Therapeutic innovation & regulatory science最新文献

{"title":"Basic Considerations for the Consistency Evaluation Based on ICH E17 Guideline.","authors":"Meihua Long, Haiyan Wu, Xiaoni Liu, Pengfei Li, Renxin Lin, Ziwei Zhao, Xiujing Kou, Chao Zhu, Chen Ji, Wei Zhang, Kezhou Zhang, Bing Yu, Yun Wang, Hua Zhang, Fan Jia, Yan Hou","doi":"10.1007/s43441-024-00737-z","DOIUrl":"10.1007/s43441-024-00737-z","url":null,"abstract":"<p><p>In the International Council for Harmonisation (ICH) guidance on General Principles for Planning and Design of Multi-Regional Clinical Trials (E17), it is important to evaluate the consistency of treatment effect across regions in a multi-regional clinical trial (MRCT). In this paper, we elaborated on some basic considerations to evaluate consistency. We first list the design considerations, and then provide consistency evaluation and interpretation on pharmacokinetics, pharmacodynamics, efficacy, safety, and benefit-risk. Furthermore, we consider special situations including non-inferiority, multiple primary endpoints, interim analyses with delayed treatment effect, adaptive design, single-arm studies, rare diseases, and statistical methods for regional treatment effect estimate and consistency evaluation. Finally, if potential inconsistency is anticipated or observed in the MRCT, an exploratory framework is provided for further investigations. Overall, this paper elaborates on consistency evaluation in MRCT, discusses possible challenges in reality and also provides strategies and methods to overcome these challenges. This could help consensus across health authorities, industries, and academic societies, which could further facilitate consistency evaluation and MRCT implementation. Effective communication with regulatory authorities is encouraged to obtain an acceptance of a global approach.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":"59 2","pages":"328-336"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543635","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":"Interim Clinical Trial Data: Who Can See What, and When?","authors":"Susan S Ellenberg, Yimei Li","doi":"10.1007/s43441-024-00728-0","DOIUrl":"10.1007/s43441-024-00728-0","url":null,"abstract":"<p><p>It has long been a basic principle of randomized clinical trials addressing serious outcomes and/or major public health issues that interim data should be inaccessible to investigators and to industry sponsors, with interim data reviewed on a regular basis by an independent data monitoring committee (DMC). Challenges to this principle may arise when sponsors and/or regulators perceive a need to review interim data while the trial remains ongoing-for example, when a trial is being considered for accelerated approval. In this paper we propose approaches that could minimize the extent of interim data that is made available to others while the trial continues.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"211-214"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955524","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: Consumer Understanding of Prescription Drug Indications in Direct-to-Consumer Television Advertisements.","authors":"Helen W Sullivan, Kathryn J Aikin, Mihaela Johnson, Kate Ferriola-Bruckenstein","doi":"10.1007/s43441-024-00738-y","DOIUrl":"10.1007/s43441-024-00738-y","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"398"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955520","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 Ethics of the \"Right-to-Try\" Movement in an Era of Regulatory Flux.","authors":"Neil Jain, David Ralston, Cheryl Erwin","doi":"10.1007/s43441-025-00758-2","DOIUrl":"10.1007/s43441-025-00758-2","url":null,"abstract":"<p><p>The Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017 signed on May 30, 2018 under President Trump has been championed by patient advocacy groups as a victory for individuals with life threatening illnesses willing to undergo experimental treatment. The act is not a novel idea, but rather a nuanced result of the previous attempts to challenge the US Food and Drug Administration's (FDA) authority on drug approval and distribution. Currently, right-to-try programs coexist with an already existing expanded access program run by the FDA. The difference is that right-to-try requests eliminate FDA guidance and authorization. The objectives of this study are to review prior historical challenges to the FDA and how they eventually influenced right-to-try movements, examine the law itself and its arguments written by advocates and critics, discuss how its implications fit into the current climate of regulatory flux, and propose the impacts it has on influencing patient care and the scientific process.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"256-263"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256735","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":"Assessment of Local Pharmaceutical Manufacturing Sector in a Low-income Country: A Descriptive Study.","authors":"Tesfa Marew, Anteneh Belete, Frances J Richmond, Tsige Gebre-Mariam","doi":"10.1007/s43441-025-00756-4","DOIUrl":"10.1007/s43441-025-00756-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;In high-income countries and emerging economies, pharmaceutical manufacturing is a driver for socioeconomic development. In sub-Saharan Africa, local pharmaceutical production is still fledgling largely because of historical economic and technological asymmetry. In Ethiopia alike, this environment has changed little despite six decades long operations and several support initiatives; access to essential medicines remained a persistent challenge. Despite a few fragmented reports on trends and profiles of the sector, in-depth investigations into underlying challenges remain limited. This study explores the perspectives and insights of upfront executives and technical personnel in the Ethiopian pharmaceutical industry on its current state, challenges and opportunities for enhancing local production capacity. The findings are triangulated with literature reports and provide valuable insights for developing intervention strategies and policy updates.