and the FDA's decision-making process regarding generic applications. The objective is to shed light on the complexities of pharmaceutical market dynamics, regulatory practices, and the balance between innovation and accessibility.</p><p><strong>Methods: </strong>The study involves a detailed analysis of the USFDA's recently published Para IV certification list and application statuses from 2020 to 2024. It reviews litigation trends among top generic manufacturers and scrutinizes the impact of patent disputes on market entry. The study also evaluates the potential effects of the BLOCKING Act on the 180-day exclusivity period and generic drug market dynamics.</p><p><strong>Results: </strong>The analysis reveals that nearly half of the ANDA applications submitted through Paragraph IV certification are deemed 'Eligible,' with significant portions either deferred or extinguished. A peak in eligible ANDA submissions was observed in 2023. Litigation trends show active patent challenges by leading generic companies like Teva, Apotex, and Actavis. The study highlights the FDA's role in facilitating first ANDA approvals, emphasizing the importance of providing safe and effective generic alternatives.</p><p><strong>Conclusion: </strong>The study concludes that while the FDA supports generic companies in their application processes, patent litigation remains a significant hurdle, delaying the availability of cost-effective generic drugs. The BLOCKING Act, if enacted, is likely to disrupt the 180-day exclusivity incentive, reducing the predictability and value of generic drug market entry.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638084","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":"Insights into Support Systems for Orphan Drug Development: A Comparative Study.","authors":"Ye Leng, Yu Tang, Weijie Yu, Yiru Hou, Hanqing He, Yanjie Han, Huiyao Huang, Wenbao Zhang, Ning Li","doi":"10.1007/s43441-025-00833-8","DOIUrl":"https://doi.org/10.1007/s43441-025-00833-8","url":null,"abstract":"<p><p>Due to great unmet medical needs, orphan drug development is a common issue of high priority for policymakers, industry leaders, researchers and patients worldwide. The establishment of a harmonized support system is the way forward to address the dilemma facing rare diseases (RDs). This study pioneers the proposal of a framework and dimensions of support systems affecting orphan drug development, covering legal (political and legal basis), technical (regulatory guidance and acceleration), motivational (economic incentives and innovation returns) and logistical (fundamental infrastructure) factors. This study, based on the framework, shows that the conditions for orphan drug development above are basically developed in the US, the EU and China. Additionally, China lags behind in terms of economic incentives and fundamental infrastructure. Continuous improvements in pricing and reimbursement, as well as the acceleration of real-world data (RWD) database and biobank repository integration, are expected in China. Based on these findings from the three study regions, action plans with three strategies (national plans and strategies, a patient-centered health system, global governance and collaborations) and eleven actions are suggested for strengthening synergies between initiatives and stakeholders to satisfy the medical needs of RD patients and families. This study can provide a reference not only for orphan drug development in the three study regions but also for all other countries worldwide, especially for those with a late start in addressing RDs.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627114","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 Clinical Studies and the FDA Adverse Event Reporting System (FAERS) Database for nirogacestat-related Adverse Events.","authors":"Yuanyuan Li, Lurong Yu, Yuxin Huang, Qing Zeng, Yao He, Limei Liu","doi":"10.1007/s43441-025-00834-7","DOIUrl":"https://doi.org/10.1007/s43441-025-00834-7","url":null,"abstract":"<p><p>Nirogacestat is the first drug specifically approved for desmoid tumours (DTs), rare, locally invasive tumours originating from connective tissue. This study aimed to explore potential safety concerns associated with nirogacestat, thereby providing references and research directions for subsequent clinical studies. We extracted data on nirogacestat from the FDA Adverse Event Reporting System (FAERS) database between Q4 2023 and Q4 2024 and mined adverse events (AEs) using the reporting odds ratio (ROR). For a separate retrospective analysis, we searched articles from PubMed, Cochrane, and EMBASE from the establishment of the databases until January 25, 2025.The study included 588 patients who were administered nirogacestat. Among all AEs, 89.78% were classified as non-serious. The most frequently reported preferred terms included diarrhoea [ROR (95% CI): 10.58 (9.22-12.13)], nausea [ROR (95% CI): 6.00 (5.06-7.12)], fatigue [ROR (95% CI): 3.77 (3.11-4.58)]. Disproportionality analysis revealed high signal strength for ovarian dysfunction [ROR (95% CI): 963.62 (306.61-3028.55)], ovarian failure [ROR (95% CI): 254.92 (101.73-638.79)], decreased blood phosphorus [ROR (95% CI): 107.66 (64.14-180.70)] and photopsia [ROR (95% CI): 91.19 (54.41-152.83)]. Notably, the risk ratios for alopecia, dermatitis acneiform, and ovarian toxicity were significantly higher in the nirogacestat group than in the placebo group. Despite the wide use of nirogacestat, most common AEs are not serious. Nevertheless, healthcare workers should proactively monitor patients for indicators of ovarian toxicity and hepatotoxicity. Additionally, photopsia and haematuria may be newly identified AEs. Further studies are required to validate our findings and explain the causal relationship between nirogacestat and AEs.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601697","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}