Phases of Clinical Research

Clinical Trial is performed in four phase for step wise evolution. The new phase of commenced only after getting satisfactory and good result from previous phases. The clinical studies started only on the satisfactory base of preclinical studies.

Phase 0

Phase 0 is a recent designation for exploratory, first-in-human trials conducted in accordance with the U.S. Food and Drug Administration’s (FDA) 2006 Guidance on Exploratory Investigational New Drug (IND) Studies.

Phase 0 (micro dose study)is included to speed up the drug development process of promising drugs or imaging agents by establishing very early on whether the drug or agent behaves in human subjects as was anticipated from preclinical studies. Micro dosing studies permit collection of human pharmacokinetic (PK) and bioavailability data earlier in the drug development process. This human data is combined with preclinical data to select the best candidates to advance to further, more expensive and extensive clinical development.

Subject number is small (10 to 15) to gather preliminary data. Microdosing uses accelerator mass spectroscopy (AMS) to count radioactive carbon atoms (¹⁴C) in blood, urine and or faecal samples from volunteers who have taken radiolabelled doses of test compounds.

A micro dose is defined as less than 1/100^th of the dose calculated to yield a pharmacological effect of a test substance and a maximum dose of <100>

Phase I

Phase I trials are the first stage of testing in human subjects. The study performed in small group (20-80) of Healthy Volunteer and usually done with non-therapeutic objectives. It evaluates safety profile, tolerability of dose range, pharmacokinetics, and pharmacodynamics of a drug. Phase I trials conducted in an inpatient under clinical supervision. The subject who receives the drug is usually observed until several half-lives of the drug have passed.

Phase I trial normally includes dose-ranging, also called dose escalation, studies so that the appropriate dose for therapeutic use can be found. The dose range will be decided the animal testing data. Phase I carried on the healthy volunteers or certain types of patients, e.g. patients with mild hypertension. Drugs with significant potential toxicity, e.g. cytotoxic drugs, are usually studied in patients.

Phase II

Once the initial safety of the study drug has been confirmed in Phase I trials, Phase II is initiated with primary objective to explore therapeutic efficacy in patients. Therefore phase II trials also called as Therapeutic Exploratory phase.

Phase II trials are performed on larger groups (20-300) and are designed to assess how well the drug works, as well as to continue Phase I safety assessments in a larger group of volunteers and patients.

Phase II studies are sometimes divided into Phase IIA and Phase IIB. Phase IIA is specifically designed to assess dosing requirements (how much drug should be given), whereas Phase IIB is specifically designed to study efficacy (how well the drug works at the prescribed dose(s)).

Phase III

Phase III studies have primary objective to confirm preliminary evidence which assessed in the Phase II studies. Phase III trials are randomized controlled multicenter trials on large patient pool (300–3,000 or more depending upon the disease/medical condition studied), and compared with current standard treatment. Phase III trials are the most expensive and time-consuming in drug development process.

These studies are intended to provide an adequate basis for marketing approval. Studies in Phase III may also further explore the dose-response relationship, to obtain additional safety data, or explore the drug's use in wider populations, in different stages of disease, or in combination with another drug. This trial allows patients to continue to receive possibly lifesaving drugs until the drug can be obtained by purchase. Other reasons for performing trials at this stage include attempts by the sponsor at "label expansion" (to show the drug works for additional types of patients/diseases beyond the original use for which the drug was approved for marketing), or to support marketing claims for the drug.

While not required in all studies, it is typically expected that there be at least two successful Phase III trials, demonstrating a drug's safety and efficacy, in order to obtain approval from the appropriate regulatory agencies (FDA (USA), TGA ( Australia ), EMEA (European Union), etc.).

Phase IV

Phase IV initiated after drug approval, which involves studies to go beyond the prior demonstration of the drug’s safety, efficacy and dose definition. Phase IV trials involve all studies or safety surveillance performed after drug approval and ongoing technical support for the approved indication of a drug after it receives permission to be sold. They are studies that were not considered necessary for approval but are often important for optimising the drug's use.

Phase IV studies may be required by regulatory authorities or may be undertaken by the sponsoring company for competitive (finding a new market for the drug) or other reasons (for example, the drug may not have been tested for interactions with other drugs, or on certain population groups such as pregnant women, who are unlikely to subject themselves to trials). The safety surveillance is designed to detect any rare or long-term adverse effects over a much larger patient population and longer time period than was possible during the Phase I-III clinical trials. Harmful effects discovered by Phase IV trials may result in a drug being no longer sold, or restricted to certain uses.