Module 9 2021

23/03/2021

Vaccines vs. Pharmaceutical products Study Populations Vaccines Generally given prophylactically to people who are well

Pharmaceutical Products Generally given as treatments to people who are ill

Large study populations available – but recruitment for studies may be difficult as people may not realize an immediate ‘benefit’ from participation

Recruitment for studies easier as patients may find a ‘benefit’ in the experimental treatment vs. the current available options, but pool of patients to recruit from is small

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Vaccine Clinical Development Process

Early Phase

Phase IIIb/IV Licensure N=millions

Phase I N=20–80

Phase II N=>100s

Phase III N=1000s–10,000s

Safety

Safety

Safety

Safety

Immunogencity ~ 20 subjects; usually adults Evaluate safety of the vaccine Might evaluate tolerability of increasing doses of vaccine (dose escalation) Determine safety of two or more Phase I : First administration in man

Immunogencity

Immunogencity

Effectiveness Protective efficacy : demonstrate that vaccine prevents infection / disease Immune correlate of protection Immunological bridge from lots used in large Phase III trials to final production scale Show consistency of 3 successive lots produced at industrial scale Co-administration with licensed vaccines Safety : Large safety database requested by Health Authorities New indications Pharmacovigilance Phase III : Protective Efficacy / Safety >10,000 healthy subjects

Proof of concept Phase II : Proof of Concept / Feasibility ~ 50 - 200 healthy subjects Select and justify final dose and formulation

Efficacy

successive vaccinations Evaluate immune response

Dose ranging Determine the most efficient vaccination schedule (primary vaccination course) Determine most efficient route of vaccination

Safety Evaluation – Loca l

– AE Confirm the safety profile Proof of Concept (POC)

– Systemic

– SAE

Leroux-Roels et al. Chapter 5 in: Garçon et al. Understanding Modern Vaccines, Perspectives in Vaccinology, Vol 1, Amsterdam, Elsevier, 2011

March 2017

All vaccine clinical studies have safety objectives, often as co-primary

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