Module 1: Introduction to Clinical Research & Advancement of ICH-GCP

1.1 Clinical Research in India
  • What is clinical research?
  • Requirements for Global clinical research
  • Clinical trial phases
  • The journey towards becoming an attractive destination
  • Infrastructure available & Advantages of India
  • Why India is becoming a hot destination for clinical research?
  • International collaboration & Challenges 1.2 Phases of Clinical Trials
  • Phase-I Clinical trial & its specification
  • Phase-II Clinical trial & its specification
  • Phase-III Clinical trial & its specification
  • Phase-IV Clinical trial & its specification
  • Difference between Phase I to III & Phase IV studies

1.3 History & Background of Good Clinical Practice
  • Stories behind the ethical research
  • Tuskegee Syphilis Study (1932-1972)
  • Outcome of Tuskegee Syphilis Study
  • Belmont Report 1979
  • Nazi Experiments (1940-1945)
  • Outcome of Nazi Experiments
  • Nuremberg Code (1947)
  • Sulfanilamide Disaster (1937)
  • Willowbrook study (1956)
  • Thalidomide Disaster (1962)
  • Outcome of Thalidomide Disaster
  • Ethics

1.4 Introduction to ICH, ICH-GCP Guideline & its advancement
  • ICH definition
  • Why need to harmonize?
  • Structure of ICH
  • Different parties of ICH
  • Various ICH Guidelines
  • GCP definition
  • ICH-GCP (E6) Guidelines
  • The Principles of ICH-GCP
  • Investigator
  • Sponsor
  • Clinical Trial Protocol & Protocol Amendment(s)
  • Investigator’s Brochure
  • Essential Documents for Conduct of a Clinical Trial
  • Integrated Addendum to ICH-GCP E6(R2)
  • Indian GCP Structure & Contents
  • GCP implementation

Module 2: Ethical & Regulatory Aspects of Clinical Trials

2.1 Ethics Committee
  • History of unethical medical experiment
  • Cleopatra’s controversial experiments (69-30 BC)
  • Synonyms
  • EC primary purpose
  • Composition of the EC
  • Composition of the EC quorum
  • Operational aspects of EC
  • Functions of EC
  • Which study needs EC permission?
  • Exemption from EC & EC approval format
  • Criteria for approval
  • Communication with EC during the trial
  • EC Registration, re-registration & NABH accreditation

2.2 Indian Council of Medical Research
  • Introduction to ICMR
  • Major areas covered under guidelines & General statements under guidelines
  • Various principles under guidelines

2.3 Declaration of Helsinki
  • Introduction to World Medical Association & Declaration to Helsinki (DOH)
  • History of development of ethical principles for medical research involving human subjects
  • General principles of DOH
  • Risks, Burdens and Benefits
  • Vulnerable Groups and Individuals
  • Scientific Requirements and Research Protocols
  • Research Ethics Committees
  • Privacy and Confidentiality
  • Informed Consent
  • Use of Placebo
  • Post-Trial Provisions
  • Research Registration and Publication and Dissemination of Results
  • Unproven Interventions in Clinical Practice

2.4 Drug & Cosmetic Act 1940, Schedule Y & its appendices
  • Introduction to Drug & Cosmetic Act 1940 & Rules 1945
  • What is Schedule Y?
  • Clinical Trials & New Drug
  • Investigational New Drug
  • AE, ADR, SAE
  • Responsibilities of Sponsor / Investigator and Ethics Committee
  • Regulatory structure in India
  • Regulatory process
  • Format of Form-44
  • Human Clinical Pharmacology
  • Periodic Safety Update Reports
  • Bioavailability/ Bioequivalence
  • Appendices of Schedule Y
  • Central Drug Standard Control Organization (CDSCO)
  • Clinical Trial Registry of India (CTRI)
  • Online submission of clinical trial application-Sugam portal

Module 3: Operations Aspects of Clinical Trials

3.1 Clinical Trial Design
  • Categories of Clinical Research
  • Observational studies
  • Prospective Observational studies
  • Concurrent prospective studies
  • Non-concurrent prospective studies
  • Cross sectional prospective studies
  • Retrospective Observational studies
  • True Retrospective studies
  • Cross sectional retrospective studies
  • Experimental studies & Community study
  • Clinical Trials
  • Categorization of clinical trial design
  • Bias & its sources
  • Control group
  • Randomization
  • Blinding & its type
  • Sample size
  • Parallel group design
  • Cross over design
  • Factorial design

3.2 Conduct of the study
  • Moral principles
  • People involved
  • Sequence of activities
  • Milestones in study conduct
  • Essential elements of protocol
  • Case record form
  • Preparation of contracts
  • Study start-up activities
  • Study initiation
  • Aspects of study conduct
  • Recruitment
  • Obtaining consent
  • Screening
  • Use of drug
  • Safety Monitoring
  • Withdrawal of subject
  • Study site monitoring
  • Study close out visit
  • Quality control & quality assurance
  • Audit & inspection

