Paralysis by analysis

Paralysis by analysis

Yesterday the Annals of Internal Medicine published an article entitled “Glycemic Control in Type 2 Diabetes: Time for an Evidence-Based About-Face?” by Victor M. Montori, MD, MSc, from the Mayo Clinic in Rochester, Minnesota, and Mercè Fernández-Balsells, MD, from Hospital Universitari de Girona Doctor J. Trueta in Girona, Spain . The authors examined findings from large randomized trials comparing clinical outcomes for patients with type 2 diabetes managed using tight vs less tight glycemic targets.

The authors concluded;

Current best evidence requires a change in emphasis in our care for patients with type 2 diabetes. Clinicians should prioritize supporting well-being and healthy lifestyles, preventive care, and cardiovascular risk reduction for these patients. Randomized trial evidence that we reviewed do not strongly support tight glycemic control as a more beneficial than harmful approach to reduce the risk for diabetes complications. Although we should not dismiss potentially effective approaches (for example, early tight glycemic control for patients with newly diagnosed diabetes), we require additional research to confirm or refute such approaches before we impose them on patients, particularly given the unequivocal patient burden, cost, and harm of serious hypoglycemia associated with tight control.

This article is just the latest in what is becoming a growing controversy over the benefits of tight glycemic control for patients with type 2 diabetes. A controversy which began when the ACCORD trail was stopped early because of mortality risk and gained momentum as the Avandia controversy became a major story.

It seems with each passing day physicians are faced with contradictory data as one study says tight control is good for the patient, while another concludes the exact opposite. Besides the confusion these contradictory findings have on physicians, their impact goes beyond the medical community and directly to the FDA, an agency which is supposed to use evidence-based medicine to make decisions.  

While Diabetic Investor has been critical of the agency this article points to just how difficult it is for the agency. Just how is the agency supposed to use evidence-based medicine when the evidence is unclear? Frankly the agency is caught between the preverbal rock and hard place. How in the world can they develop a clear set of standards when studies offer contradictory findings on the same subject?

In an attempt to quell growing criticism and please members of Congress the agency developed a new set of guidelines when approving drugs for patients with type 2 diabetes. Thanks to Dr. Nissen and his now famous meta-analysis, glycemic control is no longer the standard used to approve new drugs. Companies now have the additional burden and cost of proving their drug does not increase the risk of adverse cardiovascular events.

But the agency hasn’t stopped at worrying about adverse cardiovascular events and seems to be looking for any reason NOT to approve new drugs. Something we witnessed with the recent panel meeting for Novo Nordisk’s (NYSE:NVO) GLP-1 Liraglutide. Besides having to prove that Liraglutide adequately controlled glucose levels, something it did well, the company also had to prove patients using Liraglutide did not experience adverse cardiovascular events. But the FDA didn’t stop there as they added a new hurdle to Liraglutide with concerns over the possible connection to thyroid cancer. Unfortunately for the agency the panel that was formed to help them with this decision folded like a house of cards when it came time to follow through with their job.

Diabetic Investor can only imagine what impact this latest controversy over tight glycemic control will have on the agency. It doesn’t help matters any that different organizations have different standards for what’s considered good control. The ADA standards is an HbA1c of 7% or less, while AACE and EASD pegs good control as an HbA1c of 6.5% or less. To make matters even more confusing there’s a growing group of researchers who believe that we should no longer use HbA1c as the standard and look at glycemic variability instead.

Is it any wonder that a company that has a drug before the FDA or going to the FDA is afraid to answer any question on how the approval process will go or what additional data the agency might ask for. To illustrate this point just listen to the recent calls from Roche, Lilly (NYSE:LLY) and Amylin (NASADAQ: AMLN) and the questions they faced over their GLP-1 candidates. Listening to these questions Diabetic Investor began to feel sorry for rats and mice, as they have become the center of attention and could well control the future of the GLP-1 class of drugs. This is not unlike how monkeys must have felt during the battle between Januvia and Galvus.

What’s truly sad here is that once again millions of patients who know nothing about C-cell’s or meta-analysis are suffering. While academics, researchers, government bureaucrats and our elected officials’ debate; the very patients who desperately need new therapy options and the physicians who treat them are left to fend for themselves. Instead of giving patients and physicians more weapons to fight diabetes, they are taking away options. This is like asking our brave men and woman who are risking their lives in Iraq and Afghanistan to fight terrorism with weapons from the Civil War.  Are we approaching the day when go back to using leeches to treat diabetes?

The fact is that every medication carries some degree of risk. There is absolutely NO medication that can be taken that does not carry some form of adverse event possibility. This obsession with eliminating every possible risk factor will grind drug approval to a halt and literally cause the premature death of millions of patients. This is completely unacceptable and even criminal. This is like seeing a person with gun shooting at a room full of people and telling these people to duck, while the authorities debate the merits of gun control laws.

The bottom line here is that DIABETES IS A SERIOUS HEALTHCARE AND ECONOMIC ISSUE. The very researchers who complain that FDA is clueless only contribute to the problem. Instead of coming together and agreeing on a set of guidelines, however imperfect they may be, they continue to confuse everyone; preferring to protect their professional standing instead of helping patients and the physicians that treat them. Diabetic Investor expects this type of childish behavior from politicians who care only about getting their faces on television, not from the very people who are supposed to helping solve the problem.

What’s needed is some perspective and leadership. Unfortunately Diabetic Investor is not optimistic that either will be forthcoming. Let’s face facts here as the FDA is an agency ill-equipped to deal with these complex issues. The agency has become afraid of its own shadow, fearing that another Rezulin, Vioxx or Avandia will bring them before the Congressional inquisition. You can hardly blame them for their increasing paranoia. Issues like the Liraglutide thyroid cancer concerns, minor as they are, all of a sudden take on heightened importance when you have an agency more concerned about not making a mistake than helping millions of patients with diabetes.

In their article the authors quote John Maynard Keynes, who stated “When the facts change, I change my mind. What do you do, sir?” However, what do you do when no one agrees on just what the “facts” actually are? As Mark Twain stated; “Facts, or what a man believes to be facts, are always delightful…Get your facts first, and then you can distort ‘em as much as you please.”