The CDC's CISA Program - a Pediatrician's Experience

Even as a pediatrician and active vaccine advocate, the CDC's Clinical Immunization Safety Assessment (CISA) Project was an unfamiliar program to me.  I'm well aware of the CDC's Vaccine Adverse Event Reporting System (VAERS) - one of several programs that are integral to assuring the safety of vaccines in the US.  In over 20 years of private pediatric practice, I've made a handful of reports to VAERS:

(1)  Crying syndrome following DTaP - that child completed the rest of their vaccines except received DT instead of DTaP.

(2)  Non-febrile seizure in an adolescent after first dose of hepatitis B vaccine.  This child also finished all other vaccine series and was medically exempted from finishing the hep B series.  No sequelae.

(3)  ITP following MMR #1.  This child recovered fully.

(4)  Death within 3 weeks of 15 month vaccinations.  This child had an identified congenital syndrome and multiple medical problems with a known limited life span.  I don't believe this child's death was causally related to the vaccines given and neither does the mother.  Her brother has the same syndrome and is completely up to date on his immunizations.

I recently made another VAERS report that was a little more difficult for me to discern what my course of action should be in recommending further vaccination to this child.  The VAERS report I made (all information shared here is with the parent's permission):

[Fraternal] Twin A [37 weeks gestation] w h/o [history of]  IUGR [intrauterine growth retardation]  re-admitted to hospital on (3/13/18) for several days' history of poor feeding - found to have elevated transaminases, abdominal distention, severe ascites, respiratory distress.  Transferred to PICU at hospital where he was worked up including exam of CSF, ascites fluid, blood, urine - all negative. Clinical picture c/w [consistent with] DIC [disseminated intravascular coagulation] but no organism ever isolated. Genetics workup including microarray and WES [whole exome sequencing] is pending. Possible underlying metabolic disorder. Discharged home 4/3/18.

In addition to the VAERS report, I also emailed the CDC (NIPINFO@cdc.gov) and asked:

I filed a VAERS report online (temporary e-report #135834).  This 1 month old patient had an incredibly thorough workup at our Childrens' Hospital of a serious event (transaminitis, ascites, DIC) that occurred about a week after the birth dose of hepatitis B vaccine.  None of the testing thus far has been conclusive.  I need to know if this child should receive his next dose of hepatitis B vaccine in the next few weeks.  Thanks for any insight.

I received a reply the very next day which said that the CDC had run a comparison to hepatitis B vaccine reactions in the literature, package inserts, and VAERS.  No similar information was found in the literature or package inserts.  In VAERS, there were 55,000 reports of adverse events following hepatitis B since 1990 of which 14 reported DIC.  Of those 14 reports, only 2 had an unknown cause.  There were no reports of subsequent hepatitis B vaccination in those children.

To be clear, a VAERS report does NOT imply causality.  From the CDC VAERS site:

It was at this point that the CDC explained CISA to me:

CDC’s Immunization Safety Office sponsors the Clinical Immunization Safety Assessment (CISA) Project, which is a consortium of vaccine safety experts with expertise in infectious diseases, allergy/immunology, pediatrics, internal medicine, vaccine safety and multiple other specialties. In a CISA evaluation, vaccine safety experts from the CDC’s Immunization Safety Office and the CISA academic medical centers review complex vaccine safety cases from licensed US healthcare providers. This link provides additional information should you be interested in requesting a CISA consult:http://www.cdc.gov/vaccinesafety/activities/cisa/cisa-evaluation.html . There is no charge for this service. If you choose to have a CISA consultation, we will need to collect your patient’s pertinent medical and vaccine records (including genetic testing that was done).

The following week, I decided that I really did need some input on how to approach this child's vaccine recommendation so I contacted the CISA coordinator and received an immediate response inviting me on a call to go over the CISA consultation process.  From here forward, the process was an impressive experience for me.

I spent the next few weeks gathering medical records and results from my office, our local hospital, and our Children's Hospital and forwarding them to the lead center at Vanderbilt. I'm fortunate in that I had several contacts at the Children's Hospital who helped me gather lab results.  In the interim,  I did see this patient and his twin for a 2 month old exam and elected to vaccinate him with all of the recommended vaccines except hepatitis B. His twin received all recommended vaccines including hepatitis B.

On May 30th, 2018, this case was reviewed via tele-conference by the CISA Clinical Consultation Case Review Working Group, which included vaccine safety experts, as well as subject matters experts (SME) in neurology, infectious diseases, gastroenterology, and allergy/immunology.  There were additionally a couple of MDs from our local Childrens' Hospital as well as myself on the call.  There were 5 questions posed and addressed during the call which included a very thorough review of the case details and all lab results to date.  Relevant citations from the medical literature were also included.  There was intense discussion between all attendees and afterwards, a summary was generated and sent to all attendees for input with a final summary generated on June 26, 2018.

Several additional lab studies were recommended but the consensus of the Group was that a causal relationship between hepatitis B vaccine and this child's clinical course was inconsistent and the child should resume the recommended schedule.  This patient's parents were aware of the VAERS report that I had filed and the pending case review.  At this patient's 4 month checkup, I discussed the review process with the parents, the recommendations that had been made, and the parents elected to complete all of his vaccines that day.  He received all of the routinely recommended vaccines and had no further issues.

There are several take home points from this experience for me:

• The CDC is very interested and willing to assist providers in making clinical decisions regarding vaccinating any child and/or alterations in the recommendations should there be clinical concern to do so.
• I was extremely impressed with how easy, smooth, and thorough this process was and following the review, felt very confident in the combined experience and knowledge of this Group and the SMEs in making their recommendation.
• Serious adverse events following vaccination are very very rare.  In over 20 years of private pediatric practice covering 2 hospital nurseries and in-patient services in addition to an outpatient clinic, this was my first situation ever requiring a CISA evaluation.
• As many times as we hear about serious events that occur following vaccination and as often as we see anti-vaxxers assume causation based solely on correlation, this experience clearly demonstrates that correlation does not automatically imply causation.  Yes, things happen coincidentally to vaccination and it's not the vaccine's fault.