Central visual acuity is the most widely used measure to determine treatment success in ophthalmology. But a growing number of Eye M.D.s argue that relying on a single indicator—even one as critical as visual acuity—may blind us to the reality of a patient’s true functional ability.
Ophthalmology’s emphasis on central visual acuity as a measure of success reminds glaucoma specialist Paul P. Lee, MD, JD, of the old fable in which three blind men go off to “see” an elephant. One man touches the ear and thinks it is a fan; another touches the tail and believes he is touching a rope; still another touches the knee and assumes that it is a tree. The moral: Each man was partly right, and all were wrong.
Relying on a single measure like visual acuity is much like that, says Dr. Lee, who is part of a growing chorus of researchers who argue that an intervention may be only as good as its effect on the overall quality of a patient’s well-being. Visual acuity, they say, is an important aspect, but not the only one. While we know that people with 20/200 vision function differently from those with 20/20, Dr. Lee and others contend that there may be better techniques for measuring visual functioning that complement visual acuity—most notably, measuring quality of life.
Put the Patient First
Quality-of-life studies focus on assessing the impact of ophthalmic diseases and their management on the patient, rather than on just the eye. The priority is to keep the patient as the main outcome measure and to improve the vision-related functioning of the patient.
“Quality of life is a more comprehensive measure, which captures much more than can be captured simply by measuring visual acuity,” said Ingrid U. Scott, MD, MPH. “There is more to the person’s visual functioning, more to the person’s vision-related quality of life.”
A diagnosis of macular degeneration, for example, goes beyond visual acuity, explained Dr. Scott, who was drawn to this line of research as a medical student, after seeing the comprehensive impact of visual disease on a person. “There’s fear, anxiety, depression, questions about the future, uncertainty about how long existing vision may be retained.”
These studies, she said, “highlight the importance that our main priority should not be a change simply in a single biomedical indicator.”
The PDT Example
Relying on a single outcome can lead to unwarranted exuberance. And that, say quality-of-life proponents, can lead to unrealistic patient expectations, unnecessary treatment and misspent health care resources.
Consider, for example, the photodynamic therapy (PDT) trials of verteporfin (Visudyne) to treat AMD, which showed a reduction in the percentage of patients who lost three lines of vision with treatment vs. natural history. Then consider that while the trial proved the therapy could be effective in terms of preventing a certain degree of vision loss, it may not have altered the course of most patients’ lives.
Caption: Most ophthalmic interventions are considered cost-effective: Cataract surgery costs $2,020/QALY.
Reducing the magnitude of vision loss may have satisfied particular research endpoints, but did it do anything to improve the quality of life? That’s the question posed by Paul Sternberg Jr., MD, and Hilel Lewis, MD, in the American Journal of Ophthalmology.¹ “Does this ‘benefit’ translate into improvement in their daily life?” the authors ask. “Did photodynamic therapy allow them to drive, read or recognize faces?”
Dr. Sternberg asserted that he and Dr. Lewis were not questioning the validity of the PDT data or the ethics of the people who conducted the study. (Both doctors were investigators in the PDT trials.) “But were the endpoints meaningful?” he asked. “In this case, it achieved those goals set out as the primary endpoints of the trial. Now that this drug [verteporfin] is out in practice, however, is it as efficacious in real life? Is visual acuity alone an adequate measure of the efficacy of a drug or a treatment, particularly when the effect is reduction in vision loss, rather than improvement in vision?”
It was enough to satisfy the FDA, which allowed verteporfin to go to market. But Drs. Sternberg and Lewis question whether a single outcome is sufficient. They suggest that the FDA should consider requiring quality of life at least as a secondary outcome measure of clinical trials.
Others agree. “These are vital issues that need to be addressed,” said William F. Mieler, MD, who was principal investigator of the Collaborative Ocular Melanoma Study (COMS), one of the first major clinical trials in ophthalmology to include a quality-of-life component. The COMS looked at survival rates for two alternative treatments for primary eye cancer—radiation therapy and enucleation. When the data showed no difference in survival rates, quality of life became an important factor in choosing a treatment option.
