title: Statistical design and analysis plan for an impact evaluation of an HIV treatment and prevention intervention for female sex workers in Zimbabwe: a study protocol for a cluster randomised controlled trial.
abstract: BACKGROUND
  Pragmatic cluster-randomised trials should seek to make unbiased estimates of effect and be reported according to CONSORT principles, and the study population should be representative of the target population. This is challenging when conducting trials amongst 'hidden' populations without a sample frame. We describe a pair-matched cluster-randomised trial of a combination HIV-prevention intervention to reduce the proportion of female sex workers (FSW) with a detectable HIV viral load in Zimbabwe, recruiting via respondent driven sampling (RDS).
  
  
  METHODS
  We will cross-sectionally survey approximately 200 FSW at baseline and at endline to characterise each of 14 sites. RDS is a variant of chain referral sampling and has been adapted to approximate random sampling. Primary analysis will use the 'RDS-2' method to estimate cluster summaries and will adapt Hayes and Moulton's '2-step' method to adjust effect estimates for individual-level confounders and further adjust for cluster baseline prevalence. We will adapt CONSORT to accommodate RDS. In the absence of observable refusal rates, we will compare the recruitment process between matched pairs. We will need to investigate whether cluster-specific recruitment or the intervention itself affects the accuracy of the RDS estimation process, potentially causing differential biases. To do this, we will calculate RDS-diagnostic statistics for each cluster at each time point and compare these statistics within matched pairs and time points. Sensitivity analyses will assess the impact of potential biases arising from assumptions made by the RDS-2 estimation.
  
  
  CONCLUSIONS
  We are not aware of any other completed pragmatic cluster RCTs that are recruiting participants using RDS. Our statistical design and analysis approach seeks to transparently document participant recruitment and allow an assessment of the representativeness of the study to the target population, a key aspect of pragmatic trials. The challenges we have faced in the design of this trial are likely to be shared in other contexts aiming to serve the needs of legally and/or socially marginalised populations for which no sampling frame exists and especially when the social networks of participants are both the target of intervention and the means of recruitment. The trial was registered at Pan African Clinical Trials Registry (PACTR201312000722390) on 9 December 2013.
authors.affiliation: Centre for Evaluation Department for Social and Environmental Health Research, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, 15-17 Tavistock Place, London, WC1H 9SH, UK. James.Hargreaves@lshtm.ac.uk.
authors.forename: James R
authors.initials: JR
authors.lastname: Hargreaves
authors.affiliation: Centre for Evaluation Department for Social and Environmental Health Research, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, 15-17 Tavistock Place, London, WC1H 9SH, UK. Elizabeth.Fearon@lshtm.ac.uk.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fearon
authors.affiliation: Centre for Evaluation Department for Social and Environmental Health Research, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, 15-17 Tavistock Place, London, WC1H 9SH, UK. Calum.Davey@lshtm.ac.uk.
authors.forename: Calum
authors.initials: C
authors.lastname: Davey
authors.affiliation: Research Department of Infection and Population Health, Institute of Epidemiology and Health Care, Faculty of Population Health Sciences, University College London, Gower Street, London, WC1E 6BT, UK. andrew.phillips@ucl.ac.uk.
authors.forename: Andrew
authors.initials: A
authors.lastname: Phillips
authors.affiliation: Research Department of Infection and Population Health, Institute of Epidemiology and Health Care, Faculty of Population Health Sciences, University College London, Gower Street, London, WC1E 6BT, UK. v.cambiano@ucl.ac.uk.
authors.forename: Valentina
authors.initials: V
authors.lastname: Cambiano
authors.affiliation: Research Department of Infection and Population Health, Institute of Epidemiology and Health Care, Faculty of Population Health Sciences, University College London, Gower Street, London, WC1E 6BT, UK. f.cowan@ucl.ac.uk.|Centre for Sexual Health & HIV/AIDS Research (CeSHHAR) Zimbabwe, 9 Monmouth Road Avondale West, Harare, Zimbabwe. f.cowan@ucl.ac.uk.
authors.forename: Frances M
authors.initials: FM
authors.lastname: Cowan
mesh_terms: D002985:Clinical Protocols; D003430:Cross-Sectional Studies; D003625:Data Collection; D003627:Data Interpretation, Statistical; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000628:therapy; D006801:Humans; D012107:Research Design; D018401:Sample Size; D060386:Sex Workers; D015030:Zimbabwe