Study designs Study Designs
Overview and terminology73,74
Clinical studies of treatments in humans are classified into phases 73,74
Phase I
Small number of healthy volunteers who are closely monitored in a clinical setting
Determines a safe dosage range and identifies any common side effects or readily apparent safety concerns
May also be used to develop pharmacokinetics (PK) and pharmacodynamics (PD), to assess the half-life of the drug, estimate the maximum tolerated dose (MTD), or evaluate the effects of multiple dose levels
Phase II
May be >100 subjects
Investigates preliminary evidence of efficacy and continues to monitor safety
May be the first time the agent is administered to patients with the disease of interest to answer questions such as: What is the correct dosage for efficacy and safety in the patient type? What is the probability a patient treated with the compound will benefit from the therapy or experience an adverse effect?
Phase III
May be >1,000 subjects
Rigorous clinical trial with randomization, one or more control groups, and definitive clinical endpoints
Address questions of comparative treatment efficacy
– Involves a placebo and/ or active control group in order to assess the precise and valid estimates of differences in clinical outcomes attributable to the investigational therapy agent
Phase IV
Very large; may be >10,000 patients
Postmarketing surveillance (PMS) occurs after regulatory approval of the new agent
Opportunity to learn about rare side effects and interactions with other therapies
Can provide important information that was not apparent during the drug development
Clinical studies of treatments in humans are classified into phases 73,74
Phase I
Small number of healthy volunteers who are closely monitored in a clinical setting
Determines a safe dosage range and identifies any common side effects or readily apparent safety concerns
May also be used to develop pharmacokinetics (PK) and pharmacodynamics (PD), to assess the half-life of the drug, estimate the maximum tolerated dose (MTD), or evaluate the effects of multiple dose levels
Phase II
May be >100 subjects
Investigates preliminary evidence of efficacy and continues to monitor safety
May be the first time the agent is administered to patients with the disease of interest to answer questions such as: What is the correct dosage for efficacy and safety in the patient type? What is the probability a patient treated with the compound will benefit from the therapy or experience an adverse effect?
Phase III
May be >1,000 subjects
Rigorous clinical trial with randomization, one or more control groups, and definitive clinical endpoints
Address questions of comparative treatment efficacy
– Involves a placebo and/ or active control group in order to assess the precise and valid estimates of differences in clinical outcomes attributable to the investigational therapy agent
Phase IV
Very large; may be >10,000 patients
Postmarketing surveillance (PMS) occurs after regulatory approval of the new agent
Opportunity to learn about rare side effects and interactions with other therapies
Can provide important information that was not apparent during the drug development