Typically, the safe doses of drugs are determined in phase I clinical trials. Human test subjects are given does of the drug at values very well below the LD50 determined in animal studies and monitored for side effects. Doses are then increased until reaching the levels thought to be required for therapeutic efficacy. Obviously, these human studies stop well short of determining lethal doses, but there is some threshold at which the severity of the side effects are judged to be unsafe. However, this threshold would be different for different types of drugs (e.g. a blood pressure medicine taken every day vs a chemotherapy agent).