Therapeutic innovation & regulatory science最新文献

{"title":"Access to Innovative Medicines: Regulation Change and Factors Associated with Drug Approval Lag in Malaysia.","authors":"Wan Lee Chow, Nur Afiqah Mohd Salleh, Tse Siang Kang","doi":"10.1007/s43441-024-00620-x","DOIUrl":"10.1007/s43441-024-00620-x","url":null,"abstract":"<p><strong>Background: </strong>Drug approval lag is the time difference for new medicine to obtain marketing authorization approval in the study country compared to the first global approval. Drug approval lag delays the availability of innovative medicine to patients. This may lead to delay in treatment and severe public health implications. The study aimed to determine drug approval lag in Malaysia, the factors associated with drug approval lag (drug characteristics, regulatory factors and applicant type) and the association of the submission lag and review time with the regulation change.</p><p><strong>Methods: </strong>All new pharmaceutical products approved between January 2015 and March 2021 were examined (n = 136) using publicly available information. Factors associated with drug approval lag were determined using multiple linear regression.</p><p><strong>Results: </strong>The median drug approval lag was 855 days. Drug approval lag was associated with drug characteristics and regulatory factors. Median submission lag and median review time for products which fulfilled the requirement for the new regulations (Conditional Registration/ Facilitated Registration Pathway) were shorter compared to products which did not fulfil the requirement.</p><p><strong>Conclusion: </strong>Drug approval lag may delay the access of innovative medicine to patients, and this may lead to an increase in morbidity, mortality and healthcare costs. Good Regulatory Practices ensure efficient and transparent regulatory system which support the public health policy objectives in the most efficient way. The new regulations in Malaysia reduced the median submission lag and review time. The findings may be useful for regulators to consider for future policy development for medication access.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906514","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":"Building a Competency Framework to Integrate Inter-disciplinary Precision Medicine Capabilities into the Medical Technology and Pharmaceutical Industry.","authors":"Nicholette Conway, Orin Chisholm","doi":"10.1007/s43441-024-00626-5","DOIUrl":"10.1007/s43441-024-00626-5","url":null,"abstract":"<p><strong>Introduction: </strong>Integration of precision medicine (PM) competencies across the Medical Technology and Pharmaceutical industry is critical to enable industry professionals to understand and develop the skills needed to navigate the opportunities arising from rapid scientific and technological innovation in PM. Our objective was to identify the key competency domains required by industry professionals to enable them to upskill themselves in PM-related aspects of their roles.</p><p><strong>Methods: </strong>A desktop research review of current literature, curriculum, and healthcare trends identified a core set of domains and subdomains related to PM competencies that were consistent across multiple disciplines and competency frameworks. A survey was used to confirm the applicability of these domains to the cross-functional and multi-disciplinary work practices of industry professionals. Companies were requested to trial the domains to determine their relevance in practice and feedback was obtained.</p><p><strong>Results: </strong>Four PM-relevant domains were identified from the literature review: medical science and technology; translational and clinical application; governance and regulation and professional practice. Survey results refined these domains, and case studies within companies confirmed the potential for this framework to be used as an adjunct to current role specific competency frameworks to provide a specific focus on needed PM capabilities.</p><p><strong>Conclusion: </strong>The framework was well accepted by local industry as a supplement to role specific competency frameworks to provide a structure on how to integrate new and evolving technologies into their current workforce development planning and build a continuous learning and cross-disciplinary mindset.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11043185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140140779","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":"Approaches to Design an Efficient, Predictable Global Post-approval Change Management System that Facilitates Continual Improvement and Drug Product Availability.","authors":"Anders Vinther, Emma Ramnarine, Thierry Gastineau, Laura O'Brien, Oliver Brehm, David Fryrear","doi":"10.1007/s43441-024-00614-9","DOIUrl":"10.1007/s43441-024-00614-9","url":null,"abstract":"<p><p>The complexity and inter-connectedness of operating in a global world for drug product supply has become an undeniable reality, further underscored by the COVID-19 pandemic. For Post-Approval Changes (PACs) that are an inevitable part of a product's commercial life, the impact of the growing global regulatory complexity and related drug shortages has brought the Global PAC Management System to an inflection point in particular for companies that have their products marketed in many countries.This paper illustrates through data analyzed for the first time from 145,000 + PACs for 156 countries, collected by 18 global pharma companies over a 3-year period (2019-2021), how severe the problem of global regulatory complexity is. Only PACs requiring national regulatory agency (NRA) approval prior to implementation were included in the data set. 1 of the 156 country NRAs approved all submitted PACs within a period of 6 months. The 6-month timeline was chosen because it is the recommended review timeline for major changes in the WHO guidance for vaccines and biotherapeutic products. 