Therapeutic innovation & regulatory science最新文献

{"title":"Development of Composite Index in Psychiatry Clinical Trial.","authors":"Haiqi Zhang, Shein-Chung Chow","doi":"10.1007/s43441-025-00772-4","DOIUrl":"https://doi.org/10.1007/s43441-025-00772-4","url":null,"abstract":"<p><p>In psychiatry clinical trials, a validated instrument (or questionnaire) which consists of a number of questions (or items) is often used for evaluation of the safety and efficacy of a test treatment under investigation. This approach based on rating scales for evaluation of safety and efficacy of a test treatment under study, however, has been criticized of being subjective. To overcome the problem, the use of a composite index which combines the subjective rating scales and objective functional magnetic resonance imaging is proposed. For this purpose, statistical methods for development of composite index are derived. The proposed composite index is evaluated both theoretically and via extensive clinical simulation studies.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804316","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 Impact of the Inflation Reduction Act on Investment in Innovative Medicines: A Project-Level Analysis.","authors":"Richard Z Xie, Tess Cameron, Peter Kolchinsky","doi":"10.1007/s43441-025-00768-0","DOIUrl":"https://doi.org/10.1007/s43441-025-00768-0","url":null,"abstract":"<p><p>The impact of Medicare's price negotiation on long-term pharmaceutical innovation and patient welfare remains one of the most widely debated topics across stakeholder groups. Existing policy simulations have tried to assess the policy impacts on innovation based on either empirical estimates of elasticity of innovation from the literature or structural models estimating the joint distribution of expected revenue and expected costs at key stages of pharmaceutical development. Since investors exert significant influence on investment programs that companies advance in the real world, a program-level analysis of how investors make their investment decisions can inform the key assumptions for policy simulations and generate more realistic insights. Using an illustrative case example, we constructed a net present value (NPV) model to examine how Medicare price negotiation will impact discounted value and investment decisions at six key timepoints of new drug development, highlighting key factors in investor decision-making not explicitly considered in existing empirical literature or policy simulations. Our analyses showed that IRA would lead to a 40% reduction in the NPV at the time of launch. The reduction was greater in earlier stages of development due to expected dilution and discounting, resulting in discontinuing this project at earlier decision points. The case study demonstrated that the negative impacts of price negotiation at nine years were more pronounced for small-molecule assets in the earlier stages of development (e.g., preclinical or Phase 1) than those in the later stages, implying a possibly much larger impact on innovation than suggested by existing empirical literature and observed in the short term.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731189","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":"Increasing the Utility of Real-World Data to Inform Public Health Decision Making Through a US-based Private-Public Partnership: 10 Lessons Learned from a Principled Approach to Rapid Pandemic RWE Generation.","authors":"Nicolle M Gatto, Elizabeth M Garry, Melanie Wang, Névine Zariffa, Laura Roe, Aloka Chakravarty, Donna Rivera","doi":"10.1007/s43441-025-00748-4","DOIUrl":"https://doi.org/10.1007/s43441-025-00748-4","url":null,"abstract":"<p><p>In response to the COVID-19 pandemic, a collaborative public-private partnership was launched to harness evidence from rapidly accruing real-world data (RWD) in various healthcare settings, with the goal of characterizing and understanding COVID-19 in near real-time, by applying rigorous epidemiological methods and defining research best practices. Projects were conducted in 4 phases: Research Planning and Prioritization, Protocol Development, Protocol Implementation, and Results Dissemination. During these projects, areas were identified with a current or future need to enhance existing best practices. This report provides a summary of our research processes, including application of new and existing practices, along with key learnings related to the challenges of conducting research when the clinical landscape is rapidly evolving as was the case during the first year of the COVID-19 pandemic. Such processes and learnings may be helpful to the broader research community when using RWD to understand or address future public health priorities.