Carlin and Hwanhee Hong Regulatory Issues in Meta-Analysis of Safety Data Aloka G. The importance of a favorable safety profile to the overall success of a pharmaceutical product is well known. Prior to the marketing authorization of a drug, rigorous safety monitoring and evaluations from preclinical to all stages of clinical trials are required. Aspects related to benefit-risk assessments are also covered. Amy Xia, PhD, is an executive director of Global Biostatistical Science at Amgen Inc.
©Chi-Shiang Wang, Pei-Ju Lin, Ching-Lan Cheng, Shu-Hua Tai, Yea-Huei Kao Yang, Jung-Hsien Chiang. Controlling the false discovery rate: a practical and powerful approach to multiple testing. Specifically, the following topics are discussed: prospective program-level safety planning, evaluation, and reporting; the impact of adverse event grouping on statistical analysis; the applications of Bayesian methods in safety signal detection; meta-analysis for analyzing safety data; and safety graphics. It discusses quantitative approaches to safety evaluation and risk management in drug development, covering Bayesian methods, effective safety graphics, and risk-benefit evaluation. Graphical displays can have a variety of purposes.
Journal of the Royal Statistical Series A. This process is continued until either the first or the second decision is made. Neurotoxicity screening can be based on a battery of measurements and observations such as the functional observational battery that has been in use for a number of years. The open session is attended by the sponsor and lead investigators, including the statistician s responsible for the trial design. Only an upper boundary was used since trials are only terminated for an excess frequency of toxicity and not for a low rate.
As the industry transitions from passive to active safety surveillance activities, there will be greater demand for more comprehensive and innovative approaches that apply quantitative methods to accumulating data from all sources, ranging from the discovery and preclinical through clinical and post-approval stages. Early safety signal detection not only leads to better patient protection, but also has the potential to save development costs. On the basis of the first trial, one of the three decisions mentioned above is made. Uncertain Judgements introduces the area, before guiding the reader through the study of appropriate elicitation methods, illustrated by a variety of multi-disciplinary examples. Stakeholders in Safety Monitoring 2. Tables and figures should summarize baseline characteristics, follow-up completeness, treatment adherence, and major safety and efficacy outcomes by treatment group. Close collaboration between the statistician and the clinical investigators will be needed in order to design safety screens with good operating characteristics.
The boundary values for the first 10 events are shown in Table 1. Cai, T, Parast, L, Ryan, L. It also enables sponsors to build a safety data warehouse to better respond to safety related queries across the entire drug program. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Sponsor Clinical trial sponsors, usually pharmaceutical companies, are responsible for developing the clinical trial protocol. Text summaries should accompany the tables and figures.
Common Practice in Safety Monitoring 2. Safety evaluation is a central component in all stages of the drug development lifecycle. Prieto-Merino, D, Quartey, G, Wang, J, Kim, J. It is important to consider inclusion of safety assessment criteria in addition to the evaluation of efficacy. Conclusion: The structure, process, and outcome framework allowed for the characterization of drug safety management during clinical trials, providing a useful approach for the promoter to systematically measure and evaluate the process. Heightening these concerns is the participation not only of adults but also of children in pediatric research trials.
Data in the open report are pooled over the treatment groups. It aims at describing the principles and providing some practical rules for constructing effective graphical displays. Use and avoidance of continuity corrections in meta-analysis of sparse data. Bayesian sequential meta-analysis design in evaluating cardiovascular risk in a new antidiabetic drug development program. Amy Xia, Thomas Liu, and Violeta Hennessey Non-Inferiority Study Design and Analysis for Safety Endpoints Steven Snapinn and Qi Jiang Safety Monitoring Program Safety Analysis Plan: An Implementation Guide Brenda Crowe, H. Safety information of one product may be informative to other practitioners using a similar class of agents. The mandatory requirement on clinical trial registration and the disclosure of trial results are significant achievements in advancing science and increasing transparency in clinical research.
Morris, Use of hierarchical models to analyze European trends in congenital anomaly prevalence , Birth Defects Research Part A: Clinical and Molecular Teratology , 106 , 6 , 480-488 , 2016. Amy Xia and Karen L. Statistical graphics and reporting in drug development. Though the math underlying this procedure may be computationally intensive, implementation of the statistical rules will be easy and the continuous screening provided will give suitabley early warning when real problems were to emerge. These posterior opinions can be used by the monitoring board to anticipate the clinicians' reaction to the results. Introduction Clinical trials provide the evidentiary basis for regulatory approvals of safe and effective medicines.