Differences between observers in interpreting double-blind placebo-controlled food challenges: a randomized trial.

Background: Interpretation of double-blind placebo-controlled food challenges (DBPCFC) can be difficult, particularly with ambiguous subjective symptoms. Early opening of the challenge key (which day is verum and which placebo) may influence the clinician's interpretation of the DBPCFC result.

Methods: Fifty-one clinicians reviewing results of 19 DBPCFCs with ambiguous clinical symptoms were randomized into a key first strategy (opening the DBPCFC key before reviewing the symptoms on both challenge days and deciding on the DBPCFC result) or a symptoms first strategy (reviewing symptoms and interpreting both test days as positive or negative before opening the key and deciding on the DBPCFC result).

Results: The proportion of DBPCFCs considered inconclusive was comparable between the two strategy groups (p = 0.791). Participants in the symptoms first group were more likely to consider a DBPCFC as positive (in 14 tests, 73.7%) than subjects in the key first group (four tests, 21.1%). The number of positive tests was higher in the symptoms first group (median 50.0%, interquartile range [IQR] 23.1-76.9%) than in the key first groups (44.0%, IQR 12.0-68.0%, p = 0.031). This was independent of the participant's profession (pediatrician or other), age, gender, or years of experience (p > 0.3).

Conclusions: Clinicians differ in their interpretation of DBPCFC results when symptoms are ambiguous. Opening the key of a DBPCFC before reviewing and interpreting symptoms significantly reduces the likelihood of the challenge being interpreted as positive. Guidelines for performing DBPCFCs should standardize the moment of opening the challenge key.