the Delphi process in this context (pages 164-169). Two points raised by Morgan and Henrion (1990) merit consideration by NIH and its consultants: 1) elicited scientific judgment is not a substitute for proper scientific research; and 2) strict quality control of the process is needed.
Appendix Table 1.A of the report provides a summary of a small portion of the human and animal literature. However, the author does not distinguish clinical data from opinions or simulation results (judgments at best) in this table. For example, no inhaled doses are known for any human inhalation anthrax cases to date, yet three papers are cited for opinions or judgments about possible human infective doses. The most relevant studies for risk assessment in nonhuman primates and rabbits (recent USAMRIID) are not included in the table. Further, only four studies, two each from human and non-human primates, were included in Table 1.A for Franscisella tularensis rather than citing the extensive knowledge base for tularemia dose-response relationships for human and non-human primates (8 human infectivity studies; 11 nonhuman studies for dose-dependencies, including asymptomatic, mild, moderate, severe, and fatal tularemia). The report does not cite historical and recent evidence for laboratory-associated tularemia infections or natural outbreaks of pulmonary tularemia that merit consideration for risk assessment.
The value of the elicited results for predicting human effects is highly uncertain. The metric for eliciting human infectious doses for aerosolized particles including pathogens appears purely hypothetical, and not based on valid scientific studies that measured this parameter. A recent illustrative study with norovirus reported an average number of virions per particle of nearly 400 (Teunis et al., 2009), but the nature and impact of clumping on variability and uncertainty in dose-response relationships was not addressed in the Delphi process. Further, the value of eliciting human infectivity for airborne infectious particles is questionable for pathogens with arthropod vectors as the predominant route of infection. Similarly, the elicited parameter for potentially more vulnerable populations appears purely hypothetical rather than arising from a valid scientific study that corrects for dose.
The phrasing of the elicited parameter (median increase in vulnerability of 5 human groups (young [undefined], older [undefined], diabetes, HIV, pregnancy) that might be more susceptible, in general, to infections of unspecified bacteria and unspecified viruses) is too vague to merit inclusion in the analysis for these 13 biothreat agents. Existing scientific data for normal and more susceptible animals are inconsistent with the magnitude of susceptibility elicited by the expert panel. The maximum elicited parameter for increased vulnerability (30 percent) is dwarfed by actual variability in ID50 measured in murine populations, which shifted 5 orders of magnitude for salmonellosis infection (Bohnhoff et al., 1964). Thus, it appears that the modified Delphi process elicited “opinions” that are quite hypothetical, rather than judgments based on data. It is unclear how the experts, individually and collectively, used the background information provided, or expanded the body of evidence to form opinions about human infectivity and other unknown parameters in the process.
It is also unclear how the panel used the background information that included multiple host species and multiple routes of infection, including arthropod-borne vectors. The data on Rift Valley Fever (Table 1.A of the report) lists two experiments involving inoculation in rhesus monkeys and in rats. It states that some rats become infected asymptomatically. This disease may be spread by insects such as mosquitoes, as well as by direct contact, but precise data are scarce. How did the experts on the panel use the available data? How was a dose-response for aerosol exposure for droplets containing RVF virus particles developed? How did the experts extrapolate from data in monkeys and rats to the probability of infection in a human? What assumptions