Therapeutic innovation & regulatory science最新文献

{"title":"Detection Algorithms for Gastrointestinal Perforation Cases in the Medical Information Database Network (MID-NET®) in Japan.","authors":"Masatoshi Tanigawa, M. Kohama, Kaori Hirata, Rieko Izukura, Tadashi Kandabashi, Yoko Kataoka, Naoki Nakashima, Michio Kimura, Yoshiaki Uyama, Hideto Yokoi","doi":"10.1007/s43441-024-00619-4","DOIUrl":"https://doi.org/10.1007/s43441-024-00619-4","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140678403","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":"Safety of Linagliptin in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Clinical Trials","authors":"Hadir Aljohani, Fares S. Alrubaish, Waad M. Alghamdi, Fawaz Al-Harbi","doi":"10.1007/s43441-024-00637-2","DOIUrl":"https://doi.org/10.1007/s43441-024-00637-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Linagliptin is an oral dipeptidyl peptidase DPP‐4 inhibitor, which is indicated for the treatment of Type 2 diabetes mellitus (T2DM) as monotherapy or add-on to therapy with other hypoglycemic drugs.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>We aimed to summarize the evidence from randomized controlled trials (RCTs) to assess the safety of linagliptin focusing on cardiovascular risks among subjects with type 2 diabetes mellitus.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We conducted a systematic search across the following databases: Medline, Embase, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov from inception to November 2021. Randomized controlled trials (RCTs) of linagliptin compared to placebo in patients with Type 2 diabetes were included. The primary safety points were cardiovascular (CV) adverse events including non-fatal stroke, non-fatal myocardial infarction (MI), CV death, MI, stroke, and hospitalization for unstable angina. While, secondary safety points included 17 reported adverse events such as infections, hypoglycemia and abdominal pain. Three reviewers independently screened and reviewed each study to extract relevant information. Any discrepancies were resolved by consensus. We conducted a meta-analysis using the random effects model. Pooled risk ratios (RRs) of targeted adverse events with linagliptin compared to placebo were estimated using the Mantel–Haenszel test.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>A total of 24 studies with 19,981 adult patients were included. There was no difference in the incidence of all CV adverse events or individual CV adverse events between linagliptin and the placebo arms<i>.</i> The pooled estimate of the risk of upper respiratory tract infection was reported in twelve trials with a 38% risk reduction among patients treated with the linagliptin group compared to the placebo group (RR = 0.62, 95% CI: 0.45–0.85, and I² = 0%), while no difference was found in other infections. For gastrointestinal disorders, the risk of abdominal pain showed a 65% risk reduction among patients treated with the linagliptin group compared to the placebo group (RR = 0.35, 95% CI: 0.16–0.77, and I² = 0%).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Our study showed an overall acceptable safety profile of linagliptin in patients with T2DM. Moreover, our study showed a risk reduction of upper respiratory tract infection and abdominal pain when using linagliptin compared to placebo.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140609623","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":"Pathway for Development and Validation of Multi-domain Endpoints for Amyloid Light Chain (AL) Amyloidosis","authors":"James Signorovitch, Jialu Zhang, David Brown, Preston Dunnmon, Liang Xiu, Nicolae Done, Kristen Hsu, Yolanda Barbachano, Isabelle Lousada","doi":"10.1007/s43441-024-00641-6","DOIUrl":"https://doi.org/10.1007/s43441-024-00641-6","url":null,"abstract":"<p>Immunoglobin light chain (AL) amyloidosis is a rare disease in which a plasma cell dyscrasia leads to deposition of insoluble amyloid fibrils in multiple organs. To facilitate development of new therapies for this heterogenous disease, a public–private partnership was formed between the nonprofit Amyloidosis Research Consortium and the US Food and Drug Administration Center for Drug Evaluation and Research. In 2020, the Amyloidosis Forum launched an initiative to identify clinical trial endpoints and analytic strategies across affected organ systems and life impacts via specialized working groups. This review summarizes the proceedings of the Statistical Group and proposes a pathway for development and validation of multi-domain endpoints (MDEs) for potential use in AL amyloidosis clinical trials. Specifically, drawing on candidate domain-specific endpoints recommended by each organ-specific working group, different approaches to constructing MDEs were considered. Future studies were identified to assess the validity, meaningfulness and performance of MDEs through use of natural history and clinical trial data. Ultimately, for drug development, the context of use in a regulatory evaluation, the specific patient population, and the investigational therapeutic mechanism should drive selection of appropriate endpoints. MDEs for AL amyloidosis, once developed and validated, will provide important options for advancing patient-focused drug development in this multi-system disease.