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658709","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-approval Activities Providing Data on the Safety of Medication Use During Pregnancy and Lactation-A TransCelerate Perspective.","authors":"Maria Fernanda Scantamburlo Fernandes, Amalia Alexe, Olatayo Apara, Lindsey Force, Christine Taeter, Maria Weber, Keele Wurst, Nadezda Abramova, Anju Garg, Leesha Balramsingh-Harry, Jessica Mårlind Würtele","doi":"10.1007/s43441-025-00764-4","DOIUrl":"https://doi.org/10.1007/s43441-025-00764-4","url":null,"abstract":"<p><p>Pregnant and lactating women are frequently excluded from clinical trials, leading to a significant global unmet need for safety data regarding medication use in this population. Post-approval safety activities on pregnancy and lactation are currently the main sources of information for product labeling to guide clinical practice. However, generating this information can take years, and the data often remains insufficient for healthcare providers and patients to make informed decisions. Given the differences in regulatory guidance on this issue and the evolving perspectives on the most appropriate types of post-approval activities on pregnancy and lactation, TransCelerate BioPharma conducted a survey of its member pharmaceutical companies to evaluate common post-approval practices over the past 11 years. All survey participants reported engaging in post-approval activities on pregnancy, citing pregnancy registries as the most common type of activity, followed by database studies and enhanced pharmacovigilance. These activities resulted in outcomes, including updates to the prescribing information, however these materialized after many years. Conversely, fewer post-approval activities on lactation were conducted, with limited impact on outcomes reported to date. These results emphasize the need for a comprehensive, multi-faceted approach using a wide array of data sources for effective and timely post-approval surveillance to characterize medication use during pregnancy and lactation.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650808","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":"Development of a Safety Toolkit to Influence Inclusion Barriers for Adolescents and Young Adults (AYA) in Adult Clinical Trials.","authors":"Devona Williams, Julie Maidment, Pamela Concepcion, Gyorgy Zorenyi","doi":"10.1007/s43441-025-00761-7","DOIUrl":"https://doi.org/10.1007/s43441-025-00761-7","url":null,"abstract":"<p><p>Lack of long-term safety data for the AYA population has been identified as a key area that reduces enrolment of AYA in adult oncology clinical trials. Here we describe a potential safety assessment solution, from a pharmacovigilance and clinical patient safety perspective, to enhance the inclusion of adolescents into adult oncology trials. To help bridge gaps in safety data that limit AYA participation, a Patient Safety Oncology Toolkit for AYA patients has been developed. The safety toolkit includes recommended additional clinical study protocol templated wording for assessment and management of general AYA-related risks for oncology agents, including infertility, growth and development, new primary malignancies, and neurocognitive effects. There is also recommended language to incorporate into the study protocol for investigational product specific risk considerations based on impacted organ systems. Using the safety toolkit, a key deliverable from the evaluation of the risks is the generation of a safety go, or no-go, Red-Amber-Green (RAG) rating for each study. The RAG rating scale is intended to summarize the scope and severity of any specific treatment-related safety concerns and helps standardize company governance and investment decisions. This toolkit is intended to allow teams to safely include AYA individuals in adult oncology studies and allow this population better access to life-changing medicines.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626155","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 Beginning of a \"Regulatory Renaissance\": Positioning Regulatory Coverage at the Interface of Human Expertise and Digital Support.","authors":"James Jones, Robert M Califf","doi":"10.1007/s43441-025-00745-7","DOIUrl":"https://doi.org/10.1007/s43441-025-00745-7","url":null,"abstract":"<p><p>Following the largest reorganization in its history, the U.S. Food and Drug Administration (FDA) is now working to modernize how it defines and engages in regulatory oversight of the quality of products that the agency regulates. However, the volume and complexity of these tasks, coupled with the size and interdependent nature of the global supply chains that generate and distribute these products, raise questions about how the agency can keep up with the pace of change. This dilemma, together with the FDA's recent reorganization, create an opportunity to rethink the FDA's strategy for regulatory coverage and usher in a \"regulatory renaissance.