Increasing subject compliance in pivotal phase III clinical trials of dolutegravir (DTG, S/GSK1349572) in HIV‐infected, ART‐naïve subjects

To maximise the application of results of large‐scale clinical trials, recruitment and retention of a diverse subject population is key. With commonly used algorithms (Snapshot, TLOVR, missing = failure), all withdrawals in HIV studies, regardless of reason, are classed as failures in efficacy analyses. Good subject compliance therefore improves statistical power and the quality of trial results. In four recent GSK/ViiV‐sponsored phase IIIB/IV HIV ART‐naïve studies (HEAT, KLEAN, APV109141 and ARIES), 24% of subjects withdrew and approximately 2/3 of these withdrawals (16%) potentially were avoidable (i.e. not treatment related) [1]. To increase subject compliance in the phase III, treatment‐naïve studies of DTG (ING113086 “SPRING‐2” and ING114467 “SINGLE”), a more robust subject compliance program focussing on understanding subject needs and building sponsor‐site and site‐subject relationships was implemented. The compliance program included opt‐in study visit reminders, late study visit tracking, subject compliance support materials, subject transportation support, on‐going site training, relationship management and presentations on prior withdrawal rates and associated risk factors for attrition at investigator meetings. Week 48 withdrawals, both overall and for potentially avoidable reasons, were considerably lower in SPRING‐2 and SINGLE than historical HIV trials. Comparison of withdrawal rates prior to, and after implementation of robust patient compliance program. Addressing individual study subject needs with a customized approach in SPRING‐2 and SINGLE contributed to considerably lower percentages of withdrawals than in historical HIV studies. Identifying the specific impact of a single subject compliance initiative is difficult as study compliance can be influenced by overall study design, investigational product tolerability profile, current standard of care and treatment access for the disease under study. However, consistently reducing the number of avoidable withdrawals has the potential to lead to improved quality of trial results and smaller, quicker studies in the future, benefitting the whole HIV population.Study N Week Withdrawals from study n (%) Withdrawals for unavoidable reasons* Withdrawals for potentially avoidable reasons #HEAT/KLEAN/APV109141/ARIES ~ 2290 36–96 552 (24%) 179 (8%) 373 (16%) …SPRING‐2 822 48 103 (13%) 57 (7%) 46 (6%) SINGLE 833 48 135 (16%) 79 (9%) 56 (7%)* Due to adverse events, lack of efficacy, protocol‐defined stopping criteria. # Due to lost to follow‐up, withdrew consent, protocol deviation, investigator discretion. ~ Pooled data from HEAT (EPZ104057), KLEAN (ESS100732), APV109141, ARIES (EPZ108859). … Week 48 Kaplan‐Meier estimates=15%, 13% and 9% respectively for HEAT, KLEAN and APV109141.