PROUD pilot study

The PROUD pilot study aims to assess the feasibility of conducting a clinical trial of PrEP among gay men and other men who have sex with men in the UK, using a design that randomises men to receive PrEP immediately as part of the HIV risk reduction package or to receive PrEP after a deferred period of 12 months. As of 10th February 2014, 451 men had enrolled in the PROUD pilot study and four of the thirteen clinics have suspended recruitment in order to manage the follow up visits. Recruitment will continue until we reach a minimum of 500 men enrolled, a maximum of 550 (10% over protocol) or all clinics reach capacity.
The PROUD Trial Steering Committee (TSC) met on 19th November 2013 to discuss the possibility of proceeding with an application to conduct a large-scale clinical trial using this study design. They reviewed data based on the enrolment of 324 gay men across 13 clinics in England. The TSC supported the Trial Management Group’s (TMG) request to submit an application for trial funding to the UK National Institute of Health Research (NIHR), Health Technology Assessment (HTA) researcher led call. An outline application was submitted on 6th January 2014.

Trial application

In the PROUD trial application, we propose enrolling a further 1800 men to immediate or deferred start of PrEP. A total of 1800 participants, in addition to the data collected from 500 men in the pilot study (a total of 2300), allows the detection of a two-fold reduction in annual HIV incidence from 5% to 2.5% with 80% power at 5% level of significance, assuming a 15% rate of loss of follow-up. The network of 13 genito-urinary medicine (GUM) clinics involved in the pilot study, would be slightly expanded for the trial, which would run from 1st January 2015 to 30th June 2018. We are currently negotiating access to PrEP for all study participants until the last person exits the trial (or the last person exits the pilot study, if the trial is not funded). We will continue to involve participants and members of the Community Engagement Group (CEG) in the development of the trial application and protocol. The funding application is for a total of £2,287,366, with additional NHS support and treatment costs of £1,031,494. We expect to find out if the outline application has met the priority assessment by quarter 2 of 2014, if we are invited to submit a full application by quarter 3 of 2014, and the outcome of the application towards the end of 2014/early 2015 (date tbc). If successful, we will be able to seamlessly roll straight from the pilot study into the trial in the existing clinics, and expand into new clinics as required.

Additional investigations

The TSC reviewed a range of other evidence regarding the feasibility of conducting a large-scale clinical trial in the UK. Initially the PROUD TMG anticipated recruiting 500 men within approximately 6 months (approximately 80 men enrolled per month). However, while the first clinic initiated recruitment in November 2012 it was not until July 2013 that all 13 recruitment clinics were operational. From July to December 2013, the clinics were recruiting an average of 40 participants per month. The TMG undertook a number of evaluations to explore the reasons for the recruitment rates being lower than expected, which are described below:

1. Recruitment survey: In June 2013, we conducted a survey among PROUD study staff to explore barriers and facilitators to recruitment. The survey highlighted that the main barriers to recruitment were a lack of study staff capacity, and insufficient numbers of eligible men being referred to the study clinics. In a subsequent review, it was clear that recruitment was generally higher in clinics that received support from the NHS Comprehensive Local Research Networks (CLRN) for dedicated research staff. From the PROUD study, clinics only receive £305 per participant enrolled (including 2 years follow-up) and few clinics are enrolling sufficient numbers of men to justify dedicated staff. The survey also highlighted that the main reasons for men not being interested in joining the study related to not feeling at sufficient risk of HIV or not being interested in additional HIV prevention options. Importantly for the feasibility of the PROUD trial, only 19% of staff said that men were not interested in joining the study due to the chance of being randomised to the deferred study arm.
2. Community Engagement Group (CEG) expanded meeting: In June 2013, the PROUD Community Engagement Group invited additional representatives from the UK’s leading HIV charities, gay media and dating websites. The meeting focused on discussing awareness about PrEP and interest in the PROUD study among gay men. It was thought that the level of awareness among gay men about PrEP and the PROUD study were extremely low. As a result of the meeting the UK’s leading HIV charities released a joint statement outlining their position on Pre-Exposure Prophylaxis (PrEP) – available at http://www.proud.mrc.ac.uk/news.aspx. There was continued support for the PROUD study design and the need to evaluate PrEP uptake and usage in the UK.
3. Knowledge, Attitudes and Practices survey: In September 2013, we conducted a survey of UK healthcare providers through sexual health clinics, professional societies’ email lists, and at a sexual healthcare conference. In total 328 healthcare providers responded, three-quarters of which were not involved with the PROUD pilot study. An abstract of the results has been submitted to the joint conference of the British HIV Association and British Association of Sexual Health and HIV (BHIVA/BASHH). Importantly for the feasibility of the PROUD trial, just under half of healthcare providers not involved in PROUD had been asked about PrEP by patients in the past year. This suggests a higher awareness among gay men than was proposed in the CEG expanded meeting or the participant involvement meeting described below, and highlights the need for further exploration of both the level of awareness and interest in PrEP among gay men in the UK.
4. Participant Involvement Meeting: We held the first participant involvement meeting with eight study participants on 12th November 2013 entitled ‘Future Options for PROUD’. In discussing why fewer men than expected joined the PROUD pilot study, the overall view was that slow recruitment was mainly due to not enough men being aware of PrEP or PROUD, not a result of men not being interested in PrEP or the PROUD study. In discussing the best next steps for PrEP in the UK, the overall summary was that we should not rush to broader roll out without understanding more about adherence and the impact of PrEP on sexual behaviour. All participants agreed that PrEP should only be available in dedicated clinics (like in PROUD) and supported plans for a larger clinical trial.
5. Recruitment to treatment trials: Before the TSC, the TMG compared the number of HIV negative men enrolled into PROUD on a monthly basis, to the numbers of HIV positive men enrolled into other studies conducted by MRC. The average enrolment in the other studies was 20 per month with substantially more clinics, highlighting that our original enrolment targets may have been overly ambitious.

Further information

For further details about the PROUD study, please visit our website at http://www.proud.mrc.ac.uk/ including the newly posted page on Patient and Public Involvement or contact the PROUD study team at PROUD@ctu.mrc.ac.uk.

Updated 10 February 2014 by Mitzy Gafos (m.gafos@ucl.ac.uk)