Clinical trials involve testing a new medication or therapy in a series of steps (or phases). During this sequence of testing, researchers gradually build evidence about whether a medication or therapy 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).
New drugs must successfully complete a three-phase clinical trials process (Phase I, Phase II and Phase III) before being approved for use by the U.S. Food and Drug Administration (FDA). They also must perform well enough in each phase to be allowed to progress on to the next one. Sign up for our weekly e-news and stay up-to-date on the latest advances in Alzheimer's treatments, care and research.
Phases of a study
- 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 involves fewer than 100 volunteers. These studies look at the risks and side effects of a drug. Participants at this phase are 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. Phase II trials 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.
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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
- Not allowing health conditions other than the one being studied
- Not permitting use of other medications
- Requiring participation of a caregiver or "study partner"
To find a study that matches your personal eligibility, see Alzheimer’s Association TrialMatch®.
Scientists have learned that people can sometimes feel better, and even have improved results on medical tests, just because they believe a treatment is helping them. Doctors also can convince themselves a treatment is working because they care about their patients and want to help them get better.
There are two main strategies to reduce the likelihood that hopes and beliefs will affect the outcome of clinical trials:
- Trials are "placebo-controlled." This means that some 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. In clinical trials, experimental treatments are often compared to placebos to assess effectiveness. In some clinical trials, the control group receives a placebo at the beginning of the study but at a certain cut-off point is switched to the new drug. In other studies, the control group receives the placebo for the duration of the study, but if the drug proves effective, they receive it as part of a follow-up study. In yet other studies, the control group receives the placebo alone.
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.
- Trials are "double-blinded." This means that participants and study staff are unaware of who is getting the drug and who is getting the placebo.
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The placebo effect
The placebo effect is a physical or emotional change after taking a substance that is not the result of the substance. The change may be beneficial, reflecting the expectations of the participant or the expectations of the person giving the substance.
Although participants and study staff don't know who's getting the drug and who's getting the placebo, most trials have a separate, independent data safety and monitoring committee with access to this information. Committee members analyze data and step in if they notice any worrisome patterns of serious side effects in drug recipients.
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Informed consent is the process of learning key facts about a study before deciding whether to volunteer. The FDA requires potential participants to be given complete information about the study in writing. Researchers also meet with each potential participant to explain risks and possible benefits and answer any questions. People who decide to join the study must sign an informed consent form.
Participants are free to leave a study at any time.
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Some cognitively impaired individuals are still able to make informed decisions for themselves about participating in research. Others can no longer make these decisions, and another individual (usually a family member) serves as a proxy to decide whether the impaired individual would want to be considered for a clinical trial. Sometimes individuals in the early stages of a disease establish an advance directive (a legal document) 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 in our Legal Documents section.
When a clinical trial is believed to be of minimal risk, the Alzheimer's Association believes all individuals should be allowed to enroll. Proxy consent to participate is acceptable, as long as an individual does not have an advance directive in place that says he or she does not want to be enrolled in a research study.
Proxy consent also can be used when a clinical trial poses a greater than minimal risk but is reasonably likely to provide a benefit to an individual with Alzheimer's. The proxy's consent can be either a research-specific advance directive or the proxy's judgment of the individual's "best interests."
When 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 executed a research-specific advance directive stating that they would like to be enrolled in clinical research, are allowed to participate. In either case, a proxy must be available to monitor the individual's involvement in the research.
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