Metcalf 1994.

Methods	Randomised, double‐blind, cross‐over trial
Participants	Sample size: 92 infants enrolled; 9 infants excluded: 8 for failure to keep follow‐up visits and 1 for infection. Total of 83 infants were included in the analysis Setting: 3 general paediatric practices in distinct geographic regions Sex: boys (49.4%) Mean age: not reported (SD not reported); range 2 to 8 weeks Mean weight: not reported Mean duration of colic: not reported; 24% had severe colic at baseline Mean crying: not reported Feeding: breast fed (26.5%) Birth order: not reported Inclusion criteria: Infants with crying sufficient to meet Wessel's criteria Aged 2 to 8 weeks, appropriate gestational age Weight gain ≥ 5 ounces per week Normal history and physical exam Exclusion criteria: Infants with congenital or acquired abnormalities that might predispose them to irritability Infants with prior or currently diagnosed illness or a history of treatment for hyperbilirubinaemia
Interventions	Intervention (83 infants): simethicone; 0.3 cc of simethicone solution before each meal Control (83 infants): placebo Administration: Trial consisted of 2 study periods, each of approximately 1 week (minimum 3 days; maximum 10 days). Infants first received simethicone or placebo according to a schedule determined by random number tables, followed by the alternate substance for the second study period. Carers were given a bottle of coded medication and were instructed to give 0.3 mL with each feeding. Duration of study: 2 weeks Washout period: 1 day
Outcomes	Treatment efficacy was measured by interviews, 3‐ to 4‐hour behavioural observations and 24‐hour records in which parents described infants’ crying, fussing, eating and stools. Parents were asked to record in the daily diary each administration of medication and to provide written comments on events deemed noteworthy, including any modifications in dietary habits or feeding schedule. At the end of each day, parents were to rate their child’s colic compared with when they had first sought treatment for the infant. They used a 5‐point scale to identify the child’s symptoms as follows: '+ 2', definitely better or symptom‐free; '+ 1', possibly better; '0', the same; '‐ 1', possibly worse; '‐ 2', definitely worse. After the first study period, carers returned the diary and any unused medication to the physician’s office, or they gave these items to a nurse study co‐ordinator during a home visit. Responders to simethicone or to placebo were infants judged by the carer to have had a positive response (+ 1, + 2) only to simethicone or only to placebo.
Notes	Country: United States Funding source: This study was supported by a grant from Smart Pharmaceuticals.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Infants first received either simethicone or placebo, based on a schedule determined by random number tables, followed by the alternate substance for the second study period".
Allocation concealment (selection bias)	Unclear risk	Comment: Method of concealment was not described.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "Caregivers were given a bottle of coded medication".
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "Caregivers were given a bottle of coded medication".
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Comment: Information was insufficient to permit a judgment; researchers reported only withdrawals ‐ 8 infants were excluded for failure to keep follow‐up visits, and 1 child developed upper air respiratory infection and was excluded.
Selective reporting (reporting bias)	High risk	Comment: Study authors did not report results by study period.
Other bias	Low risk	Comment: One‐day washout was planned.