PROPS II 1995.

Study characteristics
Methods	RCT. Participants randomised to have prophylactic penicillin withdrawn or continued, by permuted block randomisation.
Participants	400 children with SS or Sb0 in the USA.
Interventions	Penicillin V (250 mg bd), or identical placebo tablet.
Outcomes	Incidence of bacteremia or meningitis caused by S pneumoniae. Average duration of follow‐up: 3.2 years.
Notes	There were no documented declarations of interests among the primary researchers.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was by permuted block method, stratified by clinical site and years of previous penicillin use.
Allocation concealment (selection bias)	Unclear risk	It was unclear whether allocation concealment had been performed.
Blinding (performance bias and detection bias) All outcomes	Low risk	Identical placebo tablets were used to maintain double blinding of the participants and centre personnel.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	400 children were recruited from 18 centres in the USA. The characteristics of participants in each group were similar at baseline. 4 children died after randomisation, but other withdrawals are not reported, and it is unclear whether an intention‐to‐treat analysis was undertaken.
Selective Reporting (Reporting Bias)	Low risk	"The primary end point was a comparison of the incidence of bacteremia or meningitis caused by Streptococcus pneumoniae in children continuing penicillin prophylaxis versus those receiving the placebo." Baseline characteristics and outcomes were adequately reported
Other potential Sources of Bias	Low risk	None known.

bd: twice daily
H influenzae: Haemophilus influenzae 
IM: intramuscular
RCT: randomised controlled trial
SCD: sickle cell disease
SS: homozygous sickle cell disease
S pneumoniae: Streptococcus pneumoniae