10 out of the 156 (6%) countries had no more than 10% of the PACs reviewed and approved in > 6 months. In 33 (22%) countries more than half of the PACs took > 6 months for approval. It is rare that the same PAC is approved globally within 6 months as individual NRAs take from a few months to years (in some cases > 5 years) for their review.The global PAC management complexity has steadily grown over the past 20 years. Attempts thus far to solve this problem have not made any meaningful difference. Senior leaders and decision-makers across the interdependent components of the complex Global PAC Management System (industry and regulators) must come together and collaboratively manage the problem holistically with the objective of ensuring global drug product availability instead of continuing with distinct stakeholder or country-focused solutions, which can tend to worsen the problem.In this paper, the Chief Quality Officers (CQOs) from 18 of the largest innovator pharma companies (see Acknowledgements) are speaking with One-Voice-of-Quality for PACs (1VQ for PACs Initiative). They are recommending a set of 8 approaches to activate a holistic transformation of the Global PAC Management System. This article presents their view on the problem of global regulatory complexity for managing PACs, it's impact on continual improvement and the risk to drug product supply, as well as approaches that can help alleviate the problem.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11043098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139900431","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":"Decentralized Clinical Trials: Scientific Considerations Through the Lens of the Estimand Framework.","authors":"Rima Izem, Emmanuel Zuber, Nadia Daizadeh, Frank Bretz, Oleksandr Sverdlov, Pascal Edrich, Janice Branson, Evgeny Degtyarev, Nikolaos Sfikas, Robert Hemmings","doi":"10.1007/s43441-024-00615-8","DOIUrl":"10.1007/s43441-024-00615-8","url":null,"abstract":"<p><p>While industry and regulators' interest in decentralized clinical trials (DCTs) is long-standing, the Covid-19 pandemic accelerated and broadened the adoption and experience with these trials. The key idea in decentralization is bringing the clinical trial design, typically on-site, closer to the patient's experience (on-site or off-site). Thus, potential benefits of DCTs include reducing the burden of participation in trials, broadening access to a more diverse population, or using innovative endpoints collected off-site. This paper helps researchers to carefully evaluate the added value and the implications of DCTs beyond the operational aspects of their implementation. The proposed approach is to use the ICH E9(R1) estimand framework to guide the strategic decisions around each decentralization component. Furthermore, the framework can guide the process for clinical trialists to systematically consider the implications of decentralization, in turn, for each attribute of the estimand. We illustrate the use of this approach with a fully DCT case study and show that the proposed systematic process can uncover the scientific opportunities, assumptions, and potential risks associated with a possible use of decentralization components in the design of a trial. This process can also highlight the benefits of specifying estimand attributes in a granular way. Thus, we demonstrate that bringing a decentralization component into the design will not only impact estimators and estimation but can also correspond to addressing more granular questions, thereby uncovering new target estimands.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693037","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":"New Benchmarks on Protocol Amendment Practices, Trends and their Impact on Clinical Trial Performance.","authors":"Kenneth Getz, Zachary Smith, Emily Botto, Elisabeth Murphy, Arnaud Dauchy","doi":"10.1007/s43441-024-00622-9","DOIUrl":"10.1007/s43441-024-00622-9","url":null,"abstract":"<p><p>The Tufts Center for the Study of Drug Development (Tufts CSDD) conducted a follow-up study in 2022 to assess trends in protocol amendment experiences and the impact amendments have had on clinical trial performance, particularly during the COVID-19 pandemic. Sixteen pharmaceutical companies and contract research organizations provided data on 950 protocols and 2188 amendments. The results show that, since 2015, the prevalence of protocols with at least one amendment in phases I-IV has increased substantially (from 57 to 76%) and the mean number of amendments per protocol has increased 60% to 3.3, up from 2.1. Phase I and III protocols saw the highest increases in the mean number of amendments implemented per protocol. A much higher percentage of amendments-77%-were deemed unavoidable with regulatory agency requests and changes to the study strategy as the top reasons cited for amending a protocol. The total average duration to implement an amendment has nearly tripled during the past decade. The time from identifying the need-to-amend to last oversight approval now takes an average of 260 days and the mean duration during which investigative sites operate with different versions of the clinical trial protocol spans 215 days. Protocols that implemented at least one amendment were more effective at increasing patient screening volume and reducing the actual number of patients enrolled relative to plan. Lastly, the prevalence of protocols with at least one amendment and mean number of amendments was significantly higher for protocols conducted during the pandemic.