\" In this article, we examine how the agency is working to develop a more quantitative, comprehensive approach to ensuring that the wide arrays of FDA-regulated commodities are produced and distributed in systems that meet societal expectations for safety and quality in a global digital environment. We discuss a number of tools and methods that the agency can bring to bear to achieve this goal, including leveraging internal FDA data and information from third-party audits; utilizing information from foreign regulators; incorporating data and findings from state and local inspections; and applying sophisticated data technologies including AI systems. The underlying concept for this regulatory renaissance is for the agency to focus on leveraging multiple sources of data, information, and analysis to inform its actions in order to optimize the quality of products produced by regulated industries, including the dimensions of safety, effectiveness, and reliability of manufacturing, as well as distribution and instructions for use throughout their product lifecycle. The degree of success of this approach will depend upon a broad recognition of similar opportunities across the regulated industries, sister federal and state agencies, and academia working on regulatory science.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606385","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":"Developing a Set of AI Ethics Principles to Shape Ethical Behavior in Drug Development.","authors":"Timothé Ménard, Katrina A Bramstedt","doi":"10.1007/s43441-025-00766-2","DOIUrl":"https://doi.org/10.1007/s43441-025-00766-2","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606397","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":"Regulatory, Translational, and Operational Considerations for the Incorporation of Biomarkers in Drug Development.","authors":"Heather Hatcher, Simona Stankeviciute, Chris Learn, Angela X Qu","doi":"10.1007/s43441-025-00763-5","DOIUrl":"https://doi.org/10.1007/s43441-025-00763-5","url":null,"abstract":"<p><strong>Background: </strong>Biomarkers are an integral component in the drug development paradigm. According to the US Food and Drug Administration (FDA), a biomarker is \"a defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or biological responses to an exposure or intervention, including therapeutic intervention\" (FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource [Internet]. Silver Spring (MD): Food and Drug Administration (US); 2016-. Glossary. 2016 [Updated 2021 Nov 29, cited 2024 Apr 14]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK338448/ Co-published by National Institutes of Health (US), Bethesda (MD)). The European Medicines Agency (EMA) defines a biomarker as \"an objective and quantifiable measure of a physiological process, pathological process or response to a treatment (excluding measurements of how an individual feels or functions\" European Medicines Agency (EMA). Biomaker. 2020a. Available from: https://www.ema.europa.eu/en/glossary-terms/biomarker#:~:text=Biomarker-,Biomarker,an%20individual%20feels%20or%20functions . Several clinical biomarkers are well-documented and have been used routinely for decades in health care settings and have long been accepted as valid endpoints for drug approval (for example, blood pressure measurement as a biomarker for cardiovascular health) (European Medicines Agency (EMA). Assessment report, TAGRISSO. 2016. Available from: https://www.ema.europa.eu/en/documents/assessment-report/tagrisso-epar-public-assessment-report_en.pdf . Accessed 15 Apr 2024). Recently, novel biomarkers have been identified and validated to accelerate developing innovative therapies indicated for serious human diseases, for example targeted/immune therapies of cancer (Chen in Med Drug Discov 21:100174, 2024). As indicators of the efficacy of new pharmacological treatments or therapeutic interventions, biomarkers can improve clinical trial efficacy and reduce uncertainty in regulatory decision making (Bakker et al. in Clin Pharmacol Ther 112:69-80, 2022; Califf in Exp Biol Med 243:213-221, 2018; Parker et al. in Cancer Med 10:1955-1963, 2021).</p><p><strong>Methodology: </strong>This article describes case studies of recent drug approvals that successfully leveraged validated and non-validated biomarkers (i.e., tofersen for the neurodegenerative disease amyotrophic lateral sclerosis (ALS) in adults; and osimertinib for treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC)).</p><p><strong>Conclusions: </strong>Best practices for biomarker selection and strategies for health authority biomarker qualification programs are presented along with an overview of current limitations and challenges to optimizing biomarker applications along the drug development continuum from regulatory, translational, and operational perspectives.