Working with the U.S. Food and Drug Administration to obtain approval of products under the Animal Rule.

While the development of medical products and approval by the U.S. Food and Drug Administration (FDA) is well known, the development of countermeasures against exposure to toxic levels of radiation, chemicals, and infectious agents requires special consideration, and there has been, to date, little experience in working with the FDA to obtain approval of these products. The FDA has published a regulation entitled "Approval of Biological Products when Human Efficacy Studies are not Ethical or Feasible." This regulation, known simply as the "Animal Rule," was designed to permit approval or licensing of drugs and biologics when efficacy studies in humans are not ethical or feasible. To date, 12 products have been approved under the Animal Rule. It is highly recommended that sponsors of products that are to be developed under the Animal Rule meet with the FDA and other government entities early in the development process to ensure that the efficacy and safety studies that are planned will meet the FDA's requirements for approval of the product.

Monitoring the quality of conduct of clinical trials: a survey of current practices.

BACKGROUND: There is a little empirical evidence to determine which, if any, monitoring practices best achieve the goals of trial monitoring set forth in ICH E6 under the variable circumstances of different clinical trial settings. PURPOSE: The purpose of this project was to describe current methods of monitoring clinical trials and to explore the rationale for the use of those methods. METHODS: An electronic survey of known monitoring practices was developed and sent to over 200 organizations involved in conducting clinical research. The survey collected information on institutional demographics, methods of overall study oversight, use of risk-based monitoring and factors that influence assessments of risk, and details on quality assurance and monitoring practices. RESULTS: Seventy-nine organizations completed the survey; our analysis included the 65 organizations that indicated they perform clinical trials. Data from the survey indicate that a wide variety of monitoring practices are currently being employed. Eighty-three percent of respondents use centrally available data to evaluate site performance, but only 12% of respondents always or frequently used centralized monitoring to replace on-site visits. Eighty-seven percent of respondents indicated that they always performed on-site visits. This varied by type of organization, with 31% of academic coordinating centers/cooperative groups/government organizations always performing on-site monitoring visits versus 84% of other organizations. The rationale for using a specific monitoring approach does not appear to be based on empirical evidence. Fifty-four percent of respondents stated that 'usual practice' determined the frequency with which they conducted on-site monitoring visits. LIMITATIONS: The overall response rate to our survey was only 30%; thus, we may not have captured the full variance of current monitoring practices, and our responding sample may not be representative. CONCLUSION: These findings underscore the necessity of research to provide an evidence base for monitoring practice.

Evaluation of Data Entry Errors and Data Changes to an Electronic Data Capture Clinical Trial Database.

Monitoring of clinical trials includes several disciplines, stakeholders, and skill sets. The aim of the present study was to identify database changes and data entry errors to an electronic data capture (EDC) clinical trial database, and to access the impact of the changes. To accomblish the aim, Target e*CRF was used as the EDC tool for a multinational, dose-finding, multicenter, double-blind, randomized, parallel, placebo-controlled trial to investigate efficacy and safety of a new treatment in men with lower urinary tract symptoms associated with benign prostatic hyperplasia. The main errors observed were simple transcription errors from the paper source documents to the EDC database. This observation was to be expected, since every transaction has an inherant error rate. What and how to monitor must be assessed within the risk-based monitoring section of the comprehensive data monitoring plan. With the advent of direct data entry, and the elimination of the requirement to transcribe from a paper source record to an EDC system, error rates should go down dramatically. In addition, protocol violations and data outside the normal range can be identified at the time of data entry and not days, weeks, and months after the fact.