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A validated structured survey questionnaire was disseminated to professionals working in local pharmaceutical companies. Multiple regression analysis was conducted to study the effects of different factors on the performance of the local manufacturing sector.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Over half of the professionals (55.1%) rated the current production technology as advanced while 68% described it as semi-automated. Close to one-third (31.6%) reported that the companies are operating at acceptable level of performance, and 51.5% reported low-capacity utilization in their companies. Most professionals (67.8%) viewed export market activities as poor and many identified weak research and development activities. Unplanned operations downtimes, limited physical infrastructure, inadequate access to foreign currency, shortage and highstaff turnover of qualified experts, lack of commitment from top management, absence of merit-based support system and limitations in compliance with regulatory and quality requirements were reported as major challenges. Multiple linear regression analysis demonstrated that capacity utilization (α = 0.008), research and development capacity (α = 0.014) and export market activities (α = 0.027) have significant impact on the sector performance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Despite commendable efforts by the industry and government, limitations in financing, infrastructure, qualified workforce, and quality system implementation are affecting capacity utilization and performance. Absence of reliable staff attraction and retention system, lack of effective leadership and non-favourable working environment were identified as missing elements. Enhancing economies of scale and capacity utilization, addressing policy and infrastructure bottlenecks, providing merit-based support for R&D and quality management, and implementing staff attraction and retention strategies are key steps towards developing competent local ph","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"379-396"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371220","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 Five-Year Analysis of Market Share and Sales Growth for Original Drugs after Patent Expiration in Korea.","authors":"Minyoung Bae, Sung Ryul Shim, Dong-Wook Yang, Kyung-Bok Son, Sang-Won Lee","doi":"10.1007/s43441-025-00741-x","DOIUrl":"10.1007/s43441-025-00741-x","url":null,"abstract":"<p><strong>Introduction: </strong>The sales patterns of original drugs after patent expiration in Korea show a relatively high market share and continuous sales growth differently from those in the U.S. and European countries. This study aims to investigates a five-year sales pattern of original drugs after patent expiration in Korea using empirical data.</p><p><strong>Methods: </strong>Using data from the Ministry of Food and Drug Safety, original drugs whose patents expired in 2012-2018 were extracted. And we used IQVIA data to determine the market share and sales growth rate of 48 original drugs, whose generic drug launched for the first time in the same molecule market, and whose sales data over five years after first generic entry were available. We analyzed the differences by the attribute of variables.</p><p><strong>Results: </strong>The sales volume of original drugs in the fifth year (Q 20) had an average growth rate of 150.6% compared with that before the first generic drug launched, indicating a continuous growth. The average market share of original drugs in the fifth year (Q 20) decreased to 70.6%, but it was higher than previously reported research results in Korea and other countries. Differences were observed across the category of attribute.</p><p><strong>Conclusion: </strong>This study demonstrated that while market share of original drugs is decreasing, the sales volume increased continuously until the fifth year, differently from those of other countries. Variations in sales patterns by attributes reflect unique dynamics in Korea.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"349-358"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955501","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":"Consumer Understanding of Prescription Drug Indications in Direct-to-Consumer Television Advertisements.","authors":"Helen W Sullivan, Kathryn J Aikin, Mihaela Johnson, Kate Ferriola-Bruckenstein","doi":"10.1007/s43441-024-00732-4","DOIUrl":"10.1007/s43441-024-00732-4","url":null,"abstract":"<p><strong>Background: </strong>Prescription drugs may be indicated to treat more than one medical condition, and companies may promote more than one indication in the same direct-to-consumer (DTC) ad. This study examined how presenting multiple prescription drug indications in one DTC television ad affects consumers' processing of drug information.</p><p><strong>Methods: </strong>We conducted two studies with adults diagnosed with diabetes (Study 1, N = 408) or rheumatoid arthritis (Study 2, N = 411). We randomly assigned participants to view one of three television ads: primary indication only (Study 1: diabetic peripheral neuropathy; Study 2: rheumatoid arthritis), primary plus a similar secondary indication (Study 1: fibromyalgia; Study 2: psoriatic arthritis), or primary plus a dissimilar secondary indication (Study 1: generalized anxiety disorder; Study 2: ulcerative colitis).</p><p><strong>Results: </strong>Remembering and understanding the primary indication was not significantly affected by the presence of a secondary indication (similar or dissimilar). Higher health literacy participants remembered and understood secondary indications.</p><p><strong>Conclusions: </strong>Including a second indication in DTC television ads does not appear to have detrimental effects and can increase awareness of the second indication for some participants. Industry and regulators should continue to ensure DTC promotion is truthful and non-misleading, irrespective of the number of indications presented.