Dr. Mieler conceded that quality of life is easier to assess in a study like COMS, which had “two quite disparate treatment arms.” In the PDT trials, it might be harder to assess in patients with a good fellow eye. Still, Dr. Mieler says that adding a quality-of-life component to clinical trials is a reasonable recommendation. “Many times we get focused on certain aspects of outcome—most of the time, on things we can measure precisely. But we still lose the significance of where that fits into patients’ ability to do daily activities. We lose sight of the overall picture of the patient.”
Putting the patient first might be called the battle cry of quality-of-life advocates. It’s a way of turning ordinary research goals and clinical practice on its head. “People don’t want to know what their pressure is. They want to be able to be sure they can function,” said Dr. Lee. “Most people don’t really care so much about what their blood pressure is, except insofar as it adjusts their risk for something they wish to prevent, such as heart attack or stroke.” The same may be said for vision. “If you talk to people with macular degeneration or glaucoma, they’re more concerned about going blind or visual limitations.”
He continued, “The average physician out there is aware of this. [Every day, physicians] try to do things and help people to function at a high level.”
Why Trials Don’t Assess Quality of Life
So why isn’t quality of life a routine part of clinical trials?
Wiley A. Chambers, MD, said it’s up to Congress, which writes the Food, Drug and Cosmetic Act, to create such a mandate. In the meantime, Dr. Chambers said that it’s difficult to assess quality of life. “We don’t have very good instruments ... We don’t have good measures of quality of life.” Besides, he added, “If you held something up for meeting good quality-of-life measurements, we might not have lots of drugs.”
In the AJO editorial, Drs. Sternberg and Lewis contend that studies are often designed “to obtain approval for the drug, rather than to optimize patient benefit.” In addition, they note that a study’s endpoints may be dictated by financial motivation. “At the end of the day, they want a drug that will seek improvement and get a return on their investment.”
Researchers also have a financial stake in these clinical studies. As department chairman, Dr. Sternberg must pay attention to research funding. “Industry-sponsored drug studies increase a department’s level of research support and may motivate many academic programs to participate in these projects,” he said.
Not a Perfect Science
Quality-of-life studies have limitations, especially when they’re part of a clinical trial, said Dr. Sternberg. The special attention showered on subjects in a clinical trial could make them feel better in the way the classic sugar pill does, thus creating a “placebo effect” that skews the results. “You’re 85 years old, and you’re coming in regularly for exams, receiving regular ‘touch base’ phone calls from the study coordinator, and they’re sending you birthday cards. They care about you, and your quality of life improves.”
Quality of life “can be somewhat difficult to measure,” agreed Dr. Scott. “It has often been perceived as subjective, and therefore, I think it has been somewhat neglected and not given the priority that should be assigned to it.” Quality of life research should be performed with the same scientific rigor employed in other types of scientific research, she said.
“Measuring quality of life is not a perfect science,” said Melissa M. Brown, MD, MN, MBA, who has developed a quantifiable measure for assessing quality. (See “How Cost-Effective Is That Treatment?”) “But having a good measure that’s consistent is far better than anecdotal notations,” she said, adding that the measures “can be improved on as we go along.” Dr. Lee agreed. “As the field grows, we’ll come up with better instruments and better ways of analyzing the results.” In the meantime, he said, “We now have techniques to explicitly measure these things.”
And unless we want to be like those blind men and the elephant, quality-of-life proponents will argue that we should start using those techniques. As Dr. Scott put it, “As ophthalmologists, we want to maximize the vision-related functional status and quality of life of our patients. In order to do this, we have to see our patients as more than an eyeball, more than simply a line on an eye chart.”
1 Am J Ophthalmol 2004;137(3):483–385.
How Cost Effective is That Treatment?
Here’s a hypothetical situation: The doctor records, “I saw Mrs. Smith today and she looked as though she was pleased at what the medication helped her be able to do.”
