Pre-clinical (or laboratory) Studies
Clinical trials are done only after preclinical findings suggest that the new drug or treatment is likely to be safe and will work in people. Pre-clinical studies, also called laboratory studies, include:
- These are often the first tests done on a new treatment.
- To see if it might work, researchers look for effects of the new treatment on cancer cells that are grown in a lab dish or a test tube.
- These studies may be done on human cancer cells or animal cancer cells.
- Treatments that look promising in cell studies are tested next on cancers in live animals.
- This gives researchers an idea of how safe the new treatment is in a living creature.
- If the pre-clinical studies are completed and the treatment still seems promising, the US Food and Drug Administration (FDA) must give permission before the treatment can be tested people.
Phase 0 Studies
- Phase 0 is a new designation for exploratory trials undertaken in accordance with the FDA’s Guidance on Exploratory Investigational New Drug (IND) Studies.
- An IND application or request must be filed with the FDA when researchers want to study a drug in humans.
The IND application must contain certain information, such as:
- Results from studies.
- How the drug is made, who makes it, what’s in it, how stable it is, and more.
- Detailed outlines for the planned clinical studies.
- Details about the clinical trial team.
The research sponsor must commit to getting informed consent from everyone on the clinical trial. They must also commit to having the study reviewed by an IRB and following all the rules required for studying IND.
Phase 1 Studies
Phase1 is regarded as the start of formal clinical research and is described as a “first-in-human” study. During this phase, researchers test the safety, side effects, dosage, and formulation of a drug with a small group of voluntary human subjects. Usually, 20 to 100 people are recruited, and trials are conducted in a clinic where full-time staff can observe trial volunteers.
Key points of phase I clinical trials:
- The first few people in the study get a very low dose of the treatment and are watched very closely.
- If there are only minor side effects, the next few participants get a higher dose.
- This process continues until doctors find a dose that’s most likely to work while having an acceptable level of side effects.
- Safety is the main concern.
- Disease response is not the main purpose of a phase I trial,
- Placebos (inactive treatments) are not used in phase I trials.
- These studies are usually done in major cancer centers.
Phase 2 Studies
Phase II studies determine the effectiveness of an experimental drug on a particular disease or condition in approximately 100 to 300 volunteers. This phase may last from several months to two years.
A secondary objective for a Phase II trial is to ascertain therapeutic dose level and dosing frequency.
Most Phase II studies are randomized, which means that subjects are assigned randomly (by chance not by choice) to receive either the experimental drug, a standard treatment or a placebo (harmless, inactive substance). Those who receive the standard treatment or placebo are called a control group.
Randomized Phase II studies are often double blind, which means that both subject and physician don’t know which treatment is being used. Blinding prevents any unscientific influence on the study results that could be caused by knowledge of the treatment.
In a single-blind study, only the subject is unaware of the treatment used.
Since larger numbers of patients receive a treatment in Phase II studies than in phase I studies, there is a greater chance to observe and compile side effect information.
Subjects in a Phase II trial may benefit from their participation if they receive an active treatment.
Approximately 33 percent of experimental drugs which pass Phases I and II will go on to Phase III.
Key points of phase II clinical trials (as per american cancer society):
- A group of 25 to 100 patients get the new treatment in a phase II study.
- They’re treated using the dose and method found to be the safest and most effective in phase I studies.
- Usually in a phase II clinical trials, everyone gets the same dose.
- But some phase II studies randomly assign people to different treatment groups. These groups may get different doses or get the treatment in different ways to see which provides the best balance of safety and response.
- Phase II studies may be done at major cancer centers, community hospitals or even doctors’ offices.
Phase 3 Studies
Phase III studies are conducted at multiple centers with several hundred to several thousand patients for whom the drug is intended. Massive testing of a drug provides continued generation of data on a drug’s safety and efficacy. As in Phase II, most Phase III studies are randomized and blinded.
Phase III trials provide the bulk of information needed for the package insert and labeling of a medicine, after it has been FDA approved.
A drug in this phase can be studied for several years and may be one of 25-30 percent that pass Phases I, II and III. Once a Phase III study is completed, a pharmaceutical company can request FDA approval to market the drug. This is called a New Drug Application (NDA). The NDA contains all the scientific data that the company has gathered throughout the phases in all trials.
Phase 4 Studies
Postmarketing studies, which are conducted after a treatment is approved for use by the FDA, provide additional information including the treatment or drug’s risks, benefits, and best use.
Study Participants: Several thousand volunteers who have the disease/condition
Purpose: Safety and efficacy
Resource Person: BARBARA PIROLA