Databases presentation Vaccine Clinical Trials Mark Hatherill - - PowerPoint PPT Presentation
Databases presentation Vaccine Clinical Trials Mark Hatherill South African Tuberculosis Vaccine Initiative (SATVI) University of Cape Town November 2014 1 Databases presentation Regulatory Environment Sponsors & Funding Study
Mark Hatherill South African Tuberculosis Vaccine Initiative (SATVI) University of Cape Town November 2014
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Regulatory Environment Sponsors & Funding Study Community Recruitment & Consenting Inclusion & Exclusion Criteria Vaccines & Vaccination Adverse Events & Morbidity Diagnostic Endpoints Subject Retention Data Management Sample Biobanks Publication
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How long does it take for ethical & regulatory approval? SATVI TB vaccine trials 2004 – 2012 Geldenhuys et al, SAMJ Challenges in Africa Developing regulatory structures/regulations… Developing regulatory capacity… Mismatch = delay (Sponsors/Funders)
Sponsors, Funders, Pharma
Regulatory Responsibility Project Management Adequate Financial Support Supply Investigational Product
Clinical Trial Sites
Regulatory Responsibility Trial Implementation Meet Agreed Targets Participant Safety Data Integrity
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Funding Infrastructure & equipment
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Adapt/refurbish buildings New structures in the field
Funding Vehicles
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Transport specimens to the Lab Transport participants & staff Access to the research clinic Urban vs Rural Infant vaccine trials Safety Families
Funding Personnel
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Staff are the main cost driver in most large-scale vaccine trials Rural Sites (distance) Infant Vaccine Trials (complexity) Need for diverse skills Administration Quality
Clinical Trial Sites
The relationship between the Major Partners and Clinical trial Sites is inherently unequal
Unavoidable imbalance arising from financial dependence
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Clinical Trial Site role = Work-for-Hire implementation of research Trial Sites may be complicit in their own scientific marginalisation, if their focus is on the financial benefits of partnership Marginalisation of Clinical Trial Sites = Opportunity lost… …to add scientific value from the Site’s unique viewpoint
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The Science!!!! Communication Transparency Respect Alignment Capacity Building Project Funding Maslow’s Hierarchy
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Selecting the Right Study Population Phase I First in human Safety and Immunogenicity Phase II Dose-finding Age De-escalation Proof-of-principle in the population of interest Phase III Efficacy in the population of interest Phase IV Post Licensure
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Low TB Exposure Settings (Europe & North America)
Birth Infancy Childhood Adolescence Adulthood Birth Infancy Childhood Adolescence Adulthood BCG MTB MTB MTB FIH & Phase 1 Phase 1b-4 Pre-exposure Post-exposure Therapeutic
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The Study Community Each study community is different! Attitudes to health & disease Attitudes to vaccination Attitudes to research Community Advisory Boards, & research workers from the community, are key to success Recruitment Retention Adverse events
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Recruitment & Consenting How are potential participants contacted? Clinics Workplace Churches/NGOs Door-to-Door Word-of-Mouth Databases Shopping malls Information sessions Consenting (family input) Assent of minors
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Compensation vs Undue Coercion What is the role of participant compensation & incentive schemes? Money – how much? Groceries, vouchers Primary health care Access to referral / best practice
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Screening & Exclusion Criteria Particularly affects FIH and Phase I vaccine trials It may be difficult to find “healthy adults” Issues: HIV, TB infection, smoking, ethanol, pregnancy, BMI
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Screening: What are the “normal ranges” for developing countries?
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Retention How do we minimize loss to follow-up? Communication is key Home visits (distance/staff) Mobile phone/text message Deal with out-migration Relationship with participants
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Vaccines & Vaccination We need more than the usual pharmacy! Pharmacist: Control of investigational product Dispensing Cold chain Documentation
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Cold Chain Not enough to maintain the cold chain Documentation & Proof
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Adverse Events vs Community Morbidity How do we distinguish AEs related to study vaccine from community morbidity? Relatedness Timing Rates Mortality & post-mortem diagnosis Surveillance (AEs and Endpoints)
Passive Active Surveillance Intensity Case Detection rate Low High PTB Disease Severity High low
The incidence rate of something we never look for is zero If we look too hard, we may not find what we seek
– TB: Disease of poverty, age-related, chronic , preventable / treatable – Trial intervention has potential to decrease case burden in study population (Hawthorne effect)
– Active surveillance
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Variability not related to components of systems (6/9 micro+radiol+clinical), but to how they were combined: “and” / “or”
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Data Management Sophisticated, secure data systems in the field Electronic vs hard copy data capture Where are the data? Security / hazards On-shore / off-shore Access to data
Data ownership Access to data for future studies Academic outputs Sample ownership and biobanking Investigators as custodians Use of samples for future studies Representation on biobank governance
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Publication Who writes the paper? Investigator vs Sponsor priorities Permission vs Right to Review