Drug development follows a structured sequence from laboratory research to general clinical use. Preclinical testing involves laboratory and animal studies to evaluate basic pharmacology and toxicology. Phase I clinical trials test safety, pharmacokinetics, and dosing in a small group of 20 to 100 healthy volunteers, identifying adverse effects and the maximum tolerated dose, with roughly 70 percent of drugs passing this stage. Phase II trials enroll 100 to 300 patients with the target disease to assess efficacy and further evaluate safety, while Phase III trials are large-scale studies in 1000 to 3000 or more patients, usually randomized, controlled, and often double-blind, comparing the new drug to standard treatment or placebo and generating the data on which FDA approval is based; about 25 to 30 percent of drugs pass Phase III. After approval, Phase IV post-marketing surveillance monitors the drug in the general population, detects rare adverse effects not seen in earlier trials, evaluates long-term outcomes, and can lead to black box warnings, restrictions, or in rare cases withdrawal from the market. Clinical trials also rely on the placebo effect, a beneficial response to an inert treatment produced by the patient's belief in its efficacy and accompanied by real physiological changes such as endorphin and dopamine release, which is why placebo controls are essential for distinguishing true drug effects.
Drugs are regulated according to their risk and abuse potential. Over-the-counter drugs can be purchased without a prescription and are considered safe for self-treatment at recommended doses, while prescription drugs require authorization from a healthcare provider because of greater risks, the need for monitoring, or potential for abuse. Controlled substances are drugs regulated by the government because of their potential for abuse and dependence; in the United States the Drug Enforcement Administration classifies them into five schedules, with Schedule I containing drugs of the highest abuse potential and no accepted medical use such as heroin and LSD, Schedule II containing drugs with high abuse potential such as opioids and amphetamines, and Schedules III through V containing substances with progressively lower abuse potential. A generic drug contains the same active ingredient in the same dose, route, and dosage form as the brand-name product and must demonstrate bioequivalence, meaning that its rate and extent of absorption fall within 80 to 125 percent of the brand product, so generics can usually be substituted while producing comparable clinical effects at substantially lower cost, typically 80 to 85 percent less, and they become available after the brand's patent, usually lasting about 20 years, expires.
The dosage form in which a drug is delivered affects its onset, duration, bioavailability, and patient adherence. Tablets are compressed powders that can be scored, split, or coated, while capsules contain powder or liquid in a gelatin shell, dissolve more rapidly, and may be easier to swallow. Enteric-coated tablets have a coating that resists acidic gastric pH and dissolves only in the alkaline environment of the small intestine, protecting acid-labile drugs such as omeprazole from destruction and protecting the stomach from irritant drugs such as aspirin. Sustained-release or extended-release formulations, often labeled SR, XR, or ER, release the drug slowly over an extended period to reduce dosing frequency and maintain stable blood levels, and they must never be crushed or chewed because disrupting the formulation can release the entire dose at once in a phenomenon called dose dumping. Other dosage forms include solutions, suspensions, injections, suppositories, transdermal patches, inhalers, creams and ointments, eye and ear drops, sublingual tablets, and lozenges, each suited to particular clinical situations and patient needs.