clinical pharmacology
Drug Efficacy and Safety
Balancing Drug Benefits and Adverse Effects
Whether a drug is indicated depends on the balance of its benefits and harms. In making such judgments, clinicians often consider factors that are somewhat subjective, such as personal experience, anecdotes, peer practices, and expert opinions. Thenumber needed to treat (NNT)is a less subjective accounting of the likely benefits of a drug (or any other intervention). NNT is the number of patients who need to be treated for one patient to benefit. For example, consider a drug that decreases mortality of a certain disease from 10% to 5%, an absolute risk reduction of 5% (1 in 20). That means that of 100 patients, 90 would live even without treatment, and thus would not benefit from the drug. Also, 5 of the 100 patients will die even though they take the drug and thus also do not benefit. Only 5 of the 100 patients (1 in 20) benefit from taking the drug; thus, 20 need to be treated for 1 to benefit, and the NNT is 20. NNT can be simply calculated as the inverse of the absolute risk reduction; if the absolute risk reduction is 5% (0.05), the NNT = 1/0.05 = 20. NNT can be calculated for adverse effects also, in which case it is sometimes called the number needed to harm (NNH). Importantly, NNT is based on changes inabsoluterisk; it cannot be calculated from changes inrelativerisk. Relative risk is the proportional difference between two risk levels. For example, a drug that decreases mortality from 10% to 5% decreases absolute mortality by 5% but decreases relative mortality by 50% (ie, a 5% death rate indicates 50% fewer deaths than a 10% death rate). Most often, benefits are reported in the literature as relative risk reductions because these make a drug look more effective than the absolute risk reductions (in the previous example, a 50% reduction in mortality sounds much better than a 5% reduction). In contrast, adverse effects are usually reported as absolute risk increases because they make a drug appear safer. For example, if a drug increases the incidence of bleeding from 0.1% to 1%, the increase is more likely to be reported as 0.9% than 1000%. Calculate the number needed to treat (NNT) based on absolute, rather than relative, changes in risks. When balancing NNT against NNH, it is important to weigh the magnitude of specific benefits and harms. For example, a drug that causes many more harms than benefits may be worth prescribing if those harms are minor (eg, reversible, mild) and the benefits are major (eg, preventing mortality or morbidity). In all cases, patient-oriented outcomes are best used. , reducing the incidence of hypersensitivity reactions and thus increasing NNH. Genetic variations in various drug-metabolizing enzymes help predict how patients respond to drugs (see Pharmacogenetics ) and also often affect the probability of benefit, harm, or both. 2), factors that are usually clinically inconsequential (eg, food-drug interactions, Drug Interactions , small errors in dosing) can have harmful clinical effects. For example, 