requires mitigation. While not as comprehensive as a risk management plan, a Risk Evaluation and Mitigation Strategy can require a sponsor to perform certain activities or to follow a protocol, referred to as Elements to Assure Safe Use, to assure that a positive risk-benefit profile for the drug is maintained for the circumstances under which the product is marketed. Risk/benefit profile of drugs Pharmaceutical companies are required by law in most countries to perform clinical trials, testing new drugs on people before they are made generally available. This occurs after a drug has been pre-screened for toxicity, sometimes using animals for testing. The manufacturers or their agents usually select a representative sample of patients for whom the drug is designed – at most a few thousand – along with a comparable control group. The control group may receive a placebo and/or another drug, often a so-called "gold standard" that is "best" drug marketed for the disease. The purpose of clinical trials is to determine: if a drug works and how well it works if it has any harmful effects, and if it does more good than harm, and how much more? If it has a potential for harm, how probable and how serious is the harm? Clinical trials do, in general, tell a good deal about how well a drug works. They provide information that should be reliable for larger populations with the same characteristics as the trial group – age, gender, state of health, ethnic origin, and so on though target clinical populations are typically very different from trial populations with respect to such characteristics. The variables in a clinical trial are specified and controlled, but a clinical trial can never tell you the whole story of the effects of a drug in all situations. In fact, nothing could tell you the whole story, but a clinical trial must tell you enough; "enough" being determined by legislation and by contemporary judgements about the acceptable balance of benefit and harm. Ultimately, when a drug is marketed it may be used in patient populations that were not studied during clinical trials (children, the elderly, pregnant women, patients with co-morbidities not found in the clinical trial population, etc.) and a different set of warnings, precautions or contraindications (where the drug should not be used at all) for the product's labeling may be necessary in order to maintain a positive risk/benefit profile in