Indian Pediatr 2016;53: 351 http://www.indianpediatrics.net/apr2016/351.pdf
Inappropriately Small Sample for Studying Adverse Events Following Immunization
*Kanika Goyal and Jacob Puliyel
Department of Pediatrics, St Stephens Hospital, Delhi, India.
We refer to the study of common illnesses before and after vaccination . The authors looked for symptoms like constipation, rash, wheeze, rhinitis and watering of eyes in 1602 children in the week after immunization, and found the frequency was same as in the week prior to immunization (except for fever). It was sought to imply that most adverse events following immunization (AEFI) are explained by the background rate. The study was seriously flawed as the sample size selected was inadequate. The authors noted that no child had hypotonic hyporesponsive episode (HHE), seizures, pruritus, difficulty in breathing or breath holding, either during the pre- or post- vaccination period, and these are the AEFI described by the Brighton Collaboration (with their specific case definitions) .
Incidence of these AEFI is rare. As per WHO surveillance data, HHE occurs less than 1/1000, seizures in less than 0.5/1000 and anaphylaxis and shock incidence in one per million doses . Thus, a sample size of 1602 is woefully inadequate to detect real AEFI. The authors have selected sample size so small that vaccine-related AEFI (other than fever) was unlikely to be picked up, and all they would see are routine symptoms unrelated to vaccination. With these figures, they concluded erroneously that AEFI can be explained or background rates.
In vaccine trials, randomized controls are used to look at the background rate. If there is a statistically significant increase in any adverse effect among the vaccinated, it is likely to be AEFI caused by the vaccine.
1. Kompithra RZ, Sarkar R, Mathew LG, Muliyil J, Kang G. Study of common illnesses before and after vaccination: A risk interval approach. Indian Pediatr. 2015;52:933-8.
2. Definition and Application of Terms for Vaccine Pharacovigilance, Report of CIOMS/WHO Working Group on Vaccine Pharmacovigilance, Geneva; WHO; 2011; Available from: http://www.who.int/vaccine_safety/initiative/tools/CIOMS_report_WG_vaccine.pdf Accessed January 12, 2016.
3. AEFI Guidelines – Ministry of Health and Family Welfare, Government of India, 2010. Available from: http://www.pbhealth.gov.in/Immunization/AEFI_Guidelines.pdf Accessed January 12, 2016.