Therapeutic innovation & regulatory science最新文献

{"title":"Enhancing Development Strategies Through Early Scientific Advice from HTA Agencies-Experiences, Expectations and Best Practices from Health Technology Developers.","authors":"Ting Wang, Neil McAuslane","doi":"10.1007/s43441-025-00851-6","DOIUrl":"https://doi.org/10.1007/s43441-025-00851-6","url":null,"abstract":"<p><strong>Introduction: </strong>Early health technology assessment (HTA) advice provides value to pharmaceutical companies during drug development by identifying potential data gaps, refining study designs, and improving understanding of HTA agencies' evidentiary requirements. This study evaluated the landscape, benefits, and challenges of early HTA advice, with a focus on European agencies and global practices amid the transition to the EU HTA Regulation.</p><p><strong>Methods: </strong>A perception survey involving 12 pharmaceutical companies explored engagement with HTA agencies, challenges, and strategic priorities. Additionally, a forum was conducted with 22 company representatives, discussing internal and external best practices. Key topics included the evolving role of Joint Scientific Consultations (JSCs), integration of real-world evidence (RWE), and incorporation of patient-reported outcomes (PROs) into advice processes.</p><p><strong>Results: </strong>The findings highlighted active engagement with national agencies such as NICE and G-BA and European initiatives like EUnetHTA Joint Actions. NICE advice was valued for cost-effectiveness insights, but its post-Brexit absence reduced collaboration at the European level. JSCs under the EU HTA Regulation were seen as critical, but resource constraints and limited availability posed challenges. Companies prioritized topics such as comparator choices, outcome measures, and RWE but faced internal barriers like resource allocation and unclear decision criteria. Outside Europe, uptake of advice services, such as those from CDA-AMC, remained limited but underscored the potential of lifecycle approaches for iterative learning.</p><p><strong>Conclusions: </strong>Early HTA advice is essential in pharmaceutical development. Enhancing JSC capacity, stakeholder engagement, and feedback mechanisms will strengthen alignment between companies and HTA agencies, fostering evidence-based decision-making and improved health outcomes.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769120","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":"Real-World Data and Causal Machine Learning to Enhance Drug Development.","authors":"Chris Anagnostopoulos, Mihaela Van Der Schaar, Jean-Paul Collet, Ramon Hernandez Vecino","doi":"10.1007/s43441-025-00849-0","DOIUrl":"https://doi.org/10.1007/s43441-025-00849-0","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769121","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":"Characterizing Gene Therapy Medicinal Products Post-Marketing Safety Reports Based on WHO Pharmacovigilance Database, VigiBase.","authors":"Min-Jung Lim, Eunah Paek, Ju-Young Shin","doi":"10.1007/s43441-025-00852-5","DOIUrl":"https://doi.org/10.1007/s43441-025-00852-5","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765563","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":"Longitudinal Descriptive Analysis of Dynamic Changes in Safety Concerns in Japanese Risk Management Plans for Medicinal Products Over 8 Years After Approval.","authors":"Chieko Ishiguro, Mahiro Sazawa, Takahiro Nonaka","doi":"10.1007/s43441-025-00801-2","DOIUrl":"https://doi.org/10.1007/s43441-025-00801-2","url":null,"abstract":"<p><strong>Introduction: </strong>A Japanese risk management plan (RMP) is a proactive planning tool for managing safety concerns (important identified risk [IIR], important potential risk [IPR], and important missing information [IMI]) for each drug and is continuously updated. However, no studies have examined the dynamic changes of safety concerns in RMPs throughout the drug lifecycle.</p><p><strong>Methods: </strong>We conducted a longitudinal descriptive analysis of safety concerns in RMPs of drugs approved for new active ingredients in 2014 in Japan. We compared safety concerns in RMPs between the first version at approval and the latest version 8 years after the approval date using the Sankey diagram. We also investigated the evidence for RMP changes.</p><p><strong>Results: </strong>This analysis included 38 drugs, whose first version RMPs included 155 IIRs, 119 IPRs, and 59 IMIs. Among them, all IIRs and 88% of the IPRs and the IMIs remained in the latest version of the RMPs 8 years after the approval date. During follow-up, 29 IIRs, 20 IPRs, and 3 IMIs were newly added, 14 IPRs were upgraded to IIRs, and 7 IMIs were deleted; thus, the final numbers of IIRs, IPRs, IMIs were 198, 125, and 55, respectively. Evidence for RMP changes was more often obtained from pharmacovigilance activities than from clinical/non-clinical studies conducted for additional approvals.</p><p><strong>Conclusions: </strong>Most of the safety concerns identified at the first approval remained over 8 years, and the number of IIRs and IPRs tended to increase after approval. Most of the RMP changes were based on pharmacovigilance activities.