Savino 2005.

Methods	Randomised, double‐blind, placebo‐controlled trial with 2 treatment groups
Participants	Sample size: 93 colicky infants (5 dropped out (2 = intervention, 3 = control); 2 did not come to the second visit, 3 were excluded because of fever. Nobody withdrew because of problems related to the trial and therefore the study population may be considered homogeneous) Setting: recruited from patients seen at the Department of Pediatrics, Regina Margherita Children's Hospital, University of Turin, Italy Mean age: 4.2 weeks (SD 1.4, range not reported) intervention; 4.4 weeks (SD 1.6, range not reported) control Sex: 41 (46.6%) boys (18 intervention, 23 control); 47 (53.4%) girls (23 intervention, 24 control) Mean weight: 3420 g (SD 390) intervention; 3510 g (SD 330) control Mean duration of colic: not reported Mean crying: 201.2 min (SD 18.3) intervention; 198.7 min (SD 16.9) control Feeding: not specified Birth order: not specified Inclusion criteria: colic according to Wessel criteria, breastfed, healthy infants with regular growth, 21 to 60 days old, born at term (gestational age 38 to 42 weeks), birth weight between 2500 g and 4000 g, no clinical evidence of gastroenterological disease, and Apgar (appearance, pulse, grimace, activity, respiration) score > 7 at 5 min after birth Exclusion criteria: infants receiving any medication, such as antibiotics or probiotics, which could affect abdominal symptoms
Interventions	Intervention 1 (n = 41): phytotherapeutic agent (extracts of Foeniculum vulgare (fennel), Matricaria recutita (chamomile), and Melissa officinalis (lemon balm)). Each dose of herbal agent consisted of 1 bottle, with tank cap, containing Foeniculum vulgare miller var. dulce (164.29 mg), Matricaria recutita L. (177.69 mg), Melissa officinalis L. (96.89 mg), vitamin B1 (0.85 mg), calcium pantothenate (3.24 mg), vitamin B6 (1.20 mg), maltodextrin (dose not specified) and syloid 244 FP (dose not specified) (ColiMil, Milte‐Milan, Italy). At the administered dosage, the herbal agent provided Foeniculum vulgare miller var. dulce 65.71 mg/kg/d, Matricaria recutita L. 71.10 mg/kg/d, and Melissa officinalis L. 38.75 mg/kg/d Control (n = 47): placebo looking like the phytotherapeutic agent with regard to colour, smell, taste and package, but containing only vitamins. Each dose of placebo consisted of 1 identical bottle, with tank cap, containing water obtained by inverted osmosis, fructose, pineapple flavour, citric acid and sorbate potassium. Administration: both herbal agent and placebo were administered twice a day at 5 pm and 8 pm, some minutes before feeding, at a dosage of 2 ml/kg/d. Infants had to take treatment consecutively for 7 days Duration: 21 days
Outcomes	Parents wrote a daily, structured diary, recording (1) the start of crying time – when the medication was administered, (2) the end of crying time, and (3) any side effects (vomiting, sleepiness, restlessness, appetite, cutaneous reactions, constipation, diarrhoea) they observed for the 7 days of therapy and until day 21 from enrolment. Before starting treatment, parents were invited to record data on daily crying time for 3 days (days 0, 1, and 2). At days 1 and 7, infants were seen in the department, and parents gave the diary to researchers. At day 21, after baseline, mothers were asked to complete a questionnaire about crying time during the observation period. To ensure that all parents noted crying time in a uniform way, and to ensure that infants were given medication correctly, a researcher was always available by phone to help parents. Therapy was considered effective if crying time was reduced by ≥ 50% per day; responders were infants who showed such a reduction in crying time
Notes	Study start and end dates: March 2001 (start) to March 2003 (end) COIs: none reported Funding source: funded, in part, by Milte who provided the study products but had no other role in the study; they were not involved in writing or checking the manuscript Adverse effects: no adverse effects Comments: none
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Comment: this was performed by computer
Allocation concealment (selection bias)	Low risk	Comment: conducted by a statistician not involved with the study
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Comment: placebo looked like the phytotherapeutic agent with regard to colour, smell, taste and packaging Quote: "Neither doctors nor parents knew whether the infants received treatment or not"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Neither doctors nor parents knew whether the infants received treatment or not"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: 5 infants (2 from the intervention group and 3 from the placebo group) dropped out: 2 did not come to the second visit, and 3 were excluded because of fever. Nobody withdrew because of problems related to the trial.
Selective reporting (reporting bias)	Low risk	Comment: study authors reported results for all outcomes declared in the Methods section
Other bias	Low risk	Comment: no significant differences between groups at baseline were reported