Rm. Jacobson et al., Adverse events and vaccination-the lack of power and predictability of infrequent events in pre-licensure study, VACCINE, 19(17-19), 2001, pp. 2428-2433
The recent setback in the development of a safe and effective rotavirus vac
cine illustrates an important problem regarding prelicensure testing and it
s ability to identify rare vaccine-related adverse effects. It is our conte
ntion that the possibility of a rare but serious vaccine adverse effect is
difficult to detect in prelicensure testing. In this paper, we review the h
istory regarding the testing and eventual studies that led to the permanent
withdrawal of that vaccine. The post-licensure discovery of a serious adve
rse event associated with the rotavirus vaccine is not unique among vaccine
s, but represents a recurrent phenomenon that in fact is mathematically pre
dictable. Prelicensure studies examine thousands of subjects and not hundre
ds of thousands. A sample size of 10,000 subjects may provide excellent est
imates of efficacy, but cannot provide an adequate denominator to rule out
rare adverse events. It lacks the power. Just as with the rotavirus vaccine
, only after hundreds of thousands of doses of vaccines are distributed. wi
ll such rare events appear often enough to permit detection. For that reaso
n, we must depend upon the modern post-licensure surveillance programs that
we already have in place. (C) 2001 Elsevier Science Ltd. All rights reserv
ed.