Reading Response Discussions

Research question of interest:

In a population of HIV-uninfected adolescent girls and young women (AGYW) in what is the enacted adherence (i.e., pill taking) and persistence (i.e., continuation of PrEP over time) in four study conditions: 1) peer mentor intervention, 2) text message reminders and 3) combined peer mentors and text message reminders intervention 4) control in Kisumu county in western Kenya.

The population of interest: HIV-uninfected adolescent girls and young women (AGYW)  (aged 15-24 years) initiating Pre-exposure prophylaxis (PrEP) in Kisumu county in western Kenya.

Study design: clustered 2X2 factorial design as seen in the figure below. Five sites will implement both interventions, five sites will implement Peer mentoring intervention only, five sites will implement the text message intervention only, and five sites will implement the existing standard of care only.

Explain how you might incorporate a sampling strategy into the study design

The study intervention is most efficiently applied at the level of the community-based drop-in centers (DiCE) as this approach circumvents potential problems of individual-level implementation such as provider compliance with the protocol, including crossover. Within Kisumu County, there are 43 registered DiCEs. The DiCE will be the unit of randomization.

Sample size: This study requires 20 DiCE and a total of 1280 adolescent girls. I have powered this study based on differences in proportions in a cluster randomized trial for our key outcomes of enacted adherence (i.e. % of AGYW who report at least 95% pill taking) and persistence (i.e., the proportion of women who continue using PrEP over two years). This sample size and power estimates are based on both clinical and logistic factors

Sampling: For this study, I will use multistage sampling.

Simple random sampling of clusters: I will develop a sampling frame of all the 43 registered DiCE in Kisumu County and select using random tables the 20 required.

To select individuals: I will use the respondent driven sampling (RDS) method to find access to potential study participants who meet the inclusion criteria. Seeds who reflect a diverse social demographic profile will be purposively selected and once enrolled, will be given up to 3-5 coded coupons to refer members of their social networks who in turn will become recruiters. Participants will receive 250ksh for every eligible person they recruit into the study. This process will continue in recruitment “waves” until the sample size is reached.

Possible logistical/practical advantages and disadvantages to this plan

The logistical advantages of this plan are:

1. Feasibility: there exists a master list of all DiCE in Kisumu county, each with very clear and distinct administrative and geographic boundaries and catchment areas. This makes it possible to do a simple random sampling of the clusters. By using the simple randomized sampling techniques of the clusters, we can avoid selection bias at this level
2. AGYW who are in need of and willing to use PrEP are a hard to reach population given the stigma associated with HIV as a disease and the impression that PrEP promotes promiscuity. Moreover, when it comes to decision making, AGYW are disempowered.
3. Traditionally RDS methods have been found to be cheaper and cost effective methods of recruitment

Disadvantages

-       The RDS can lead to potential selection bias of participants especially if the study population is not adequately “networked.” As such this can lead to the systematic exclusion of sub-populations of AGYW who are less networked than others, for example, AGYW who are female sex workers may be more networked than AGYW who are injection drug users

-       Some participants will know more people than other participants as such not everyone has the equal chance of being included in the study. (This can potentially be managed through weighting techniques)

-       There is a risk of non-independence if participants are more likely to recruit people who are like themselves from their own in-group (homophily)

-       The combined multistage sampling has a greater risk of a nonrepresentative sample

Discuss whether incorporating the sampling strategy might help

(1)  reduce bias in the estimation of univariate quantities (such as disease prevalence)

In general, the RDS sampling method can reduce bias in the estimation of univariate quantities after several waves of recruitment when the total sample is no longer influenced by the initial sample (seeds). This is because after several waves, subsequent waves begin to represent the underlying population. However, this statement only true if the following assumptions are met:

1) Sampling is with replacement, in which selected peers may be recruited multiple times;

2) Network size: that participants can accurately report personal network size;

3) Random recruitment: peer recruitment is a random selection from recruiter’s network.

Unfortunately for this proposed study, we violate some of these assumptions and as such this method may not  reduce bias in the estimation of univariate quantities e.g.

-       we will do sampling without replacement and preventing individuals from participating more than once.

-       The 250ksh incentive that we provide incentives may reduce the randomness of peer recruitment as participants may preferentially recruit peers based on their relationship and/or assumptions of who will participate.

(2) reduce bias in the estimation of causal effects.

The multistage cluster and RDS sampling are more likely associated with an increased risk of a non-representative sample which may bias the estimate of causal effects. In particular, the RDS method as earlier alluded to has inherent problems such if the study population is not adequately “networked,” average network size and homophily which adversely affect effect size estimation