ab Gutman 1977

Methods	Placebo‐controlled clinical trial to asses safety and reactogenicity of monovalent A/New Jersey/8/76 administered as whole virus or split‐product (disrupted virion) vaccine in four different preparation from licensed manufacturers
Participants	Children aged 3 to 10 years appeared at the Lincoln Community Health Center (LCHC, Durham, North Carolina) between May 24th and May 28th 1976, whose physicians allowed participation to the trial. Children were divided in two age groups (3 to 6 years and 6 to 10 years) and assigned to the preparation by continuous rotation of the vial numbers
Interventions	All vaccines were prepared from virus strain A/New Jersey/76 (Hsw1N1). Employed preparations were: MN 100, MN 200 ; MN 400 (Merrell –National Laboratories, Cincinnati, Ohio). Whole virus vaccine containing respectively 100, 200 or 400, chick cell‐agglutination units) MSD 100 (Merck Sharp & Dohme, West Point, Pa). Whole virus vaccine cont. 100 CCA units W 100, W 200, W 400 (Wyet Laboratories, Philadelphia, PA). Split product vaccine cont 100, 200, 400 CCA units PD 100, PD 200, PD 400 (Parke, Davis and Company, Detroit, Michigan). Split product vaccine cont. 100, 200 or 400 CCA units Placebo were also prepared by the same manufacturers as the vaccines. No information about composition given Vaccines and placebos were administered in the deltoid muscle as single dose of 0.25 ml
Outcomes	Serological 3 weeks after vaccination, a serum sample was taken to determine the antibody titre HAI to A/Victoria/3/75, A/swine/1976/31; A/Mayo Clinic / 103 /74 and A/ New Jersey/76 viruses. Children with titre above 1:20 to A/New Jersey were offered additional vaccination with MN 100 vaccine Effectiveness N/A Safety After immunisation children were observed at the LCHC for 20 minutes. Mothers were provided with 2 thermometers to record temperatures 6 and 9 hours later. Both were returned on the next day to be read by investigators. On the day after, children returned to be examined for adverse reactions or fever. Mothers recorded on a sheet adverse reactions (pain at the injection site, malaise, myalgia, headache, fever, nausea and tenderness, redness, induration). Sheets were completed the day after immunisation at the LCHC. During the study a physician was available when an adverse reaction was recognised or suspected by the parents
Funding Source	Government
Notes	The authors conclude that reactogenicity of both types of vaccines were similar. It is not clear if assignation to the vaccine or placebo group was made separately for the 2 age groups. Safety data are expressed considering only the vaccine group type (i.e. Split or whole virus) and not each arm , that was effectively randomised. The placebo arm is reported in an aggregate fashion with no age breakdown, making vaccine comparison impossible
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not used
Allocation concealment (selection bias)	Unclear risk	No descriptions
Blinding (performance bias and detection bias) All outcomes	Low risk	Double‐blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	No losses
Summary assessments	Unclear risk	It is not clear if assignation to the vaccine or placebo group was made separately for the 2 age groups