Prevnar IS Safe – Have a Look at the Studies!
In November of 2008, a report was published about a halted vaccine trial in India. Here is an excerpt which can be found on Livemint :
New Delhi: Patient trials of an advanced pneumonia vaccine by the domestic unit of US drug giant Wyeth Inc. have been suspended by India’s drug quality regulator after the death of an infant on whom the vaccine was tested in a trial in Bangalore.
The child had a pre-existing cardiac disorder. Indian drug rules prohibit testing on human subjects with such conditions without the prior approval of the drugs controller general of India (DCGI), the drugs quality regulator.
Indian authorities said that the trial was stopped because:
“The baby was suffering from a cardiac abnormality and should not have been included in the trial at all. It seems that the ‘inclusion-exclusion’ criteria protocol has not been adhered to by the investigator,” said Surinder Singh, drugs controller general. “We have suspended all further trials across the country.”
Inclusion-exclusion criteria exist for two reasons: to protect the participants in the study and to avoid skewing the results of the study. The testers were careless and a baby died; the testers were careless and the results of a study are now questionable. But was there already a problem built into the basic structure of the trial?
Wyeth, the pharmaceutical company which is testing the safety, tolerability and immunogenicity of their advanced pneumonia vaccine, pointed out that the baby who died was in the placebo arm of the study. What was being used as a “placebo”?
Wyeth said the child who died had been administered Prevnar and not the new 13-strain variant.
“The event occurred in the control group, which used the current worldwide standard vaccine for prevention of pneumococcal disease and which has been administered safely more than 200 million times worldwide during the past seven years,” a company spokesperson said in an email. The test was comparing efficacy of Prevnar and the new variant.
Regular readers of Inside Vaccines will know that using a different vaccine as the “placebo” in vaccine safety and effectiveness trials is standard. It is of particular interest to note that the upcoming PCV13 is being compared to the current 7 valent version, Prevnar. This is the standard method in the U.S. right now as you can see here.
Prevnar (PCV7) was recommended by the CDC in the US in October of 2000.
In the Morbidity and Mortality Weekly Report where the recommendation appeared, the Advisory Committee on Immunization Practices (ACIP) explains how the vaccine was deemed safe (see page 23 of the PDF) here:
Safety of Administration of PCV7 Series Among Infants
Rates and types of adverse events associated with PCV7 administered at ages 2, 4, 6, and 12–15 months are acceptable when compared with the demonstrated benefits of vaccination. In the Northern California Kaiser Permanente efficacy trial, rates of adverse events were compared between children who received PCV7 and those who received the control vaccine (investigational group C meningococcal conjugate). Routine childhood vaccines were administered concurrently with PCV7 and control vaccines.***** To assess vaccine safety, information regarding local and systemic reactions was collected at 48–72 hours and 14 days after each dose. Using telephone interviews, investigators collected adverse-event histories for two subsets of the study population — initially a group receiving DTwP (N = 6,000) and later a group receiving diphtheria toxoid-tetanus toxoid acellular pertussis (DTaP) vaccine (N = 1,500). Frequency of uncommon events requiring medical attention after vaccination was evaluated for the entire study cohort and included emergency room and outpatient clinic visits occurring <30 days and hospitalizations occurring <60 days after receiving the study vaccines.
The full text of the study can be found here. (1)
The FDA licensing papers, here, include a few very small trials where Prevnar was compared to DTaP or to Hib. One of the studies had 80 infants in the Hib group.
On page 26 the FDA states:
The bulk of the safety data regarding local and systemic reactions and other adverse events comes from the NCKP Efficacy study.
Most of the safety data on Prevnar is based on a study comparing one new vaccine, Prevnar with an experimental vaccine, “investigational group C meningococcal conjugate”. What is wrong with this picture?
The Helsinki Declaration states:
32. The benefits, risks, burdens and effectiveness of a new intervention must be tested against those of the best current proven intervention, except in the following circumstances:
* The use of placebo, or no treatment, is acceptable in studies where no current proven intervention exists; or
* Where for compelling and scientifically sound methodological reasons the use of placebo is necessary to determine the efficacy or safety of an intervention and the patients who receive placebo or no treatment will not be subject to any risk of serious or irreversible harm. Extreme care must be taken to avoid abuse of this option.
How could an investigational vaccine be the best current PROVEN intervention? If there was no proven intervention, then why not use a real placebo?
Are the safety studies discussed above what Paul Offit was describing when he said (referring to people like the readers and writers of this blog):
“If they were willing to look at all the studies that were done with vaccines, they would find that they are, I think without question, the safest, best-tested thing we put into our bodies.”
(1) STEVEN BLACK, MD, HENRY SHINEFIELD, MD, BRUCE FIREMAN, MA, EDWIN LEWIS, MPH, PAULA RAY, MPH, JOHN R. HANSEN, BA, LAURA ELVIN, KATHY M. ENSOR, RN, JILL HACKELL, MD, GEORGE SIBER, MD,
FRANK MALINOSKI, MD, PHD, DACE MADORE, PHD, IH CHANG, PHD, ROBERT KOHBERGER, PHD, WENDY WATSON, MD, ROBERT AUSTRIAN, MD, KATHY EDWARDS, MD AND THE NORTHERN CALIFORNIA
KAISER PERMANENTE VACCINE STUDY CENTER GROUP. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Pediatr Infect Dis J, 2000;19:187–95 Vol. 19, No. 3.