Course

Unit 1

UNIT I Drug discovery and development process:- 10hours

• Introduction of drug discovery and development-6hrs
  • Need for drug discovery
  • Drug discovery (Target identification and validation
  • Lead finding
  • Lead optimization, Early safety tests)
  • Pathways of drug development (Discovery
  • Preclinical and clinical development)

· Various Approaches to drug discovery-Pharmacological:

• Selectivity testing,
• Pharmacological profiling (In vitro profiling, in vivo profiling: Testing in animal models of disease), Validity criteria in context to animal testing (Face validity, Construct validity, Predictive validity), Safety pharmacology-2hrs

Toxicological testing

• Preclinical toxicity testing: Acute toxicity (Acute tolerance testing), Sub chronic and chronic toxicity, Tissue specific toxicity-1hr

Investigational new drug application submission and Abbreviated New Drug Application submission.-1hr

Unit 2

UNIT II-Clinical development of drug: 8hours Introduction to Clinical trials:4hrs

• History
• Scurvy trial
• Nuremberg trials
• Different types of clinical trials

· Ethical guidelines in Clinical Research:4hrs

• Ethical Issues in Biomedical Research – Principles of ethics in biomedical research,
• Historical Perspectives: Nuremberg Code, Thalidomide study, Nazis Trials, Tuskegee Syphilis Study, The Belmont Report,
• The declaration of Helsinki, Origin of International Conference on Harmonization – Good Clinical Practice (ICH-GCP) guidelines.

• ICH, GCP, Central drug standard control organization (CDSCO) guidelines

Unit 3

Unit III: Ethics in Biomedical Research -3hours

• Ethical Issues in BiomedicalResearch – Principles of ethics in biomedical research, Ethical committee [institutional review board] – its constitution and functions, Challenges in implementation of ethical guidelines.
• ICH- GCP guidelines and ICMR guidelines in conduct of Clinical trials- 4hours

Composition, responsibilities, procedures of IRB / IEC.

Unit 4

Unit IV :Types and Designs used in Clinical Research:4hours

Planning andexecution of clinical trials, Various Phases of clinical trials, Bioavailability and Bioequivalence studies, Randomizationtechniques (Simple randomization, restricted randomization, blocking method and stratification)

• Types of research designs based on Controlling Method (Experimental, Quasi experimental, and Observational methods)
• Time Sequences (Prospective andRetrospective)
• Sampling methods (Cohort study, case Control
• Study and cross sectional study), –
• Health outcome measures (Clinical & Physiological, Humanistic and economic) -1hour

Unit 5

• UNIT V -Drug Safety Reporting -3hours

• Mehods of –safety reporting _ Pharmacovigilance
• Methods of post marketing surveillance

Unit 6

• UNIT VIOverview of regulatory environment in USA, Europe and India.-2hours

Unit 7

• Unit VII: Conducting clinical trials and clinical trial documents- 10hours

• Clinical Trial Study team: Roles and responsibilities of:Investigator, Study Coordinator, Sponsor, Monitor, ContractResearch Organization, clinical research associate, Quality assurance staff -2hrs
• Clinical trial Documents: Guidelines to the preparation of following documents: Protocols, Investigator’s Brochure, Informed Consent Form, Case report forms, Contracts and agreements,Dairy Cards – 1hr
• Clinical Trial Start up activities: Site Feasibility Studies,Site/Investigator selection, Pre-study visit, Investigator meeting,Clinical trial agreement execution, Ethics committee document preparation and submission-2hrs
• Investigational Product: Procurement and Storage of investigation product -1hr

• Filing procedures: Essential documents for clinical trial, TrialMaster File preparation and maintenance, Investigator Site File,Pharmacy File, Site initiation visit, Conduct, Report and Follow up -1hr
• Clinical Trial Monitoring and Close out:-1hr
• Preparation and conduct of monitoring visit: Review of sourcedocuments, CRF, ICF, IP storage, accountability and reconciliation, Study Procedure, EC communications, Safety reporting, Monitoring visit reporting and follow-up – 1hr
• Close-Out visit: Study related documents collection, Archival requirement, Investigational Product reconciliation anddestruction, Close-Out visit report.-1hr

