The Constant Struggle

Most medical innovation comes through profit motive. This has pluses and minuses.

When I review evidence for the This Week in Cardiology podcast, I fight the urge to become cynical. No, John, don’t go there.

A voice in my head says it would be foolish to diminish the gains that medical scientists have made in recent years.

Certain types of cancers are routinely cured or transformed into chronic diseases. New cardiac drugs and devices have extended life and diminished suffering. I see this every day I do clinic. And there is even a tantalizingly optimistic injection to treat Western society’s number one problem: obesity.

The problem is that these sorts of success are rare. Most of the things we do are either incremental or non-beneficial.

On the latest #TWICPodcast I discussed two studies promoted as progress but surely were not. Before presenting the studies, I started with the tension inherent in a system that innovates via capitalism.

For better or worse, most of the Western world of Medicine depends on profit motive for innovative devices and drugs.

If you are smart, lucky, and hard-working you might make a drug or device that helps millions. The companies that made ACE inhibitors, pacemakers and stents have made gazillions. That is good, they deserve it.

But the other side of that tension is that not all new things are as clearly beneficial as ACE-I, pacers and stents. This means consumers of innovation have to be clear-headed about what is innovative and what is flat-of-the-curve low value therapy.

We have to be careful not to be bamboozled by spin.

This post will consider one of the studies. It was presented during a premiere session of a major European medical meeting. These are called “late-breaking” science sessions. If you are an innovator, it’s important to get into these sessions because the media feel obliged to cover these studies.

In the old days, these sessions were reserved for landmark practice-changing trials. But these are rare. So that leaves a space that needs to be filled.

The study involved use of a device that creates a hole in the septum between the left and right atrium in patients with heart failure. In heart failure, the pressure in the left atrium increases and gets transmitted back to the lungs, causing fluid buildup and shortness of breath.

The idea behind the device is that if you create and maintain a Goldilocks-sized hole, you could relieve pressure in the left atrium without overloading the right atrium and ventricle. Bio-engineering is pretty amazing, so such things are plausible.

Okay, now the study.

Readers of Stop and Think know what to expect: you expect a randomized controlled trial with one group getting the device and the other a sham placebo procedure. The trial would measure something important and unbiased like rates of death or hospitalizations. If the device worked, it would save lives or reduce hospital admissions vs the placebo.

But that is not what the study did. Instead, the study, which was presented during a premiere session, reported the effects the device had on ultrasound measurements in just 61 patients. There was no control arm; no clinical outcomes like hospital admissions. The study was a part of a roll in for a bigger trial, called RELIEVE HF.

These sorts of preliminary studies are important to sort out the basics of what may work. But they do not belong in sessions that are reserved for studies that may change practice. They give doctors no relevant information for patient care.

You might be saying, come on, Mandrola, who cares about one little study that eked by organizers to get into a media-heavy slot at a meeting.

Well, let me tell you more, and then connect it with the capitalism and innovation tension.

The first fact is that a few months ago a major randomized trial, with a sham placebo, and more than 600 patients, studied the effects of creating a shunt between the two atria. The Lancet published the REDUCE-LAP-HF-2 trial, which found no differences in clinical outcomes. There was no way to spin these results. All that could be said is that it this device did not work.

But that was with device X.

Another company has a slightly different device that creates a slightly smaller hole in the septum. Key opinion leader Dr. William Abraham speaking at the meeting said that the negative REDUCE-LAP-HF-2 trial is different from the RELIEVE HF trial. Not only will it use a different device, but it will have a different design and enroll a different group of patients.

The message I hear is that the newer device has a positive pilot study, it makes a smaller hole, and it will be studied in different patients. Translation: the strategy of using a shunt between the atria is not dead.

Now…guess who Dr. Abraham is? He is now the chief medical officer for V-Wave, the maker of the new atrial shunt device.

See the problem?

Companies that make devices and scientists who study these devices have dualities of interest. They both benefit if a device works. Companies make profits. Scientists get promoted because “positive” studies get published in higher impact journals. And professional societies also indirectly benefit because they depend on industry funding.  

The key ideas though is this: When said therapies really work, patients also benefit.  

While I wish scientists and professional societies were more impartial, I don’t see the process as nefarious. It is our system. And sometimes it produces huge wins.

(There is an argument about public vs private funding of innovation, but that is for another post.)

For now, in this system, it is the job as consumers of the evidence to learn to be neutral judges. This takes effort and consideration of the dualities of interest.

This newsletter and the #TWICPodcast will try to help—without cynicism.