Paging Dr. Cheryl Wu, MD: Should I Space Out My Child’s Vaccines?

If there is one topic that is guaranteed to spark a lively debate , it’s the topic of vaccines.  As a mother I am definitely pro-vaccinations and know firsthand how incredibly dangerous it can be for other children when one child remains unvaccinated. But I do know that many smart moms disagree.  One compromise has been to space out the current vaccine schedule recommended by the American Academy of Pediatrics.  Is that really a safe alternative?  To find out, I asked Dr. Cheryl Wu, MD, of LaGuardia Place Pediatrics in the West Village to answer the question: should I space out my child’s vaccines?

Should I Space Out My Child’s Vaccines? 

One of the most frequent questions I get regarding vaccines is whether giving infants 6 vaccines all at once is too many. The vaccines in question are the Diphtheria-Tetanus-acellular-Pertussis (DTaP), Haemophilus influenzae type B (HiB), Pneumococcal, Poliovirus, Hepatitis B, and Rotavirus vaccines given at 2, 4, and 6 months of age, according to the childhood immunization schedule recommended by the American Academy of Pediatrics. Then as the infant turns one, the Measles-Mumps-Rubella (MMR) vaccine, Chicken pox vaccine (Varicella Zoster Virus – VZV), and Hepatitis A vaccine.

What a lot of parents are not aware of is the amount of research, the complexity of the vaccine approval process, and the extent of post-marketing surveillance that happen in between discovering a vaccine, and injecting it into their baby’s thighs. Even before a vaccine is marketed to the general public, a minimum of ten years’ of research has been undertaken. There is a large network of checks and balances at play in the approval and safety monitoring of vaccines. This network includes governmental agencies, vaccine manufacturers, and independent groups that constantly review emerging data on safety and adverse reactions. There are large panels of experts who are affiliated with many well-known universities and medical schools who meet on a regular basis to look at the studies and data on giving these vaccines together, and make recommendations accordingly. These people are the exact reasons pediatricians like myself can have the unfaltering confidence to tell parents, “Yes, your baby needs these vaccines; and no, 6 vaccines at once is not too many, and this schedule is perfectly safe.”

Basic Vaccine Research and Animal Trials

Vaccines are consisted of antigens, the distilled parts of a virus or bacteria that trigger a lasting immune response in the host. Typically, scientists with federal funds research natural or synthetic antigens for about 2-4 years; they investigate the efficacy of early vaccines in animal studies and make modifications that increase efficacy and/or decrease adverse reactions. At this point, a sponsor, usually a private company, will work with the scientist to write up a clinical protocol that describes how it will test this brand new vaccine in human subjects. It will submit an application to the Federal Drug Administration for studies on an Investigational New Drug (IND).  The IND application can be fifty to several hundred pages detailing how the vaccine will be manufactured, how it was tested for safety, the supporting laboratory documentation, and the clinical trial protocol itself. This protocol describes in detail how the studies will be carried out, how the subjects are selected, and how the company will provide ongoing safety monitoring.

Vaccine Clinical Trials, or Pre-Marketing Research

Once the FDA approves of the IND application, then 3 phases of clinical trials commensurate, and several departments come together to closely monitor the safety and efficacy of the product being tested. The 3 phases basically go from small human subjects groups (and yes, this involves babies! A search for infant vaccines at clinicaltrials.gov shows that infants as young as 45 days have been tested), to large groups of subjects that include tens of thousands of infants and children. During this time, the pharmaceutical companies have to report any significant adverse events.  If there is data that indicates any concern for vaccine safety, the FDA may require the company to halt the trials. When studies are conducted in large groups of people, rare side effects can be documented for full transparency. The FDA also publishes guidelines such as the Good Clinical Practice to ensure these trials fully meet ethical codes of study conduct. Clinical trials typically last between 8-10 years for vaccines.

FDA Vaccine Approval

If the last and final phase of clinical testing is successful – ie, the vaccine has been tested in tens of thousands of babies, a clear benefit has been proven (babies develop significant immunogenic response to the vaccine compared to the placebo group), and risks are clearly low in administering this vaccine to a large group of infants – then the pharmaceutical company submits a Biologics Licensure Application to the FDA. A multidisciplinary reviewer team at the FDA, which includes physicians, biostaticians, microbiologists, pharmacologists, and chemists, will examine the complete application for clear-cut benefits of the vaccine, as well as ensure a good safety profile. This committee then makes a determination to recommend or oppose the approval of this vaccine.

An advisory committee that is independent of the FDA, named the Vaccines and Related Biological Products Advisory Committee, consisting of experts and professors in medical universities across the nation, will review this application as well, and advises the FDA in the process of vaccine approval. The manufacturing facilities also have to pass a site inspection from the FDA to ensure safe handling and production of these vaccines.

