• This study shows so much of what’s wrong with medical research today

    It’s in JAMA Internal Medicine. “Effect of Remote Ischemic Preconditioning on Kidney Injury Among High-Risk Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial“. The gist of it is that with cardiac surgery, there’s a significant risk of developing acute kidney injury. Up to 30% of patients wind up with it, and there’s not much we can do about it. But there’s a growing belief that “remote ischemic preconditioning” might help. What they do is fool the body into being concerned that ischemia, or periods of no oxygen, are coming. The theory is that this gets the tricked tissues to release certain factors that warn the rest of the body (ie kidneys) to slow down and prepare for badness. Then, when the cardiac surgery comes, the kidneys are better prepared for a hit.

    Basically, doctors place a blood pressure cuff on the upper arm. Then they inflate it to at least 200 mm Hg (which is high) for five minutes. Then they deflate it for five minutes. They do this three times in a row. Then they go ahead and operate normally. There had been some small RCTs on this, but they were conflicting, so this was the first major multicenter trial.

    This was a randomized controlled trial. Half the patients got remote ischemic preconditioning, and the other half got the blood pressure cuff tightened, but to a much lesser extent. It’s a simple study.

    The results are pretty impressive. More than half (52.5%) of the patients who received the placebo developed an acute kidney injury. Much fewer (37.5%) of those that received remote ischemic preconditioning developed one. That’s an absolute risk reduction of 15%, meaning the NNT for avoiding an acure kidney injury in this population is less than 7. The NNT for avoiding renal replacement therapy (ie dialysis) was 10.

    Awesome, right? This costs pretty much NOTHING, and it reduced bad outcomes in a high risk population hugely. I bet you didn’t even hear about this. Here’s a bit from the accompanying editorial:

    Before RIPC is adopted for clinical use, the potential risks and adverse effects must be considered carefully. For example, prolonged unilateral kidney ischemia leads to changes in the contralateral kidney and heart. Cardiac changes after experimental renal ischemia include cytokine induction, leukocyte infiltration, cell apoptosis, and impaired cardiac function. While remote kidney/cardiac preconditioning after limb muscle ischemia may differ from the changes observed in the heart after kidney ischemia, effects of repeated limb ischemia with RIPC are not known and clinicians should be mindful of potential harms before adopting this approach widely.

    I dispute none of this. Of course, we should be concerned about potential harms. More research is fine. But this is where I’d like to list the many things about all of this that show how we’re doing medical research wrong:

    1. If these results had come from a drug, or some new device, it would be all over the news. The results are amazing. People would be lining up to invest. Instead—crickets. Why? There’s no money to be made from this.
    2. The final word is that this “warrants further investigation“. That will be nearly impossible to do. Why?
      1. There’s no money in this.
      2. It will require doing another study just to replicate old results.
    3. No one will rush to fund that work. Any further research in this area will be difficult to sell as “innovation”.
      1. And, you may not know it, but the NIH (for instance) has “innovation” as one of its five major criteria for judging a grant. If it’s not “innovative”, it’s hard to get it funded.
    4. Because of this, it’s hard to fund work that confirms findings. This is one of the major reasons we have a problem with research replicability in science.
    5. This is too “simple”. It’s tightening a blood pressure cuff. That won’t interest any rich donors to fund it. It won’t interest foundations. And industry won’t fund it—there’s no money in it.

    And so we will remain in this exact spot for years. There may be an incredibly simple intervention out there that could cost nothing and save lives, but we won’t implement it. Doctors will point to it, and argue about it, but it won’t go anywhere for a long, long time. There’s no money in it. It’s not sexy. Confirming the results and checking for harms will require research funding, and no one will want to do it.* Even when the potential upsides are much, much larger than the many, many projects we will fund. It’s maddening.

    @aaronecarroll

    *For the record, I searched for NIH support for studies involving “remote ischemic preconditioning”. I found two. Neither is an interventional trial.

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