van Kempen 2006.

Study characteristics
Methods	This study was performed in parallel with Veenhoven 2003 (OMAVAX‐trial), but analysed separately due to differences in study population. Randomised: yes, at individual level Design: standard parallel‐group design Intention‐to‐treat: unclear Follow‐up: 26 months
Participants	N: 74 children with a history of AOM Age: between 1 and 7 years Setting: ENT department of the Ghent University Hospital in Belgium Inclusion criteria: children aged 1 to 7 years with a history of AOM defined as at least 2 separate clinically diagnosed AOM episodes in the past year Exclusion criteria: children with any underlying illnesses including immunocompromising conditions other than partial serum IgA and IgG2 deficiencies, craniofacial abnormalities, previous pneumococcal vaccination, or documented hypersensitivity to any of the vaccine components Baseline characteristics: described and balanced (Table 1 of trial publication)
Interventions	Children were randomly allocated to either a CRM197‐PCV7 or a hepatitis A vaccine (containing 720 units of inactivated hepatitis A virus). Children aged 12 to 24 months received 2 intramuscular injections with a 1‐month interval, whilst those aged over 2 years received 1 intramuscular injection. Children allocated to CRM197‐PCV7 additionally received PPV23 6 months (in children aged 12 to 24 months) or 7 months (in those aged over 2 years) later. Tx: CRM197‐PCV7 plus PPV23; N = 38 (N = 35 completed the vaccination scheme) C: hepatitis A vaccine; N = 36 (N = 33 completed the vaccination scheme) Additional vaccines: not described
Outcomes	Primary outcome: number of AOM episodes during the 18‐month follow‐up Secondary outcomes: immunogenicity; nasopharyngeal carriage of conjugate vaccine‐related serotypes; and antibiotic‐resistant pneumococci. At scheduled hospital visits at 7, 14, 20, and 26 months after randomisation, a medical history was taken, antibiotic usage noted, and an otomicroscopic examination performed. When at least 1 month following complete vaccination a new AOM episode was suspected, parents were asked to bring their sick child to the study centre within 24 hours for otoscopic diagnosis. In case of all other AOM episodes during follow‐up, participants were allowed to visit the study centre, their family physician, or a paediatrician, who was asked to report otoscopic findings, diagnosis, and treatment on an AOM registration form. AOM was defined as an abnormal tympanic membrane on otomicroscopy (red, dull, or bulging) plus at least 1 of the following symptoms or signs of acute infection: earache, acute otorrhoea, fever (> 38.5 °C rectally), or irritability.
Funding sources	Study was supported by the Netherlands Organisation for Health Research and Development (ZonMw) and the Dutch health insurance company Zilveren Kruis‐Achmea as part of the OMAVAX‐trial. Wyeth‐Lederle Vaccines and Pediatrics provided the pneumococcal vaccines, and GlaxoSmithKline provided the hepatitis A vaccines.
Declarations of interest	The authors declared no conflicts of interest.
Notes	Participants lost to follow‐up:total: 6/74 (8.1%) did not complete the follow‐up period specified in the protocol Participants lost to follow‐up:Tx: 3/38 (7.9%) did not complete the follow‐up period specified in the protocol Participants lost to follow‐up:C: 3/36 (8.3%) 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)	Unclear risk	Method of random sequence generation not described, randomisation stratified according to age (12 to 24 months versus 25 to 84 months) and number of previous AOM episodes per year (2 to 3 versus 4 or more episodes).
Allocation concealment (selection bias)	Low risk	2 study nurses immunised all children according to a randomisation list provided to them in a sealed envelope by a third party (the Julius Center for Health Sciences, Utrecht, the Netherlands).
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The nurses that vaccinated children were not allowed to reveal the child's allocation to either the study team or the parents.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	When a new AOM episode was suspected, parents were asked to bring their sick child to the study centre within 24 hours for otoscopic diagnosis. In case of all other AOM episodes during follow‐up, participants were allowed to visit the study centre, their family physician, or a paediatrician, who was asked to report otoscopic findings, diagnosis, and treatment on an AOM registration form.
Incomplete outcome data (attrition bias) All outcomes	Low risk	In total, 6 of the 74 children (8.1%) did not complete the follow‐up period specified in the protocol (equally distributed across groups). Reasons for withdrawal are described in the Results section of the article.
Selective reporting (reporting bias)	Unclear risk	No study protocol available.
Other bias	Low risk	No other sources of bias identified.