Post-Marketing Surveillance of Vaccines [Part 1 of 4]

Posted on April 12, 2008
Filed Under Continuing Education

Reprinted with Permission

Benefits and Risks of Immunization
Over ten million childhood vaccinations are given to children (birth through 5 years) annually, and many millions of doses are given to adults.  All medicinal products, including vaccines, have risks and benefits.  Vaccines protect many people from dangerous illnesses, but, like drugs, can cause side effects, a small percentage of which may be serious.  The benefit of vaccines is measured as prevented disease, and the risk of vaccination is measured as potential side effects; both are monitored as part of the US public health system. 

Pre-Licensure Evaluation of Vaccines
Licensure requires extensive clinical evaluation of the vaccine’s safety and effectiveness which is completed in stages over several years.  First, laboratory and animal studies are performed. Then candidate vaccines are tested in small groups of adult volunteers to establish first the safety, and then, the efficacy of the vaccine.  Finally larger-scale clinical trials, usually randomized and placebo-controlled, measure the rates of the more common adverse events and the protective efficacy of the vaccine.  The control groups in these clinical trials who do not receive vaccine are critical to distinguishing between vaccine-related events and an event unrelated to vaccine but occurring spontaneously in the study population.  Rates of the most common vaccine reactions, such as injection site reactions and fever, can be estimated before licensure, but the comparatively small number of patients enrolled in these trials  generally limits detection of rare events or events that occur after long-term exposure.  Even the largest pre-licensure trials (>10,000 persons) are inadequate to assess the vaccine’s potential to induce rare but serious side effects.  Consequently, it is essential to continue to collect information on vaccine-associated adverse events after licensure which may only occur after wide-scale use of the vaccine in the general population.

Post-Marketing Surveillance
Post-marketing surveillance is a necessary component of vaccine safety monitoring.  The manufacturers’ label/product information approved at licensure has the potential to be continuously updated as significant adverse event information which differs from what was originally known at the time of approval is compiled.  Due to the relatively small number of patients studied in pre-licensure studies, rarer side effects or events that may only occur in a sub-group of the population not significantly represented in pre-marketing studies (e.g., neonates and infants who receive hepatitis B vaccine, pregnant women, immunosuppressed patients), or side effects that occur only with chronic or
repeated exposure to a vaccine-induced antigen may not be revealed until the vaccine is licensed to the general public.

The objectives of post-marketing surveillance are to identify rare adverse reactions not detected during pre-licensure studies, monitor increases in known reactions, identify risk factors or pre-existing conditions that may promote reactions, and identify particular vaccine lots with unusually high rates or types of events.

Adapted from: Post-marketing surveillance for adverse events after vaccination: the national Vaccine Adverse Event Reporting System (VAERS), U.S. Food & Drug Administration.

Comments

2 Responses to “Post-Marketing Surveillance of Vaccines [Part 1 of 4]”

  1. Belemba on April 17th, 2008 5:02 am

    Despite widespread concerns that MMR immunisation causes autism, no study has ever looked at serological markers of brain damage following immunisation. Yet many such studies have been done with serological markers of brain damage in anaesthesia (eg after bypass) and delayed childbirth, motor accidents etc.

    One can only wonder why such simple studies have not been done which would only require small numbers. Small scale studies with such specific markers would be far more powerful than large scale community studies with fuzzy markers.

    One could test for markers of brain injury and also test for antibodies against brain proteins over 8 weeks post immunisation. The antibodies could look for eg anti-myelin basic protein which is frequently elevated in autism.

    Br J Anaesth. 2000 Mar;84(3):304-7.

    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10793601&dopt=Abstract
    Page 380 Table 3 gives a list of potential biochemical markers:
    Glia- S100, myelin basic protein (MBP), Glial fibrillary acidic protein (GFAP)
    Neurones- Neuron specific enolase (NSE), adenylate kinase (AK), CPK brain isoform (CPK-BB) Guanine nucleotide binding protein G0, calbidin-D. Lactate dehydrogenase (LDH), glutamate
    Inflammatory cells- IL-6m transforming growth factor-Beta, adhesion molecules (ICAM-1, E-selectin, neural cell adhesion molecule-NCAM)
    Metabolic- Lactate, Cu-Zn superoxide dismutase (CuZn-SOD).

    Now, you’re not really looking at oxidative stress so the 2 metabolic ones are no help.

    You are looking at autoimmune mechanisms, so you’re going to need to test for MBP, and later on antibodies to it, and probably also choose a very specific neuron marker, and perhaps antibodies to that. NSE sounds interesting. CK-BB - I don’t know if the assay is difficult in the presence of CK-MM from skeletal muscle. There are old papers on CK-BB in closed head injury in kids but I haven’t looked any of it up lately.

    The safety of MMR until these simple safety tests have been done.

  2. Bayrak on April 23rd, 2008 12:54 am

    do you know any information about this subject in other languages?

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