III.QUANTAL DOSE-RESPONSE CURVES The quantal dose-response relation describes the percentage of the population of subjects (experimental animals or patients) that show a prede?ned response as the dose or concentration of drug is incrementally increased (Figure 5, ?Therapeutic? curve). The response criterion may be a yes/no response (eg, occurrence of sepsis, death, etc.) or it may be some pre-selected magnitude of change in a continuous variable (eg, a 10 mm drop in systolic blood pressure). This dose-response relation is most useful for describing the spread of sensitivity to the drug within the population, ie, a ?at curve denotes a broad range of sensitivity, a steep one denotes a very narrow range. This approach can also be used to investigate the spread of sensitivities to both therapeutic responses and toxic effects. The dose of drug that causes a de?ned therapeutic response in 50% of subjects is de?ned as the ED50. The dose that causes a de?ned toxic effect (eg, headache, bleeding, nausea) in 50% of subjects is de?ned as the TD50 and the dose that causes death in 50% of subjects (usually laboratory animals) is the LD50. Traditional measures of ?safety? have been extracted from these types of studies. The ?therapeutic index? is de?ned as the ratio of the TD50 to the ED50; a drug with a large therapeutic index is generally safer than one with a small therapeutic index. In Figure 5, the therapeutic index for the toxic and therapeutic responses that were studied is 10.