By Heather White
A new 8-paged study published by combined efforts from research the departments of Denmark, and Sweden is now circulating the Internet. This published peer-review was initiated based upon the descriptions of HPV vaccines associated with central nervous system diseases (Sutton et al., 2008; Chang et al., 2011; Wildemann et al., 2009; DiMario et al., 2010; Menge et al., 2012).
Scheller et al. (2015). Quadrivalent HPV vaccination and risk of multiple sclerosis and other demyelinating diseases of the central nervous system. JAMA. Retrieved fromhttp://jama.jamanetwork.com/article.aspx?articleID=2088853
Retrospective Cohort Study: The authors used data (ICD codes) from the Civil Registration System in Denmark and Statistics Sweden. The International Statistical Classification of Diseases (ICD) codes were calculated between October 2006, until December 2012. The vaccination status of these populations (Denmark & Sweden) was obtained using the Childhood Vaccination Database, National Prescription Registry, Svevac, and the Swedish Prescribed Drug Register. Hazards to appraise: selection, misclassification, or information bias. Temporal relationships are hard to evaluate, and the research is largely dependent on accurate record-keeping of others.
International Statistical Classification of Diseases
The study looked for 9 specific codes from the nationwide patient registers in two countries with the index event date defined as the date of diagnosis.
- Multiple Sclerosis (ICD-10 code G35)
- Optic Neuritis (ICD-10 code H46)
- Neuromyelitis Optica (ICD-10 code G360)
- Transverse Myelitis (ICD-10 codes G373)
- Acute Disseminated Encephalomyelitis (ICD-10 codes G040, G378)
- Other Central Demyelinating Diseases (ICD-10 codes G368, G369, G379)
9 ICD codes between October 2006, until December 2012. Girls, and women who did not have a diagnosis of MS or central demyelinating disease prior to vaccination. A 2-year (730 day) risk period following the last course of HPV vaccination (0, 2, 6 month doses). This risk period was set based upon a study assessing the hepatitis B vaccine and MS (Ascherio et al., 2001). The authors also base this on a study that showed that the diagnostic delay was estimated to be less then 1 year in more than 50% of cases occurring after 2000 (Marriee et al., 2005).
If vaccination doses (1 of 3) were closely spaced (within 7 days) in the Danish data the first recording was dropped. HPV vaccine prescriptions given withing 14 days prior to the vaccine date were disregarded in the Swedish cohorts. Individuals that only received one HPV vaccine, although the authors tried to counter that bias (discussed later).
- 4 alternative risk windows: 0-179, 180-364, 365-729, and more than 729 days after vaccination
- stratified age groups (10-29, 30-44 years)
- stratified country baseline incidence of demyelinating disease
- 2 additional analyses to address “if becoming a case contraindicates or delays vaccination in a significant number of participants”. A) excluded a 30-day prevaccination period, B) including only vaccinated cases
The confidence intervals (CI) set at 95% and the P-Value at < 0.05 is a very strong and valid statistical measure. They did have a control group, and this was a very large cohort. They did stratify the data based upon exposure times in the age of the cohorts etc.
3,983,824 girls and women made it through the inclusion criteria. 789,082 were vaccinated against HPV during the studies time-frame. A total of 1,927,581 vaccine doses; 670,687 ≥ 2 doses, and 467,812 received 3 doses.