Table 3

Research gaps for self-collection of STI samples

Clinical, programmatic, values-based or human rights question		Current WHO recommendation	Strength of recommendation	Source or quality of evidence	Key GER considerations	Ideal study design(s)	Feasibility and practical constraints	Alternative study design	Methodological issues arising in the alternative study design
Benefits versus harms	PICO: should self-collection of samples for STIs be made available as an additional approach to deliver STI testing services?	Self-collection of samples for Neisseria gonorrhoeae and Chlamydia trachomatis should be made available as an additional approach to deliver STI testing services.	Strong.	Moderate.	No data from LMIC. Availability and accessibility.	RCT conducted in LMIC with inclusion of outcomes to measure availability and accessibility.	As a strong WHO recommendation exists, it would be unethical to repeat an RCT of the intervention.	Prospective non-controlled cohort study to be conducted in several LMICs where the intervention is or will be implemented. Analysis to combine quantitative survey supplemented with focused in-depth qualitative interviews with general population (with attention given to ensure sampling of vulnerable populations) to explore GER outcomes of availability and accessibility. Cost analyses can be nested in the cohort study.	Confounding: participants in cohort self-select to self-collect and may have other similar characteristics that may influence their ability to access STI self-collection. Measurement bias: self-reporting bias an issue for qualitative component. This will require well-trained researchers and validated tools. The triangulation of the qualitative data with the quantitative survey results provides an element of additional validation of outcomes.
		Self-collection of samples for Treponema pallidum (syphilis) and Trichomonas vaginalis may be considered as an additional approach to deliver STI testing services.	Conditional.	Low.	Availability, accessibility and acceptability.	Randomised controlled trial specific to self-collection of these organisms.	This is a feasible design.		Generalisability: the choice of setting and user population will determine how widely the results can be applied. The focus should be on testing this in LMIC settings and with vulnerable populations.
	What is the impact of self-sampling for STIs on partner screening?			GDG.	Privacy and confidentiality.	Randomised controlled trial with uptake of partner screening included as an outcome.	As a strong WHO recommendation exists, it would be unethical to repeat an RCT of the intervention.	Cross-sectional study of women who respond to results following STI self-collection to ascertain how many have notified their partners to be screened, and of those how many partners have gone for screening. Acceptability of screening for partners, and availability and accessibility of partner screening will be important to measure.	Selection bias: surveys will only capture those women who have responded actively to the results and may not be representative of those women who do not respond actively to their results.
	What is the impact of self-sampling for STIs on linkage to care and case-finding?			GDG.	Acceptability and non-discrimination.	RCT with inclusion of outcomes to measure linkage to care and case-finding.	As a strong WHO recommendation exists, it would be unethical to repeat an RCT of effectiveness of the intervention.	Interrupted time series using repeated cross-sectional surveys of populations attending STI clinics for treatment before, during and after implementation of policy to ascertain proportion of women who self-sampled prior to linkage to care.	Attrition bias: the results may indicate that more people who link to care used self-sampling, but this does not provide information on how many people who self-sampled with a positive result did not link to care.
	What is the benefit and harm of self-sampling for STIs of viral aetiology?			GDG.	Availability, accessibility and acceptability.	Randomised controlled trial specific to self-collection of STIs of viral aetiology. Outcomes to include measurement of availability and accessibility, as well as acceptability of self-sampling, especially regarding sampling of bloods (eg, hepatitis B virus).	This is a feasible design.		Performance bias: it is not possible to mask users or providers to mode of sampling. This can be mitigated by considering conducting a cluster RCT rather than an individually randomised trial, or a stepped wedge design where the intervention is delivered at staggered time periods.
Values and preferences	What are the values and preferences of marginalised populations (eg, Men who have sex with men, sex workers, trans populations) regarding self-sampling?	Not applicable.		GDG and survey.	Accessibility acceptability, privacy and confidentiality, and non-discrimination.	Qualitative key informant study of women and men who are marginalised regarding their values and preferences of self-sampling and the barriers that they experience or may experience when accessing self-sampling, receiving their results and when linking to care.	This is a feasible study.		Selection bias: as with all qualitative studies, participants are purposively selected. However, this is an advantage in this study design as marginalised women and men—including trans populations—who have considered this issue will have rich experiences and observations to share.
Human rights and equity	What are the best practices for avoiding coercion in self-sampling?	Not applicable.		GDG.	Non-discrimination, privacy and confidentiality.	Qualitative study using focus groups of vulnerable populations in contexts where self-sampling is implemented to understand how they perceive coercion could be avoided. This can allow creation of an expanded version of the intervention for further evaluation with measurement of non-coercion included as an outcome.	This is a feasible design.		Selection bias: as with all qualitative studies, participants are purposively selected. However, this is an advantage in this study design as marginalised women and men who have considered this issue will have rich experiences and observations to share.
Resource use	Is self-collection for STIs cost-effective?	Not applicable.	Not applicable.	GDG.	Accessibility.	Modelling studies of cost- effectiveness across broader range of settings, taking both a healthcare provider and societal perspective.	This is a feasible study, but its quality and usefulness depend on the reliability of the parameters for unit costs and effectiveness, which would be drawn from costing studies and the RCTs with effectiveness data. It will also require more long-term modelling to capture downstream effects on linkage to care.		Measurement bias: the results are dependent on selection of variables included in the model, assumptions regarding discount rates, cost-effectiveness thresholds and accurate estimates of current and projected costs. For example, vulnerable populations with limited access to care are likely to generate different results based on the probability that they would have limited or no access to care without self-sampling. Data accuracy: unit costs may not be available for many or any LMIC, especially where self-sampling has not been available. To avoid assumptions, this may require prior assessment via an initial implementation process to ascertain reasonable costings.
	Does self-collection offer a cost-efficient approach to case detection in low-income settings?	Not applicable.	Not applicable.	GDG.	Availability and accessibility.	Empirical costing studies to estimate the costs and targeting efficiency of self-collection in LMICs using various feasible models of delivery.	As above.		As above.

GDG, Guideline Development Group; GER, gender, equity and human rights; PICO, Population, Interventions, Comparison and Outcomes; RCTs, randomised controlled trials; STI, sexually transmitted infection.