BackgroundIllicit drug use increases the risk of poor physical and mental health. There are few effective drug prevention interventions.ObjectiveTo assess the acceptability of implementing and trialling two school-based peer-led drug prevention interventions.DesignStage 1 – adapt ASSIST, an effective peer-led smoking prevention intervention to deliver information from the UK national drug education website [see www.talktofrank.com (accessed 29 August 2017)]. Stage 2 – deliver the two interventions, ASSIST + FRANK (+FRANK) and FRANK friends, examine implementation and refine content. Stage 3 – four-arm pilot cluster randomised control trial (cRCT) of +FRANK, FRANK friends, ASSIST and usual practice, including a process evaluation and an economic assessment.SettingFourteen secondary schools (two in stage 2) in South Wales, UK.ParticipantsUK Year 8 students aged 12–13 years at baseline.Interventions+FRANK is a UK informal peer-led smoking prevention intervention provided in Year 8 followed by a drug prevention adjunct provided in Year 9. FRANK friends is a standalone informal peer-led drug prevention intervention provided in Year 9. These interventions are designed to prevent illicit drug use through training influential students to disseminate information on the risks associated with drugs and minimising harms using content from www.talktofrank.com. Training is provided off site and follow-up visits are made in school.OutcomesStage 1 – +FRANK and FRANK friends intervention manuals and resources. Stage 2 – information on the acceptability and fidelity of delivery of the interventions for refining manuals and resources. Stage 3 – (a) acceptability of the interventions according to prespecified criteria; (b) qualitative data from students, staff, parents and intervention teams on implementation and receipt of the interventions; (c) comparison of the interventions; and (d) recruitment and retention rates, completeness of primary, secondary and intermediate outcome measures and estimation of costs.Results+FRANK and FRANK friends were developed with stakeholders [young people, teachers (school management team and other roles), parents, ASSIST trainers, drug agency staff and a public health commissioner] over an 18-month period. In the stage 2 delivery of +FRANK, 12 out of the 14 peer supporters attended the in-person follow-ups but only one completed the electronic follow-ups. In the pilot cRCT, 12 schools were recruited, randomised and retained. The student response rate at the 18-month follow-up was 93% (1460/1567 students). Over 80% of peer supporters invited were trained and reported conversations on drug use and contact with trainers. +FRANK was perceived less positively than FRANK friends. The prevalence of lifetime illicit drug use was 4.1% at baseline and 11.6% at follow-up, with low numbers of missing data for all outcomes. The estimated cost per school was £1942 for +FRANK and £3041 for FRANK friends. All progression criteria were met.ConclusionsBoth interventions were acceptable to students, teachers and parents, but FRANK friends was preferred to +FRANK. A limitation of the study was that qualitative data were collected on a self-selecting sample. Future work recommendations include progression to a Phase III effectiveness trial of FRANK friends.Trial registrationCurrent Controlled Trials ISRCTN14415936.FundingThis project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full inPublic Health Research; Vol. 5, No. 7. See the NIHR Journals Library website for further project information. The work was undertaken with the support of the Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer). Joint funding (MR/KO232331/1) from the British Heart Foundation, Cancer Research UK, the Economic and Social Research Council, the Medical Research Council, the Welsh Government and the Wellcome Trust, under the auspices of the UK CRC, is gratefully acknowledged.