Tuesday, September 8, 2009

Expert group recommendations: limitations of prediction based on insufficient data

If you convene an expert group to issue a set of recommendations, they will be issued.  What the groups' report may omit is an explanation of the sufficiency of the data.  Nor will their report provide an idea of how statistically likely the conclusions are to be right or wrong.  Historically, the experts usually issue the recommendations that the agency that convened them most wants to hear. 

Often, the experts may come from fields other than the one they are asked to examine.  And because the field of vaccine pharmacovigilance is only now being birthed, the science of vaccine safety offers little in the way of guidance.  Thus scientific analysis of vaccination risks and benefits may receive short shrift.

Let's look at some of the WHO Strategic Advisory Group of Experts on Immunization recommendations, released July 13:

 * All countries should immunize their health-care workers as a first priority to protect the essential health infrastructure. As vaccines available initially will not be sufficient, a step-wise approach to vaccinate particular groups may be considered. SAGE suggested the following groups for consideration, noting that countries need to determine their order of priority based on country-specific conditions: pregnant women; those aged above 6 months with one of several chronic medical conditions; healthy young adults of 15 to 49 years of age; healthy children; healthy adults of 50 to 64 years of age; and healthy adults of 65 years of age and above. [Currently, this list looks reasonable.  However, it should be made clear, as some UK advisories have done, that pregnant women should only be vaccinated when in the second or third trimester.  Update Sept. 10NIH knows better than to test the vaccine in the first trimester of pregnancy.  Under-5 children have had a low illness burden, at least in the US.--Nass]
    * Since new technologies are involved in the production of some pandemic vaccines, which have not yet been extensively evaluated for their safety in certain population groups, it is very important to implement post-marketing surveillance of the highest possible quality. In addition, rapid sharing of the results of immunogenicity and post-marketing safety and effectiveness studies among the international community will be essential for allowing countries to make necessary adjustments to their vaccination policies. [The experts credulously assume that postmarketing surveillance will suffice for the lack of premarketing safety assessment; yet this method is of little value for recipients given the vaccine simultaneously throughout the world, en masse.  Furthermore, postmarketing surveillance barely exists in much of the developing world.  Postmarketing surveillance was enhanced for the 1976 swine flu vaccine program, resulting in the program ending after only 10 weeks, which seems extremely efficient to me.  Yet 45 million Americans were vaccinated before the data were adequate to halt the program.  Enhanced surveillance is being initiated for Guillain Barre in the US now.--Nass]
    * In view of the anticipated limited vaccine availability at global level and the potential need to protect against "drifted" strains of virus, SAGE recommended that promoting production and use of vaccines such as those that are formulated with oil-in-water adjuvants and live attenuated influenza vaccines was important. [We have not seen significant drifted strains, and whether low-risk individuals even need vaccine is questionable.  Yet two untested methods of vaccination are espoused, justified by a false sense of the pandemic's severity and urgency.--Nass]

CDC's MMWR published "early release" H1N1 vaccine recommendations on August 21.   The MMWR lists ACIP's July 29, 2009 "Initial Target Groups" for vaccination, which comprise more than 50% of the US population, and are virtually identical to the WHO/SAGE targeted groups.  [Despite CDC data suggesting lower illness burden in infants, and Cochrane Collaboration data indicating lack of effectiveness of seasonal vaccination in this age group, children 6 months-4 years are a priority group for H1N1 vaccines.--Nass]  The document acknowledges that if oil-in-water emulsion adjuvants are used, they will require issuance of an Emergency Use Authorization.

The President's Council on Science and Technology projected a "worst case" but "plausible" scenario of up to 1.8 million hospitalizations, filling of more than half the nation's ICU beds and up to 90,000 US deaths.  The Council urged that vaccine production be accelerated.  Reportedly, the Council based its predictions on prior pandemics, particularly those of 1957 and 1968.  But since prior pandemics have had a wide range of behaviors, it is difficult to base predictions on them.  CDC spokespeople immediately played down these estimates.

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