TABLE 2.

Themes and subthemes in the qualitative interview data set of the larger project; themes covered in this paper in italics

Theme	Subthemes: challenge studies in general	Subthemes: endemic settings/LMICs
Scientific justification	‐ Accelerate /improve vaccine development Selecting vaccine candidates ‐ Identify correlates of protection ‐ Develop models of infection ‐ Study pathogenesis, immunity, and transmission	‐ Justification in endemic settings/LMICs Improved generalizability Unique results Capacity building Responsiveness to local health problems
Public health benefit	‐ Acceleration of vaccine development ‐ Studying pathogenesis, immunity, and transmission ‐ Maximizing data collected per challenge	‐ Improved generalizability (developing vaccines for target populations) ‐ Capacity building
Participant risk	‐ Risks related to challenge infection ‐ Burdens related to participation Mental health risks ‐ Risks related to absconding ‐ Limits to risk Long‐term risks, lasting harms, and rare but severe harms Comparison to organ donation Analogy to higher risk employment Comparison to Phase I drug trials	‐ Reduced risk in endemic settings ‐ Comparison to background risk of infection ‐ Ability to access healthcare outside the study
Direct benefit to participants	‐ Lack of direct participant immunity benefit in non‐endemic settings	‐ Immunity as direct benefit
Third‐party risk	‐ Right to withdraw ‐ Co‐ordination with local public health agencies	‐ Need for adequate research and/or public health infrastructure ‐ Third‐party risks related to insect vectors of vector‐borne diseases ‐ Comparison to background risk of infection ‐ Site selection: endemic vs. non‐endemic areas within LMICs ‐ Comparison between challenge strain and locally prevalent strains
Participant selection	‐ Implications of selection criteria for generalizability of results ‐ Altruism among participants ‐ Recruitment of students ‐ Recruitment of (other) vulnerable populations ‐ Need for more data on participant motivations	‐ Altruism among LMIC participants ‐ Improved generalizability in endemic settings ‐ Selection related to immunity and/or innate resistance ‐ Recruitment of HIV positive individuals
Children	‐ Need for prior safety data from adults ‐ Generalizability from adults to children ‐ Reputational risk ‐ Inducement of parents	‐ Potential scientific rationale for infections primarily affecting children ‐ Consideration of local views regarding research with children
Payment of participants	‐ Rationales for payment ‐ Models of payment ‐ Potential for undue inducement ‐ Recruitment of underprivileged groups ‐ Over‐volunteering ‐ Comparison to other types of work/labor ‐ Appropriate levels of payment	‐ Locally appropriate levels of payment ‐ Inducement in the context of severe poverty ‐ Cultural views regarding payment ‐ Local sustainability of research payment
Expert review	‐ Benefits and limitations of: Standard institutional review Multi‐center review National review Independent expert review Need for expertise related to: Relevant pathogen(s) Challenge studies Research ethics ‐Risk‐benefit assessment ‐Conflicts of interest	‐ Importance of local review and approval ‐ Capacity building of ethics review expertise
Consent	‐ Education level and consent ‐ Vulnerability and consent ‐ Undue inducement Accepting risks Concealing health information ‐ Test of understanding ‐ Understanding of third‐party risks	‐ Translation of consent into local languages ‐ Greater knowledge of disease in endemic settings ‐ Avoiding labeling entire LMIC populations as “vulnerable” ‐ Information‐giving during community engagement (prior to consent)
Community engagement	‐ Conditions under which engagement particularly useful or necessary ‐ Definition of relevant community ‐ Need for mutually informative engagement between researchers and community	‐ Appropriate community engagement for particular settings ‐ Collaboration between clinical and social scientists ‐ Understanding local attitudes to research, vaccines, payment of participants ‐ Addressing local concerns and rumors
Regulatory considerations	‐ Regulation of: Research Challenge strains Experimental interventions (vaccines, treatments) ‐ Lack of international standardized regulations of challenge strains	‐ Lack of specific local regulation of challenge strains ‐ Capacity building of regulators