JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD Pharm. D V Year CLINICAL RESEARCH Previous Question Paper (November/December - 2021 - R08)

The pharmacological approach to drug discovery focuses on identifying and validating drug targets, such as receptors, enzymes, or ion channels, that are involved in disease pathophysiology. This involves high-throughput screening (HTS) of chemical libraries to identify 'hits' that interact with the target, followed by lead optimization to improve potency, selectivity, and pharmacokinetic properties. The goal is to establish a clear structure-activity relationship (SAR) to translate molecular interaction into a therapeutic effect.

The toxicological approach runs concurrently to ensure safety. Initial in vitro studies assess cytotoxicity, genotoxicity (e.g., Ames test), and cardiotoxicity (e.g., hERG channel inhibition). Subsequent in vivo studies in animal models determine the No-Observed-Adverse-Effect-Level (NOAEL), acute and chronic toxicity, reproductive toxicity, and carcinogenicity. These studies are essential to calculate the therapeutic index and determine the safe starting dose for human clinical trials.

The Principal Investigator (PI) is the individual responsible for the conduct of the clinical trial at a trial site. Their primary responsibilities include:

• Protocol Compliance: Ensuring the trial is conducted strictly according to the approved protocol, Good Clinical Practice (GCP) guidelines, and regulatory requirements.
• Informed Consent: Personally overseeing the informed consent process to ensure all subjects are fully informed of risks and benefits before participation.
• Subject Safety: Monitoring the health and well-being of trial participants, managing adverse events, and reporting serious adverse events (SAEs) to the sponsor and Institutional Review Board (IRB) within mandated timelines.
• Data Integrity: Ensuring that all clinical data are accurate, complete, and verifiable, and that case report forms (CRFs) are maintained correctly.
• Resource Management: Supervising the study team, ensuring adequate training, and maintaining accountability for the investigational product (IP) inventory and storage.
• Communication: Serving as the primary liaison between the sponsor, the IRB/Ethics Committee, and regulatory authorities.