Williams 1990.

Methods	Randomized, single blind cross‐over study. Duration: 10 weeks in total, 2‐week run‐in period followed by 4 weeks for each treatment arm. Not clear if multi‐ or single‐centre study based in the UK. Home setting.
Participants	39 children with symptoms of CF, at least 2 abnormal sweat chloride results and pancreatic insufficiency. Age: median (range) 9.7 (5 ‐ 17) years. Clinical state, as measured by the Shwachman score (100 = normal) ranged from 37 to 91 with a median value of 79. 12 participants were unsuitable for analysis, the remaining 27 children (15 boys and 12 girls) completed the trial.
Interventions	Group 1: ECM Creon® (lipase 8000 BP units, amylase 9000 BP units, protease 210 BP units). Group 2: ECM Pancrease® (lipase 5000 BP units, amylase 2900 BP units, protease 330 BP units). Participants took same number of capsules per day during both treatment periods.
Outcomes	CFA, participant preference, nitrogen excretion, weight change, symptom score for appetite, number, colour and consistency of stools, abdominal pain and general condition.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Described as randomized, but further information not given.
Allocation concealment (selection bias)	Unclear risk	Information not given.
Blinding of participants and personnel (performance bias) Participants	High risk	Blinding not done.
Blinding of participants and personnel (performance bias) Clinicians	Low risk	Study medication was issued by pharmacist and order of treatment was not known to the doctor.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Blinding not done.
Incomplete outcome data (attrition bias) All outcomes	High risk	12 participants (31%) were withdrawn from trial for various reasons and not included in analysis: 7 withdrew because of respiratory exacerbations or infective illnesses that interfered with dietary intake such that their standard individualised menu could not be followed; 1 failed to attend for follow up; 1 withdrew because of intolerable symptoms of steatorrhea on Pancrease®, further assessment on Creon® (her usual treatment) showed poor control of fat malabsorption with a CFA of 77%; 3 participants inadvertently took unequal numbers of capsules during the 2 treatment periods and were therefore excluded from the analysis.
Selective reporting (reporting bias)	High risk	Change in weight and symptom scores for abdominal pain, stool frequency were measured but were reported incompletely, so cannot be entered in a meta‐analysis.
Other bias	High risk	Corresponding author was financially supported by Cilag Limited (Pancrease).

CF: cystic fibrosis
 CFA: co‐efficient of fat absorption
 CFQ‐R: Cystic Fibrosis Questionnaire‐Revised
 CNA: co‐efficient of nitrogen absorption
 ECM: enteric‐coated microspheres
 ECMM; enteric‐coated mini‐microspheres
 ECT: enteric‐coated tablets
 FFE: fecal fat excretion
 NECT: non enteric‐coated tablets
 QoL: quality of life
 SD: standard deviation
 TPE: total pancreatic extracts