Unit 8

• Unit VIII: Quality Assurance and Quality Control in Clinical Trials:– 3hrs

• Types of audits, Audit criteria, Audit process, Responsibilities of stakeholders in audit process, Audit follow-up and documentation,Audit resolution and Preparing for FDA inspections, Fraud and misconduct management –
• Data Management: Infrastructure and System Requirement for DataManagement: Electronic data capture systems, Selection and implementation of new systems, System validation and test procedures, Coding dictionaries, Data migration and archival –

• Clinical Trial Data Management: Standard Operating Procedures, Data management plan, CRF & Data base design considerations, Study set-up, Data entry, CRF tracking and corrections, Data cleaning, Managing laboratory and ADR data,
• Data transfer and database lock, Quality Control and Quality Assurance in CDM, Data mining and warehousing. –

This course aims to provide the students an opportunity to learn drugdevelopment process especially the phases of clinical trials and also the ethical issues involved in the conduct of clinical research. Also, it aims to impart knowledge and develop skills on conceptualizing, designing, conducting and managing clinical trials. The course will facilitate the learner with national and global level regulatory requirements of clinical trials,inclusive of safety monitoring and reporting of adverse drug reactions during clinical trials.

Learner will understand the preparation and reviewing of SOPs for clinical trials, know the site preparationfor effective conduct of clinical trials, eligigility criteria of Principal investigator and requirements of study site.The duties of clinical research associate, custodian, sponsor, contractor, study investigator are described. Data generation, data analysis , interpretation, coding in clinical trials are learnt to make the final report of clinical study.

KNOWLEDGE

K1: Define SOPS for review and approval for clinical trials

K2: Describe the concept of new drug development process

K3 : Illustrate ethical and regulatory requirements of clinical trials in USA, Europe and India

K4: Assess the roles and responsibilities of stake holders in clinical trials

K5: Analyse the data for making clinical study report

K6: Design data collection forms appropriate for clinical trials

SKILL

S1: Recognise the risk associated with investigational drug

S2: Prepare the study site as per regulatory requirements for conduct of clinical trials

S3: Analyse the published research papers

S4. Apply appropriate statistical tests to clinical data S5: Design data collection forms to suit trial protocol S6: Detect ADR

ATTITUDE

A1: Ensure the confidentiality of trial subjects

A2: Communicate the clinical trial status effectively to clinical trial team

A3: Foster identification of serious adverse reactions to save lives

A4: Exhibit liaison with healthcare team members

A5:Practice ethics in clinical trials

A6 Prioritize patient benefits in clinical trials

REFERENCE BOOKS

• Lionel, Edward, Aadrew .J.Flether Anthony W Fos, Peter D Sloaier :Principles and practice of pharmaceutical Medicine, Second edition, Publisher: Wiley,2007
• Julia Lloyd and Ann Raven, Hand Book of Clinical Research . Edinburgh ; New York

: Churchill Livingstone, 1994, updated in 2022

• David Machin, Simon Day and Sylvan Green, Textbook of Clinical Trials edited, , John Wiley and Sons, 2005.
• Giovanna di Ignazio, Di Giovanna and Haynes. ,Principles of Clinical Research,

Petersfield, UK ; Philadelphia : Wrightson Biomedical Pub., ,2001

• R K Rondels, S A Varley, C F Webbs Data Management. Second Edition, Wiley Publications., 2000,
• SK Gupta Basic Principles of Clinical Research and Methodology, First Edition, Jaypee brothers, 2007,
• Dr Guru Prasad Mohanta Textbook on Clinical Research, a guide for aspiring professionals , PharmaMed Press, 2011
• Lawrence Friedman Curt D. Furberg David L. DeMets David M. Reboussin Christopher B. Granger, Fundamentals of Clinical Trials 5th Edition, Springer ,2015

JOURNALS

• Clinical Medicine and Research-Marshfield Clinic .
• Indian journal of Medical research- Medknow Publications
• International journal of clinical practice- John Wiley & Sons
• Clinical research and reviews- John Wiley & Sons Ltd

ASSIGNMENTS

• FDA and its function in brief (specifically write about FDA IND Review Team, Approval procedure of Investigational New Drug (IND) application by FDA review team)
• FDA’s Center for Drug Evaluation and Research (CDER) and its role in drug approval
• What are the Major components of the clinical research enterprise, Write roles of the FDA, industry sponsors, and the investigator in the clinical research enterprise
• Guidance for NDA application