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140609622","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: Comparative Assessment of Drug Lag for Approved Oncology Targeted Therapies Between Saudi Arabia, the United States, and the European Union","authors":"Mohammed Alnuhait, Abdullah Alshammari, Manar Alharbi, Lina Alotaibi, Reem Alharbi, Attiah Khobrani, Nora Alkhudair, Majed Alshamrani, Abdullah M. Alrajhi","doi":"10.1007/s43441-024-00653-2","DOIUrl":"https://doi.org/10.1007/s43441-024-00653-2","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568488","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 FDA Reclassification of Cervical Pedicle and Lateral Mass Screws: A Case Study in Regulatory History","authors":"Jonathan H. Sussman, Ahmed Albayar, Anissa Saylany, Bhargavi R. Budihal, Dominic Romeo, Jason Xu, Joshua Rosenow, Robert F. Heary, William C. Welch","doi":"10.1007/s43441-024-00654-1","DOIUrl":"https://doi.org/10.1007/s43441-024-00654-1","url":null,"abstract":"<p>The classification of medical devices by the Food and Drug Administration (FDA) involves rigorous scrutiny from specialized panels that designate devices as Class I, II, or III depending on their levels of relative risk to patient health. Posterior rigid pedicle screw systems were first classified by the FDA in 1984 and have since revolutionized the treatment of many spine pathologies. Despite this early classification by the FDA, posterior cervical pedicle and lateral mass screws were not reclassified from unclassified to Class III and then to Class II until 2019, nearly 35 years after their initial classification. This reclassification process involved a decades-long interplay between the FDA, formal panels, manufacturers, academic leaders, practicing physicians, and patients. It was delayed by lawsuits and a paucity of data demonstrating the ability to improve outcomes for cervical spinal pathologies. The off-label use of thoracolumbar pedicle screw rigid fixation systems by early adopters assisted manufacturers and professional organizations in providing the necessary data for the reclassification process. This case study highlights the collaboration between physicians and professional organizations in facilitating FDA reclassification and underscores changes to the current classification process that could avoid the prolonged dichotomy between common medical practice and FDA guidelines.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568383","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":"Reflections on the Saudi FDA Regulatory Experience with Smart GxP Inspections","authors":"Ali M. Alhomaidan, Nawaf G. Al-Murikhi, Morae A. Al-Qarni, Fahad A. Al Fahaadi, Khalid S. Al Otaibi, Radwan Hafiz, Ohoud A. Almadani, Turki A. Al Rafie, Mohammed A. Al Ageel, Mohammed A. Dahhas","doi":"10.1007/s43441-024-00647-0","DOIUrl":"https://doi.org/10.1007/s43441-024-00647-0","url":null,"abstract":"<p>Smart GxP inspections have gained increasing attention due to the COVID-19 pandemic, which, understandably, made it challenging for regulatory authorities to conduct on-site inspections. Smart GxP inspections are an oversight approach developed by the SFDA to enable remote compliance assessments of establishments. In this type of inspection, appropriate technical methods and tools (such as livestreaming video) are used without requiring the presence of inspectors onsite, ensuring efficient utilization of resources and the efficiency of inspection process. The objective of this research is to examine and document the shared encounters involving remote inspections and evaluations carried out by SFDA from 2020 to 2022. This will be achieved through the evaluation of the accuracy of document evaluation and the extent to which the objectives of smart GxP inspections were met. Data were collected from local and international smart inspections reports conducted by SFDA between 2020 and 2022, covering medical device manufacturers, pharmaceutical manufacturing sites, warehouses, accreditation offices, scientific offices, and food manufacturing facilities. The results indicate that smart GxP inspections were effective in achieving visit objectives, showing a high degree of document evaluation accuracy. The findings of this study support the use of smart GxP inspections as a valuable alternative to on-site inspections, offering a practical solution to regulatory compliance during the pandemic and beyond. Although the SFDA recognizes the usefulness of smart inspections in upholding regulatory oversight in the face of various challenges, it does not endorse the complete replacement of conventional on-site inspection methods. The SFDA acknowledges significant limitations associated with the current technological resources used in remote regulatory assessments, and these limitations will be explored in the relevant sections.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568382","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":"Improvement of Midpoint Imputation for Estimation of Median Survival Time for Interval-Censored Time-to-Event Data","authors":"Yuki Nakagawa, Takashi Sozu","doi":"10.1007/s43441-024-00640-7","DOIUrl":"https://doi.org/10.1007/s43441-024-00640-7","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Progression-free survival (PFS) is used to evaluate treatment effects in cancer clinical trials. Disease progression (DP) in patients is typically determined by radiological testing at several scheduled tumor-assessment time points. This produces a discrepancy between the true progression time and the observed progression time. When the observed progression time is considered as the true progression time, a positively biased PFS is obtained for some patients, and the estimated survival function derived by the Kaplan–Meier method is also biased.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>While the midpoint imputation method is available and replaces interval-censored data with midpoint data, it unrealistically assumes that several DPs occur at the same time point when several DPs are observed within the same tumor-assessment interval. We enhanced the midpoint imputation method by replacing interval-censored data with equally spaced timepoint data based on the number of observed interval-censored data within the same tumor-assessment interval.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The root mean square error of the median of the enhanced method is almost always smaller than that of the midpoint imputation regardless of the tumor-assessment frequency. The coverage probability of the enhanced method is close to the nominal confidence level of 95% in most scenarios.