Prince 1997.

Methods	Two‐phase trial (phase 1 trial length: 2 years; phase 2 study length: 3 years). Only phase 1 was an RCT. Phase 1: Randomised controlled parallel trial. Inclusion of all randomized participants in the final analysis: Phase I: unclear, data not shown; Not included in this review: Phase 2: historic control trial. Only 25 of 28 randomized participants were included.
Participants	Phase 1: Number of participants: 28 enrolled, ages 4 to 10 years. Inclusion criteria: diagnosed with moderate to severe PKU; ages 4 to 10 years; currently treated by a protein‐restricted diet supplemented with protein substitute. Exclusion criteria: none indicated. Not included in this review: Phase 2: historic control trial.
Interventions	Phase 1: 1. Novel protein substitute: 100% US RDA for protein (1989) for 2 years. The novel protein substitute contained 10 g protein equivalent for 400 kcal (100 g dry powder) and included a reduction in methionine and cystine, and eliminated aspartic acid and glutamic acid. 2. Control protein substitute (PhenylFree, Mead‐Johnson Co., Evansville, IN, USA): 100% US RDA for protein (1989) for two years. Not included in this review: Phase 2: historic control trial.
Outcomes	Phase 1: 1. Growth 2. Serum protein (prealbumin and transferrin) concentrations 3. Serum phenylalanine concentrations 4. Serum essential amino acid concentrations 5. Protein substitute intake assessed by 4‐day diet records 6. Protein substitute intake assessed by product acquisition records Not included in this review: 7. Compliance rating Phase 2: historic control trial.
Notes	Location: USA
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomization process not described.
Allocation concealment (selection bias)	Unclear risk	Unclear if allocation concealment was used.
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Unclear if blinding was used.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Unclear as data not shown whether all randomized participants were included in the final analysis.