Therapeutic innovation & regulatory science最新文献

Recent progress in materials chemistry has resulted in the development of several ceramic materials that are now being used in dental implants. The advantages of ceramic materials over conventional metallic materials are that they do not induce allergic reactions in individuals with metal allergies, they do not interfere with magnetic resonance imaging, and they provide improved esthetics. In addition, some ceramic materials are tougher than metallic materials and less brittle. However, despite these advantages, few ceramic dental implant materials are currently approved for use in Japan. In FY2022, the Ministry of Health, Labour and Welfare of Japan commissioned a project called the "Project for the Development of a Guideline for the Evaluation of Ceramic Dental Implants," the goal of which was to consider how best to facilitate swift clinical development and approval of emerging ceramic dental implant materials. At a meeting of experts from professional societies, related industry organizations, and government agencies, the issues related to evaluation of the efficacy and safety of ceramic implant were discussed. Here, we summarize the outcomes of that meeting as a set of principles for the premarketing evaluation of ceramic dental implant materials in Japan.

The European Union Clinical Trials Regulation (EU CTR) provides new regulatory requirements for the preparation and submission of clinical trial documents. The United Kingdom Drug Information Association Medical Writing (UK DIA MW) Committee, with members from across the pharmaceutical industry, have reviewed the EU CTR and in this report, provide expert guidance on writing documents for submission in the EU CTR Clinical Trials Information System (CTIS) portal. Medical writers should be aware that the Investigator's Brochure containing the Reference Safety Information (RSI) must align with the annual safety report, and the RSI format must comply closely with the EU CTR. For clinical study protocols, medical writers should prepare a single integrated EU protocol that receives consolidated approvals from all participating EU member states, with different versions of a protocol for different EU member states no longer permitted. This report also provides details of experiences and recommendations on protocol synopses from the UK DIA MW Committee. In addition, plain language summaries are new EU CTR documents required for each study presenting summaries of clinical trial results for laypersons. Some of these documents will be published in the publicly accessible CTIS portal which has created concerns amongst many companies who are keen to protect commercially confidential information (CCI). Medical writers may help reduce CCI through lean writing, but specifically identifying CCI may require specialist legal evaluation. This report by the UK DIA MW Committee highlights the key processes for medical writers to ensure compliance with the EU CTR when preparing documents for submission to the CTIS portal.

Background and objective: Denosumab is widely used for osteoporosis and cancer treatment. However, hypocalcemia induced by denosumab is a frequent adverse event. The objective of this study is to comprehensively investigate the safety signals and the occurrence of hypocalcemia in real-world patient cases reported through the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

Methods: Reports from January 1, 2017 to December 31, 2021 were extracted from the FAERS. Only cases of hypocalcemia suspected to denosumab were eligible in pharmacovigilance study. Denosumab-related hypocalcemia safety signal were identified to characterize their clinical features. A safety signal for hypocalcemia was evaluated using reporting odds ratios (ROR).

Results: Among the 102,413 cases related to denosumab, 1042 cases were reported with denosumab-related hypocalcemia. The affected patients were mainly elderly (median age 70 years) and male (n = 568, 63.5%). In available data, the median onset time of 23 (range 0-1601) days. Most patients required drug interruption (n = 226, 72.9%) and can achieve a recovered-resolved state (n = 318, 62.1%). For the whole database, denosumab exhibited a safety signal for hypocalcemia (ROR = 14.09, 95% Cl 13.18, 15.06). In the sensitivity analyses, denosumab also showed a safety signal for hypocalcemia in cancer (ROR = 21.28, 95% Cl 18.79, 24.11) and osteoporosis (ROR = 9.29, 95% Cl 6.80, 12.59). Compared with bisphosphonates, denosumab still has safety signal for hypocalcemia (ROR = 1.88, 95% Cl 1.67, 2.11).

Conclusions: This pharmacovigilance database analysis indicates a high safety signal for hypocalcemia associated with denosumab, particularly in cancer patients.

Background: To construct a competency model for clinical investigators involved in the process of new drug development, providing a reference for the training, selection and assessment of clinical investigators.

Methods: The Behavioral Event Interview (BEI) method was used to interview 12 excellent clinical investigators and 8 clinical investigators of average performance. Each competency characteristic was extracted from the interview text by semantic coding. Total frequency, total score, average score and highest score were calculated for each competency element. Category agreement coefficient, coefficient of reliability and Spearman correlation coefficient were used to assess the consistency of two coders for coding and classification. Independent-samples Mann-Whitney U test was applied to compare the differences in competency elements between the group of excellent clinical investigators and the group of average investigators.

Results: The average coefficient of category agreement was 0.671, and the average coefficient of reliability was 0.803. No significant differences were observed between the two groups in the aspect of interview time (P = 0.190) and the interview words (P = 0.184), indicating comparability between the two groups. However, there was a clear performance difference between the excellent and average groups. In addition, we found that the competency model for clinical investigators contained 24 prominent competence elements and 8 benchmark competency elements.

Conclusions: Clinical investigator is a medical professional who is involved in a highly research-intensive and practical job, where prominent competency element largely reflects clinical practice skills, innovation and awareness of Good Clinic Practice (GCP). Our results provide a reference for assessing clinical investigators' competencies, encouraging and guiding them to modify their behaviors according to the competency model, and also cultivating clinical investigators so as to improve the competence level of clinical investigators.

