Flex-IT! Applying "Platform Trials" Methodology to Immunotherapy for Food Allergy in Research and Clinical Practice.

There is an increasing trend in the management of food allergy toward active treatment using allergen immunotherapy (AIT). Although AIT is efficacious, treatment-related adverse events are common, particularly with oral immunotherapy in those with high levels of allergen-specific IgE sensitization. In clinical practice, these adverse events inevitably create challenges: clinicians and patients routinely face decisions whether to alter the dose itself, the frequency of dosing, and the pace of escalation, or indeed discontinue AIT altogether. Flexibility is therefore needed to adapt treatment, particularly in clinical practice, so that participants are "treated-to-target." For example, this may entail a significant change in the dosing protocol or even switching from one route of administration to another in response to frequent adverse events. We refer to this approach as flexible immunotherapy. However, there is little evidence to inform clinicians as to what changes to treatment are most likely to result in treatment success. Classical clinical trials rely, by necessity, on relatively rigid updosing protocols. To provide an evidence base to optimize AIT, the food allergy community should adopt adaptive platform trials, where a "master protocol" facilitates more efficient evaluation, including longer-term outcomes of multiple interventions. Within a single clinical trial, participants are able to switch between different treatment arms; interventions can be added or dropped without compromising the integrity of the trial. Developing platform trials for food AIT may initially be costly, but they represent a significant opportunity to grow the evidence base (with respect to both treatment outcomes and biomarker discovery) at scale. In addition, they could help understand longitudinal disease trajectories that are difficult to study in clinical trials for food allergy due to the time needed to demonstrate changes in efficacy. Finally, their adoption would achieve greater collaboration and consistency in approaches to proactive management of food allergy in routine clinical practice. As a community, we need to actively pursue this with funders and established research collaborations to deliver the very best outcomes for our patients and their families.