Miller 1990.

Methods	Double‐blind, cross‐over trial with 2 treatment groups
Participants	Sample size: 15 (0 dropped out) Setting: infants recruited from a family care centre serving the northern suburbs of Sydney, Australia Sex: 5 boys (33%) 10 girls (67%) Mean age: 6.5 weeks (SD 2.2, range 3 to 9) Mean weight: not reported Mean duration of colic (baseline): not reported Mean crying (baseline): not reported Feeding: breastfed (100%) Birth order: not reported Inclusion criteria: total duration of crying and fussing of at least 3 h in 2 consecutive 24‐h periods; crying and fussing behaviour not responding to mother‐craft skills, and no apparent cause for the crying and fussing Exclusion criteria: hydrogen concentration in breath of over 20 ppm
Interventions	Intervention (n = not reported): lactase (Lactaid) in glycerol, 6 drops into baby's mouth within 5 min of commencing feed Control (n = not reported): glycerol with water and caramel, 6 drops into baby's mouth within 5 min of commencing feed Duration: 7 days in each treatment arm
Outcomes	Mothers instructed on how to complete a 24‐h recording form detailing durations of infant behaviours such as sleeping, being awake and content, crying, fussing and feeding, to determine the mean number of minutes of crying or fussing in 24 h. Also, measurement of H2 concentrations in pre‐and post‐prandial breath tests, to determine the effect of yeast lactase on the mean value of each infants' breath hydrogen
Notes	Study start and end dates: July 1987 (start) to June 1988 (end) COIs: none reported Funding source: Sharpe Laboratories, which seemed to have produced the active and placebo preparations, but no details available as to any further extent of their involvement Adverse effects: none reported Comments: cross‐over study but we reported on the first arm only. Based on PhD Thesis by John Miller
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "infants were randomly allocated" Comment: we contacted the study author who was unable to confirm how the random list was generated Quote: "Dr D Shaw, Principal Consultant, Siromath, Sydney, performed the sample size calculation and I recall that he also provided a randomisation schema for allocation of the treatments to the breast fed, and to the formula‐fed infants. I don't remember how these randomisation schema were derived"
Allocation concealment (selection bias)	High risk	Comment: no details. Wrote to study author who was unable to confirm whether this was done
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Comment: described as double‐blind but method not specified. Wrote to study author who responded stating, "The active & placebo enzyme preparations were aseptically filled into plastic squeeze bottles, capped, packed into tamper‐proof plain cardboard cartons and labelled with a code by Sharpe Laboratories, Sydney. The packaged preparations were indistinguishable except for the labelled code."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Comment: no details. Wrote to study author who responded stating, "The active & placebo enzyme preparations were aseptically filled into plastic squeeze bottles, capped, packed into tamper‐proof plain cardboard cartons and labelled with a code by Sharpe Laboratories, Sydney. The packaged preparations were indistinguishable except for the labelled code."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: 15 entered the study, but only 12 completed the study and no reasons for non‐completion are provided in the paper. We contacted the study author who replied stating, "Of these infants, 2 ‘dropped out' – 1 on active treatment, the other on placebo. In the former case, active treatment was discontinued after 48 hours because the parents considered the treatment worsened crying and fussing behaviour. In the latter case, the mother stopped using the placebo after 4 days because of lack of effect. One infant was withdrawn from the study. In this case, the mother was admitted to hospital with a breast abscess. The infant was temporarily weaned. However, at the mother's request, active treatment was continued."
Selective reporting (reporting bias)	Low risk	Comment: results are based on per protocol, not intention‐to‐treat, but all major outcomes are reported, with adverse effect data given by study author
Other bias	Unclear risk	Comment: designed as cross‐over trial but we reported on the first arm only. Sharpe Laboratories were the study sponsor and seemed to have produced the active and placebo preparations but no details were available as to any further extent of their involvement. The study author confirmed no involvement.