Tag Archives: Clinical Trials

Improving the Evidence

All good physicians want to do the right thing. They want to recommend effective therapies to their patients that will improve outcomes or alleviate symptoms. It is widely accepted that the best way to discover new effective therapies is through the use of clinical trials. Among clinical trials, the reference standard is the randomized, double-blinded, placebo-controlled trial, which is designed to minimize bias in the selection of therapies or the interpretation of results.

I have written before about the limitations of clinical research in advancing medical practice. As I have said, it is literally impossible to study every clinically relevant question, and it is also impossible even in theory to use randomized controlled trials as the methodology for many of the questions that can be studied.

A recent article in the New York Times highlighted another challenge to the paradigm of clinical trials as the engine for improving medical practice. The piece was about a change in policy at the National Institutes of Health, being implemented by Michael Lauer, the “newly appointed deputy director for extramural research.” In the interest of full disclosure, I have known Mike for many years (we were cardiology fellows in the same program at Boston’s Beth Israel Hospital in the late 1980’s) and you would be hard-pressed to find a nicer, smarter or more upstanding guy.
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Rethinking a No-Brainer

What does someone having a heart attack look like? I think the New York Times captured what many of us probably have in mind, when they published this picture as part of a recent series on advances in cardiovascular care:

Nash_Blog_ImageMark Makela for The New York Times. Retrieved from http://www.nytimes.com/2015/06/21/health/saving-heart-attack-victims-stat.html

Here is the iconic middle-aged guy, in extremis, pointing to his chest, with a team of health care professionals at the bedside. There are also signs of initial management – he has ECG electrodes on his chest, an IV in his left arm, what looks like monitor/defibrillator pads on his right chest and below his left arm and, of course, an oxygen mask.

What is wrong with this picture?
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The New Paradigm

A recent FDA advisory panel recommended the approval of 2 new agents in a novel class of cholesterol lowering drugs known as PCSK-9 inhibitors. What makes this remarkable is that these drugs illustrate all the promise and pitfalls of modern pharmaceutical development.

First, a little science. The target of the new drugs – a protein named proprotein convertase subtilisin/kexin type 9 (PCSK-9) – was discovered in 2001. Two years later, investigators reported that “gain-of-function” mutations in the gene that codes for PCSK-9 were associated with familial hypercholesterolemia and high rates of atherosclerotic vascular disease. Mutations of the gene that led to reductions in the function of PCSK-9 were associated with low LDL-cholesterol levels, and a lower incidence of vascular disease. That made the compelling case that PCSK-9 had a counter-regulatory function in LDL-cholesterol metabolism, so that interfering with its function would lead to lower cholesterol levels.

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