Clinical trials: Treatment results are just the tip of the iceberg

Key Points

Atlanta-Clinical trials are not intended just to assess treatment effects, they also provide a great deal of invaluable information, said Frederick L. Ferris III, MD, in the Jackson Memorial Lecture during the opening session of the annual meeting of the American Academy of Ophthalmology (AAO).

"Clinical trials have slowly evolved to their current status as the gold standard by which we decide if treatments are safe and effective," said Dr. Ferris, clinical director of the National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, MD. "However, we have an opportunity to learn far more than this with each clinical trial.

Importantly, he said that all of this information, beyond a determination of the safety and efficacy of a given treatment, adds to the value of the clinical trials and the ability of physicians to care for patients.

Evolution of clinical trials

Interestingly, the design strategy of clinical trials harkens back to biblical times, with the first clinical trial described in the book of David, according to Dr. Ferris. One of the most famous of the first clinical trials identified a treatment for scurvy among British sailors in 1747.

"Studies such as these, however, were not well organized, and the outcomes were often ignored," he said. Remarkably, 42 years passed before the clinical observation that limes aboard ships prevented scurvy and resulted in the introduction of citrus in sailors' diets, he added.

Historical bias and clinical impressions seemed to be more important to early physicians than organized comparisons of treatment groups. Randomization was initiated relatively late in the mid-1940s, when standard care was compared with streptomycin for treating tuberculosis. In ophthalmology, randomization dates back to the first clinical trials in 1952 for the use of oxygen as the treatment for retinopathy of prematurity (ROP). By the late 1960s, there was rapid development of randomized clinical trial methodology, and the new NEI was founded. The Diabetic Retinopathy Study (DRS) was the first clinical trial conducted by the NEI.

"Clinical trials have progressed radically over the past four decades," Dr. Ferris said. Numerous trials were conducted during the first 30 years of NEI existence, and some leveling off was seen during the past decade.

Clinical trial networks, however, have developed. This structure, according to Dr. Ferris, has the potential to allow researchers to perform multiple studies that involve larger groups of clinical investigators and improve the clinical trial's generalizability and translation.

"We can also assess the growth of clinical trials by looking at the number of clinical studies published during the past four decades," he said, noting that more than 12,000 eye and vision reports have been counted.