Adverse Effects

Clinically related adverse effects are patient-oriented outcomes; examples involve the following:

• A loss of life
• Disability
• Discomfort

Surrogate adverse (e.g., altered serum marker concentrations) are often used, but, as with surrogate efficacy outcomes, they should ideally correlate with patient-oriented adverse effects. Clinical trials designed to demonstrate efficacy may still need help identifying adverse effects if the time required for an adverse effect to develop longer than required for an advantage to occur or if the adverse strength is rare. For example, cyclooxygenase-2 inhibitors relieve pain rapidly, and thus their efficacy can be shown in a comparatively short study. However, the growing incidence of myocardial infarction caused by some COX-2 inhibitors occurred over a long period and was not evident in the shorter and smaller trials. For this reason, because clinical trials may preclude certain subgroups and high-risk patients, adverse strength may only be fully known once a drug has been in widespread clinical use for years.

Many of the adverse effects of medications are dose-related.

 The Balance Between The Advantage And Adverse Effects Of Drugs

Whether a drug is indicated depends on the equivalence of its profit and harm. In such judgments, clinicians often consider somewhat subjective factors, such as personal experience, anecdotes, peer practices, and expert opinion.

The number needed to treat (NNT) is a less subjective measure of the potential benefits of a drug (or any other intervention). The NNT is the number of patients that are important to be treated for one patient to profit. For example, consider a drug that reduces mortality from a certain disease from 10% to 5%, an absolute danger reduction of 5% (1 in 20). That means that out of 100 patients, 90 would live even without treatment and, therefore, would not benefit from the drug.

The relative danger is the proportional difference between two levels of risk. For example, a drug that loses mortality from 10% to 5% reduces absolute mortality by 5% but decreases relative mortality by 50% (i.e., a 5% mortality rate indicates 50% fewer deaths than a 5% mortality rate). The mortality rate of 10%). Profits are often reported in the literature as relative danger reductions because these make a drug seem much more effective than absolute risk reductions (in the example above, a 50% reduction in mortality sounds much better). Then a reduction of 5%). Rather, adverse effects are generally reported as an increased risk because they make a drug appear safer. For example, if a drug gain the incidence of bleeding from 0,

When balancing NNT and NNH, weighing the magnitude of the specific benefits and harms is important. For example, a drug that causes much more harm than good may be worth a prescription if the harm is minor (e.g., reversible, mild) and the benefits are important (e.g., prevention of mortality or morbidity ). In all cases, it is better to use patient-oriented results.

Genetic profiling is increasingly used to identify subgroups of patients more susceptible to some drugs’ benefits and adverse effects.

Therapeutic

One of the goals of drug development is to have a large difference between the effective dose and the dose that cause adverse effects. A large difference is called a therapeutic index, therapeutic quotient, or wide therapeutic window. Suppose the therapeutic index is narrow (e.g., < 2). Usually, clinically insignificant factors (e.g., food-drug interactions, drug-drug interactions, small dosing errors) can have detrimental clinical effects. Insufficient anticoagulation grows the risk of complications from the anticoagulated disease (e.g., increased risk of stroke in atrial fibrillation), while excessive anticoagulation increases the risk of bleeding.