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>We believe that the enhanced method, which builds upon the midpoint imputation method, is more effective than the midpoint imputation method itself.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568227","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":"Different Development Strategies Affecting Japan’s Drug lag between Japan-Based and Foreign-Based Companies","authors":"Masayasu Hidaka, Hideki Hanaoka, Yoshiaki Uyama","doi":"10.1007/s43441-024-00649-y","DOIUrl":"https://doi.org/10.1007/s43441-024-00649-y","url":null,"abstract":"<p>We examined the development strategies of new molecular entities approved during a 10-year period (fiscal years of 2012–2021) in Japan to determine the differences in drug lag between Japan and foreign companies. The results demonstrated a clear difference in development strategies. For example, products were usually developed through a “only-Japan” strategy by Japan companies (51.1% of products), compared to a “MRCT (multi-regional clinical trials)” strategy by foreign companies (54.9% of products). Regarding types of licenses, for Japan companies, the percentage of original products was higher in the category of less drug lag, such as “no approval in the US and EU” (59.1%), whereas the percentage of “license-in” products was markedly higher in the “drug lag ≥ 5 years” category (52.5%). Such differences were not observed for products developed by foreign companies. Of 64 license-in products developed by Japan companies with a drug lag &gt; 5 years, 51 (79.7%) had already been approved in the US or EU at initiation of clinical development in Japan. The origin of approximately half (34) of the products was from the emerging companies (non-member foreign companies of the Japan Pharmaceutical Manufacture Association). These results suggest that more global cooperation of Japan companies, particularly with emerging foreign companies, is necessary in terms of the earlier timing of license-in and development strategies of products to promote drug development without drug lag or drug loss in Japan.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568131","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":"Benchmarking Site Activation and Patient Enrollment","authors":"Mary Jo Lamberti, Abigail Dirks, Nicholas Kikuchi, Neha Patel Cervantes, Kenneth Getz","doi":"10.1007/s43441-024-00638-1","DOIUrl":"https://doi.org/10.1007/s43441-024-00638-1","url":null,"abstract":"<p>Clinical trial conduct poses numerous challenges, many pertaining to patient recruitment. The primary objectives of this study were to update benchmarks on site activation and patient enrollment gathered in previous Tufts CSDD studies and examine current usage of recruitment and retention tactics. The data collection focused on site activation and patient enrollment metrics used for studies. Analyses were conducted comparing results from 2012, 2019 and 2023. The results indicate that actual enrollments exceeded planned enrollments for a majority of studies and timelines were shorter than expected. In addition, differences were found for enrollment achievement by global region and site type. Further investigation into studies conducted during a later time frame and post-pandemic could be compared with current benchmarks to examine differences.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568500","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":"Diversity Plans and Postmarketing Studies: First Impressions of Anticipated Diversity Requirements in the United States","authors":"Blake Schouest, Krithi Rao Bindal","doi":"10.1007/s43441-024-00643-4","DOIUrl":"https://doi.org/10.1007/s43441-024-00643-4","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Recent Food and Drug Administration (FDA) draft guidelines are intended to improve representation and formalize the assessment of race and ethnicity in drug development, but how regulators and industry stakeholders plan to implement and enforce new requirements is still being determined.</p><h3 data-test=\"abstract-sub-heading\">Materials and methods</h3><p>Here, a 10-question survey was developed to assess the experiences of industry stakeholders in developing diversity plans. These survey results informed an analysis of postmarketing studies to understand how diversity requirements have been enforced to date.</p><h3 data-test=\"abstract-sub-heading\">Results and Discussion</h3><p>Among 13 survey responders, experience submitting and receiving feedback on diversity plans was limited. A variety of challenges have been associated with developing these plans, including questions regarding regulatory guidance. Sponsors have utilized several data sources, including real-world datasets, to define enrollment goals. Diversity-related postmarketing studies most commonly related to oncologic diseases, and endpoints frequently related to efficacy. Most marketing applications associated with diversity-related postmarketing studies received Orphan drug designation (ODD) and Accelerated Approval.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>These results show that industry experience with diversity plans remains limited in the absence of finalized regulatory guidance. Sponsors are beginning to develop strategies for submitting diversity plans, which include identifying key functions and data sources to support enrollment goals, although definitive conclusions were difficult to draw from the small responder pool. In the postmarketing setting, studies are already underway to improve the understanding of racial and ethnic differences in responses to approved drugs. Development programs relating to oncology, which has historically suffered from a lack of diverse representation, have been a primary focus of such studies thus far.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568225","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}