Determining the Childhood Immunization Schedule

At this point, a vaccine has been approved by the FDA and deemed important for the health of an infant. The American Academy of Pediatrics, the CDC’s Advisory Committee on Immunization Practices (ACIP), and the American Academy of Family Physicians hold an annual meeting that examines the available studies in detail, the FDA application, as well as all information regarding the efficacy and side effects of the vaccines. This panel then makes the recommendation to incorporate vaccines into the schedule, which typically comes out January or February of every year.

Post-Marketing Vaccine Surveillance

After a vaccine is approved by the FDA for licensure, and after a vaccine is deemed safe by the AAP’s new schedule, and after it is marketed to the general public, many companies will run Phase 4 clinical trials, which gather data from the general population and physician offices. They will be able to tell whether there are truly rare side effects that can only be elicited when the vaccines have been used in hundreds of thousands of patients. The FDA will also continue to hold facility inspection as long as the company holds a license to market the vaccine. The CDC and FDA have also set up a Vaccine Adverse Event Report System (VAERS), a safety surveillance program that requires health practitioners and vaccine manufacturers to report any side effects of the vaccine. This program will aggregate all the data and look for any pattern in previously unidentified adverse events.

My Personal Experience

In my office, when parents ask me whether we space out vaccines, my answer is, No, we do not. We go by the AAP recommendation of childhood vaccine schedule. We simply do not have the data that backs up the “split” vaccination schedule as safe, but we have tons of data that say the recommended schedule is safe. We also have no data that indicates the current schedule does any harm to our children. In fact, we know that the longer a child is unvaccinated, the more likely she will be exposed to communicable diseases. Unvaccinated children are like islands in the sea of immunized children onto which diseases like measles and whooping cough can land.

A problem I often see with a split vaccine schedule is that it becomes quite confusing which vaccines a child has received. If a child is fully immunized, I know exactly what shots he has had based on his age. If a child is incompletely immunized, because of the specific booster vaccine schedule we have to follow, mistakes are very often made. For example, in the Hepatitis B series, the third dose has to be given 8 weeks after the second dose, but at least 16 weeks after the first dose; MMR and chicken pox, both live vaccines, can be given on the same day, but not within one month of each other; and depending on the age, the second dose of MMR is given at least one month after the first dose of MMR, but the second dose of chicken pox has to be given at least 3 months after the first shot – but none of which can be given within one month of each other. It’s very easy to see how even the most seasoned practitioners can become confused and make mistakes in a child who does not follow the standard vaccine schedule. Unfortunately, even with such well published “alternative” vaccine schedules (some have even made it into books), mistakes are still very often made. In the end, the person who suffers incomplete immunity and exposure to communicable diseases is the child.

My own son is five years old, and he cries and whines every time he has to come to my office for a shot, regardless of how many lollipops my staff offers him (he still tearfully accepts them, of course). But he knows the shots are good for him, and will keep him from getting sick. And as I tell all expectant parents who walk into my office: I will never recommend something for their children that I won’t do for my own son. I encourage all parents who have concerns or questions about vaccines, their schedule, the antigenicity, the adverse reactions, to discuss them with their doctor. It is an open conversation we should all have, and it is important to come to an agreement. Because at the end of the day, in order to have a successful pediatrician-child-parent relationship, we have to all be on the same page. And that page tells the story of a healthy and safe child, lollipops notwithstanding.

References

http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/OfficeofScienceandHealthCoordination/ucm2018191.htm

National Vaccine Advisory Committee. “United States Vaccine Research: A Delicate Fabric of Public and Private Collaboration.” Pediatrics, Vol 100(6), Dec.1997, pp. 1015-1020.

Parkman PD, Hardegree MC. “Regulation and Testing of Vaccines.” In Plotkin SA, Orenstein WA, [eds.]. Vaccines, 3d ed. Philadelphia: Saunders; 1999, pp.1131-1143.

Stehlin, Isadora. “How FDA Works to Ensure Vaccine Safety.” FDA Consumer Magazine, March 1996.

http://www.historyofvaccines.org/content/articles/vaccine-development-testing-and-regulation

http://www.niaid.nih.gov/volunteer/vrc/Pages/understanding.aspx

http://www.fda.gov/BiologicsBloodVaccines/DevelopmentApprovalProcess/BiologicsLicenseApplicationsBLAProcess/ucm133096.htm

http://clinicaltrials.gov/show/NCT00205803

http://pediatrics.aappublications.org/content/131/2/397.full.pdf+html

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6002a1.htm

http://www.iom.edu/~/media/Files/Report%20Files/2013/Childhood-Immunization-Schedule/ChildhoodImmunizationScheduleandSafety_RB.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148611/

http://vaers.hhs.gov/index/about/index

http://www.fda.gov/Drugs/ResourcesForYou/Consumers/ucm289601.htm

Tags: vaccines