Placebo reactions in double-blind, placebo-controlled food challenges in children.
BACKGROUND
A cardinal feature of the double-blind, placebo-controlled food challenge (DBPCFC) is that placebo administration is included as a control. To date, the occurrence and diagnostic significance of placebo events have not extensively been documented.


OBJECTIVE
To analyse the occurrence and features of placebo events in DBPCFCs and to assess their contribution to the diagnostic accuracy of the DBPCFC in children.


METHODS
The study population consisted of 132 challenges in 105 sensitized children (age range 0.7-16.6 years, median 5.3 years), who underwent DBPCFCs with cow's milk, egg, peanut, hazelnut and soy. Placebo and active food challenges were performed on different days.


RESULTS
A total number of 17 (12.9%) positive placebo events occurred, which could be classified as immediate (9/17), late-onset (8/17), objective (11/17) or subjective (6/17). Four of 74 (5.4%) positive active food challenges were revealed to be false positive by administration of a placebo challenge. This is 3% (4/132) of all challenges. When computed by a statistical model, the false positive rate was 0.129 (12.9% of all challenges).


CONCLUSIONS
Placebo events with diverse clinical characteristics occur in DBPCFCs in a significant number of children. The diagnostic significance of the administration of a placebo challenge is first, to identify false positive diagnoses in DBPCFCs by refuting false positive tests in individual patients. Secondly, to allow for blinding of the active food challenge. Thirdly, applying a statistical model demonstrates that some positive challenges may be false positive and that the test may need to be repeated in selected cases.
Vlieg-Boerstra
B J
BJ
Division of Paediatric Pulmonology and Paediatric Allergy, Department of Paediatrics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
van der Heide
S
S
Bijleveld
C M A
CM
Kukler
J
J
Duiverman
E J
EJ
Dubois
A E J
AE
D000293:Adolescent; D000465:Algorithms; D002648:Child; D002675:Child, Preschool; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D005189:False Positive Reactions; D005260:Female; D005512:Food Hypersensitivity / Q000175:diagnosis* / Q000276:immunology; D006801:Humans; D007223:Infant; D008297:Male; D010919:Placebos; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012882:Skin Tests / Q000379:methods
D010919:Placebos