A Comprehensive Look at Clinical Trials

Clinical Trial Terms

As you review the informed consent form, you may come across some of these terms:

Inclusion and Exclusion Criteria

Inclusion and exclusion criteria are the rules that say who is allowed to join a trial. The rules are different for every trial.

Inclusion criteria are characteristics you must have to participate in the trial. Some examples of inclusion criteria are:

• T-cell count greater than 200

• Willing and able to sign informed consent form
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• Viral load greater than 10,000 copies

Exclusion criteria are characteristics that you must not have in order to participate in the trial. Some examples of exclusion criteria are:

• Active opportunistic infection

• Women who are pregnant or breastfeeding

• Any vaccination within the past month

Inclusion and exclusion criteria are used so that researchers can design trials to study the effects of medications at different stages of HIV infection. For example, a trial for people who are failing on their current treatment will only include people with high viral loads.

Inclusion and exclusion criteria are also used to protect people in trials. For example, if a medication is known to cause liver problems, people with damaged livers will not be allowed to participate in the trial.

Placebos

A placebo is a substance that looks like a trial medication but does not contain active drug. The placebo is a pill if the trial medication is a pill, and it is a shot if the trial medication is a shot.

Placebos may seem unfair or unethical. Why would a doctor give something that doesn't work to someone with HIV? Placebos are used to help determine if an experimental medication works. Some people get the medication, other people get placebo, and the results are compared. That way, researchers can see if the medication being studied really works. Placebos are used if there is no approved drug to use for comparison.

Placebos are sometimes added to an approved regimen. When used this way, one group adds the experimental medicine to their treatment regimen and another group adds a placebo. The results are compared to see if there is any benefit to adding the experimental medication.

As an example, let's look at how a placebo was used in a clinical trial of a drug called GM-CSF. The trial was designed for people taking anti-HIV medications who had a viral load higher than 1,500 copies. The main purpose of the study was to learn if GM-CSF lowers viral load in people with HIV. In this study, one group added GM-CSF to their treatment regimen and another group added placebo.

These people were assigned by chance to one of the two groups in a process called randomization. Randomization is like flipping a coin to see who gets what, the medication or the placebo. It is used to make sure that there is no bias in the trial.

Trials that use placebos are usually double-blind, which means that neither the research doctor nor the trial participant knows which medication the participant is taking. If both the research doctor and the trial participant know which medication is being used, the trial is open-label.

ACTG Study A5041 Trial medication: GM-CSF, a medication approved by the FDA to increase and improve white blood cell function in people with leukemia. GM-CSF is not approved for the treatment of HIV infection. Purpose of the trial: The main purpose of the trial is to learn if GM-CSF reduces viral load in people with HIV. Trial groups: Part one (Weeks 1-16) -- Randomized and double-blind: Group 1 -- GM-CSF shot three times a week for 16 weeks. Group 2 -- Placebo shot three times a week for 16 weeks. Part two (Weeks 17-48) -- Open-label: All participants receive GM-CSF shot three times a week for 32 weeks. At the end of the first 16 weeks of this trial, researchers will compare the viral loads of people who took GM-CSF with the viral loads of people who took placebo. If viral loads are lower in people who took GM-CSF, it shows that GM-CSF is effective against HIV. If viral loads in the two groups are about the same, it shows that GM-CSF works about the same as a "dummy" shot and is not effective against HIV. Not all trials use placebos. But if the informed consent form says that a trial uses a placebo, ask lots of questions. Find out if you will eventually have a chance to get the experimental medication as part of your participation in the trial if the drug is shown to work. Make sure that you are comfortable with the idea that you might get a placebo before you start the trial.