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029070","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 Finkelstein-Schoenfeld Test: A Note on Some Overlooked Issues Concerning Power.","authors":"Rong Tang, Wei-Chen Chen, Heng Li, Nelson Lu, Yu Zhao","doi":"10.1007/s43441-023-00608-z","DOIUrl":"10.1007/s43441-023-00608-z","url":null,"abstract":"<p><p>In this note, we express our viewpoint regarding power considerations, via simulation studies, in clinical study design using hierarchical composite endpoint and Finkelstein-Schoenfeld test.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11043162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693038","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":"Quality Tolerance Limits: A General Guidance for Parameter Selection and Threshold Setting.","authors":"Annett Keller, Nathalie van Borrendam, Patrice Benner, Steven Gilbert, Stefano Saino, Debra Jendrasek, Steve Young, Marcus Muli, Jim Wang, Marta Kozińska, Jun Liu","doi":"10.1007/s43441-024-00617-6","DOIUrl":"10.1007/s43441-024-00617-6","url":null,"abstract":"<p><p>The past years have sharpened the industry's understanding of a Quality by Design (QbD) approach toward clinical trials. Using QbD encourages designing quality into a trial during the planning phase. The identification of Critical to Quality (CtQs) factors and specifically Critical Data and Processes (CD&Ps) is key to such a risk-based monitoring approach. A variable that allows monitoring the evolution of risk regarding the CD&Ps is called a Quality Tolerance Limit (QTL) parameter. These parameters are linked to the scientific question(s) of a trial and may identify the issues that can jeopardize the integrity of trial endpoints. This paper focuses on defining what QTL parameters are and providing general guidance on setting thresholds for these parameters allowing for the derivation of an acceptable range of the risk.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139698392","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":"Correction: Incorporating Prior Data in Quantitative Benefit-Risk Assessments: Case Study of a Bayesian Method.","authors":"Sai Dharmarajan, Zhong Yuan, Yeh-Fong Chen, Leila Lackey, Saurabh Mukhopadhyay, Pritibha Singh, Ram Tiwari","doi":"10.1007/s43441-024-00625-6","DOIUrl":"10.1007/s43441-024-00625-6","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724097","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":"Comprehensive Assessment of Risk-Based Quality Management Adoption in Clinical Trials.","authors":"Abigail Dirks, Maria Florez, Francois Torche, Steve Young, Brian Slizgi, Kenneth Getz","doi":"10.1007/s43441-024-00618-5","DOIUrl":"10.1007/s43441-024-00618-5","url":null,"abstract":"<p><strong>Background: </strong>Risk-based monitoring (RBM) and risk-based quality management (RBQM) offer a compelling approach to increase efficiency, speed and quality in clinical trials by prioritizing and mitigating risks related to essential safety and efficacy data. Since 2013, the FDA and EMA have encouraged the use of RBM/RBQM, however adoption has been slow with limited understanding of the barriers to adoption.</p><p><strong>Methods: </strong>The Tufts Center for the Study of Drug Development conducted an online survey among pharmaceutical, biotechnology, and contract research organizations and gathered 206 responses on 32 distinct RBQM practices.</p><p><strong>Results: </strong>On average, companies implemented RBQM in 57% of their clinical trials. Lower levels of adoption were observed among companies conducting fewer than 25 trials annually (48%) compared to those conducting more than 100 trials annually (63%). Primary barriers to adoption include lack of organizational knowledge and awareness, mixed perceptions of the value proposition of RBQM, and poor change management planning and execution. Insights into improving the level of adoption are discussed.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11043178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747465","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 Next Horizon of Drug Development: External Control Arms and Innovative Tools to Enrich Clinical Trial Data.","authors":"Kelly H Zou, Chelsea Vigna, Aniketh Talwai, Rahul Jain, Aaron Galaznik, Marc L Berger, Jim Z Li","doi":"10.1007/s43441-024-00627-4","DOIUrl":"10.1007/s43441-024-00627-4","url":null,"abstract":"<p><p>Conducting clinical trials (CTs) has become increasingly costly and complex in terms of designing and operationalizing. These challenges exist in running CTs on novel therapies, particularly in oncology and rare diseases, where CTs increasingly target narrower patient groups. In this study, we describe external control arms (ECA) and other relevant tools, such as virtualization and decentralized clinical trials (DCTs), and the ability to follow the clinical trial subjects in the real world using tokenization. ECAs are typically constructed by identifying appropriate external sources of data, then by cleaning and standardizing it to create an analysis-ready data file, and finally, by matching subjects in the external data with the subjects in the CT of interest. In addition, ECA tools also include subject-level meta-analysis and simulated subjects' data for analyses. By implementing the recent advances in digital health technologies and devices, virtualization, and DCTs, realigning of CTs from site-centric designs to virtual, decentralized, and patient-centric designs can be done, which reduces the patient burden to participate in the CTs and encourages diversity. Tokenization technology allows linking the CT data with real-world data (RWD), creating more comprehensive and longitudinal outcome measures. These tools provide robust ways to enrich the CT data for informed decision-making, reduce the burden on subjects and costs of trial operations, and augment the insights gained for the CT data.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11043157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140289045","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}