Giavi 2016.

Methods	Double‐blind placebo controlled randomized pilot study
Participants	29 egg‐allergic children, 1 year to 5.5 years old, diagnosed with an IgE‐mediated egg allergy based on a positive skin prick test (SPT) to egg white within the last three months as well as a positive oral challenge or a convincing history, defined as an immediate (< 1 h) reaction following isolated ingestion of egg and positive sIgE (> 0.35 kU/L) for at least one of the following: egg, egg white, ovalbumin or ovomucoid, within the last 12 months.
Interventions	On day 1, tolerance of the randomized product was assessed by an oral food challenge. 91 g of product was diluted in liquid (1/5 orange juice and 4/5 carrot juice) to a final volume of 50 mL. Every 20 to 30 min the final product was administered with increasing doses as follows: Step 1, 1.5 mL; Step 2, 3.5 mL; Step 3, 10 mL; Step 4, 15 mL; and Step 5, 20 mL. Both objective and subjective symptoms were recorded. The participant passed the tolerance assessment test if no symptoms occurred after having consumed all doses. In case no adverse reaction occurred, the subject was administered 1 day later with a full dose (91 g) at once incorporated in a solid meal and again adverse events were recorded. In case of no adverse events, a sachet containing 9 ± 1 g hydrolysed egg or placebo was administered daily for 6 months. Controlled group: placebo
Outcomes	The primary outcome was a positive or negative result of the challenge test, and the cumulative dose ingested without reaction (maximum cumulative dose tolerated). The severity of the allergic reactions at the final oral food challenge was evaluated. An overall score was calculated by multiplying two scores: maximum dose tolerated (0 g: grade 3, < 1 g: grade 2, > 1 g: grade 1, equal to maximum dose tolerated: grade 0) and severity of symptoms (no reaction: grade 0, mild: grade 1, moderate: grade 2, severe: grade 3). Egg‐specific IgE and IgG4 antibodies (anti‐egg white, anti‐egg yolk, anti‐ovomucoid (OVO), anti‐ovalbumin(OVA)) and Basophil activation were assessed at the start (V0) and end (V5) of the study.
Vested interest	Quote: "Several authors (YMV, AM, SN, AW) are or were employees of Nestec Ltd."
Notes	No funding information was available.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The randomization at 1:1 hydrolysed egg:placebo ratio was applied by using the software TrialSys (developed at Nestle, Lau‐sanne). Stratification was performed by gender (male or female), centre (Greece, Italy or Switzerland) and age (12 months to 35 months or 36 to 66 months).
Allocation concealment (selection bias)	Low risk	Study products were packaged, labelled and stored at Eurofins, France. A study box containing 110 sachets of the randomized product was sent to the study site (and provided to the parents) directly after randomization of the child and after 2.5 months. Each centre received at the start of the study ‘SPT kits’ containing each a sachet of hydrolysed egg and a sachet of placebo.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Study products were packaged, labelled and stored at Eurofins, France. A study box containing 110 sachets of the randomized product was sent to the study site (and provided to the parents) directly after randomization of the child and after 2.5 months. Each centre received at the start of the study ‘SPT kits’ containing each a sachet of hydrolysed egg and a sachet of placebo.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No information provided
Incomplete outcome data (attrition bias) All outcomes	High risk	All outcomes accounted for and imbalance in numbers for missing data across intervention groups
Selective reporting (reporting bias)	Low risk	The trial was registered at ClinialTrials.gov (registration identifier NCT01526863)