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{{Use dmy dates|date=August 2021}}
{{short description|Intentional exposure of test subjects to a pathogen to test a vaccine or drug}}
A '''human challenge study''', also called a '''controlled human infection trial''', is a type of [[clinical trial]] for a [[vaccine]] or other [[drug|pharmaceutical]] involving the intentional exposure of the test subject to the condition tested.<ref name="lamb">{{Cite journal|last1=Lambkin-Williams|first1=Rob|last2=Noulin|first2=Nicolas|last3=Mann|first3=Alex|last4=Catchpole|first4=Andrew|last5=Gilbert|first5=Anthony S.|date=
During the
Over the
==Design==
The intent of a challenge study is to fast-track the timeline for providing evidence of safety and efficacy of a [[prescription drug|therapeutic drug]] or vaccine, especially by compressing (to a few months) the usually lengthy duration of [[Phases of clinical research|Phase{{nbsp}}II–III trials]] (typically, many years).<ref name=eyal/><ref name=callaway/><ref name="boodman">{{Cite web|url=https://www.statnews.com/2020/03/11/researchers-rush-to-start-moderna-coronavirus-vaccine-trial-without-usual-animal-testing/|title=Coronavirus vaccine clinical trial starting without usual animal data|publisher=STAT|author=Eric Boodman|date=13 March 2020|access-date=19 April 2020}}</ref> Following preliminary proof of safety and efficacy of a candidate drug or vaccine in laboratory animals and healthy humans, controlled "challenge" studies may be implemented to bypass typical Phase{{nbsp}}III research, providing an accelerated path to regulatory approval of the test compound for widespread prevention against an [[infectious disease]], such as COVID‑19.<ref name=eyal/><ref name=cohen20/>
The design of a challenge study involves first, simultaneously testing a vaccine candidate for [[immunogenicity]] and safety in laboratory animals and healthy adult volunteers (100 or fewer){{snd}}which is usually a sequential process using animals first{{snd}}and second, rapidly advancing its effective dose into a large-scale Phase{{nbsp}}II–III trial in low-risk, healthy volunteers (such as young adults), who would then be deliberately infected with the disease being tested against for comparison with a [[placebo]] control group.<ref name=eyal/><ref name=callaway/><ref name=cohen20/> In a challenge study for a vaccine to prevent an infectious disease, participants would be closely monitored for signs of [[toxicity]] and adequate [[immune response]], such as by producing substantial levels of [[antibody|antibodies]] against the
==Ethics==
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==Vaccines for viral infections==
Challenge studies have been used to expedite evaluation of vaccines for several pandemic viral diseases,<ref name="callaway" /> such as cholera,<ref>{{Cite journal|title=Oral vaccines for preventing cholera|last1=D|first1=Sinclair|last2=K|first2=Abba|date=
Other than expediting clinical evaluation of vaccine properties, advantages of using challenge studies for vaccine candidates include minimizing bias which is inherently part of traditional [[Cohort study|cohort studies]], as both the exposure (timing of infection, virus challenge dose) and outcome (assessment of blood [[biomarker]]s) are standardized.<ref name=tuju/> Disadvantages include high cost of conducting the trial at multiple locations and the complex management of infrastructure for a challenge trial, especially for obtaining national regulatory approval, organizing participants and trial personnel, and implementing laboratories with [[Good Clinical Laboratory Practice]] qualifications.<ref name=tuju/> Before beginning a challenge study, a vaccine sponsor must have demonstrated [[Good Manufacturing Practice]] standards for approval to use the candidate vaccine in humans, including expensive [[toxicology]] and [[immunogenicity]] testing.<ref name=tuju/><ref name="plotkin">{{cite journal|pmc=7167540|pmid=32331807|title=Extraordinary diseases require extraordinary solutions|first1=Stanley A.|last1=Plotkin|first2=Arthur|last2=Caplan|journal=Vaccine|volume=38|issue=24|pages=3987–8|date=
===COVID-19===
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Human challenge studies are under consideration to hasten the development of a [[COVID-19 vaccine]],<ref name=callaway/><ref name=cohen20/><ref>{{cite news |url=https://www.bbc.com/news/health-54612293 |title=UK plan to be first to run human challenge Covid trials |work=BBC News |date=20 October 2020}}</ref> including one proposal made by bioethicist [[Nir Eyal (bioethicist)|Nir Eyal]],<ref name=eyal/> and another by [[rubella]] vaccine inventor [[Stanley Plotkin]] with bioethicist [[Arthur Caplan]].<ref name=plotkin/> These authors propose that the multi-year duration and multinational ___location of a typical Phase III efficacy clinical trial will continue as usual, while people infected with COVID-19 will continue to suffer or die.<ref name=plotkin/> As an alternative based on emerging results from COVID-19 vaccine challenge studies, regulatory agencies could allow early [[Emergency use authorization|emergency use]] of the vaccine, while the challenge study continues collecting data for eventual licensure.<ref name=plotkin/>
In May 2020, a guidance document was issued by the WHO on criteria for conducting challenge clinical trials and providing clinical care for the participants.<ref name=who-chall/> Following the challenge infection with or without the candidate vaccine, volunteers would be monitored closely in hospitals or clinics managed by physicians treating people with COVID-19 disease and with life-saving resources, if needed.<ref name=eyal/><ref name=callaway/><ref name=who-chall/> Volunteering for a vaccine challenge study during the COVID‑19 pandemic is likened to the emergency service of
==References==
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==External links==
* {{cite journal |last1=Callaway |first1=Ewen |title=Hundreds of people volunteer to be infected with coronavirus |journal=Nature |date=22 April 2020 |doi=10.1038/d41586-020-01179-x |pmid=32322034 |doi-access=free}}
* [https://www.theatlantic.com/ideas/archive/2020/04/challenge-trial-ethical-imperative/610309/ Let volunteers take the COVID challenge: Young, healthy, informed people should be allowed to participate in vaccine trials.] Conor Friedersdorf, ''The Atlantic'',
* [https://1daysooner.org/ 1 Day Sooner], US-UK advocacy organization for human challenge studies of candidate COVID-19 vaccines (25,104 volunteers from 102 countries, as of late May
{{Medical ethics}}
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