Types

One way of classifying clinical trials is by the way the researchers behave.

• In a clinical observational study, the investigators observe the subjects and measure their outcomes. The researchers do not actively manage the study.
• In an interventional study, the investigators give the research subjects a particular medicine or other intervention to compare the treated subjects with those receiving no treatment or the standard treatment. Then the researchers measure how the subjects' health changes.

Another way of classifying trials is by their purpose. The U.S. National Institutes of Health (NIH) organizes trials into five different types:^[26]

• Prevention trials look for better ways to prevent disease in people who have never had the disease or to prevent a disease from returning. These approaches may include medicines, vitamins, vaccines, minerals, or lifestyle changes.
• Screening trials test the best way to detect certain diseases or health conditions.
• Diagnostic trials are conducted to find better tests or procedures for diagnosing a particular disease or condition.
• Treatment trials test experimental treatments, new combinations of drugs, or new approaches to surgery or radiation therapy.
• Quality of life trials (supportive care trials) explore ways to improve comfort and the quality of life for individuals with a chronic illness.
• Compassionate use trials or expanded access trials provide partially tested, unapproved therapeutics to a small number of patients who have no other realistic options. Usually, this involves a disease for which no effective therapy has been approved, or a patient who has already failed all standard treatments and whose health is too compromised to qualify for participation in randomized clinical trials.^[27] Usually, case-by-case approval must be granted by both the United States Food and Drug Administration and the pharmaceutical company for such exceptions.

A third classification is whether the trial design allows changes based on data accumulated during the trial.

• Fixed trials consider existing data only during the trial's design, do not modify the trial after it begins and do not assess the results until the study is complete.
• Adaptive clinical trials use existing data to design the trial, and then use interim results to modify the trial as it proceeds. Modifications include dosage, sample size, drug undergoing trial, patient selection criteria and "cocktail" mix.^[28] Adaptive trials often employ a Bayesian experimental design to assess the trial's progress. In some cases, trials have become an ongoing process that regularly adds and drops therapies and patient groups as more information is gained.^[29] The aim is to more quickly identify drugs that have a therapeutic effect and to zero in on patient populations for whom the drug is appropriate.^[30][31]

Finally, a common way of distinguishing trials is by phase, which in simple terms, relates to how close the drug is to being clinically proven both effective for its stated purpose and accepted by the regulatory authorities for use for that purpose.

Phases

Main article: Phases of clinical research

Clinical trials involving new drugs are commonly classified into five phases. Each phase of the drug approval process is treated as a separate clinical trial. The drug-development process will normally proceed through all four phases over many years. If the drug successfully passes through phases 0, 1, 2, and 3, it will usually be approved by the national regulatory authority for use in the general population. Before pharmaceutical companies start clinical trials on a drug, they will also have conducted extensive preclinical studies. Each phase has a different purpose and helps scientists answer a different question.

Phase	Aim	Notes
Phase 0	Pharmacodynamics and pharmacokinetics in humans	Phase 0 trials are the first-in-human trials. Single subtherapeutic doses of the study drug or treatment are given to a small number of subjects (10 to 15) to gather preliminary data on the agent's pharmacodynamics (what the drug does to the body) and pharmacokinetics (what the body does to the drugs).[32] For a test drug, the trial documents the absorption, distribution, metabolization, and removal (excretion) of the drug, and the drug's interactions within the body, to confirm that these appear to be as expected.
Phase 1	Screening for safety.	Testing within a small group of people (20–80) to evaluate safety, determine safe dosage ranges, and begin to identify side effects. A drug's side effects could be subtle or long term, or may only happen with a few people, so phase 1 trials are not expected to identify all side effects.
Phase 2	Establishing the efficacy of the drug, usually against a placebo.	Testing with a larger group of people (100–300) to determine efficacy and to further evaluate its safety. The gradual increase in test group size allows for the evocation of less-common side effects.
Phase 3	Final confirmation of safety and efficacy.	Testing with large groups of people (1,000–3,000) to confirm its efficacy, evaluate its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow it to be used safely.
Phase 4	Safety studies during sales.	Postmarketing studies delineate additional information, including the treatment's risks, benefits, and optimal use. As such, they are ongoing during the drug's lifetime of active medical use. (Particularly relevant after approval under FDA Accelerated Approval Program)