cb Bardage 2011.

Methods	Large, prospective, cohort study assessing the possible association between monovalent, pandemic, H1N1 flu vaccine Pandemrix (GSK) and neurological and/or autoimmune disease
Participants	The study population comprised 1,945,024 people and corresponds to all people registered in Stockholm County on 1 October 2009 who had lived in the region since 1 January 1998.
Interventions	Monovalent A (H1N1) pandemic vaccine Pandemrix (GlaxoSmithKline, Middlesex, UK) containing adjuvants AS03 and squalene. H1N1 vaccination campaign was initially targeted at healthcare workers and groups considered to be at high risk of complications from influenza (children with multifunctional disorders; pregnant women; people with chronic heart or lung disease, diabetes mellitus, chronic liver failure, chronic renal failure, or immunosuppression; people with body mass index > 40; people with neuromuscular disease affecting breathing capacity). For the campaign an apposite register was established (Vaccinera) in which information on the dates of a first and second dose of vaccine, batch number, medical contraindications against vaccination, and chronic conditions defining high‐risk patients were recorded. The vaccination campaign began on 13 October 2009 with 2 phases. During the first 6 weeks (from 13 October through November 2009), participants with a high‐risk condition were preferentially vaccinated; the vaccination was then offered to the remainder of the population during the second phase (from December 2009 onwards). In total, 1,024,019 participants received at least 1 vaccine dose (446,770 during phase I, 577,249 during phase II).
Outcomes	Data on vaccination (Vaccinera database) were linked to data on utilisation of inpatient and specialist health care (admissions to hospital and visits to specialist care in the county, dates, diagnoses, responsible medical departments, and length of hospital stay) contained in the common healthcare registers for Stockholm County Council (GVR) from 1 January 1998 to 31 August 2010. Neurological and autoimmune diagnoses to consider for follow‐up were selected based on indication of the European Medicines Agency and defined by the ICD‐10 classification for hospital admissions and visits to specialist care: Guillain‐Barré syndrome: G61 Multiple sclerosis (demyelinating disease): G35 (G36.0 + G37.9) Bell's paralysis: G51 Narcolepsy: G47.4 Polyneuropathy, unspecified: G62.9 An/hypoaesthesia: R20.0 + R20.1 Paraesthesia: R20.2 Rheumatological disease: M05‐M06 + M08 Inflammatory bowel disease (Crohn's disease and ulcerative colitis): K50‐K51 Insulin‐dependent diabetes among individuals born in 1990 and later: E10 Entering diagnoses into the county healthcare database is part of the doctor’s routine diagnostic work and therefore depends on patients seeking health care. An active search for adverse events during the study period was not performed. For each investigated pathology, the prevalent diagnoses were considered (i.e. those registered between 1 January 1998 and 30 September 2009) and the incident diagnoses (i.e. those during or after the pandemic period for unvaccinated people and after a first vaccination for vaccinated people between 1 October 2009 and 31 August 2010). Since risk groups were prioritised for vaccination, risk estimates analysis data were stratified for the first and second phase of the vaccination campaign (the cut‐off point was 45 days from 1 October 2009), considering vaccination as a time‐varying covariate and also time since first vaccination (6 weeks).
Notes	Preliminary assessment (prevalence in vaccination phase I and II): All but 1 (narcolepsy) of the investigated neurological and autoimmune disorders were significantly more prevalent in those vaccinated in the early phase of the campaign (first 45 days) than in the unvaccinated cohort. Comparing those vaccinated in the late phase (> 45 days) with the unvaccinated cohort, the prevalence of the investigated diseases was not statistically relevant, except for inflammatory bowel disease (prevalence OR 1.17, 95% CI 1.12 to 1.22), Guillain‐Barré syndrome (OR 0.79, 95% CI 0.67 to 0.95), and type 1 diabetes (OR 0.77, 95% CI 0.64 to 0.92, for those born in 1990 and later). Government funded
Risk of bias
Bias	Authors' judgement	Support for judgement
PCS/RCS ‐ selection exposed cohort All outcomes	Low risk	Selected group of users
PCS/RCS ‐ selection non‐exposed cohort All outcomes	Unclear risk	Drawn from the same community as the exposed cohort
PCS/RCS ‐ comparability All outcomes	High risk	Not assessed
PCS/RCS ‐ assessment of outcome All outcomes	Low risk	Record linkage
Summary assessment	High risk	“The study is a retrospective datalinkage cohort study, with unclear data quality”