bb Goodman 2006.

Methods	Industry‐funded case‐control study conducted among healthy children of both sexes who were part of an HMO (or group practice?), HPMG, in Minneapolis, USA. The study was conducted to assess the safety of split TIV in small children after the 2002 decision by ACIP to extend the immunisation to this age group, and study data span 2 "seasons": 2002 to 2003 and 2003 to 2004. There is no declaration of conflicts of interest of the authors. Cases Healthy children aged 6 to 23 for 1 or more days during the TIV administration period enrolled in HPMG for 1 day or more during the study period and had 1 or more diagnostic code for an HPMG clinic during the study period Controls Children with same eligibility criteria matched by birth date and gender
Participants	13,383 children of which 3697 received vaccination
Interventions	TIV or no vaccination. Ascertainment of exposure was carried out through HPMG registry but no description of content or lot is given, although the authors report that this information is available. For the effectiveness, 1‐liner with no description of community viral circulation is reported. The authors report that they carried out multivariate modelling to allow for the effects of co‐administration of other vaccines.
Outcomes	Effectiveness Influenza 1‐liner ‐ no case definition given, although it appears to be based on ICD‐9, which means ILI Safety The following outcomes were identified either by physicians combing the exposed population for possible outcomes of interest and then clustering the diagnosis by ICD categories and then using VSD categories. Purpura (window of observation ‐ days after immunisation 0 to 42) White blood cell disorders 0 to 42 Rheumatic diseases 0 to 42 Nephrotic syndromes 0 to 42 Alopecia 0 to 42 Urticaria 0 to 3 Muscle weakness 0 to 42 Myalgia 0 to 42 Neuralgia 0 to 42 Seizures 0 to 42 Polyarteritis 0 to 42 Myoglobinuria 0 to 42
Funding Source	Industry
Notes	The authors conclude that "We found no statistically significantly elevated hazard ratios for the first TIV dose. An elevated risk of pharyngitis was found for children receiving a second TIV dose. No elevated risk of seizure was found. CONCLUSION: These results, for a population of healthy children, showed no medically significant adverse events related to TIV among children 6 to 23 months of age". Definitions of cases and controls are not reported and were reconstructed by the extractor. More worrying is the fact that the text clearly states that the authors identified the cases by looking at outcomes AND exposure, almost certainly introducing bias in the evaluation and not carrying out blinded assessment of exposure. Numerators and denominators are not reported by case and control status but only HR by first or second TIV injection. Population was selected, and there are very few data to compare cases and controls. 1‐liner by‐the‐ by effectiveness assessment of vaccine. Multivariate modelling use is unclear. How can you adjust for the effects of many concurrent vaccines if you do not have a non‐exposed window and the safety outcomes are highly unspecific (e.g. urticaria)? High risk of bias
Risk of bias
Bias	Authors' judgement	Support for judgement
CC‐Case Selection	High risk	No description
CC‐Control Selection	High risk	Insufficient description
CC‐Comparability	Unclear risk	No description
CC‐Exposure	Low risk	Secure record
Summary assessments	High risk