Clinical Success versus Attrition of Investigational Pharmaceuticals: A Vignette.

Abstract

The clinical success of investigational pharmaceuticals remains doubtful due to an unacceptable level of attrition during clinical drug development and declining clinical approval rates. Countless molecules are being withdrawn during drug discovery and clinical trial phases due to poor pharmacokinetics (ADME), lack of safety and efficacy, commercial interests, market competition, and patent protection expiry. Consequently, the novel drug pipelines are running dry. Because huge capital is involved in different clinical trial phases, the task of bringing a new drug or drug formulation to the market is a very costly venture. Running a clinical trial is a complex, expensive, and time-intensive project. It is often tedious and troublesome to change a study design after its inception; thus, it is necessary to design the study for easy and comprehensive data analysis and interpretation. Cohort, cross-sectional, and case-control studies, collectively touted as observational studies, provide an option for solving clinical problems when a randomized controlled trial (RCT) is not feasible due to time, money, or ethical restraints. This review article presents three prime observational research methodologies using relevant examples, common causes of spurious results, and ways to trivialize their impacts, including the most popular indices for measuring clinical relevance of the treatment effects. The article also explores attrition issues and issues related to the improvement of clinical approval success, with an emphasis on possible applications of drug delivery technologies to salvage drug molecules.