A new international perspective led by UNC School of Medicine researchers highlights that oral food challenges, historically considered essential to food allergy clinical trials, are now limiting who can participate and threatening to slow progress in food allergy research.
Food allergy research has advanced significantly over the years transforming management from strict food avoidance to prevent allergic reactions to today’s proactive treatments to reduce the risk of food allergy. But now the future landscape for conducting clinical trials is facing new barriers. The oral food challenge (OFC), the reference standard test for food allergy diagnosis, has long been considered essential to clinical trials. However, continued reliance on OFCs may now pose a threat for both researchers and patients.
According to a new perspectives article published in Allergy, an expert panel of leading food allergy researchers in the U.S. and the United Kingdom found that while oral food challenges were the most reliable test for a diagnosis in past decades, they were not without limitations. The expert panel, led by UNC School of Medicine’s Edwin Kim, MD, associate professor, Department of Pediatrics, and Alexandra Santos, MD, King’s College London, highlighted that OFCs involve the risk of anaphylaxis or other allergic reactions, as well as the requirement of significant resources, costs, and time. These factors can create a difficult and sometimes unpleasant experience for participants.
“Particularly difficult were oral food challenges performed at baseline where potential patients would undergo the risk of anaphylaxis prior to any opportunity for treatment benefit,” said Kim, lead author. “Fast forward to today and there are now both approved and off-label treatments available for food allergy in clinics. We have also advanced our interpretation of diagnostic tests and know better what to expect from investigational treatments. Yet, clinical trials are still run the same way as two decades ago including a requirement of oral food challenges.”
With a 97% accuracy in food allergy diagnosis, OFCs do have advantages. Results from the challenge are typically expected during peer review of manuscripts and, for companies seeking drug approval, these results are also expected by regulatory agencies. However, as clinicians attempt to apply these OFC-based outcomes to patients seen in clinical practice, it has become clear that food‑challenge‑based data has some drawbacks. What works in a controlled trial does not always translate perfectly to everyday clinical practice.
In addition to the risk of severe allergic reactions, OFC disadvantages can also include:
- Anxiety, possible trauma for patients and family
- Participant and family missed days of school and work
- Negative incentive for trial participation in lieu of clinically available treatments
- Requirement of multi- day, multi- hour specialist oversight adding substantial expense to the trial
Because food challenges are difficult for many people to participate in, fewer patients are able or willing to join these studies. This reduces the diversity of participants and makes it harder for researchers to know whether the results apply broadly to the general public. Low recruitment and high cost of clinical trials could discourage further development of treatments for food allergy. Dr. Kim notes that while there is no perfect replacement for the oral food challenge at this time, alternative approaches using currently available diagnostics may be possible.
“Potential concepts include an algorithmic use of multiple diagnostic tests as well as incorporation of single-day open oral food challenges,” said Kim, who is also Division Chief of Pediatric Allergy and Immunology and director of the UNC Food Allergy Initiative. “While these ideas are not intended to be prescriptive, the hope is that it can open up a dialogue among stakeholders to evolve our approach to clinical trials and keep the research moving forward.”
The success and rapid growth of food allergy research have led to the availability of multiple therapeutics in clinical practice. To continue making progress, the authors suggest clinical trials need to evolve to maintain an appropriate balance between potential benefit and participation risk and burden. They conclude that it is important to leverage existing technologies and approaches to ensure that food allergy research can continue unhindered.
“To continue to advance in food allergy research, future studies will include discussion among researchers, industry sponsors, regulators, and patient groups about clinical trial requirements and design that can expand access, manage costs, and be ethically sound while not sacrificing scientific rigor,” said Kim.
Media Contact: Brittany Phillips, Communications Specialist, UNC Health | UNC School of Medicine