How Clinical Trials Work

Overview

Clinical trials test new interventions or drugs in a series of steps (or phases) to prevent, detect or treat disease. During this sequence of testing, researchers gradually build evidence about whether an intervention or drug is effective and whether it has an acceptable safety profile — that is, whether the risks associated with its use are reasonable given its potential benefit.

Phases of pharmacological (drug) clinical trials

New drugs must successfully complete a three-phase clinical trial process (Phase I, Phase II and Phase III) before being approved for use by the Food and Drug Administration (FDA); they must perform well enough in each phase to progress to the next one. Preclinical studies in laboratories establish a scientific basis for believing a drug is reasonably safe and may be effective.

• Phase I trials, the first stage of human testing, typically involve fewer than 100 volunteers and look at the risks and side effects of a drug. Participants at this phase are often healthy volunteers.
• Phase II trials enroll up to a few hundred volunteers who have the condition the drug is designed to treat. These studies provide further information about safety and help to determine the best dosage of a drug, and are generally too small to provide clear evidence about a treatment's benefit.
• Phase III trials enroll several hundred to thousands of volunteers, often at multiple study sites worldwide. They provide the chief evidence for safety and effectiveness that the FDA will consider in deciding whether to approve a drug.
• Phase IV trials, also called post-marketing studies, are often required by the FDA after a drug is approved. During this phase, researchers continue to monitor the health of people taking the medication to gain further insight into its long-term safety and effectiveness.

Criteria to participate

Before joining a clinical trial, an individual must qualify for the study. All clinical trials have guidelines about who can participate. Researchers define these guidelines as inclusion and exclusion criteria. Examples of these criteria include: 

• Limiting participants to a certain age range.
• Requiring participants to be in a certain stage of the disease being studied.
• Not allowing health conditions other than the one being studied.
• Not permitting use of certain medications other than the study drug.
• Requiring participation of a caregiver or “study partner.”

Individuals living with dementia, caregivers and healthy volunteers without dementia are needed for Alzheimer’s clinical trials. To find a study that matches your personal eligibility, visit Alzheimer’s Association TrialMatch®.

Placebos

Scientists have learned that people sometimes feel better, and even have improved results on medical tests, when they believe a treatment is helping them. Doctors may also convince themselves a treatment is working because they care about their patients.

There are two main strategies to reduce the likelihood that hopes and beliefs will affect the outcome of clinical trials:

1. Trials are placebo-controlled. Study participants are randomly chosen to receive the experimental treatment and some receive a placebo, an inactive pill, liquid or powder that has no treatment value. Experimental treatments are often compared to placebos to assess effectiveness.
2. Trials are “double-blinded.” Participants and study staff are unaware of who receives the drug and who gets the placebo.

When a standard of care — a typical treatment plan for a condition — is available, it is often used instead of a placebo. In such cases, the experimental treatment and the standard treatment are compared.

Safety

Although participants and study staff don’t know who’s getting the treatment and who’s getting the placebo, most trials have a separate, independent Data Safety and Monitoring Committee that has access to this information. Committee members regularly analyze data and step in if they notice any worrisome patterns of serious side effects.

Informed consent

Informed consent is the process of learning key facts about a study before deciding whether to volunteer. The FDA requires potential participants to have complete information about the study in writing. Study staff members are required to meet with each prospective participant to explain risks, possible benefits and answer any questions. People who decide to join the study must sign an informed consent form. Individuals who are invited to participate in a study are not required to join. Participants are free to leave a study at any time.

Capacity and proxy issues

Some cognitively impaired individuals are still able to make informed decisions for themselves about participating in research. His or her attending physician can provide a medical opinion about an individual’s decision making capacity. While an individual still has decision-making capacity, he or she may choose to execute a health care power of attorney or other power of attorney under his or her’s resident state laws that appoints an individual or entity as his or her agent to make health care decisions for that person. If an individual is determined to no longer have decision making capacity and does not have a health care power of attorney or other power of attorney in place, a court will have to appoint a legal guardian to make health care decisions for that person.

Sometimes individuals in the early stages of a disease establish an advance directive that specifies whether or not they wish to be considered for clinical research should they no longer be able to decide for themselves. Learn more about advance directives from your personal attorney.

An organization or institution’s Institutional Review Board (IRB) determines safety and the level of risk associated with a clinical trial. When a clinical trial is believed to be of minimal risk, an individual’s representative or guardian may give consent for that person to participate, as long as that individual does not have an advance directive in place that says he or she does not want to be enrolled in a research study or clinical trial.

If an organization or institution’s IRB determines that the clinical trial poses a greater than minimal risk but is reasonably likely to provide a benefit to an individual living with Alzheimer's or dementia, a representative or guardian may enroll the individual in the trial if the representative or guardian believes the trial is in the individual’s best interests. Or, a previously executed research-specific advance directive may also be used to enroll the participant in the trial.

If an IRB determines that a clinical trial poses greater than minimal risk without a reasonable potential benefit to the individual, only those individuals who (1) are capable of giving their own informed consent or (2) have previously executed a research-specific advance directive stating that they would like to be enrolled in clinical research, are allowed to participate. If the individual has executed a research-specific advance directive, that person’s representative or guardian must be available to monitor the individual’s participation in the clinical trial.

When clinical trials end

All clinical trials end, and while the early termination of a trial may cause strong emotions in participants, it’s important to understand that researchers have gathered important data even if the results aren’t positive. Everything we know about current and potential Alzheimer’s treatments has come from clinical trials, including those that didn’t meet their intended outcomes.

All trial participants are notified of important changes to their study. This process can be complicated when a trial ends early.

Learn more: When Clinical Trials End