phase studyPharmacology A series of clinical trials assessing the safety and efficacy of an 'investigational new drug'–IND being 'sponsored' by a drug company hoping to bring it to the marketplace. See Compassionate investigational new drug, IND, NDA, Premarket approval process, Treatment IND.
Phase I Early clinical stage Phase I studies are designed to examine the safety of a new medication and understand how it will work in humans by gathering extensive data on how it is absorbed, distributed, metabolized and eliminated from the human body; other data include assessment of how quickly therapeutic concentrations is achieved, how long the drug remains in the body, and what, if any, the effect drug metabolite by-products may have; with step-by-step increases in dose, the optimal dosage is determined where minimum side effects are coupled with maximum therapeutic effect, termed the toxic-therapeutic window; a trial to determine the best way to give a new treatment and what doses can be safely given; phase 1's involve 20-80 subjects and generate data on toxicity and maximum safe dose, to later allow a properly controlled trial; FDA's review at this point ensures that subjects are not exposed to unreasonable risks; phase I studies generally enroll only healthy persons to evaluate how a new drug behaves in humans, but may enroll Pts with the disease that the new drug seeks to treat; candidates are enrolled in a study only after a review of their Hx and physical confirms eligibility and informed consent for treatment is given; the number of Pts enrolled in a phase I trial will vary depending on the step-wise progression established for achieving optimal dosing as well as prior clinical experience with similar compounds and approaches; followup time periods may range from just a few days to 6+ months; further trials may continue only if phase 1 results indicate that the new therapy is reasonably safe in humans, and the FDA approves further work; the ultimate goal of phase 1 trials is to obtain sufficient information about the drug's pharmacokinetics and pharmacological effects to permit the design of well-controlled, sufficiently valid phase 2 studies; other examples of phase 1 studies include studies of drug metabolism, structure-activity relationships, and mechanisms of actions in humans, as well as studies in which investigational drugs are used as research tools to explore biological phenomena or disease processes Glossaries, nih.gov-6/99
Phase 2 Later clinical stage Phase 2 studies are designed to evaluate the short-term therapeutic effect of a new drug in Pts who suffer from the target disease, and confirm the safety established in phase I trials; phase 2 studies are sometimes placebo-controlled, often double-blinded, enroll a larger number of Pts than in phase 1 and Pt followup may be for longer periods; phase 2 studies are tailored to specific treatment indications for which the company plans to seek broader approval; where compelling scientific evidence is presented, the FDA expedites review of a company's application for market clearance; expedited review of phase 2 clinical data, and clearance of that early application, can obviate requirements for phase 3 trials; phase 2's involve several hundred Pts and generate enough data to.
1. at least suggest–if not prove that the drug actually works–efficacy and.
2. demonstrate the most common side effects Glossaries, nih.gov-6/99; phase 2 trials are sometimes divided into phase 2a pilot trials and phase 2b well-controlled trials
Phase 3 Final clinical stage Phase 3 trials are designed to demonstrate the potential advantages of the new therapy over other therapies already on the market; safety and efficacy of the new therapy are studied over a longer period of time and in many more Pts enrolled into the study with less restrictive eligibility criteria; phase 3 studies are intended to help scientists identify rarer side effects of treatment and prepare for a broader application of the product; phase 3 trials enroll 1,000-3,000 Pts to verify efficacy and monitor adverse reactions during longer-term use–sometimes divided into Phase 3a trials, conducted before regulatory submission and Phase 3b trials, conducted after regulatory submission, but before approval
Phase 4 Post-FDA approval/post-marketing Phase 4 studies involve many thousands of Pts and compare its efficacy with a gold standard; some agents have been withdrawn from the market because they increase the mortality rate in treated Pts; concurrent with marketing approval, FDA may seek agreement from the sponsor to conduct certain postmarketing–phase 4 studies to delineate additional information about the drug's risks, benefits, and optimal use, and could include, but would not be limited to, studying different doses or schedules of administration than were used in phase 2 studies, use of the drug in other Pt populations or other stages of the disease, or use of the drug over a longer period of time 21 CFR §312.85
Note: Occasionally, an agent's benefit is so obvious, eg zidovudine–AZT that the need for phase 3 studies, a stage immediately preceding an official NDA, may be obviated; NDA–new drug applications were often rejected because the data from the phase 2 and 3 trials revealed study design flaws, forcing the sponsor to repeat work, which has been largely eliminated by the '1987 rewrite' of the IND status