Therapeutic innovation & regulatory science最新文献

Background: Youth nicotine addiction is a major public health concern in the United States. Disposable Electronic Nicotine Delivery Systems (ENDS), or disposable vapes, are commonly sought out by youth despite not having received premarket authorization from the FDA. The objective of this study was to identify factors contributing to underage consumption of disposable ENDS.

Methods: An anonymous survey was deployed to college students to understand young adults' perceptions and patterns of use of disposable ENDS.

Results: Disposable ENDS are very popular among youth. The results of this study revealed the popular brands, flavors, modes of access, and attractive aspects of disposable ENDS. Survey results combined with information from the literature reveal that disposable ENDS gained popularity in the years following the decline in the popularity of pod-based ENDS, such as JUUL, following strict regulatory action from the FDA.

Conclusion: To ultimately address underage nicotine addiction, the FDA must hold disposable ENDS to the same regulatory standards as other tobacco products and produce regulations specifically targeted at disposable ENDS. The results of this study emphasize the importance of making effective regulatory reform and functional educational resources to prevent young people from initiating the use of disposable ENDS.

Purpose: This study aimed to assess the current regulatory review process of the Zambia Medicines Regulatory Authority (ZAMRA) by identifying the key milestones and target timelines achieved for products approved from 2020 to 2023, as well as good review and quality decision-making practices implemented in the review process.

Methods: A standardised, validated questionnaire; Optimising Efficiencies in Regulatory Agencies (OpERA) and the OpERA Data Collection Template were completed by the author.

Results: Three review models are used by ZAMRA to review new active substances (NASs) and generic products: verification, for products prequalified by the World Health Organization or approved by a stringent regulatory authority (SRA); abridged, for well-established molecules or SRA-approved products; or full, for products not otherwise prequalified. Good review practices and quality decision-making processes were followed but could be improved.

Conclusion: This study assessed the overall ZAMRA operation and identified the key milestones in the review process for products approved from 2020 to 2023, target timelines achieved and the compliance to standard good review and quality decision-making practices.

Introduction: 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.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Introduction: One of the main objectives of pharmacovigilance activities is to confirm unknown adverse drug reactions (ADRs), and data-mining methods have been developed to detect signals that are candidates for ADRs. Reference sets have been developed to evaluate the performance of the data-mining methods. However, reference sets generated in previous studies are not based on Japanese safety information; therefore, they are not suitable for use in evaluation studies in Japan because some drugs have not been approved or marketed for a long time in Japan. This study aimed to develop a reference set using drug safety information marketed in Japan and to evaluate its performance.

Methods: A reference set was developed for 43 drugs and 15 events. For each combination of the selected drug and event, those that were listed as important identified risks in the Japan Risk Management Plan (J-RMP) were set as "positive controls" and those that were not listed as adverse reactions in the package insert were set as "negative controls." In addition, we performed data-mining using Japanese Adverse Drug Event Report database (JADER) and evaluated the results against the reference set to empirically confirm its effectiveness.

Results: The reference set included 127 positive and 386 negative controls. A comparison of the signals obtained from data-mining using JADER with the reference set revealed higher correlations than those in previous studies.

Conclusion: A reference set was developed using the safety information of drugs approved in Japan to promote research on data-mining methods.

Background: 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.

Methods: 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).

Results: 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.

Conclusions: 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.

A data monitoring committee (DMC) can have an extremely challenging job. Stop a trial too soon, and results are inconclusive and the trial fails to obtain answers to important questions that could inform future clinical practice. Stop a trial too late, and trial participants are exposed to potentially harmful or ineffective interventions longer than necessary. Securing convincing and conclusive evidence and the ethical responsibility to current and future patients are weighed carefully during DMC deliberations. The ability to interpret complex information, and appreciation of issues affecting scientific integrity, are critical for the DMC to protect trial participants and public trust. Challenges faced by and issues of prudence faced by DMCs are discussed including interim analysis issues, assessing the totality of information with statistical boundaries as guidelines, interpretation of composite and surrogate outcomes, reactions to early trends, benefit:risk assessment, landscape changes, subgroup analyses, composing information for a comprehensive understanding of patient-centric effects, and evaluating the value of additional data. Case studies illustrate how DMCs addressed the challenges.

Background: Alzheimer's disease (AD) is a neurodegenerative disease for which many clinical trials failed to detect treatment effects, possibly due to the heterogeneity of disease progression among the patients. Predicting and clustering a long-term trajectory of cognitive decline from the short-term cognition data of individual patients would help develop therapeutic interventions for AD.

Methods: This study developed mixture disease progression model to predict and cluster the long-term trajectory of cognitive decline in the population. We predicted the 30-year long-term trajectories of the three cognitive scales and categorized the individuals into rapid and slow cognitive decliners by applying the method, which was based on the two-component normal mixture nonlinear mixed-effects model, to the short-term follow-up data of the Mini-Mental State Examination, the 13-item Alzheimer's Disease Assessment Scale-Cognitive, and the Clinical Dementia Rating Scale-sum of boxes collected in patients with mild cognitive impairment and AD in the Alzheimer's Disease Neuroimaging Initiative.

Results: For each cognitive scale, the models identified two distinct subpopulations, including a population of comprising approximately 10-20% of individuals experiencing rapid cognitive decline, wherein the posterior means of the differences in cognitive decline speed between the two groups ranged from 2 to 3 years. We also identified baseline background factors associated with rapid decliners for three cognitive scales.

Conclusion: Identifying the risk factors associated with rapid decline of cognition by the proposed method aids in planning eligibility criteria and allocation strategy for accounting for the varying disease progression speeds among the patients enrolled in clinical trials for AD.

Since 2019, the Association of Clinical Research Organizations has conducted a landscape survey of risk based quality management (RBQM) adoption in clinical trials. Here, we present data from four years of surveys, with an emphasis on the most recent: the 2022 survey included data from 4958 trials across seven contract research organizations, of which 1004 were new studies started in 2022. Results indicate that while overall risk assessment adoption is strong, it is lagging in other risk-based components which suggests companies are not deriving the full expected benefits of performing a risk assessment and mitigation process to their trials. The 2022 study also suggests new study starts showing promising traction, with adoption hovering near 50% for most RBQM elements. At the same time, the survey suggests industry has mixed views on the potential value of quality tolerance limits (QTLs). Ultimately, centralized monitoring is being underutilized despite the potential of increased patient safety oversight and improved data quality. The authors of this paper developed a case study based on a trial in clinicaltrials.gov to demonstrate how RBQM adoption could include the key RBQM elements such as centralized monitoring, reduced source data review and source data verification as well as implementation of QTLs in a real-world scenario. The authors believe the clinical trial industry has an obligation to utilize centralized monitoring to produce more efficient and effective clinical trials and will make a case to do so in this paper.

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.