ab Levine 1977

Methods	Double‐blind placebo‐controlled phase 1 randomised trial carried out in the summer of 1976 in Baltimore, USA. The aim was to compare reactogenicity and safety of various concentrations of whole‐virion vaccines with split products of various manufactures
Participants	158 Maryland children aged 3 to 5 years. 103 children took part in the 1‐dose evaluation of split products, 47 took part in the 1‐dose evaluation of whole virion products and 28 took part in the 2‐dose evaluation of whole virion products
Interventions	50, 100 and 200 CCA units of split vaccines (Parke Davis or Wyeth) or 50 or 100 CCA units of whole‐virion vaccines (MSD or Merrell) or placebo. All vaccines were monovalent containing A/New Jersey/8/76 (H1N1). All were administered as single doses except for a follow‐up of second doses only for whole‐virion vaccines. Discontinuation of the use of split vaccines was caused by the disappointing antibody responses
Outcomes	Serological Paired sera for antibody titres Effectiveness N/A Safety Fever, nausea and malaise and a reactogenicity score with definitions described in the Lerman 1977 study
Funding Source	Government
Notes	The authors conclude that both vaccines were generally well tolerated with whole‐virion products causing low grade pyrexia and split products being virtually non‐immunogenic in 1‐dose schedules. A well described study
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient descriptions
Allocation concealment (selection bias)	Low risk	"preparations of vaccines and placebo in coded vials were supplied by the Bureau of Biologics"
Blinding (performance bias and detection bias) All outcomes	Low risk	Double‐blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	No losses to follow‐up
Summary assessments	Low risk	A well described study