Phases Flashcards
Phase I Trials
FIH researchers test an experimental drug or treatment in a small group of people for the first time. The researchers evaluate the treatment’s safety, determine a safe dosage range, and identify side effects.
Study Participants
20-100 healthy volunteers (Cancer/ HIV exception)
Length: Several Months
Purpose: Safety and dosage
. Researchers test new drug in healthy volunteers
. Closely monitored and gather info about how a drug interacts w/the human body. Approximately 70% of drugs move to the next phase
. FIH subjects
. Non blinded (open)
. Study mainly to investigate safety, PK’s, and PD’s and MTD of investigational dug in humans
. PK what the body does to the drug
. PD what the drug does to the body
. Patient observed until several half lives of the drug have passed.
Phase II
. First time the IP (drug) is used on people w/the disease
. Typically enrolls 100-300 patients
. Purpose is to test efficacy(does it work). First time efficacy is being looked at. They also still checking for safety and AE’s (side effects)
. Subjects are treated using the dose and method found to be the safest and most effective in phase I studies
. Both IP and placebo are being giving to the subjects in a random order, but not at the same time
. Randomization of IP can also be given to patients w/the disease in different dosage to see different AE’s
. Provide researchers w/ more safety data which is used to refine research questions and develop methods and design new Phase 3 research protocols
. 10-30 clinics for the study. Usually 10 patients per clinic. Last from several month to 2 yrs
. Approx 33% of drugs move to the next phase
Types of Phase II Trials
Single-blind design (not in Cancer trials)
. Subjects do not know if they are receiving placebo or study drug
. Reduce the risk of errors
Double-blind design
. Participant nor researcher know who is receiving what treatment
. Sponsor will know who get what
. Prevent placebo effect and researcher bias
Phase III (Aka Pivotal Study)
. Experimental study drug is giving to large numbers of people
. Researchers confirm effectiveness, monitor AE’s, compared to known used treatments, and collect info so the drug or treatment can be used safely
. Study Participants 300-3k volunteers who have the disease or condition. 25%-30% of the drug move to the next phase
. Purpose: Efficacy over a longer period of time and monitor adverse reactions
Length: 1-5yrs (allow researchers to see long term efficacy and safety)
. Different to design, expensive to execute b/c of large # of patients
. PI’s are usually specialists in the disease being treated
. Double-blind and crossover techniques are frequently used
. In/Exclusion must be used to prevent AE and SAE (Real world patients)
. In/Exclusion is more open to patients who may have things other than the drug treating the patient
. Open label period - extension of the protocol. Patients are guaranteed the IP. They also may be guaranteed a certain dosage.
. Last study prior to FDA deciding to approve the drug once Sponsor presents them w/all the data. FDA has to decide to grant a NDA.
. Getting approved by FDA means any physician can prescribe the drug
.
New Drug Application
If a drug developer has evidence from early tests, pre clinical and clinical research that the drug is safe and effective for intended use, the company can file an app to market the drug. FDA review team thoroughly examines all submitted data on the drug and makes a decision to approve or disapprove it.
. A NDA tells the full story of a drug. Purpose is to show that a drug is safe and effective for intended use in the population study.
. Developer must include everything about a drug - from preclinical data to Phase 3 trial data - in an NDA. Developers must include reports on data and analyses. Along with clinical results, developers must include
. Proposed labeling, safety updates, drug abuse info, patient info, any data from studies outside of the U.S. , IRB compliance info, and directions for use
FDA Review
After receiving NDA the FDA decides if its complete or not. If its not complete the review team can refuse to file. If its complete then review team has 6-10mo to make a decision to approve the drug.
. Each review team member conducts a full review of their section of the application
. FDA inspectors travel to site study to conduct routine inspection. They look for evidence of fabrication, manipulation, or withholding of data
. The project manager assembles all individual reviews and other documents such as the inspection report into an action package. The document becomes the FDA review. The review team issues a recommendation, and a senior FDA official makes a decision
FDA Approval
Once FDA determines that the drug is safe and effective for intended use, it’s then required for them to work w/the applicant to refine prescribing info.
. This method is known as “Labeling. It describes the basis for approval and how best to use the drug.
. Often though remaining issues need to be resolved before the drug can be approved for marketing. Sometimes FDA requires the developers to address questions based on the data.
Phase IV Trials
Post marketing studies, which are conducted after the treatment is approved for use by the FDA, provide additional info including the treatment of the drug’s risks, benefits, and best use.
Phase IV
Study Participants: Several thousand volunteers who have the disease/condition
Purpose: Safety and Efficacy
. Carried out once the drug or device has been approved by FDA during the Post-Market Safety Monitoring
. To further evaluate the characteristics of the new drug w/regard to safety, efficacy, new indications for additional patient populations, and new info
. Drug is now on the market
. Not usually placebo or randomized controlled
. Open label
Supplement Applications
Developers must file a supplemental app if they wish to make significant changes from the original NDA.
Generally any changes in formulation, labeling, or dosage strength must be approved by FDA before they can be made.
