Research Development and Clinical Trial Phases

Defining a Clinical Trial

A clinical trial is indeed a systematic investigation of an intervention in human subjects. The subjects are assigned to a group and biomedical and/or behavioral outcomes are observed. Clinical trials can test lots of different interventions.

Non-Randomized Trial

A non-randomized trial is one in which the participants are intentionally placed in a certain treatment group. In some instances the participants choose the treatment group and in others the investigator placed the participant in a specific group.

Randomized Trial

A randomized trial is one in which the participants are randomly placed into a treatment group, just like the flip of a coin or roll of the dice. This design helps to eliminate any bias in the study.

Applying to Test in Humans

After a drug has gone through pre-clinical trials and all necessary safety information is obtained, an Investigational New Drug (IND) application can be submitted to the FDA. Once this is submitted and approved, clinical trials testing the compound can begin!...but what exactly is a clinical trial?! Take your best guess!

Goal of Pre-Clinical Studies

Before a compound is tested in human subjects, safety and toxicity information must be obtained from pre-clinical studies. It is also necessary to narrow down an approximate dosage and route of administration for when it is tested in human subjects. All this information will be submitted to the Food and Drug Administration (FDA) before the drug can be tested in humans.

Controlled Trial

In a controlled trial, the investigational product is tested against a control. The control can be a placebo (medically ineffectual treatment) or standard of care. For example, a new medication can be tested against an inert compound or against an approved medication that has already been shown to be effective.

Double-blind study

In a double-blind study, both the researcher and participant are unaware of which treatment the participant is receiving. This helps to eliminate bias on both the part of the participant and researcher.

Single-blind study

In a single-blind study, either the participant or the researcher knows which treatment group the participant is in. Usually it is the researcher that knows which group the subject is in.

Open Label Study

In an open label study, both the participant and the researcher knows the drug and dose that are being administered to the participant. Next we will discuss single-blind and double-blind studies. Be prepared to contrast these with open label studies.

Which of the following can be interventions tested in a clinical trial?

New drugs , FDA approved drugs , New medical approaches or procedures , Vaccines

Pre-Clinical Studies

Once a drug is discovered and the properties check out, we still can't test it in humans! Sometimes drugs have unintended side effects that couldn't be predicted. Therefore, the next step is to run pre-clinical studies. This includes in vitro (testing in an artificial environment), in vivo (conducted in living animal/human system), and animal studies.

Phase I

Phase I Trial: -First time drug or test article is studied in human subjects -Small number of subjects -Goal: determine metabolic, pharmacological properties of drug in humans -Primary concern: subject safety

Phase II

Phase II Trial -More subjects enrolled than Phase I -Goal: Determine if drug or treatment is efficacious -Primary concern: Is Phase I dose effective?

Phase III

Phase III Trial: -Only occurs if Phase I and Phase II proved that the drug/treatment is safe -Thousands of subjects enrolled -Goal: Study long-term safety and efficacy -Primary concern: long-term effects

Phase IV

Phase IV Trial: -Occurs AFTER new drug application approval -Goal: obtain additional safety and efficacy data -Secondary goal: study different formulations, dosages, interactions, etc.

Gold Standard Explanation

The controlled aspect of the design allows for a comparison between the investigation product and either a placebo or standard of care. This means that at the end of the trial we can determine if the test treatment was efficacious. The randomized aspect helps to eliminate bias because subjects are not systemically placed into specific groups. The double-blind aspect also allows us to eliminate bias because the participants and researchers won't have expectations about the expected outcomes which would inherently introduce bias into the results.

Why do you think the double-blind randomized controlled trial is the gold standard study design?

The double-blind portion eliminates bias on the part of the participant , The double-blind portion eliminates bias on the part of the research , The study is controlled by a comparison group such as a placebo , Subjects are randomly assigned to a group which helps eliminate bias.

Drug Discovery

The first stop in the process is drug discovery. When you think drug discovery, think microscopes and chemistry! This is when scientists are creating the molecules and forming the drugs. They are studying the properties and mechanics of the drug that would allow it to function as intended.