Use of Placebo in Pediatric Inflammatory Bowel Diseases: A Position Paper from ESPGHAN, ECCO, PIBDnet and the Canadian Children IBD Network

Performing well designed and ethical trials in pediatric inflammatory bowel diseases (IBD) is a priority to support optimal therapy and to reduce the unacceptable long lag between adult and pediatric drug approval. Recently, clinical trials in children have been incorporating placebo arms into their protocols under conditions that created controversy. Therefore, four organizations (ESPGHAN, ECCO, the Canadian Children IBD Network and the global pediatric IBD network (PIBDnet)) jointly provide a statement on the role of placebo in pediatric IBD trials. Consensus was achieved by 94/100 (94%) voting committees’ members that placebo should only be used if there is genuine equipoise between the active treatment and placebo. For example, this may be considered in trials of drugs with new mechanisms of action without existing adult data, especially when proven effective alternatives do not exist outside the trial. Placebo may also be used in situations where it is an ‘add-on” to an effective therapy or to evaluate exit-strategies of maintenance therapy after long-term deep remission. However, it has been agreed that no child enrolled in a trial should receive a known inferior treatment both within and outside the trial. This also includes withholding therapy in children who show clinical response after a short induction therapy. Given the similarity between pediatric and adult IBD in regards to pathophysiology and response to treatments, drugs generally cannot be considered being in genuine equipoise with placebo if it has proven efficacy in adults. Continued collaboration of all stakeholders is needed to facilitate drug development and evaluation in pediatric IBDPerforming well designed and ethical trials in pediatric inflammatory bowel diseases (IBD) is a priority to support optimal therapy and to reduce the unacceptable long lag between adult and pediatric drug approval. Recently, clinical trials in children have been incorporating placebo arms into their protocols under conditions that created controversy. Therefore, four organizations (ESPGHAN, ECCO, the Canadian Children IBD Network and the global pediatric IBD network (PIBDnet)) jointly provide a statement on the role of placebo in pediatric IBD trials. Consensus was achieved by 94/100 (94%) voting committees’ members that placebo should only be used if there is genuine equipoise between the active treatment and placebo. For example, this may be considered in trials of drugs with new mechanisms of action without existing adult data, especially when proven effective alternatives do not exist outside the trial. Placebo may also be used in situations where it is an ‘add-on” to an effective therapy or to evaluate exit-strategies of maintenance therapy after long-term deep remission. However, it has been agreed that no child enrolled in a trial should receive a known inferior treatment both within and outside the trial. This also includes withholding therapy in children who show clinical response after a short induction therapy. Given the similarity between pediatric and adult IBD in regards to pathophysiology and response to treatments, drugs generally cannot be considered being in genuine equipoise with placebo if it has proven efficacy in adults. Continued collaboration of all stakeholders is needed to facilitate drug development and evaluation in pediatric IB