Tuesday, October 6, 2009

Vaccines: Safety and Efficacy Evaluation

There are only two questions you need to ask about any drug or vaccine.  Does it work?  Is it safe?

Efficacy is commonly measured by a rise in antibody titer.  However, the antibody being measured has not always been a good surrogate for level of protection.  What one really needs to do is measure the number of cases prevented by vaccination in order to determine true effectiveness of a vaccine.  That has not been done so far for swine flu vaccines.  Often, true effectiveness (as measured by cases of illness prevented) has been found to be less than titers had suggested.

Safety is determined many ways, but in terms of the data needed to license a vaccine, recipients are often followed for 30 days after being vaccinated.  When anthrax vaccine was licensed in 1970, the pivotal clinical trial evaluated subjects for adverse events for only 48 hours following vaccination.  A key piece of information (when evaluating safety testing) is how completely vaccine recipients were followed, which has varied greatly.

How good is the manufacturing process?  How many deviations from the regulations were found during inspections?  Is the vaccine produced identical from all vaccine lots?

GSK has announced it now has orders for swine flu vaccine from many countries, worth about 3.2 billion dollars.  According to the Guardian:
GSK has received 22 government contracts since the summer, with a total of 440m doses ordered. The company makes the vaccine in Dresden and Quebec but the demand is so great – about 60% higher than for usual seasonal vaccines – that it is also outsourcing production to third-party manufacturers.
Outsourcing production brings up new questions about safety and efficacy.  Is vaccine from company A the same as from Company B, when produced on different equipment by different  personnel?  In the US, vaccine from a new production plant would have to be tested again before being approved for use, since historically it has not been identical when produced in a different factory.

Dan Rather raised this question about the 1976 swine flu vaccine when he interviewed then-CDC director Dr. David Sencer on camera:  was the 1976 vaccine that was tested the only one used, or was another used?  Dan Rather claimed another was used.

Does this matter?  We won't know until many millions have been vaccinated and months or years have gone by.

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