RESUMO
BACKGROUND: A controlled human infection model (CHIM) involves deliberate exposure of volunteers to pathogens to assess their response to new therapies at an early stage of development. We show here how we used public involvement to help shape the design of a CHIM to support future testing of candidate vaccines for the neglected tropical disease cutaneous leishmaniasis, a disease transmitted by the bite of infected sand flies in tropical regions. METHODS: We undertook a public involvement (PI) consultation exercise to inform development of a study to test the safety and effectiveness of a sand fly biting protocol using uninfected sand flies (FLYBITE: ClinicalTrials.gov ID NCT03999970 ) and a CHIM using Leishmania major-infected sand flies (LEISH_Challenge: ClinicalTrials.gov ID NCT04512742 ), both taking place in York, UK. We involved 10 members of the public including a patient research ambassador and a previous CHIM volunteer. The session took place at The University of York, UK and examined draft study volunteer-facing material and included the CHIM study design, potential adverse events and therapeutic interventions at study endpoints. A discussion of the scientific, ethical, humanitarian and economic basis for the project was presented to the participants to provoke discourse. An inductive, thematic analysis was used to identify the participants' key concerns. RESULTS: Themes were identified relating to i) quality of volunteer-facing written information, ii) improving study design, and iii) factors to motivate involvement in the research. Group participants responded positively to the overall study aims. Initial concerns were expressed about potential risks of study involvement, but further explanation of the science and mitigations of risk secured participant support. Participants provided advice and identified improved terminology to inform the volunteer-facing material. Lastly, treatment options were discussed, and excision of any cutaneous lesion was favoured over alternatives as a treatment. CONCLUSION: The consultation exercise provided invaluable information which led to improved study design and enhanced clarity in the volunteer-facing material. The session also reinforced the need to maintain public trust in scientific rigour prior to initiation of any study. The investigators hope that this description strengthens understanding of PI in clinical research, and encourages its use within other studies.
Our research team is designing a type of research study known as a controlled human infection model (CHIM). In CHIM studies, volunteers are exposed to infections on purpose and then studied to help understand diseases. Similar experiments, where humans are infected deliberately, have been used for hundreds of years to help test treatments. CHIM studies have already been used more recently to help test vaccines for diseases such as malaria.The disease leishmaniasis, a disease affecting millions each year, is spread by the bite of an infected sand fly in tropical countries. There are currently no vaccines for leishmaniasis that are available for use in humans. It is thought that by using CHIM studies, new vaccines might be tested and then approved more quickly. Scientific researchers have had many discussions about how useful CHIM studies are, especially in terms of the science behind them, the safety of volunteers and the ethics of these studies. Researchers also understand how important it is to involve the public in designing and carrying out research, especially studies involving humans, to get an independent point-of-view. We have therefore involved the public, in some parts of designing this research, in a group discussion. We also included a person who has already taken part in a different CHIM study. These discussions have had an important effect and have changed how we plan to carry out our future research studies. We also hope that this description will encourage other researchers to include the public when planning future research.