Kilpi 2003.

Study characteristics
Methods	This trial was part of a study including Eskola 2001 (FinOM Vaccine Trial). Both Eskola 2001 and Kilpi 2003 used the same control group (hepatitis B vaccine containing 5 μg of recombinant hepatitis B surface protein) but a different PCV7 type. Eskola 2001 used CRM197‐PCV7, whilst Kilpi 2003 used OMPC‐PCV7. Randomised: yes, at individual level Design: standard parallel‐group design Intention‐to‐treat: no, per‐protocol analysis Follow‐up: 22 consecutive months (children were followed up to 24 months of age)
Participants	N: 1666 healthy infants Age: 2 months Setting: 8 study clinics in the communities of Tampere, Kangsala, and Nokia, Finland Inclusion criteria: healthy children aged 2 months Exclusion criteria: not described Baseline characteristics: described and balanced (Table 1)
Interventions	Children were randomly allocated to either OMPC‐PCV7 or a hepatitis B vaccine at 2, 4, 6 and 12 to 15 months of age. From 3 November 1997 onwards, for the children randomised to receive OMPC‐PCV7, the fourth dose of the conjugate vaccine was replaced by PPV23, Pneumovax23 including serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, and 33F. Tx: OMPC‐PCV7; N = 835 (N = 805 completed the follow‐up as specified in the protocol) C: hepatitis B vaccine; N = 831 (N = 794 completed the follow‐up as specified in the protocol) Additional vaccines: a diphtheria–tetanus toxoids–pertussis vaccine with a whole‐cell pertussis component, combined with a Haemophilus influenzae type b conjugate vaccine (DTP‐Hib), was administered concomitantly with the first 3 doses of the study vaccine; an inactivated poliovirus vaccine was administered with the fourth dose. In 4 study clinics, the carrier protein in the DTP‐Hib conjugate combination was CRM197, whilst in the other 4 study clinics it was tetanus toxoid.
Outcomes	See Eskola 2001.
Funding sources	Supported by Aventis Pasteur, Merck, and Wyeth‐Lederle Vaccines and Pediatrics
Declarations of interest	Not described; from Eskola 2001: Dr Eskola and Dr Kilpi have served as consultants to Wyeth‐Lederle Vaccines
Notes	Participants lost to follow‐up:total: 67/1666 (4.0%) did not complete the follow‐up period specified in the protocol Participants lost to follow‐up:Tx: 30/835 (3.6%) did not complete the follow‐up period specified in the protocol Participants lost to follow‐up:C: 37/831 (4.5%) did not complete the follow‐up period specified in the protocol
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	6 letters corresponding to the 3 treatment options were randomly allocated to consecutive participant identification numbers, using an allocation of 1:1:1 and a block size of 12.
Allocation concealment (selection bias)	Low risk	Individual treatment assignments were kept in sealed envelopes until vaccination.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Use of vaccinators who were not otherwise involved in the trial follow‐up. Letter code was destroyed immediately after vaccination.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessment of the outcome was done according to a strict definition of AOM. Assessment was performed by personnel other than those who vaccinated the children (vaccinators were not otherwise involved in the trial follow‐up).
Incomplete outcome data (attrition bias) All outcomes	Low risk	No reporting of reasons for dropout or loss to follow‐up. This is not expected to have a major impact on outcome since 96.0% in the OMPC‐PCV7 and 95.5% in the control group completed the follow‐up as specified in the protocol.
Selective reporting (reporting bias)	Unclear risk	Prespecified outcomes (primary and secondary) are listed in ClinicalTrials.gov (although uploaded after study end).
Other bias	Unclear risk	Mixed schedule with 187 children boosted with PPV23. Unclear how researchers identified those allocated to OMPC‐PCV7 to receive PPV23 after November 1997