Physicians must apply art, science of medicine to customize patient treatment plans
Click Here to Manage Email Alerts
The accompanying OSN cover story, which interviews retina specialists around the world, confirms that evidence-based medicine and personalized medical care are priorities for ophthalmologists globally.
Evidence-based medicine (EBM) has been defined as “the conscientious, explicit and judicious use of current best evidence in making decisions about the care of patients.” Integrated with the EBM process is personalized medical care, which takes into account the individual patient’s needs, beliefs, culture, physiology and genetic makeup to develop a personalized treatment plan for any disease or health care/wellness issue. The goal is to achieve optimal individual health care decisions for best-case treatment regimens.
EBM is ideally based on well-performed prospective randomized clinical trials. One of the first recorded examples of a prospective clinical trial was Jan Baptist van Helmont’s study of bloodletting vs. conservative therapy in fever and pleurisy in 1662, looking at comparative death rates. Conservative supportive therapy with no bloodletting was shown to be superior. Another famous early prospective clinical trial was that of James Lind, a Scottish naval surgeon who stratified sailors on his ship into six groups and found that men treated with lemons or oranges were the most resistant to scurvy.
Today, the quality of evidence is considered critically important to EBM decisions, and in 1989, the U.S. Preventive Services Task Force put forth a guide. Level I evidence was defined as that developed in a well-designed, properly powered prospective masked randomized clinical trial with an appropriate control group. Level II-1 is evidence achieved through a similar prospective study without randomization. Level II-2 evidence requires a well-designed cohort or case-control study. Level II-3 requires confirmatory evidence from multiple uncontrolled studies. And finally, Level III has the opinions of respected authorities based on clinical experience.
Three or more confirmatory studies at any level increases one’s confidence in the validity of the evidence. Thus, three separate well-designed, properly powered prospective masked randomized clinical trials with an appropriate control group from totally distinct investigators and investigational sites remain the best evidence something is true. A single expert opinion, which we all hear (and present) frequently from the podium as “in my personal experience” is the weakest and least reliable source of evidence. A large number of totally independent experts coming to the same opinion can strengthen Level III evidence, and this is often achieved through consensus panels of experts, but the gold standard remains three or more well-designed, properly powered masked prospective clinical trials with an appropriate control.
I have often found myself saying with humility when lecturing that “a significant number of the opinions I present to you today will likely at some future date be proven wrong, and sadly, I do not know which ones.” But those of us who teach others must often rely on imperfect evidence and teach what we believe to be true at the moment using the best evidence available integrated with our own clinical experience. In addition, many personal and external biases reduce the value of even Level I evidence, including risk bias, imprecise measurement, inconsistent data gathering, publication bias, and inappropriate application or interpretation of statistical analysis, among others. Presenting a further challenge to the clinician, once a physician or surgeon has what they believe to be reliable evidence, they must apply it to a unique patient with a wide variation in personality, culture base, intelligence, physiology and genetic makeup. This is the entry point of personalized medicine and the art of patient care.
With the completion of the Human Genome Project in 2003, an amazing international collaboration that extended for 13 years, physicians and scientists around the world began to perform genome-wide association studies (GWAS). Of significant interest to me was the fact that the first GWAS study in the world reported in 2005 was on patients with age-related macular degeneration. Researchers found that two single nucleotide mutations, so-called single nucleotide polymorphisms, were related to the development of visually significant AMD. Since that first study, another 1,300 GWAS studies have been completed. These studies have helped physicians customize treatment with anticoagulants and many cancer drugs based on an individual patient’s genetic profile.
Today, as an ophthalmologist in private practice, I rarely order genetic profiling except for rare instances in children with corneal dystrophies or possible inherited syndromes. But Level I evidence is accumulating that the treatment of many eye diseases, including numerous retinal dystrophies, AMD, diabetic retinopathy, glaucoma, optic nerve disease, corneal diseases such as keratoconus, and even common maladies such as ocular allergy and dry eye disease, may be improved by knowledge of an individual’s genetic profile.
Finally, the potential benefit of evidence-based medicine, personalized medical care and genetic profiling may be further enhanced by the application of artificial intelligence. It remains the duty of every physician to apply both the art and science of medicine to customize a treatment plan for each individual patient. As I enter my 50th year in ophthalmology, it remains a daunting challenge to do so at the highest level, but do so we must.
Collapse
Read more about
Click Here to Manage Email Alerts