The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment.
[1] If the drug successfully passes through Phases I, II, and III, it will usually be approved by the national regulatory authority for use in the general population.
[1] Phase 0 is a designation for optional exploratory trials, originally introduced by the United States Food and Drug Administration's (FDA) 2006 Guidance on Exploratory Investigational New Drug (IND) Studies, but now generally adopted as standard practice.
[3][4] Phase 0 trials are also known as human microdosing studies and are designed to speed up the development of promising drugs or imaging agents by establishing very early on whether the drug or agent behaves in human subjects as was expected from preclinical studies.
[5] A Phase 0 study gives no data on safety or efficacy, being by definition a dose too low to cause any therapeutic effect.
They enable go/no-go decisions to be based on relevant human models instead of relying on sometimes inconsistent animal data.
These studies are usually conducted in tightly controlled clinics called Central Pharmacological Units, where participants receive 24-hour medical attention and oversight.
In addition to the previously mentioned unhealthy individuals, "patients who have typically already tried and failed to improve on the existing standard therapies"[13] may also participate in Phase I trials.
This particular design assumes that the maximally tolerated dose occurs when approximately one-third of the participants experience unacceptable toxicity.
There is no formal definition for these two sub-categories, but generally: Some Phase II trials are designed as case series, demonstrating a drug's safety and activity in a selected group of participants.
If the estimated activity level is less than 20%, the researcher chooses not to consider this drug further, at least not at that maximally tolerated dose.
Thus, a typical cancer phase II study might include fewer than 30 people to estimate the response rate.
"[18] While not required in all cases, it is typically expected that there be at least two successful Phase III trials, demonstrating a drug's safety and efficacy, to obtain approval from the appropriate regulatory agencies such as FDA (US), or the EMA (European Union).
Once a drug has proved satisfactory after Phase III trials, the trial results are usually combined into a large document containing a comprehensive description of the methods and results of human and animal studies, manufacturing procedures, formulation details, and shelf life.
While most pharmaceutical companies refrain from this practice, it is not abnormal to see many drugs undergoing Phase III clinical trials in the market.
[28] A 2010 review found about 50% of drug candidates either fail during the Phase III trial or are rejected by the national regulatory agency.
[30] The amount of money spent on Phase II or III trials depends on numerous factors, with therapeutic area being studied and types of clinical procedures as key drivers.
[1] Phase IV trials involve the safety surveillance (pharmacovigilance) and ongoing technical support of a drug after it receives regulatory approval to be sold.
[11][8] 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.
[8] Harmful effects discovered by Phase IV trials may result in a drug being withdrawn from the market or restricted to certain uses; examples include cerivastatin (brand names Baycol and Lipobay), troglitazone (Rezulin) and rofecoxib (Vioxx).
[citation needed] The entire process of developing a drug from preclinical research to marketing can take approximately 12 to 18 years and often costs well over $1 billion.