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754374","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":"Optimizing Biomedical Health Efficiency: Unlocking the Full Potential of Life Science Innovation Through System Design.","authors":"Gigi Hirsch, Sharon E Phares, Jane Barlow, Murray Aitken, Mark Cziraky, Gregory Daniel, Chester Good, Annie Kennedy","doi":"10.1007/s43441-025-00847-2","DOIUrl":"https://doi.org/10.1007/s43441-025-00847-2","url":null,"abstract":"<p><p>Major advances in biomedical science have transformed healthcare. However, system barriers to the appropriate, timely, and equitable use of biomedical innovations have led to slow and inconsistent adoption, limiting and delaying our ability to leverage their full potential to improve health. System barriers include inconsistent coverage, imperfect information systems for decision making and real word evidence, policy constraints, system capacity, social influences on health, and infrastructure gaps.We propose the development of an open access dynamic design \"engine\" to align biomedical and health system innovation. This engine will include coordinated collaborative design processes, frameworks, and tools, developed with input from all stakeholders, and centered around two critical, interdependent capabilities: (1) system design and (2) impact measurement. These capabilities will build capacity for efficient, model-driven design and implementation planning of sustainable, patient centered system innovations.The stakes are high for both the clinical promise of transformational products and their budget impact. Our current healthcare system is not ready to maximize benefit from transformational science and emerging biomedical innovations. We need to help the healthcare system catch up with the science.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144733427","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":"Assessing the Malaysian Regulatory Process for Medicinal Product Approval: An OpERA Methodology and Standardized Reporting Approach.","authors":"Noraisyah Mohd Sani, Siti Hidayah Kasbon, Kian Yee Yap, Muhamad Firdaus Abdullah, Rosliza Lajis, Azuana Ramli, Neil McAuslane, Magda Bujar, Adem Kermad","doi":"10.1007/s43441-025-00846-3","DOIUrl":"https://doi.org/10.1007/s43441-025-00846-3","url":null,"abstract":"<p><strong>Background: </strong>The Malaysian National Pharmaceutical Regulatory Agency (NPRA) has partnered with the Centre for Innovation in Regulatory Science (CIRS) since 2018 to analyze the approval processes for new active substances (NASs) and biosimilars. Findings from the study on approvals in the year 2017 led to the introduction of several improvement strategies. This study provides an overview of the current review process, including registration pathways, and compares approval times for NASs approved in 2019 vs 2017 to evaluate the impact of the improvement strategies.</p><p><strong>Methods: </strong>NPRA representatives completed the Country Report using CIRS' Optimizing Efficiencies in Regulatory Agencies (OpERA) questionnaire, identifying key milestones, target timelines, good review and quality decision-making practices, and provided metrics on 24 NASs approved in 2019.</p><p><strong>Results: </strong>Most indicators for good review practices were implemented by NPRA, with guidelines, standard operating procedures, review templates, and several identifiable quality decision-making practices being in place. NPRA has also introduced several registration pathways with the aim of accelerating approval timelines. Median total approval time decreased from 515 calendar days in 2017 to 399 calendar days in 2019. Reductions were also noted in the median time between dossier receipt and initiation of NPRA scientific assessment.</p><p><strong>Conclusions: </strong>The study indicates that improvement strategies implemented in 2018 favorably reduced approval times, based on a comparison of products approved in the year 2017 and 2019. Ongoing evaluation of regulatory processes and performance is crucial to identify areas for improvement, eliminating unnecessary steps, and enabling a streamlined and efficient approach.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708776","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":"Incorporating Patient Needs and Perspectives in Additional Risk Minimization Measures and Other Pharmacovigilance Deliverables - A Framework and Implementation Roadmap.","authors":"Linda Smeding, Robert Massouh, Farai Moyo, Marilyn Metcalf, Shannon Altimari, Ekaterina Edle von Dall'Armi, Elisa Formenti","doi":"10.1007/s43441-025-00844-5","DOIUrl":"https://doi.org/10.1007/s43441-025-00844-5","url":null,"abstract":"<p><p>Various initiatives and guidelines exist to support patient engagement (PE) throughout the lifecycle of a medicinal product. While the recent European Medicines Agency guideline on good pharmacovigilance practices (Module XVI; Revision 3) reinforces the importance of involving patients to create effective risk minimization strategies, frameworks supporting the systematic adoption of PE by Marketing Authorization Holders (MAHs) across pharmacovigilance, including the risk management system, are lacking. Furthermore, little is presented on the impact of patient review of additional risk minimization measures materials. We present a tested Pharmacovigilance Patient Centricity Framework describing key focus areas that can create the necessary infrastructure for systematic PE in effective risk minimization materials. Implementation of this framework highlighted the importance of collaboration to drive PE across the company at both local and global level, and externally, as relationships are established with patient organizations and best practices are shared with other MAHs. Therefore, this framework can be considered by other companies as a basis for developing a patient-centric approach to integrate the patient's voice into pharmacovigilance deliverables.