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Ophthalmology has a rich history of leadership in clinical trials. In the early 1950s, Arnall Patz, MD, headed one of the first major, randomized prospective clinical trials (about retinopathy of prematurity). The Diabetic Retinopathy Study and the Early Treatment Diabetic Retinopathy Study of the 1970s and 1980s are still considered benchmarks in trial design and conduct. They addressed questions of significant public health importance, and their results resonate in our treatment plans today.
The Comparison of AMD Treatments Trial (CATT) stands with these investigations as a “first” in its own right and a landmark study in the emerging field of comparative effectiveness research. Results reported in the New England Journal of Medicine1 show that two treatments for neovascular AMD—ranibizumab (Lucentis) and bevacizumab (Avastin)—are equally effective in terms of visual acuity in eligible patients, according to one-year data. The data also show that “as-needed” dosing is very effective using either drug. It must be emphasized that in the as-needed arm, patients were still examined and imaged monthly with OCT to determine whether treatment was indicated.
In addition to clinical efficacy, the CATT delivered some intriguing information regarding adverse events. The median patient age was over 80, and a high rate of concurrent diseases, hospitalizations and death was expected. In the trial, the cumulative rate of serious adverse events was low at 24 percent for patients receiving bevacizumab and 19 percent for ranibizumab. Whether this observation is pertinent to the study and/or will hold up with the year two results is unclear. It is notable both that the half-life of ranibizumab is shorter than bevacizumab and that the dose of bevacizumab used for AMD is 500 times lower than the dose used for cancer treatment.
Whether the CATT will lead to substantive changes in treatment patterns remains to be seen. But several things appear self-evident. First, our decisions can now be made in the context of more scientific evidence. Second, we are fortunate to have available two agents of significant efficacy.
The choice of treatment plan should be made in concert by the treating ophthalmologist and the patient. The choice can be complex, involving issues of prior treatment, coincident systemic disease, cost, logistical factors and personal preference. Both drugs need to be available to patients, but the choice should be based on evidence from carefully controlled trials.
Much will be made of the economic and health policy implications of CATT, since we have two drugs of such widely varying cost and similar efficacy. It is important that these discussions take place, since the science of ophthalmology is enmeshed within health care policy, coverage decisions and systemic economic impact.
We should not underestimate the importance of CATT as a touchstone for future comparative effectiveness research. The CATT leaders literally had to establish coalitions to help with thorny issues of Medicare drug payment in clinical trials, copayments, treatment masking and gaining approval from individuals and agencies not normally involved in more typical clinical trials. The work that they did, the policies that were changed, and the legislation passed benefited not only CATT, but many trials yet to come. The Academy was proud to facilitate that work. The impact of this trial will go far beyond AMD, retina and ophthalmology. It will impact how future clinical trials research is conducted in all of medicine. As ophthalmologists, we should be proud to have blazed this new trail and continued the rich history of seminal clinical trials design begun by Dr. Patz and his coworkers.
Finally, we thank the 1,200 patients whose commitment to the importance of answering critical clinical questions led them to participate in the trial.
David W. Parke II, MD, is executive vice president/CEO of the Academy.
1 N Engl J Med Online April 28, 2011.
This Outlook is excerpted from Dr. Parke’s online statement at www.aao.org/catt.cfm.