Martinez‐Moragon 1997.

Methods	Single centre RCT of tetracycline vs bleomycin pleurodesis in MPE (Spain)
Participants	Inclusion: MPE (all cell types) causing respiratory symptoms, proved by cytological examination or pleural biopsy and an expected survival of at least one month, with a KPS ≥ 50 Exclusion: prior intrapleural instillation therapy; chest radiotherapy during the preceding two weeks; previously received systemic bleomycin; trapped lung; allergy to study drugs 70 participants randomised
Interventions	All participants underwent tube thoracostomy with suction drainage until < 100 ml/day output Tetracycline group: 1.5 g in 100 ml saline intrapleurally, with 9 ml 5% lignocaine Bleomycin group: 60 mg in 100 ml saline intrapleurally Tube clamped for four hours after instillation, then suction drainage. Drain removed when < 100‐150 ml/day output
Outcomes	Response to pleurodesis (defined as 'complete response' (CR) (no clinical or radiological recurrence of effusion), 'partial response' (PR) (small amount of fluid re‐accumulation on CXR but no symptoms), 'failure' (re‐accumulation of fluid causing symptoms or needing thoracocentesis)) Adverse effects of the procedure
Notes	People with trapped lung excluded from trial entry For this review, CRs and PRs included as pleurodesis successes Included in network meta‐analysis for pleurodesis efficacy, fever and pain
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer randomisation
Allocation concealment (selection bias)	Low risk	Computer randomisation
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	No mention of blinding in the paper. Agents given in the same volume but no comment on whether appearances were similar
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not stated if CXR interpretation was blinded. Other symptom and side effect outcomes could be biased if participants and personnel not blind to treatment allocation, but not stated if this was the case
Incomplete outcome data (attrition bias) All outcomes	Low risk	8/70 (11%) excluded from analysis due to death (5) or LTFU (3)
Selective reporting (reporting bias)	Low risk	All stated outcomes reported
Other bias	Low risk	No other biases identified