Blog | Monday, September 18, 2017

Of Research, RxESPECT, And Silver Spoons


Among the predominant themes of modern medicine is a consistent emphasis on high standards of evidence. For purposes of this column, we may forgo consideration of all the implied methodologic minutiae, from randomization to statistical power, confounding to external validity. It suffices here to note there are many subtleties involved in producing high quality evidence as the foundation of something nearing certainty about the effects of X on Y, with many of them well established and universally acclaimed, others more controversial.

There is, however, a considerably larger potential problem than the reliability of any given P value, and that is the matter of parity in what research gets done, how it is reported, and what becomes of the results. From my vantage point, more than 20 years running a clinical research lab, over 25 years of clinical care, I see a very unlevel playing field. I am concerned in particular that lifestyle as medicine gets all too little respect.

Let's start with the most recent case. A study was just published in JAMA comparing a lifestyle intervention comprising both dietary modification and exercise, to standard care relying principally on drugs for blood glucose control in type 2 diabetes. The primary outcome measure was change in glycohemoglobin (HgbA1c), a kind of “weighted average” of blood sugar over time, and the participants were followed for a year.

There was an unusual element in the study design that hints already at the biomedical biases of modern society. Since standard care that relies preferentially on medication is, indeed, “standard,” the researchers designed a “non-inferiority” study, otherwise known as an equivalence study. The statistical techniques were chosen to show that the lifestyle intervention was as good as standard care; most studies are designed to show that treatments differ.

At 12 months, the treatment assignments were not equivalent. HgbA1c had improved more in the lifestyle treatment group than the standard care group, despite what the authors described as a “substantial and parallel reduction in glucose-lowering medication” in that group. In plain words, with the lifestyle intervention, participants had better blood glucose despite taking less medication. In this “lifestyle as medicine” versus “medicine as medicine” contest, lifestyle won, reminding us all of the same result when lifestyle was compared to medication in a much larger, and rather famous study of diabetes prevention.

The new study made the medical news, but that's where things took an odd turn. The headline at MedPage Today, since changed (at my request), was originally: “Exercise Not on Par with Meds for Glucose Control in T2D.” That's true. It was “not on par” because it was better!

The headline in the American College of Physician's JournalWise, a personalized literature updating service available to ACP members and widely distributed to physicians, was: “In adults with type 2 diabetes for < 10 y, a lifestyle intervention was not equivalent to standard care for glycemic control.” Again, that is technically true; it was “not equivalent” … because it was better.

Admittedly the odd reporting in this case had much to do with the investigators' choice of an equivalence design, and with the very tempered language the investigators themselves used in their paper. But still, it's hard to imagine a drug study showing effects greater than the control group being reported as “failure to show equivalence” under any circumstances. There is a ubiquitous bias at play.

As noted, the evidence has long been clear that lifestyle intervention is superior to medication in the prevention of type 2 diabetes in those at high risk (twice as good, in fact). The Diabetes Prevention Program does enjoy wide support now. But still, vastly less money is spent on translating what we know about diabetes prevention with lifestyle into routine practice than is spent on developing and disseminating new medical treatments.

While we generally use the term “standard of care” to imply state of the art, the standard may refer more reliably to the state of the status quo, the nature of which is to defend itself. My friend and colleague, Dr. Dean Ornish, developed a lifestyle intervention that could treat and reverse life-threatening coronary artery disease as effectively as coronary bypass surgery, but without the need to have your chest cracked open. The chest-cracking surgery was, of course, reimbursed by major insurers, including Medicare and Medicaid, as soon as it was established; it took Dr. Ornish, and those running a comparably robust program at the Pritikin Longevity Center, years and even decades to achieve the same for the lifestyle alternative.

Some years back, I was working as the medical director at a boarding school for adolescents with severe obesity. The results achieved were stunning in every way. But the school has since folded, because the kids who most needed the help came from families that could least afford it, and the third party payers who will, as a matter of routine, cover bariatric surgery for a 17-year-old, don't have policies to cover the even better results intensive lifestyle medicine can achieve.

My final illustration of our costly societal bias is a tale I have long been telling. A tiny, brief, and presumably fairly inexpensive study of coenzyme Q10 for heart failure published in 2000 in Annals of Internal Medicine failed to show any benefit. An editorial in the same issue asserted that the “final nail” had been driven into the CoQ10 for heart failure hypothesis. Can you imagine such an editorial accompanying a small, brief study that failed to show some particular effect of a newly patented drug? I cannot either; I have never seen any such thing.

Within a year (2001), results of the much larger, longer, and vastly more expensive CAPRICORN trial were published in The Lancet, showing the therapeutic benefits of the proprietary drug, carvedilol, in heart failure. The predictable ensued: carvedilol has long been incorporated into the standard care of congestive heart failure, whereas CoQ10 has not.

What's the problem? When the money was finally scraped together to run a study of CoQ10 roughly comparable to the CAPRICORN trial, in 2013, this result was reported: “first drug to significantly reduce heart failure mortality in over a decade.” A rather impressive resurrection for a nutrient decisively nailed into its coffin 13 years prior.

Lifestyle as medicine is the best medicine we have, the only one appropriate for universal application, suitable for children and octogenarians and breast-feeding mothers; the only one that can add years to almost everyone's life, add life to almost everyone's years. But lifestyle medicine is undermined by those profiting from the propagation of lifestyle disease, and gets too little respect from those selling the standard remedies of modern medicine.

In other words, those holding the silver spoons may not want you to have the spoon you need to help lifestyle as medicine go down. That just means it's time to invent new spoons.

David L. Katz, MD, FACP, MPH, FACPM, is an internationally renowned authority on nutrition, weight management, and the prevention of chronic disease, and an internationally recognized leader in integrative medicine and patient-centered care. He is a board certified specialist in both Internal Medicine, and Preventive Medicine/Public Health, and Associate Professor (adjunct) in Public Health Practice at the Yale University School of Medicine. He is the Director and founder (1998) of Yale University's Prevention Research Center; Director and founder of the Integrative Medicine Center at Griffin Hospital (2000) in Derby, Conn.; founder and president of the non-profit Turn the Tide Foundation; and formerly the Director of Medical Studies in Public Health at the Yale School of Medicine for eight years. This post originally appeared on his blog at The Huffington Post.