Assessing public perception of a sand fly biting study on the pathway to a controlled human infection model for cutaneous leishmaniasis

Abstract

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.

A clinical study to optimise a sand fly biting protocol for use in a controlled human infection model of cutaneous leishmaniasis (the FLYBITE study)

“…It is increasingly recognised that public involvement in research is critical in ensuring high quality outcomes and robust practices and accountability 87,88 . As such, prior to undertaking this study we carried out a public involvement (PI) exercise to inform the design and practical considerations in this research area 49 . The outcomes from this exercise suggested that such a study was acceptable to participants and reinforced the need for clear and thorough written materials in order for true informed consent to be taken.…”

“…The specific aims of the current study are to assess the biting frequency and proportion of P. papatasi and P. duboscqi females successfully taking a blood meal when exposed to human skin and to record adverse events through clinical examination including dermatoscopy, evaluation of routine biochemistry and the use of a visual analogue scale assessing severity of signs and symptoms. In addition, following a previous public involvement (PI) consultation group exercise 49 , that was used to shape the current protocol, we conducted a follow-up focus group with volunteers to record their attitudes and experiences of the FLYBITE study, and to help refine the development of a cutaneous leishmaniasis CHIM. This study is reported in line with the Consolidated Standards of Reporting Trials (CONSORT) guidelines 50 .…”

Vaccines against leishmaniasis: using controlled human infection models to accelerate development

“…There are limited studies that assess public awareness of issues concerning leishmaniasis [ 78 ], and until recently no such studies at the intersection of CHIMs and leishmaniasis. Parkash et al recently described a public involvement study related to the development of a cutaneous leishmaniasis CHIM using infected sand flies [ 79 ]. Ten members of the public, including a National Institute for Health Research (NIHR) patient research ambassador and a previous CHIM study participant were recruited to discuss the basis of a Leishmania CHIM, in a focus group chaired by a health psychologist.…”

“…The motivations given for this choice being both the altruistic aspect of donating tissue for analysis to gain potential new insights into pathogenesis as well as a psychological component that the procedure may ‘remove’ the infection. This activity subsequently informed the development of a study protocol to develop a CHIM [ 79 , 80 ]. Unfortunately, no participant who had previously undergone treatment for leishmaniasis was able to be recruited for this public engagement study.…”

“…In Australasia, the use of the term ‘sand fly’ encompasses non-phlebotomine flying insects that are associated with anaphylaxis and severe bite reaction [ 86 , 87 ]. Although these adverse effects associated with non-phlebotomine sand flies are not directly relevant, evidence from public engagement work has suggested that such connotations can impact on recruitment if not accounted for [ 79 ]. In a recent non-infected sand fly biting study, mitigations included robust exclusion criteria, including history of atopic disease, history of exaggerated response to insect bite and history of anaphylaxis.…”