Dr. Brown believes there’s a better way. “I’d like to be able to say, ‘Mrs. Smith, what was the improvement in the quality of your life, given the intervention?’”
And for the past four years, Dr. Brown and her husband, Gary C. Brown, MD, have been doing just that. Using rigorous research methodology known as utility analysis, they have posed that question to recipients of various medical interventions. They ask, “How many years do you expect to live, and how much of that time would you be willing to trade to get back to perfect health?” For eyes, the trade-off would lead to good vision.
The Browns didn’t concoct this time trade-off methodology. Utility analysis, of which time trade-off is one variant, was developed in the 1940s to measure uncertainty. It was first applied to health care in the 1970s to objectively measure quality and attribute the value of a particular intervention to a given health state.
Dr. Brown believes so strongly in the power of this methodology that she stopped practicing ophthalmology four years ago and established the Center for Value-Based Medicine in Flourtown, Pa., where she pursues this line of questioning full time.
Her motivation for the switch was the combination of a great deal of talk about health care reform and little discussion of various health interventions. While she said the vast majority of interventions are “terrific,” some deliver negligible or no value. “We previously had no dependable and reproducible way of knowing which is which.”
Utility analysis, which measures the actual value of a therapy to a patient, makes it possible to distinguish good interventions from the bad, Dr. Brown said.
Such analysis, however, entails moving beyond simply measuring central visual acuity, which is the standard measure used by most ophthalmologists.
In an editorial published two years ago, the Browns note that visual acuity has become the primary benchmark for most evidence-based data, and that most ophthalmologists regard it as the most important factor related to quality of life of the ophthalmic patient. “And over a century of experience suggests that they are probably right,” they write.1 Even so, they argue, relying on that single measure doesn’t provide the best value-based data.
What’s the difference? “Evidence-based medicine incorporates the most reliable and reproducible data from clinical studies,” they write. Value-based medicine goes a step further and measures the actual value of the therapy to a patient. While this may sound nebulous, they say it can be quantified by assessing the improvement in length of life and/or quality of life conferred by an intervention.
Here’s how it works: If a patient with 20/40 vision is willing to trade four of 20 hypothetical remaining years in return for perfect vision, the utility would be 1 – 4/20 = 0.80 (where 1.0 equals perfect health and 0 equals death). This analysis can be combined with a cost analysis, to assess the value received from the money expended.
Value-based medicine, in essence, provides a consumer’s report to all stakeholders in health care, Dr. Brown said. If a treatment works well, it will be cost-effective even if it is expensive. But if it delivers no value, it will not be cost-effective at almost any price.
By convention, an intervention is cost-effective if it costs < $100,000 per QALY (quality-adjusted life-year gained), Dr. Brown explained. The most common major operation for ophthalmologists, cataract surgery, is very cost-effective at $2,020/QALY. In fact, cataract surgery is so cost-effective that even surgery in a second eye has a cost-effectiveness of $2,727/QALY.
Dr. Brown contends that value-based medicine takes evidence-based data one step further, by incorporating the evidence to measure the value of the therapy to the patient. It puts the patient first. “Unless we can improve the length of the life or the quality of life, then we ought not to be practicing medicine.”
1 Br J Ophthalmol 2002;86:2–3.
Meet the Experts
Melissa M. Brown, MD, MN, MBA Director of the Center for Value-Based Medicine in Flourtown, Pa.; adjunct assistant professor of ophthalmology at the University of Pennsylvania; and adjunct senior fellow at the Leonard Davis Institute of Health Economics at the University of Pennsylvania.
Wiley A. Chambers, MD Deputy director for the FDA’s Division of Anti-Inflammatory, Analgesic and Ophthalmologic Drug Products.
Paul P. Lee, MD, JD Professor of ophthalmology at Duke University.
William F. Mieler, MD Professor and chairman of ophthalmology at the University of Chicago.
Ingrid U. Scott, MD, MPH Associate professor of ophthalmology at the University of Miami.
Paul Sternberg Jr, MD Chairman of ophthalmology and visual sciences at Vanderbilt University.