Human challenge study

A human challenge study, also called a challenge trial or controlled human infection model (CHIM), is a type of clinical trial for a vaccine or other pharmaceutical involving the intentional exposure of the test subject to the condition tested.[1][2][3] Human challenge studies may be ethically controversial because they involve exposing test subjects to dangers beyond those posed by potential side effects of the substance being tested.[2][3] Controlled human infection studies are also used to study viruses and immune responses.[4][5]

During the mid 20th and 21st century, the number of human challenge studies has been increasing.[6][7] A challenge study to test promising vaccines for prevention of COVID-19 was under consideration during 2020 by several vaccine developers, including the World Health Organization (WHO),[8][9] and was approved in the UK in 2021.[10]

Over the second half of the 20th and the 21st centuries, vaccines for some 15 major pathogens have been fast-tracked in human challenge studies while contributing toward vaccine development to prevent cholera, typhoid, seasonal flu, and other infections.[11] Since the 1980s, challenge trials which reported about adverse events have had only 0.2% of patients with serious adverse events, and no deaths.[6] According to medical ethicists, methods of conducting clinical trials by human challenge testing have improved over the 21st century to satisfy ethical, safety, and regulatory requirements, becoming scientifically acceptable and ethically valid as long as participants are well-informed and volunteer freely, and the trials adhere to established rigor for conducting clinical research.[2][3][11]

  1. ^ Lambkin-Williams, Rob; Noulin, Nicolas; Mann, Alex; Catchpole, Andrew; Gilbert, Anthony S. (22 June 2018). "The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics". Respiratory Research. 19 (1): 123. doi:10.1186/s12931-018-0784-1. ISSN 1465-993X. PMC 6013893. PMID 29929556.
  2. ^ a b c Eyal N, Lipsitch M, Smith PG (31 March 2020). "Human challenge studies to accelerate coronavirus vaccine licensure". The Journal of Infectious Diseases. 221 (11): 1752–1756. doi:10.1093/infdis/jiaa152. PMC 7184325. PMID 32232474.
  3. ^ a b c Callaway E (April 2020). "Should scientists infect healthy people with the coronavirus to test vaccines?". Nature. 580 (7801): 17. Bibcode:2020Natur.580...17C. doi:10.1038/d41586-020-00927-3. PMID 32218549. S2CID 256820005.
  4. ^ Killingley, Ben; Mann, Alex J.; Kalinova, Mariya; Boyers, Alison; Goonawardane, Niluka; Zhou, Jie; Lindsell, Kate; Hare, Samanjit S.; Brown, Jonathan; Frise, Rebecca; Smith, Emma; Hopkins, Claire; Noulin, Nicolas; Löndt, Brandon; Wilkinson, Tom; Harden, Stephen; McShane, Helen; Baillet, Mark; Gilbert, Anthony; Jacobs, Michael; Charman, Christine; Mande, Priya; Nguyen-Van-Tam, Jonathan S.; Semple, Malcolm G.; Read, Robert C.; Ferguson, Neil M.; Openshaw, Peter J.; Rapeport, Garth; Barclay, Wendy S.; Catchpole, Andrew P.; Chiu, Christopher (May 2022). "Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults". Nature Medicine. 28 (5): 1031–1041. doi:10.1038/s41591-022-01780-9. hdl:10044/1/96278. PMID 35361992. Retrieved 12 April 2024.
  5. ^ Lindeboom, Rik G. H.; Worlock, Kaylee B.; Dratva, Lisa M.; Yoshida, Masahiro; Scobie, David; Wagstaffe, Helen R.; Richardson, Laura; Wilbrey-Clark, Anna; Barnes, Josephine L.; Kretschmer, Lorenz; Polanski, Krzysztof; Allen-Hyttinen, Jessica; Mehta, Puja; Sumanaweera, Dinithi; Boccacino, Jacqueline M. (July 2024). "Human SARS-CoV-2 challenge uncovers local and systemic response dynamics". Nature. 631 (8019): 189–198. Bibcode:2024Natur.631..189L. doi:10.1038/s41586-024-07575-x. ISSN 1476-4687. PMC 11222146. PMID 38898278.
  6. ^ a b Adams-Phipps, Jupiter; Toomey, Danny; Więcek, Witold; Schmit, Virginia; Wilkinson, James; Scholl, Keller; Jamrozik, Joshua; Roestenberg, Meta; Manheim, David (11 October 2022). "A Systematic Review of Human Challenge Trials, Designs, and Safety". Clinical Infectious Diseases. 76 (4): 609–619. doi:10.1093/cid/ciac820. PMC 9938741. PMID 36219704.
  7. ^ Cohen, Jon (18 May 2016). "Studies that intentionally infect people with disease-causing bugs are on the rise". Science. 352 (6288): 882–885. doi:10.1126/science.aaf5726.
  8. ^ "Key criteria for the ethical acceptability of COVID-19 human challenge studies" (PDF). World Health Organization. 6 May 2020. Retrieved 18 May 2020.
  9. ^ Cohen, Jon (31 March 2020). "Speed coronavirus vaccine testing by deliberately infecting volunteers? Not so fast, some scientists warn". Science. doi:10.1126/science.abc0006. S2CID 216451224. Retrieved 19 April 2020.
  10. ^ "World's first coronavirus Human Challenge study receives ethics approval in the UK". GOV.UK. Retrieved 18 February 2021.
  11. ^ a b Wade Hemsworth (13 May 2020). "McMaster researcher contributes to WHO guidelines for COVID-19 vaccine testing". McMaster University Medical School, Hamilton, Canada. Retrieved 25 May 2020.