Use of Operational and Decisional Approaches in Clinical Pharmacology Research to Optimize Clinical Trial Managemnt, Design and Analysis

Abstract

This thesis comprises of three different domains of rational approaches in clinical trial management woven together by the idea that Critical Path Analysis, Meta analysis and Interim Analysis which influence organizational operations and decision making strategies in the pharmaceutical industry, i.e. an essential ingredient of clinical trial studies. This is a modular thesis in which three modules of rational approaches to clinical trials have been laid out serially. In the first module, we described the application of Critical Path Analysis in development of new clinical trial projects to avoid complexity in schedules, enhancement of project control and handling project constraints for optimized decision. In the second module, we concentrate on how several things be considered while selecting a hypothesis and study design. There should be some specific knowledge to be gained from Meta Analysis of several projects aimed to explore the same clinical trial goals. Some reasons to perform Meta-Analyses are to establish the presence of an effect, determine the magnitude of an effect such that it resolves the differences in a literature if any and determine important moderators of an effect. At the end and the third module of this thesis examines monitoring of response variables to predict the final outcome through an impartial and statistically valid approach, viz. Interim Analysis. Such interim analysis and monitoring of specially sizeable (and/or risky) trials keep the decision process free of conflict of interest while considering cost, resources and meaningfulness of the overall project. Whenever necessary such interim analysis can also call for potential termination or appropriate modification in sample size, study design and even an early declaration of success. Given the extraordinary size and complexity of clinical trial today, my research explains a few pivotal rational approaches to plan, analyze and predict the outcomes of a clinical trial that incorporate what is learned during the course of a study or a clinical development program. It also gives us a fine handle on how the project is completed, without compromising its validity or integrity. The goal of these methods is to make better and more timely decisions to allocate all study resources more efficiently, reduce costs and timelines, and better achieve informational goals compared to traditional study and program approaches. Such approaches can also fill the gap by directing the resources towards relevant and optimized clinical trials between unmet medical needs and interventions being tested currently rather than fulfilling only business and profit goals only. Context & Objective Clinical researches are operating in a strictly regulated environment that can be described by many best practices in management sciences. However, a distinct model for the management of clinical trials still needs exploration and research by virtue of which scope, time, and resources are scientifically managed and predicted. Implementation of such a Critical Path Analysis (CPA) will quantify real-time performance and operational processes of the projects most optimally. This will evaluate the performance and operational processes for possible improvements as well as strategize efforts to get the desired end results. Methodology, Results & Discussion Activities of a model clinical trial were listed as 78 different items, which were further merged into 35 major activities. Performing dependence analysis, the latter activities were finalized into 25 items which were then incorporated in activity predecessor table for the purpose of network diagram and CPA. The CPA was carried out considering patients, conduct and outcome. Activities were inclusive; described the trial entirely with accuracy, in chronological and logical sequences. CPA is a procedure for using network analysis to identify those tasks which are on the critical path: i.e. where any delay in the completion of these tasks will lengthen the project timescale, unless action is taken. This approach does not replace an adherence to the requirements contained in all applicable regulations, guidelines or SOPs governing the clinical trials but ensures the proper use of operational and decisional approaches for optimal resource management. Conclusion As the need to meet deadlines becomes more and more important to produce good and stable project plans; the CPA is very useful for determining activities that can overcome the project delays. We found that project mutation, i.e. protocol amendments and also other critical activities, had a statistically significant effect on the time factors of a study Clinical trial resources can only be carried out effectively if a series of accurate resource models can be produced that can provide a range of project execution alternatives. In this way the project may be effectively monitored and realistic schedules can be maintained.