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Background and Aims Timely access to approved medications is a priority in paediatric inflammatory bowel disease [IBD]. To date, the timing of drug studies in paediatric IBD has been suboptimal, with most studies conducted long after approval has been granted for adult IBD. This delay in approval leads to extensive off-label prescribing of medications in children, often without clear guidance on optimal dosing. The European Medicines Agency [EMA] and U.S. Food and Drug Administration [FDA] have implemented drug development frameworks in an attempt to address these challenges. However, access to information on these regulatory pathways in paediatric IBD is limited. We summarised the time from adult to paediatric approval of IBD therapies, outlining the regulatory approval pathway between the EMA and FDA, with the goal of identifying areas for improvement. Methods We reviewed publicly accessible data from the EMA and the FDA to identify therapeutic agents approved over 2005–2021 for paediatric IBD. Results and Conclusions Five drugs are currently approved for use in the paediatric IBD population, with long interval delays after adult approval. The impact of these drug development processes in paediatric IBD is awaited. Further consideration needs to be given to the age of enrolment along with novel, more efficient trial designs in an effort to improve access for paediatric IBD patients to newer therapies.

Background and Aims Quantifying placebo rates and the factors influencing them are essential to inform trial design. We provide a contemporary summary of clinical, endoscopic, histological and safety placebo rates in induction and maintenance clinical trials of ulcerative colitis, and identify factors influencing them. Methods MEDLINE, EMBASE and the Cochrane library were searched from April 2014 to April 2020, updating a prior meta-analysis that searched from inception to April 2014. We included placebo-controlled trials of aminosalicylates, corticosteroids, immunosuppressives, small-molecules and biologics in adults with ulcerative colitis. Placebo rates were pooled using random-effects and mixed-effects meta-regression models to assess the associated study-level. Results In 119 trials [92 induction, 27 maintenance] clinical, endoscopic and histological remission placebo rates for induction trials were 11% (95% confidence interval [CI] 9–13%), 19% [95% CI 15–23%] and 15% [95% CI 11–19%], respectively; for maintenance trials, clinical and endoscopic placebo remission rates were 18% [95% CI 12–25%] and 20% [95% CI 15–25%], respectively. Higher endoscopic subscore and a higher rate of exposure to prior biologic therapy at enrolment were associated with lower clinical and endoscopic placebo remission rates. Absence of central reading was associated with an increase in placebo endoscopic response and remission rates. More follow-up visits and increasing trial duration were associated with higher clinical placebo rates. Conclusions Placebo rates in ulcerative colitis trials vary according to the endpoint assessed, whether it is for assessment of response or remission, and whether the trial is designed for induction or maintenance. These contemporary rates across different endpoints and drug classes will help to inform trial design.