proaches and planned efforts for evaluation and safety studies related to smallpox vaccination. These issues may need to be addressed in order to have reliable findings from all the evaluation and research efforts. By listing these guiding principles, the committee is not saying that CDC is not already implementing such measures, but rather, that these principles should be considered for every evaluation or safety study undertaken by CDC to assess the smallpox vaccination program:

  • Small, unrepresentative samples should be kept to a minimum. Small samples sizes could detract from the generalizability of the study.

  • Sample sizes for many studies may be limiting for subgroup analyses. The majority of vaccinees in the first phase of the civilian program have been re-vaccinees. Considering the differential adverse reaction profile for primary vaccinees versus re-vaccinees, care should be taken to ensure that there are enough data on primary vaccinees.

  • Since the vaccination program is moving to a more heterogeneous pool of vaccinees, evaluation efforts should focus on gathering data from people with less health knowledge than those vaccinated in the first phase.

  • As with all studies, efforts should be taken to maximize participation rates in each study. Maximizing participation rates is not only important for generalizability, but also for the ability to validly compare rates (e.g., adverse event rates for the newer attenuated vaccines versus the old vaccines).

  • CDC has made a specific effort to gather information from hospitals on their participation in the first phase of the smallpox vaccination program. However, the issues that are relevant to hospitals often also are relevant to health care systems. A concomitant effort should be made to gather information from health care systems.

  • As has been noted in previous reports, the committee has stressed the importance of concurrent control groups for many of the studies. Control groups and cases should be studied using the same methods. The committee again encourages CDC to develop concurrent control groups for as many of their studies as possible, given the current realities of the pace of the smallpox vaccination program. The use of such control groups would greatly aid the investigations of the recently reported cases of cardiomyopathy (CDC, 2003n) and myo/pericarditis.

  • There is a general need for longer follow-up in some of the vaccinee studies. Particularly, there is a need to follow those who experienced serious adverse events in order to learn about long-term outcomes, especially for those who experienced cardiac adverse events. Right now, this involves a relatively small number of people, but the information gained from long-term follow-up will be extremely important. There also may be value in long-term follow-up of a sample of vaccinees who experienced no adverse

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