3.3 Data Safety Monitoring Board (DSMB)
  • Introduction
  • Role & Responsibilities
  • Review & Recommendations
  • Membership
  • Meetings
  • Study Reports for DSMB Meetings
  • Reports from the DSMB • Reimbursement

3.4 Clinical Data Management (CDM)
  • What is data management?
  • What are data?
  • Who can collect the data?
  • Where is the data?
  • What is a source document?
  • What do you collect?
  • CRF work flow
  • Electronic data capture
  • Manage data collection
  • Data Management Plan
  • Elements of data management
  • Data management tool
  • CRF data checks
  • Data acquisitions
  • Data base development & validation
  • Essential characters of data base
  • Coding
  • Query generation
  • Data base lock (soft lock, hard lock)
  • Code of ethics for CDM professionals

Module 4: Pharmacovigilance at Glance

4.1 Introduction to Pharmacovigilance
  • Definition of Pharmacovigilance
  • Aims of pharmacovigilance
  • Why pharmacovigilance is increasing?
  • History of Pharmacovigilance
  • Examples of product recalls due to toxicity
  • Responsibilities
  • Why we do need pharmacovigilance?
  • Adverse Drug Reactions (ADR)
  • Economic impact of ADR
  • Different safety profile due to International differences
  • Topics to be studied after study approval
  • Changes that occur from the PV findings
  • Governing bodies for Pharmacovigilance
  • What should be reported?
  • Who can report?
  • Report to whom?
  • Reporting Requirement
  • International collaboration in the field of pharmacovigilance
  • WHO Pharmacovigilance programme
  • Pharmacovigilance programme of India (PVPI)
  • Introduction
  • Goals & Objectives
  • Governance structure
  • Steering committee
  • Three layered structure
  • Collaboration with WHO-UMC
  • Programme communication
  • Working of PvPI
  • Monitoring & Evaluation
  • Reporting trends
  • Application/Role of Pharmacovigilance

4.2 Pharmacovigilance-Glossary and related terms
  • Clinical operation-Various definitions & their brief description/concept clearance
  • Pharmacovigilance- Various definitions & their brief description/concept clearance

4.3 Pharmacovigilance Methods
  • Passive surveillance
  • Spontaneous Reports
  • Case series
  • Stimulated Reporting
  • Active surveillance
  • Sentinel sites
  • Drug event monitoring
  • Registries
  • Comparative Observational Studies
  • Cross-Sectional Study (Survey)
  • Case-Control Study• Cohort Study
  • Targeted Clinical Investigations
  • Descriptive Studies
  • Natural History of Disease
  • Drug Utilization Study

4.4 Pharmacovigilance Data Management and Case Processing
  • Importance of safety monitoring
  • Sources of report
  • Spontaneous report
  • Literature
  • Solicited sources
  • Contractual agreements
  • Regulatory authority sources
  • Call centers
  • Triage of cases
  • The minimum information required for reporting purpose
  • Case processing
  • Data entry into safety database
  • Narratives
  • Medical coding
  • QC review
  • Medical review
  • Different Pharmacovigilance Software

Module 5: Signal Management, ADR Reporting System & Dictionaries

5.1 Signal Identification, Development and Analysis
  • Adverse Reaction Signal
  • Factors favoring signal detection
  • Speed of signal detection
  • Qualitative V Quantitative signals
  • Criteria for Signal Assessment
  • Signal validation
  • Signal strengthening
  • Seriousness
  • Mechanism
  • Risk Groups
  • Frequency determination
  • Effectiveness/Risk Evaluation
  • Making Decisions
  • Information
  • Follow-up
  • Steps from Signal to Policy

