Sensible Medicine - a platform for diverse views & debate about biomedicine

For some time, I’ve been an admirer of many of the articles published on Sensible Medicine, a site that usually features articles written by physicians and scientists with diverse opinions on a wide range of biomedical topics. But don’t be scared off by that. I know that I have a mixed following on this Substack - physicians, scientists, journalists, and patients and consumers (of news and of health care). Some of the articles may be over the heads of some readers. But there are often gems that can help any reader improve their critical thinking about health care, biomedical research, published studies, etc. I’ve been saving some recent posts that I really liked, so here’s a brief overview.

John Mandrola, MD, is a cardiac electrophysiologist who is one of the editors of Sensible Medicine. Recently, he wrote:

A team of researchers reported that treatments with a drug named tirzepatide “led to a lower risk of a composite of death from cardiovascular causes or worsening heart failure than placebo and improved health status in patients with heart failure with preserved ejection fraction and obesity.” The first author on the New England Journal of Medicine paper that reported the study results is a “Distinguished Scholar in Cardiovascular Science” at his institution. But Mandrola wrote:

The positive results made news. At least 57 news organizations covered the study. Experts called the study “practice-changing.” If this were true, it would be a big deal….

Yet the trial falls way short of practice-changing. And it’s quite surprising that experts would say these things about it.

He reviewed the data and agreed that at first glance the results could look positive: statistically significant, fewer heart failure events, quality of life was better.

But he found what he considered to be glaring problems. His summary:

It’s curious to me that Eli Lily and the academic authors designed such a small underpowered trial. (These) are two of the most common medical conditions. Previous trials enrolled many thousands of patients. The sponsor clearly has the funds.

Instead, we get a trial with 13 total cardiovascular deaths, less than 50 hospitalizations for heart failure, and biased quality of life endpoints (because of unblinding).

(These) drugs may be disease-modifying… but it would take a far more robust trial to show it. Why this was not done is a mystery.

He also wrote recently about “A Story about Surrogate Outcomes.” A surrogate outcome has been defined as:

an indicator or sign used in place of another to tell if a treatment works. They may be used instead of stronger indicators, such as longer survival or improved quality of life, because the results of the trial can be measured sooner. Surrogate endpoints are not always true indicators or signs of how well a treatment works.

And that’s just the point Dr. Mandrola made in this post - and in a journal article he co-authored - about heart failure treatment trials.

These are the types of article you get from Dr. Mandrola on a regular basis

As one sign of the diversity of opinions on the site - even among site contributors - see this article, in which Adam Cifu, MD expresses “contrasting ideas and opinions” with what another contributor, The Skeptical Cardiologist (Anthony Pearson, MD) had written earlier.

Buying What SELECT is Selling: Semaglutide

You can read the entire piece here. In brief, a trial named SELECT tried to answer whether the drug semaglutide can reduce cardiovascular risk associated with overweight and obesity in the absence of diabetes. The trial “showed that obese (BMI>27), non-diabetic patients with established cardiovascular disease did better when treated with (the drug) semaglutide.”

The Skeptical Cardiologist concluded:

I can’t help but view the SELECT trial as cynically engineered to achieve an indication for preventing cardiovascular disease in a population that was not being appropriately treated with currently available and much more accessible therapy.

Dr. Cifu countered:

Where I disagree is in how I think about using SELECT’s results clinically. Even if I accept that maximizing current therapy might be as beneficial as beginning semaglutide (I am not sure I do), I think my patients would/will prefer the semaglutide option. Instead of weeks/months of adding and adjusting medications, let’s add one new drug. A drug with the added benefit of weight loss in overweight patients. And, maybe after 4 years and — are you ready for this? — loss of 8% of body weight, 2.5 inches in waist circumference, and 3 points in systolic BP, maybe we can stop some of those other meds.

The disagreement was respectful, arguments were made clearly, and readers walk away with a lot to think about.

As a career-long health care journalist, I often think about the words of Fred Friendly of CBS News, who worked with Edward R. Murrow on See It Now and CBS Reports:

Our job is not to make up anybody’s mind, but to open minds, and to make the agony of decision-making so intense you can escape only by thinking.

Sensible Medicine authors do that to you on a regular basis. Check them out.