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Objective To explore the approach to participant coenrolment in publicly funded randomized controlled trials (RCTs) and to consider its impact on study recruitment. Study Design and Setting A cross-sectional study of the UK National Institute for Health Research Journals Library was undertaken. RCTs funded between 2010 and 2019 were eligible. The reporting of coenrolment criteria was assessed through inspection of publicly available study protocols. Where present, the approach to coenrolment was examined, including circumstances in which it was permitted/prohibited and the mechanism for decision-making. For completed RCTs, the impact on recruitment was explored by comparing rates of early recruitment (completion before the expected end date) and extensions (completion after the expected end date) between studies, which did and did not permit coenrolment. Results Of 219 eligible protocols, coenrolment was addressed in 94 (42.9%). Twenty-three (24.5%) of these did not allow recruitment to multiple studies, while 71 (75.5%) permitted it according to a series of caveats, including considerations of study outcomes, intervention type, and patient burden. The final decision for coenrolment rested with the local recruitment team in 57 (60.6%) and with the central organizing team in 37 (39.4%). Early completion of recruitment occurred in 8 of 64 (12.5%) RCTs where coenrolment was permitted and 5 of 20 (25.0%) where it was not (P = 0.285). An extension to recruitment time was required in 31 of 64 (48.4%) RCTs where coenrolment was permitted and 9 of 11 (45.0%) where it was not (P = 0.788). Conclusions The reporting of coenrolment in protocols of publicly funded RCTs is infrequent, and where present, the approach to decision-making is widely variable. In this study, policies of coenrolment were not associated with gains in trial recruitment.

Introduction Targeting the infiltrative nature of GBMs with anti-migratory drugs as combination treatment for prevention of tumour recurrence is an attractive disease management option. One such class of drugs are the GSK-3 inhibitors 6-bromoindirubin-3′-oximes (BIO). BIO has been proposed for use in combination therapy, however, the administration of indirubins remains problematic due to low solubility causing low bioavailability. We describe the characterisation of a BIO derivative, VTIND42, identified from a screen of 450 compounds with improved solubility. Method The compounds were initially screened on the following criteria, selective anti-migratory effect with enhanced potency over the lead compound BIO. Effect on cell migration in two cell subpopulations (core obtained, edge obtained) from the patient derived GBM40 was assessed by 3D migration/invasion assays and for cytoskeletal rearrangements by immunofluorescence. Results VTIND42 (1 µM) showed the best performance overall in terms of specificity and efficacy in comparison to BIO with a pronounced effect on GBM40 edge cell populations. Anti-migratory effects over 72 hours in GBM40 edge (24h, 10.74% p=0.04; 48h, 6.52% p=0.06, 72h, 4.26% p=0.06) in comparison to the control were observed; BIO (5 µM) significantly reduced migration over 72 hours (24h, 12.79% p Discussion VTIND42 displayed increased efficacy in comparison to BIO, further investigations will determine its potential as a bioavailable anti-migratory drug for glioblastoma treatment potentially improving disease outcome in patients.