Potential Cost-Effectiveness of a Tuberculosis Vaccine: Implications for Clinical Trials

1. Potential Cost-Effectiveness of a Tuberculosis Vaccine: Implications for Clinical Trials Jared Ditkowsky Kevin Schwartzman MD, MPH Montreal Chest Institute, McGill University Supported by: Montreal Chest Institute Research Centre *No conflicts to disclose

2. Background Aims • Bacille Calmette-Guérin (BCG) vaccine is currently the only licensed tuberculosis vaccine • Previous modeling has highlighted the potential role of novel vaccines in TB control • The new MVA85A vaccine (Oxford-Emergent) has completed accrual in a Phase IIb clinical trial in South African infants • To compare cost, projected TB cases, and projected TB mortality, between current practice (neonatal BCG) and the addition of an MVA85A booster, in a cohort of South African infants using a 10-year time frame, and a societal perspective. • To examine different scenarios for vaccine efficacy and attendant clinical trial size and costs.

3. Methods • Decision analysis model with multiple Markov processes calibrated to simulate characteristics of the South African population (TreeAge Pro®) • Cohort of 960,763 infants entering the population, with outcomes projected over the following 10 years • TB annual risk of infection 4.12%, HIV prevalence at birth 5.45% • Vaccines assumed to prevent primary progression to active TB disease; protective efficacy 50% for BCG alone • Research and development costs (prorated to South Africa’s potential global market share) were incorporated into the cost per infant • Research and development reflected different sample size requirements for phase 3 studies, according to varying efficacy values for the combination of neonatal BCG + MVA85A booster.

4. Predicted Outcomes with Varying Efficacy Values for BCG + MVA85A Booster * Costs expressed in millions USD (2009)

5. Sample Size and Trial Costs for Varying MVA85A Efficacy Values * Length of follow-up 2 years; assumed active TB risk = 3% in control arm †All costs expressed in millions USD (2009) ‡Current Phase IIb clinical trial is designed to detect a 60% increase in efficacy over BCG alone, with 90% power

6. Sensitivity Analysis • Favorable Scenario • Halved: MVA85A Cost per Dose Probability of TB Diagnosis • Doubled: Probability of Drug-Resistant TB Probability of Acquiring HIV Cost per DOT Visit • BCG + MVA85A Efficacy = 85% Unfavorable Scenario I Halved: Probability of Drug-Resistant TB Probability of Acquiring HIV Cost per DOT Visit II Doubled: MVA85A Cost per Dose III Probability of TB Diagnosis = 90% IV BCG + MVA85A Efficacy = 70%

7. Discussion • The BCG + MVA85A booster strategy appears cheaper than BCG alone, and to reduce TB morbidity and mortality for all combined efficacy values of ≥ 70% • Even when prorated clinical trial costs are built into vaccination program costs • With the “unfavorable” scenario, there were still associated cost savings as well as health gains • This analysis underestimates health gains and cost savings, to the extent that it focuses on a single birth cohort