Science Education

Apr 14, 2015

Need-to-Know Information about Clinical Trials

A primer on what you can expect from clinical trials.

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Pho of a patient getting an eye axam

With about 15 clinical trials underway for inherited retinal diseases, and several more poised to begin in a few years, patients are eager to sign up for access to potential vision-saving therapies.

However, a clinical trial isn’t a promised land. It’s an experiment with risks, and a person’s motivation for participating in the study should be to help advance the research. Though investigators take extensive precautions to protect the patients, they continue to learn about a therapy’s safety and effect on vision and the body, especially during early stages of the study.

Also, participants often make a big commitment to visiting research centers, perhaps several times a year, for many hours of grueling tests. Sometimes, they travel long distances to get to the center. Some drop out of studies, because the commitment is too much. Unfortunately, losing patients can jeopardize the study and the future of the treatment.

It’s also important to understand that, in some trials, participants might not actually be treated. In masked, randomized studies, some will get a placebo, and won’t know whether they received the placebo or the therapy until the study concludes. Those who get the placebo are still helping to advance the trial. Hopefully, the emerging therapy performs better than the placebo.

Phase I
A participant’s experience also depends on what phase of the study he or she has enrolled in. For example, in a Phase I study, investigators are focused on safety, ensuring that the potential treatment does no harm. In some cases, they may recruit healthy volunteers to evaluate the systemic effects of a treatment.

For a therapy that’s applied directly to the eye — for example, a gene or stem-cell therapy — they may enroll patients with very little remaining vision; so there’s little vision to lose if something goes wrong. Phase I studies are usually of short duration, from a few months to a year, and involve about a dozen patients.

Investigators may also evaluate increasing doses of a treatment in different patient groups, often referred to as dose escalation, to identify the maximum tolerable level.

Phase II
In a Phase II study for an inherited retinal disease, researchers are still monitoring safety, but also begin evaluating efficacy. Is the treatment saving or restoring vision? Depending on the therapy and the prevalence of the diseases included in the trial, the number of participants could range from two dozen to a few dozen. A Phase II is likely to last from two to four years.

Phase III
A Phase III study is the final, or “pivotal,” stage before seeking marketing approval from the U.S. Food and Drug Administration or the European Medicines Agency. In this phase, investigators are looking for strong evidence of efficacy. The therapy may be studied at multiple clinical sites to determine if investigators can achieve the same results independently.

For a blockbuster drug, for example, a new therapy for high blood pressure, thousands of patients may be enrolled in a Phase III. But in the world of rare, inherited retinal conditions, researchers may only be able to enroll a few dozen participants. A Phase III usually lasts from two to four years.

Combined Phases
For many emerging therapies for rare conditions, clinical phases are combined. For example, Phase I and II can be combined as a Phase I/II, or Phase II and III as a Phase II/III. This is done to save time and money and accommodate the limited number of participants available for the clinical trial.

For instance, the gene therapy clinical trial for Leber congenital amaurosis (RPE65 mutations)at the Children’s Hospital of Philadelphia was organized in two phases: a 12-patient Phase I/II and a 24-patient Phase III. The University of Iowa was added as a site for the Phase III. This study began in late 2007 and is scheduled to conclude later this year.

Qualifying for a Study
Finally, it’s important to understand that clinical trials have several inclusion and exclusion criteria for participants. One’s age, genetic profile, level of vision and medical history are all factors in determining eligibility for a study.

Help Drive the Research
I hope my cautionary comments do not dissuade anyone from considering a clinical trial. We need participants, because without them we would have no trials or treatments. But at the same time, it’s important for anyone considering participating to have realistic expectations.

To learn more about clinical trials underway for inherited retinal diseases, visit www.clinicaltrials.gov.