5.2 Adverse Drug Reaction Reporting System
  • Definition and examples of Adverse Event (AE)
  • Adverse Drug Reaction (ADR)
  • In the pre-approval clinical experience
  • Regarding marketed medicinal products
  • Unexpected Adverse Drug Reaction
  • Serious Adverse Event/Reaction (SAE/R)
  • Suspected Unexpected Serious Adverse Reaction (SUSAR)
  • Types of ADR
  • Non immunological ADR
  • Immunological ADR
  • Miscellaneous
  • Rawlins and Thompson classification of ADRs
  • Limitations of Rawlins and Thompson classification
  • Wills and Brown classification of ADR
  • Steps of ADR monitoring
  • Assessment of ADR
  • Seriousness
  • Definition of Life threatening & example
  • Definition of Disability & example
  • Important medical events with example
  • Intensity
  • WHO classification
  • Hartwig and Seigels scale
  • Serious vs. Severe
  • Relationship/Causality
  • WHO Definitions
  • NARANJO algorithm for assessing the causality
  • Commonly used criteria for Adverse Event Relationship to Study Products
  • Adverse Event Relationship to Study Products In India
  • Difficulty Assessing Relationship of AEs with drug
  • Expectedness/Unexpectedness
  • Expected AE/R
  • Unexpected AE/R
  • Outcome of Adverse Events
  • Reporting of ADR
  • Significance of ADR reporting
  • Notification of ADR
  • Notification of ADR to Regulatory agency
  • Types of ADR Reporting
  • Standards for Expedited reporting
  • Others needing expedited reporting
  • Not expedited reporting
  • Minimum Criteria for Reporting
  • Key data elements for expedited reports
  • Reporting format
  • Sponsor Responsibilities
  • Monitor Responsibilities
  • Principal Investigator Responsibilities
  • Coordinator Responsibilities
  • Clinical Trial: Reporting Time Frame India
  • Post Marketing Reporting Time Frame

5.3 Medical Dictionary for Regulatory Activities
  • Objectives for MedDRA Development
  • MedDRA and the MSSO
  • MedDRA Definition
  • Regulatory Status of Mandate
  • MedDRA and E2B
  • WHO and MedDRA
  • Scope of MedDRA
  • MedDRA Structure
  • MSSO’s MedDRA Browsers
  • MedDRA Desktop Browser
  • MedDRA Web-Based Browser
  • MedDRA Maintenance
  • Standardized MedDRA Queries (SMQs)
  • SMQs in Production – Examples
  • SMQ Benefits and Limitations
  • SMQ Applications
  • How to “Run” SMQs
  • Browser Demonstration SMQ View
  • MedDRA Training Resources

5.4 WHO Drug Dictionary
  • General information
  • Drug/Medicinal Product Classification
  • The WHO Drug Dictionary (WHO-DD)
  • A source of international drug names
  • Medicinal product names
  • Types of medicinal products in WHO-DD
  • Codes and IDs
  • How do we use WHO-DD
  • The WHO-DD linked to ICSRs
  • ATC in WHO Drug Dictionary
  • ATC Classification Main Groups
  • How to access the WHO-DD
  • WHO Drug Dictionary – VigiSearch
  • WHO Drug Dictionary – VigiFlow
  • WHO Drug Dictionary- DD Browser

Module 6: Regulatory Aspects of Pharmacovigilance

6.1 Different ICH & Other requirements for Drug Safety
  • E2B: Clinical Safety Data Management: Data Elements for Transmission of Individual Case Safety Reports
  • E2c: Periodic Benefit-Risk Evaluation Report (PBRER)
  • E2F: Development Safety Update Report (DSUR)
  • E3: Structure And Content of Clinical Study Report
  • Summary of product characteristics (SmPC/SPC)
  • Patient information leaflet (PIL)
  • Company Core Safety Information (CCSI)
  • Reference Safety Information (RSI)
  • Developmental Core Safety Information (DCSI)
  • The Council for International Organizations of Medical Sciences (CIOMS)

6.2 Periodic Safety Update Report (PSUR)
  • Introduction
  • Objectives of PSUR
  • History of the PSUR
  • General Principles of PSUR
  • Implication of PSUR
  • Sources of Information
  • PSUR contents
  • Quality systems for PSUR
  • Training related to PSUR process
  • Criteria used for defining the frequency of submission of PSURs
  • Responsible parties for PSUR
  • PSUR Submission Timelines

6.3 Good Pharmacovigilance Practice (GPP)
  • Definition of GVP
  • Guidelines on GVP
  • Module III: Pharmacovigilance inspections
  • Types of Pharmacovigilance inspections
  • Routine pharmacovigilance inspections
  • Elements to consider for Routine inspections
  • For cause pharmacovigilance inspections
  • Pre-authorisation inspections
  • Post authorisation inspections
  • Announced and unannounced inspections
  • Re-inspections
  • Remote inspections
  • Inspection planning
  • Inspection process
  • Inspection follow-up
  • Regulatory action

Module 7: Career orientation and Interview Preparation

7.1 Career guide
  • Why we fail?
  • What can make the difference?
  • Why careers in clinical research can be the best choice?
  • Clinical Research Domains
  • Clinical Research Coordinator
  • Business Development Executive
  • Clinical Trial Assistant/Associate
  • Statistical Analyst
  • Data Coordinator
  • Quality Assurance Executive
  • Medical Writer
  • RA-Officer
  • Am I eligible to start career in Pharmacovigilance?
  • How will start my career?
  • How will I grow in this industry?
  • Pharmacovigilance career path?
  • What will be my job responsibilities?
  • PV work flow
  • Where I will be placed?
  • When & how should I start?