Murata 1965.

Methods	Quasi‐randomised trial. Women allocated to different groups on alternate days. Experimental group on even number days and placebo on odd number days.
Participants	59 women presenting with breast engorgement (˝mammal swelling or induration˝...˝complaining of pain or tenderness˝) on 3rd to 5th day post‐delivery.
Interventions	Intervention group (35 women): day 1: 2 tablets of protease complex, an enteric‐coated tablet consisting of bromelain and trypsin, taken 4 times a day (after each meal and before bed time); day 2 and 3: 1 tablet 4 times a day; total of 16 tablets. Control group (24 women): lactose containing placebo tablets given according to the above regime.
Outcomes	Swelling and pain on the afternoon of the 4th day; maternal opinion of treatment; size of breast; shape of nipple; coagulation, prothrombin and bleeding time.
Notes	It was not clear whether all women were breastfeeding. The outcomes were measured using grades according to the degree of improvement of symptoms. In situations where there was no change the grade allocated was 0, where the symptoms became worse, the grade was ‐ 1, in cases where there was a 1 stage improvement the grade given was 1 and where there was a 2 stage improvement, the grade was 2. No change was detected before and after treatment in regard to coagulation, prothrombin and bleeding time. No complaints were made in regards to gastro‐intestinal troubles or poor uterine involution.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Quasi‐randomisation, allocation by day of the week. This method introduced bias in the way the participants were allocated to different groups.
Allocation concealment (selection bias)	High risk	Group allocation could be anticipated in advance as it was known which arm of the study was allocated to which day of the week.
Blinding (performance bias and detection bias) Women	Unclear risk	The study was placebo‐controlled but the authors do not mention whether the placebo was identical to the treatment or if it was easy for women to see what they were getting.
Blinding (performance bias and detection bias) Clinical staff	Unclear risk	There is no mention of blinding of the clinician who administered the treatment.
Blinding of outcome assessment (detection bias)	Low risk	2 outcome assessors recorded the change in swelling and pain on the 4th day and were not informed as to which participant belonged to which group.
Incomplete outcome data (attrition bias) All outcomes	Low risk	There were no exclusions and no losses to follow‐up.
Selective reporting (reporting bias)	Low risk	The authors reported on all pre‐specified outcomes.
Other bias	Unclear risk	Protease complex tablet was supplied by Mochida Pharmaceutical Company under the trademark 'Kimotab'. Possible vested interest may have lead to a risk of bias in favour of tested drug.