First Do No Harm? Modeling Risks and Benefits of Challenge Trials for Hepatitis C Vaccine Development

Clin Infect Dis. 2023 Aug 14;77(Suppl 3):S231-S237. doi: 10.1093/cid/ciad379.

Abstract

Background: In 2019, about 58 million individuals were chronically infected with hepatitis C virus. Some experts have proposed challenge trials for hepatitis C virus vaccine development.

Methods: We modeled incremental infections averted through a challenge approach, under varying assumptions regarding trial duration, number of candidates, and vaccine uptake. We computed the benefit-risk ratio of incremental benefits to risks for challenge versus traditional approaches. We also benchmarked against monetary costs of achieving incremental benefits through treatment.

Results: Our base case assumes 3 vaccine candidates, each with an 11% chance of success, corresponding to a 30% probability of successfully developing a vaccine. Given this probability, and assuming a 5-year difference in duration between challenge and traditional trials, a challenge approach would avert an expected 185 000 incremental infections with 20% steady-state uptake compared to a traditional approach and 832 000 with 90% uptake (quality-adjusted life-year benefit-risk ratio, 72 000 & 323 000). It would cost at least $92 million and $416 million, respectively, to obtain equivalent benefits through treatment. BRRs vary considerably across scenarios, depending on input assumptions.

Conclusions: Benefits of a challenge approach increase with more vaccine candidates, faster challenge trials, and greater uptake.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cost-Benefit Analysis
  • Hepatitis C* / prevention & control
  • Humans
  • Quality-Adjusted Life Years
  • Risk Assessment
  • Vaccine Development
  • Vaccines* / adverse effects

Substances

  • Vaccines