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"278-287"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865540","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":"Data Monitoring Committee Reports: Telling the Data's Story.","authors":"Lijuan Zeng, Toshimitsu Hamasaki, Scott R Evans","doi":"10.1007/s43441-024-00727-1","DOIUrl":"10.1007/s43441-024-00727-1","url":null,"abstract":"<p><p>A Data Monitoring Committee (DMC) plays a pivotal role in monitoring participant safety and efficacy and overseeing the integrity of clinical trials. DMCs accomplish this mission by periodically reviewing accumulating data to assess benefits and harms of interventions in ongoing studies and making subsequent recommendations regarding future clinical trial conduct to the trial sponsor. Reports summarizing data from the clinical trial are prepared for the DMC by statistical and data analysis centers to inform DMC decision-making. In practice however, these reports are often disorganized, complex, and provide overwhelming detail yet insufficient information, that hinders accurate and efficient interpretation of interim data. This review paper delves into the nuances of preparing effective DMC reports, highlighting the importance of simplicity, clarity, and thoughtful relevance in data presentation. We discuss structured approaches for preparing closed reports, which deal with sensitive and sometimes messy interim data, and underscore the use of visual summaries and narrative elements that enhance comprehension and facilitate efficient assessments of trial data. The paper outlines key principles for preparing DMC reports and provides practical guidance on their structure. Ultimately, this guidance seeks to ensure that the data's story is clearly and efficiently conveyed to facilitate the DMC decision-making process.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"222-233"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802263","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":"Descriptive Analysis of Good Clinical Practice Inspection Findings from the Saudi Food and Drug Authority.","authors":"Omaima O Arab, Mohammed Aldayan, Khalid Almowaizri, Ahmad Alghamdi, Jahad Alghamdi, Adel Alharf","doi":"10.1007/s43441-024-00731-5","DOIUrl":"10.1007/s43441-024-00731-5","url":null,"abstract":"<p><strong>Introduction: </strong>The Saudi Food and Drug Authority (SFDA) conducts inspections in accordance with Good Clinical Practice (GCP) to safeguard clinical trial integrity and protect the rights, safety, and welfare of study participants. These inspections ensure that trials are conducted in compliance with GCP and applicable laws.</p><p><strong>Objectives: </strong>The study aims to provide a description of GCP inspection findings, analyze their impact on the clinical trial ecosystem, and provide recommendations to improve clinical trial conduction in Saudi Arabia.</p><p><strong>Methods: </strong>A review was conducted on inspection reports, with two senior independent inspectors examining, collecting, and categorizing the data. Descriptive statistics were used to summarize the categorical variable via frequency distributions.</p><p><strong>Results: </strong>A total of 131 GCP inspections were performed between 2017 and 2023, totaling 722 observations from 116 (88.5%) inspection visits. The remaining 15 (11.5%) inspection visits recorded no observations. The highest number of visits were conducted in contract research organizations (CRO) (n = 50; 38.2%) with 118 observations, followed by clinical investigator sites (n = 46; 35.1%) with 313 observations, then bioequivalence (BE) centers (n = 33; 25.2%) with 256 observations, and the last 2 (1.5%) visits were conducted in phase I clinical trial units with 35 observations.</p><p><strong>Conclusion: </strong>This study assesses GCP inspection reports and examines the types of deficiencies and their grades in each area. Observation categories and grades were found to vary by organization type, which indicates the need for specific action plans addressing each organization type separately. This report provided recommendations based on the most common findings to assist researchers and sponsors when conducting clinical trials in Saudi Arabia.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"295-303"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898310","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":"Global Harmonization of Biosimilar Development by Overcoming Existing Differences in Regional Regulatory Requirements - Outcomes of a Descriptive Review.","authors":"Thomas M Kirchlechner, Hillel P Cohen","doi":"10.1007/s43441-024-00740-4","DOIUrl":"10.1007/s43441-024-00740-4","url":null,"abstract":"<p><p>Global harmonization of biosimilar developmental requirements will facilitate development leading to increased patient and societal benefits. However, there are several technical and regulatory hurdles that must be addressed to harmonize the regulatory requirements in different countries and regions. At times, there is a requirement for use of locally sourced reference product, forcing biosimilar developers to repeat analytical or clinical comparability studies against reference product batches sourced from within a given country. While most health authorities no longer require comparative animal toxicology studies of the proposed biosimilar and reference product, these are still required in several countries, forcing biosimilar companies to conduct such studies or risk non-approval of their product. At times, different health authorities request different clinical study designs. In some jurisdictions there is a requirement to generate clinical data in local ethnic populations. Some health authorities require a hybrid label that combines clinical data from the reference biologic and the biosimilar, in the patient leaflet. Recommendations are provided to address each of these hurdles to facilitate global regulatory harmonization of biosimilars. Overcoming these barriers will ultimately increase patient access to these medicines in all regions while providing financial relief to healthcare systems.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"245-255"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011664","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}