Introduction: Until around 2000, the number of medicinal products labelled for paediatric use was limited worldwide. Regulatory measures to promote paediatric drug development in the US and Europe and the establishment of an international guideline (ICH-E11) have led to an increase in the number of paediatric labels. In Japan, efforts have been made to promote the development of paediatric drugs. This study was aimed to examine whether these supportive efforts are successful in Japan.

Methods: This study examined the number of new drugs approved for paediatric indications in Japan from 2006 to 2023, as well as the clinical data package, that is, characteristics of the approved paediatric drugs and paediatric clinical trials, and the percentage of extrapolation of adult data, in the most recent 9-year period.

Results: The number of paediatric drug approvals showed an increasing trend between 2006 and 2023 with some fluctuations. The proportion of drugs indicated for paediatric patients to the total number of approved drugs was about 30% until 2022, but increased to 48% in 2023. During the period from 2015 to 2023, simultaneous development in adults and children accounted for 59% (159/269) of paediatric development, but the complete extrapolation of adult data to paediatric populations has not been widely utilized (11.2%, 30/269).

Conclusions: The number of paediatric drug approvals has shown an upward trend, suggesting that measures to promote the development of paediatric drugs may have been exerting a favourable effect in Japan. However, there is still a limited number of drugs that have additional indications for paediatric use. Appropriate development strategies, such as the extrapolation of adult data to paediatric populations, should be considered if scientifically justified.

'Risk Management Plan Educational Materials' (RMP EMs) are additional risk minimization measures (aRMMs) intended to prevent or reduce the occurrence of adverse reactions associated with the exposure to a medicine, or to reduce their severity or impact on the patient. While the healthcare sector is embracing various digital tools and platforms for educational and/or awareness building purposes, paper-based materials have remained the mainstay approach for implementation of aRMMs by pharmaceutical companies. Novartis in Singapore conducted a pilot on the feasibility of distributing electronic copies of RMP EMs (e-RMP). Post-pilot, e-RMP was officially implemented in Novartis Singapore. A year following the launch of e-RMP, a survey was performed with healthcare professionals (HCPs) to understand end-users' experience. The survey responses revealed a general preference by both HCPs and patients towards e-RMP. Digital methods of delivering educational aRMMs offer great benefits over traditional paper-based programs. e-RMP significantly reduces the time needed for updated RMP EMs to reach HCPs and their patients/caregivers. This is important to ensure that HCPs and patients/caregivers are made aware of any updates in key safety messages of the products in a timely manner to ultimately ensure patient safety. The successful transition to digital solutions requires purposeful collaborations between key stakeholders of the healthcare ecosystem including regulatory authorities, pharmaceutical companies, HCPs, patients and caregivers. This article aims to provide insights on the digitalization journey of e-RMP, a case study in Singapore, outlining the value but also some of the challenges faced during this transformation.

For many years, the European Forum for Good Clinical Practice (EFGCP) Children Medicines Working Party has organised a Paediatric conference annually. In the past, this event was organised jointly with the European Medicines Agency who was used to host it, along with the Drug Information Association (DIA). This conference is the opportunity for all involved in paediatric drug development, i.e., regulators, HTA bodies, patients' representatives, academia and industry, to share learnings and raise awareness about new regulatory requirements of interest to optimise paediatric drug development. The theme of the 2021 conference was "Challenges and Solutions - the path forward" while in 2022 it focused on "Progress made and Continuing Challenges". Because of the COVID-19 pandemic these two conferences were organised virtually. However, this has not impacted the attendance and value of the conference, since because of a broad and attractive agenda there was a wide stakeholder participation, which provided a compendious overview of the leading issues to improve children's access to innovative medicines.

Post-marketing surveillance refers to the process of monitoring the safety of drugs once they reach the market, after the successful completion of clinical trials. In this work, we investigate a computational approach using data mining tools to detect safety signals from post-market safety databases, or in other words, to identify adverse events (AEs) with disproportionately high reporting rates compared to other AEs, associated with a particular drug or a drug class. Essentially, we view this as a problem of cluster analysis-based anomaly detection on post-market safety data, where the goal is to 'unsupervisedly' detect the anomalous or the signal AEs. Our findings demonstrate the potential of using a clustering ensemble method to detect drug safety signals. It employs multiple clustering or anomaly detection algorithms, followed by a performance comparison of the candidate algorithms based on a collection of appropriate measures of goodness of clustering results. The method is general enough to include any number of clustering or anomaly detection algorithms and goodness measures, and performs better than any of the candidate algorithms in identifying the signal AEs. Extensive simulation studies illustrate that the ensemble method detects the AE signals from synthetic post-market safety datasets pretty accurately across the different scenarios explored. Based on the cases reported to the FDA Adverse Event Reporting System (FAERS) between 2013 and 2022, we further demonstrate that the ensemble method successfully identifies and confirms most of the adverse events that are known to occur most frequently in reaction to antiepileptic drugs and $\beta$ -lactam antibiotics.

This commentary addresses the recent U.S. Food & Drug Administration (FDA) proposed rule to expand access to nonprescription drugs through additional conditions of nonprescription use (ACNU). It surveys the various pathways to market for pharmaceutical products, noting the distinct requirements for over-the-counter (OTC) products differentiating them from prescription products. It subsequently reviews the ACNU proposed rule, weighing its potential benefits against possible limitations. With a view towards the future, the ACNU proposed rule is acknowledged as part of a longstanding tradition to expand drug channels in a risk-stratified fashion with increasing clinical oversight to address in tandem increasing consumer risks. Finally, the proposed rule also serves as a potential prelude for a future behind the counter drug pathway.