Poupon 1991.

Methods	Multicenter double‐blind, placebo controlled randomised clinical trial with parallel group design (two interventions groups). Trial duration: 2 years. Follow‐up: 5 patients receiving ursodeoxycholic acid and 6 placebo withdrew.
Participants	Country: France and Canada. Number of patients randomised: 146, from 22 centres in France and Canada, mean age 56 years (92% females). Inclusion criteria: ‐ liver biopsy compatible with PBC; ‐ serum alkaline phosphatase > 2.0 upper normal limit; ‐ positive AMA. Exclusion criteria: ‐ PBC treatment within last six months; ‐ serum bilirubin > 150 µmol/l; ‐ serum albumin < 25 g/l; ‐ past or active bleeding oesophageal varices; ‐ presence of extrahepatic obstruction; ‐ excessive alcohol consumption; ‐ positive hepatitis B surface antigen.
Interventions	Patients were randomly assigned to receive: Intervention group 1: ursodeoxycholic acid 13 to 15 mg/kg/day, n = 73; Intervention group 2: placebo, n = 73.
Outcomes	Mortality. Liver transplantation. Symptoms. Liver biochemistry. Liver histology.
Notes	All patients treated for two years with placebo were offered ursodeoxycholic acid and further followed‐up for another two years together with patients continuing on ursodeoxycholic acid. One patient, included in the publications of the study up to 1993, was excluded from the 1994 publication due to a raised serum bilirubin at entry, which violated the entry criteria. Data were extracted at the maximum follow‐up where applicable, if not the end of treatment was used for data extraction.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	The trial is described as randomised, but the method of sequence generation was not specified.
Allocation concealment (selection bias)	Unclear risk	The trial was described as randomised but the method used to conceal the allocation was not described, so that intervention allocations may have been foreseen in advance of, or during, enrolment.
Blinding (performance bias and detection bias) All outcomes	Low risk	The trial was described as blinded, the parties that were blinded, and the method of blinding was described ‐ placebo was 'identical capsule', so that knowledge of allocation was adequately prevented during the trial.
Incomplete outcome data (attrition bias) All outcomes	Low risk	The numbers and reasons for dropouts and withdrawals in all intervention groups were described.
Selective reporting (reporting bias)	Low risk	Pre‐defined, or clinically relevant and reasonably expected outcomes are reported on.
Other bias	Low risk	The trial appears to be free of information that could put it at risk of bias.