Published in the Bulletin of Experimental Treatments for AIDS April 1999 issue, by the San Francisco AIDS Foundation.

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Volunteering for Clinical Trials

April 1999 Table of Contents

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Nuts and Bolts of Clinical Trials

By Bruce Mirken

What Are Clinical Trials?

Clinical trials are an important part of the drug development process in the U.S. The Public Health Service's Glossary of HIV/AIDS-Related Terms defines a clinical trial as: "a carefully designed and executed investigation of the effects of a drug (or vaccine) administered to human subjects. The goal is to define the clinical efficacy (benefit) and pharmacological effects (toxicity, side effects, incompatibilities or interactions) of the drug. The U.S. government, through the Food and Drug Administration (FDA), requires strict testing of all new drugs and vaccines prior to their approval for use as therapeutic agents."

In other words, clinical trials are the way that governmental licensing agencies collect information about whether a specific drug or treatment for a specific disease or condition in fact does what the manufacturer claims that it does. All drugs licensed in the U.S. are required to undergo this process and meet the necessary criteria. If well-designed, these trials are scientifically based and "statistically powered" so as to answer the question being asked by investigators.

This means that a sufficient number of people have been enrolled in order to detect a significant difference, if the difference indeed exists in the population being studied.
HIV/AIDS clinical trials normally occur in four phases. Phase I studies examine the safety and dosing effects of the drug being studied and often determine the highest dose that can be tolerated. These studies usually enroll a small number of subjects and last a short period of time.

Phase II trials assess whether a new drug is effective. These may include testing different doses to find the dose or doses best tolerated that involve the least side effects. Phase II trials often enroll a larger number of subjects.

Phase III trials continue to collect information on the drug's effectiveness and side effects and enroll an even larger number of subjects. They generally last months to years, and may generate information on the long-range effects of a drug, including side effects as well as benefits. Following drug approval by the FDA, some subjects in phase III may be offered participation in phase IV trials.

Phase IV trials are often called post-marketing studies. Post-marketing studies are designed to address any questions about the medication that remain unanswered by following recipients of the drug and collecting long-term data. However, these post-marketing studies, which are the responsibility of the drug companies and are not required by the FDA, are rarely conducted.

Where Do Clinical Trials Take Place?

Many groups design and conduct HIV clinical trials. The trials are either funded publicly (by the government) or privately. Publicly funded groups that conduct trials include the Community Programs for Clinical Research on AIDS (CPCRA) and the AIDS Clinical Trials Group, which includes both Adult (AACTG) and Pediatric (PACTG) units. The publicly funded groups are supported primarily through the auspices of the National Institutes of Health (NIH). The privately funded groups are mostly contract research companies (CROs), some of which are funded by pharmaceutical companies.

The federally funded CPCRA and ACTG have similar goals. These include using scientifically sound methodologies to test drugs or technologies and to evaluate clinical markers in order to find effective treatments for HIV disease and its complications. Both groups primarily conduct phase II and III studies that target underserved populations in addition to testing approved drugs. When these networks were originally established their participating sites were very different.

Since its inception the CPCRA has conducted its research in primary care settings (e.g., hospitals and clinics) across the nation. The ACTG originally conducted its research at university-based research centers but has now expanded to include some primary care sites as well. The original ACTG has split such that the pediatric trials are now separate from the adult clinical trials: the AACTG coordinates adult trials while the PACTG administers pediatric trials. (Note: there may be some overlap between AACTG and PACTG trial enrollment criteria in the case of adolescents with HIV; for more information about lower age eligibility, contact a clinical trial recruiter or study coordinator.)

The ACTG took advantage of their central locations at university-based centers close to lab facilities to focus on early development of new drugs while the CPCRA, located in primary care sites, conducted longer, larger, later-stage studies.

Because of the historic differences between the two networks, their trial designs have tended to differ. Yet today both are conducting strategy trials. Strategy trials, of increasing importance, are those that try to answer questions regarding treatment approach, as opposed to questions peculiar to a specific therapy. Examples of strategic questions include which drug or drugs to use first and when to change therapies after it is determined that change is necessary.

Privately funded clinical trial research is often conducted for a shorter period of time and usually evaluates a single treatment versus a placebo or another drug. Compensation is often provided for privately funded trials. These trials may take place at a physician's office, a private company, or a research organization.

Understanding both the risks and the benefits that might occur if one chooses to participate in a clinical trial is of crucial importance. The informed consent process is critical to this understanding. Hopefully, clinical trials will meet the needs of people living with HIV, clinicians, and researchers, and will continue to provide data that translate effectively into clinical practice.