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718728","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":"Statistical Considerations and Challenges with Time-to-Event Analyses for Composite Endpoints in Clinical Trials.","authors":"Kaiyi Chen, Yu Du, Yuxin Zhu","doi":"10.1007/s43441-025-00840-9","DOIUrl":"https://doi.org/10.1007/s43441-025-00840-9","url":null,"abstract":"<p><p>The use of composite endpoint is a common strategy often employed to enhance statistical power and address the low incidence of individual outcomes, particularly in cardiovascular and kidney outcome studies. By merging multiple clinically relevant events into a single variable, these endpoints negate the need for multiple testing adjustments and augment the event rate, thus enabling studies of reasonable size and duration. However, as underscored by the FDA's guidance, a thorough evaluation of each component's impact is equally important to ensure the clinical relevance of these endpoints. This article delves into controversies surrounding the interpretation of hazard ratios derived from analyzing the composite endpoint and its individual components, exemplified by an observation from the CLEAR outcome trials. It highlights a paradoxical scenario where the combined treatment effect for the composite endpoint appeared less favorable than when assessing individual components separately. Moreover, we did a re-evaluation of the suitability of using Cox proportional hazards model in this context through theoretical investigation and simulation studies.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691643","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":"Treatment Comparison for a Single Arm Study Utilizing External Control: Performing Inference when Imputing Potential Outcomes.","authors":"Wei-Chen Chen, Nelson Lu, Chenguang Wang, Yunling Xu","doi":"10.1007/s43441-025-00839-2","DOIUrl":"https://doi.org/10.1007/s43441-025-00839-2","url":null,"abstract":"<p><p>Non-randomized comparative studies are often used to compare treatment effects between an investigational product and a control when randomization is not feasible or difficult in practice. A typical situation is that the product is investigated in a single-arm study, and the control data are collected in an external data source. For such a situation, we propose an alternative approach to draw inference on the treatment effect difference. First, a potential outcome model (POM) for the outcome under control treatment is built based on the external control data source. Next, the POM is utilized to impute outcomes of subjects in the single-arm study as if they were treated with the control treatment. Then the inference on the treatment effect difference can be made by comparing imputed outcomes (for the control) and observed outcomes (for the investigational product). The main purpose of this paper is to provide a proof of concept regarding how to perform inference on the treatment effect between the investigational product and the control under this scenario. We illustrate our approach by assuming the endpoint to follow a normal distribution and the POM to be a linear regression model.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691644","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":"Post-marketing Safety Assessment of CAR T-cell Therapies: Analysis of Individual Case Safety Reports in the VigiBase.","authors":"Meshael M AlRasheed, Solaiman M AlHawas, Nora N AlOrf, Nouf S AlFadel, Fawaz F AlHarbi","doi":"10.1007/s43441-025-00826-7","DOIUrl":"https://doi.org/10.1007/s43441-025-00826-7","url":null,"abstract":"<p><strong>Purpose: </strong>Chimeric Antigen Receptor (CAR)-T cell therapies have emerged as potential therapy for hematological malignancies, however, their safety profiles should be monitored after approval. Therefore, we aimed in this study to explore and analyze individual case safety report (ICSRs) associated with CAR-T cell therapies and reported to the World Health Organization (WHO) global database (VigiBase).</p><p><strong>Methods: </strong>A retrospective pharmacovigilance study was conducted to describe and characterize Adverse drug reactions (ADRs) reported to Vigibase from inception to March 31st, 2024 and associated with use of the following CAR-T cell therapies: Tisagenlecleucel, Axicabtagene ciloleucel, Brexucabtagene autoleucel, Lisocabtagene maraleucel, Idecabtagene vicleucel, and Ciltacabtagene autoleucel.</p><p><strong>Results: </strong>A total of 11,693 ICSRs were identified with the use of CAR-T cell therapies in VigiBase (Axicabtagene ciloleucel (N = 5668, 48.5%), Tisagenlecleucel (N = 3364, 28.8%), Brexucabtagene autoleucal (N = 1027, 8.8%), Lisocabtagene maraleucel (N = 304, 2.6%), Idecabtagene vicleucel (N = 579, 4.9%), and Ciltacabtagene autoleucel (N = 751, 6.4%)). ICSRs completeness score was averaged between 0.2 and 0.57 among all included products and the majority of reported ADRs were serious (67-91%). Among serious ADRs, death was reported with an average percentage of (8.8-21.5%). The majority of ADR reports with fatal outcome occurred in accordance with their approved indications. About 18% of fatal events reported with Tisagenlecleucel as the suspected drug were in the pediatric population.</p><p><strong>Conclusion: </strong>Our study provides an overall exploration of the post-marketing safety profiles of currently approved CAR-T cell therapies. The significant proportion of fatalities occurred in accordance with approved indications, emphasizes the need for ongoing investigation into ADRs with fatal outcomes, particularly in the pediatric population.</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":"144675643","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}