her home several hundred miles away. After returning to the laboratory she became ill and once again traveled to her home by train where her mother, a physician, admitted her to a hospital and treated her. The student was asked if she worked with SARS/CoV (she said no because her research involved another virus). It was not until the mother became ill and died that SARS/CoV was identified. Other laboratory workers also became ill and other hospital personnel died. This case study illustrates several important points: people make mistakes (improper PPE); not everyone follows procedures (failure to test sample for inactivity); people may die if not properly diagnosed and treated.

Metrics

The committee believes that Tetra Tech should carefully consider what might be the appropriate metric(s) when evaluating the transmission of pathogens in heterogeneous human populations. The metric presented to the committee was the probability that a release would not lead to secondary transmission (probability of > 0 transmissions). This probability arises naturally and easily out of multiple stochastic simulations—and may be of interest to a policymaker concerned with the health and well being of the population as a whole—but it will be of no interest to those groups at particular risk of infection. Such at-risk groups will want to know what might happen to them should an introduction in fact lead to a secondary transmission.

SUMMARY

NIH and its contractors have not yet been responsive to the committee’s recommendation for tiered qualitative and quantitative analyses. The committee strongly recommended that qualitative analyses address the three questions raised in its 2008 letter report —What could go wrong? What are the probabilities? What are the consequences?—be prepared first for all 13 agents of concern using available data and case studies to scope or bound the problem broadly. The committee intended that this first tier of qualitative analyses would then be supplemented by second tier quantitative analysis for a subset of agents as necessary for decision making.

However, instead of beginning with a first tier qualitative analysis of both direct and indirect scientific evidence to bound the analysis for the 13 pathogens, a modified Delphi process was used to gather expert opinions on multiple unknown parameters. The results were then used as a substitute for data for all 13 agents. The median opinions for three infectious doses were fitted to empirical models intended to predict human infectivity for exposures generated by plume/puff models that also relied on opinions for influential parameters. Circumventing the absence of data with a Delphi process and then conducting modeling based on opinions was a tactical error. The committee considers the approach flawed in large measure because reliance on opinions for quantitative second tier modeling was unnecessary. In addition, the approach is problematic because the elicited opinions about possible parameter values, and the models fitted to them, may be incorrect and misleading without validation.

To expedite completion of a robust risk assessment, the committee strongly urges a mid-course correction to the use of tiered qualitative and quantitative analyses. The first tier should use narrative descriptions based on case studies and actual data reporting, with supporting scientific rationales provided for interpretation. Then, a more targeted second tier quantitative analysis should be developed where the existence of quantitative data allows. The quantitative analyses should reflect what is known from case studies and real world experience about transmission modes and other critical parameters.



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