Intended for healthcare professionals


Modernising vaccine surveillance systems to improve detection of rare or poorly defined adverse events

BMJ 2019; 365 doi: (Published 31 May 2019) Cite this as: BMJ 2019;365:l2268

Wrong About Post-Marketing Surveillance of Vaccine Adverse Events. Response to Jacob Puliyel, John Stone, Allan Cunningham, etc.

Puliyel (2019) writes: “In the new causality assessment, only reactions that have previously been acknowledged in epidemiological studies to be caused by the vaccine, are classified as a vaccine-product–related-reactions. Reactions observed for the first time during post-marketing surveillance (Phase 4 clinical trial) are not considered as consistent with causal association with vaccine’. All new serious adverse reactions are labelled as coincidental events inconsistent with causal association,’ or ‘unclassifiable’ and the association with vaccine is not acknowledged.

According to the WHO manual (2013) referred to by Puliyel: “The selection of cases for causality assessment should focus on:

“Serious AEFI1 that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect;
The occurrence of events above the expected rate or of unusual severity;
Signals generated as a result of individual or clustered cases as these could
signify a potential for large public health impact.

WHO recommends that other AEFI should also be assessed if the reviewing team or review committee decides that causality needs to be determined as a special case or in order to conduct special studies. Such AEFI could include:
AEFI that may have been caused by immunization error (e.g. bacterial abscess, severe local reaction, high fever or sepsis, BCG lymphadenitis, toxic shock syndrome);
Significant events of unexplained cause occurring up to 30 days after a vaccination (and that are not listed on the product label);
Events causing significant parental or community concern (e.g. hypotonic hyporesponsive episode (HHE), febrile seizures).”

I strongly recommend reading either of the WHO manuals (2013;2018). It will be obvious that Puliyel’s claims that post-marketing surveillance doesn’t take new serious adverse reactions seriously is just plain WRONG.

Stone (2019) writes: “It might be interesting to contrast the US's Vaccine Adverse Event Research System which has over the same period accumulated 717,653 reports [2] (reports are not confirmed cases but neither actually are compensated cases, which are "no fault" awards). Moreover, this is a passive database and as Peter Doshi has observed "inaccessible to most users”.

Cunningham (2019b) writes: “I recently did a VAERS search for "acute flaccid myelitis" (AFM). Their database includes just 4 case reports of AFM since August 2014. The number of cases of acute flaccid myelitis confirmed by the CDC during the same period is 567. This is one more example of the vast underreporting of potential adverse effects following vaccination.”

I went to the Vaccine Adverse Event Reporting System (VAERS) website (CDC. About; see also: VAERS, 2017), then their Request page. First, scroll through the Symptoms list, quite extensive. However, acute flaccid myelitis was not listed. So, I used several other search terms with the following results:

Myelitis = 256
Myelitis Transverse = 381
Paralysis Flaccid = 59

However, there is a gross misconception on how VAERS works and ignoring that it is just one of several surveillance systems. Briefly, VAERS is an underreported system, though studies have found that serious adverse reactions are reported at higher rates (e.g., Rosenthal, 1995). The CDC has teams who monitor VAERS. If there are even a small number of a serious adverse event reported, they investigate. “Although underreporting is a limitation, VAERS is capable of detecting possible safety problems through disproportionality analyses and other methods (Shimabukuro, 2015).” According to Moro: “Signal detection/hypothesis generation . . . Detect new, unusual, or rare adverse events (Moro, 2015, page 17).

The vast majority of the VAERS reports are for minor adverse events, short-lived fever, sore arm, etc (VAERS, 2017). The Vaccine Safety Datalink is a “real-time” link to several large HMOs with membership topping 2 million. Every vaccine, including lot number, child or adults age, gender, comorbidities, and medical problems following vaccinations are available. And there is another project, the Clinical Immunization Safety Assessment (CISA) Project (CDC, 2018).

So, while not super easy to use, VAERS is accessible and Cunningham’s finding of only 4 cases indicates a poor limited search strategy. The CDC uses a wide net of numerous sources, both passive and active. As an aside, Cunningham (2019a) claims vaccines responsible for a number of adverse reactions which I clearly refuted (Harrison, 2019 abcd).

Wendy Stephen (2019) and others criticize that clinical trials and post-marketing surveillance detected narcolepsy as an adverse event to the Pandemrix vaccine; yet, delayed informing the public, etc. This is a rather complicated topic, not as straight forward as Stephen and others would like, so, I will attempt to write a Rapid Response just focusing on this topic.


CDC. About The Vaccine Adverse Event Reporting System (VAERS). Available at:

CDC. Request page. [note need to click “I agree” on About page at bottom, then “I agree” a second time] Available at:

CDC (2018 Oct 19). Vaccine Safety Publications. [check out Vaccine Adverse Events System, Vaccine Safety Datalink, Clinical Immunization Safety Assessment (CISA) Project and CDC Vaccine Safety Publications by Year]. Available at:

Cunningham AS (2019a May 9). Unlimited tolerance of vaccines? BMJ Rapid Responses. Available at:

Cunningham AS (2019b Jun 8). Thank you BMJ! BMJ Rapid Responses. Available at:

Harrison JA (2019a May 9). Response to Allan S. Cunningham. BMJ Rapid Responses. Available at:

Harrison JA (2019b May 16). Response 2 to Allan S. Cunningham. BMJ Rapid Responses. Available at:

Harrison JA (2019c May 15). Response 3 to Allan S. Cunningham. BMJ Rapid Responses. Available at:

Harrison JA (2019d). Response 4 to Allan S. Cunningham. BMj Rapid Responses. Available at:

Moro PL (2015 Oct 15). Signal detection and signal strengthening in CDC’s vaccine safety monitoring systems. CDC Vaccine Safety/VAERS Webinar. Available at:

Puliyel J (2019 Jun 2). The New WHO Causality Assessment Algorithm Needs Revision to Restore Public Trust. BMJ Rapid Responses. Available at:

Rosenthal S, Chen R (1995 Dec). The Reporting Sensitivities of Two Passive Surveillance Systems for Vaccine Adverse Events. American Journal of Public Health; 85: 1706-1709. Available at:

Shimabukuro TT, Nguyen M, Martin D, DeStefano F (2015 Aug 26). Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS). Vaccine; 33(36): 4398-4405. Available at:

Stephen W (2019 May 31). Re: Checking social media for vaccination misinformation: five minutes with . . . Claire Milne. BMJ Rapid Responses. Available at:

Stone J (2019 Jun 23). Re: US data on vaccine injury pay-outs show strong immunisation safety record - is this a useful measure? BMJ Rapid Responses. Available at:

VAERS (2017 Oct). VAERS Data Use Guide. Available at:



Competing interests: No competing interests

01 July 2019
Joel A Harrison
Long-Retired Epidemiologist
I have NEVER worked for the FDA, NIH, CDC, any pharmaceutical company, nor ever purchased pharmaceutical stocks