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587101","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":"An Evaluation of Time Spent Completing Electronically Collected Patient-Reported Outcomes in Clinical Trials.","authors":"Lucy Andersen, Michael Williams, Sheryl Pease, Harman Dhatt, Patricia Delong","doi":"10.1007/s43441-025-00767-1","DOIUrl":"10.1007/s43441-025-00767-1","url":null,"abstract":"<p><strong>Objectives: </strong>Patient-reported outcomes (PROs) are important measures of efficacy in the context of clinical trials but are sometimes identified as time and resource intensive to study participants and site personnel. The objective of this research was to evaluate the amount of time that participants spend completing PROs via an electronic device in phase 2 and 3 clinical trials across several disease areas.</p><p><strong>Methods: </strong>The electronic Clinical Outcome Assessment (eCOA) data were obtained from Johnson & Johnson clinical trials across various disease areas from 2016 to 2023. Data were acquired from internal and external sources including clinical trial sites and eCOA partners. In total, 82 trials were analyzed, containing data from 33,633 unique participants, and 1,083,994 measurements of completed electronic PRO instruments. After data cleaning, descriptive and multivariate analyses were performed. Electronic PRO completion time was examined in two ways: by time-per-item and time-per-instrument for each PRO.</p><p><strong>Results: </strong>On average, participants spend about 16 s per item and an average of 2 min to complete a PRO instrument electronically. The average time to complete PRO instruments varied significantly by disease area and most eCOA were completed on study site tablets (68%) or personal handheld devices (31%).</p><p><strong>Conclusions: </strong>Overall, patients spend an average of 16 s per item and 2 min per PRO instrument in clinical trial studies. PROs are a crucial component of clinical trial outcomes data and can be efficiently completed electronically by participants in clinical trials in a short amount of time.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582343","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 Proposed Confidence Ellipse Approach for Benefit-Risk Assessment in Clinical Trials.","authors":"Yinuo Zhang, Xiaofang Zhang, Peijin Wang, Yangfeng Wu, Shein-Chung Chow","doi":"10.1007/s43441-025-00762-6","DOIUrl":"https://doi.org/10.1007/s43441-025-00762-6","url":null,"abstract":"<p><p>In clinical development, an independent data safety monitoring committee (IDMC) is often established to ensure the test treatment's integrity, quality, safety, and efficacy under investigation. In clinical trials, IDMC may recommend stopping the trial early due to safety, futility/efficacy, or both after reviewing observed data in the interim based on pre-specified stopping boundaries. In practice, the interim data is often too small to reach clinically meaningful differences with statistical significance (i.e., the observed clinically meaningful difference is reproducible and not purely by chance alone). To provide an overall assessment (or complete clinical picture) of the performance of the test treatment under investigation, the FDA (2023) published guidance on the benefit-risk assessment (BRA) framework to facilitate IDMC decision-making. Several methods have been studied in the literature following the FDA's recommended framework. However, these methods did not consider the uncertainties and heterogeneities. Alternatively, a BRA approach is proposed based on a confidence ellipse of primary safety and efficacy endpoints. The proposed confidence ellipse approach was evaluated both theoretically and via a clinical trial simulation. The results indicate that the proposed confidence ellipse provides consistent and stable metrics, particularly as sample sizes increase. The derived metrics of Benefit-Risk Difference (BRD) and Benefit-Risk Ratio (BRR) showed favorable performance across different scenarios and thresholds. Applied to the TESTING trial data (Lv et al. JAMA. 327(19):1888-98, 2022), our method confirmed and extended the original finding that a reduced methylprednisolone dose offered a more favorable benefit-risk profile. Specifically, the confidence ellipse method highlighted that the reduced dose consistently provided a better balance between efficacy and safety, particularly under stricter criteria for clinical significance. This method validated the original conclusions and provided additional insights into how different dosing regimens perform across various clinical scenarios, potentially offering a more refined tool for optimizing treatment decisions in complex therapeutic contexts.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543626","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}