MacDonald 2003b.

Methods	Randomised controlled cross‐over trial. Generation of allocation sequence: randomization process not described. Allocation concealment: adequate. Blinding: not used. Inclusion of all randomized participants in the final analysis: No.
Participants	Number of participants: 16 enrolled, 15 included in analysis, ages 1 to 10 years. Inclusion criteria: well controlled plasma phe concentrations over the past 6 months; parents able to collect blood specimens. Exclusion criteria: none indicated.
Interventions	1. Protocol A: protein substitute administered in 3 equal doses over a 10‐hour period (7 days) 2. Protocol B: protein substitute administered in 3 equal doses over a 14‐hour period (7 days) 3. Protocol C: protein substitute administered in 4 equal doses over a 14‐hour period (7 days) 4. Protocol D: protein substitute administered in 6 equal doses over a 24‐hour period (3 days)
Outcomes	1. 24‐hour plasma phenylalanine variation 2. 24‐hour dietary phenylalanine distribution 3. Energy intake (% EAR) Outcomes not reported in manuscript: 4. Other nutrient intakes (carbohydrates, fat)
Notes	Location: UK. Initially only 13 participants were randomised into protocols A, B, and C. A further 3 participants were randomized into protocols A, B, and D. Since the 3 participants were introduced after the initial randomisation phase, their results may not be included in the review. At the present time only information from protocol C can be used as the extra participants did not enter this group. Individual patient data must be sought from the author. This would enable the 3 extra participants to be identified within groups A and B and D and excluded from the analysis.

EAR: estimated average requirements
 Phe: phenylalanine
 PKU: phenylketonuria
 RCT: randomised controlled trial