certain safety factor
The therapeutic index, based on two midpoints, can flatter a drug whose curves overlap at the edges. The certain safety factor closes that loophole by comparing the extremes: it asks how the dose that begins to kill just a few relates to the dose that already helps almost everyone.
It is defined as LD1 divided by ED99 — the dose lethal to 1 percent of the population over the dose effective in 99 percent. A certain safety factor greater than 1 means there is real daylight between a dose that works for nearly everybody and a dose that starts killing the most susceptible; a value at or below 1 means those two doses overlap, a serious warning even if the conventional therapeutic index looks reassuring.
Because it uses the tails of the curves rather than their centres, the certain safety factor accounts for curve slope and is a stricter, more conservative safety measure than the therapeutic index. It is most informative when the effective and toxic dose–response curves are not parallel, the very situation where the simple midpoint ratio can mislead.
Same drug, different verdict: a drug can have a comfortable therapeutic index of, say, 10 yet a certain safety factor below 1 if its toxic and effective curves are steep and overlapping at their tails.