Teach one thing, or the rule of thirds

When I was a medical student, I did a lot of rotations at the Boston VA in JP. I loved my patients there -- they were patient and kind and stoic. One of the best rotations I did was Hematology, where Lou Fiore was my preceptor. Lou was not only an excellent teacher, but also a terrific doctor and a good human being all around. He used to start our days together by saying, "I'm gonna teach you one thing today." And teach us he did, at least one thing per day. Now I teach. And on occasion I have used the Lou Fiore "I'm gonna teach you one thing today" promise. Well, today is one of those days: I'm gonna teach you one thing.

And here is that thing. I am sure I am not the first one to notice this, but I still think of it as the "Zilberberg rule of thirds." The gist of it is that, for clinical research purposes, one can think of patient populations crudely in thirds: there is one third who are too sick to benefit from any of our interventions, there is one third who are too healthy, so that no matter how we try to tweak, their outcomes will not change, and the middle third, which comprises the "sweet spot" for intervention. So it is a fool's errand to pursue proof of concept studies in either of the bracketing thirds, since it is only the middle third that is likely to show a signal.

Pharmaceutical manufacturers do not always appreciate this trichotomy. Look at Vioxx, for example: when used in patients who were essentially healthy, an unacceptable safety signal arose that drove the drug off the market. Same for SSRIs, where the ill-conceived enthusiasm for treating marginal depression cases seems to be debunking the entire serotonin hypothesis. The flip side is sepsis research: septic shock patients are so far gone that it is difficult for any single therapy to alter their outcomes. Just look at the Xigris story, as well as myriad other therapies that tried and failed. This is the rule of thirds at its most pronounced.

In HEOR the rule of thirds holds as well. To prove cost effectiveness the following questions need to be asked:
1. Is the disease in question prevalent?
2. Is the economic impact of the disease known and substantial?
3. Does the diagnostic/therapy in question alter the course of the disease in such a way as to be significant?
If the answer to any of the questions above is "no," you really need to think carefully about the value proposition.

Some of you will bring up the inter-individual differences, the heterogeneous treatment effect, etc. And yes, these are supremely important. However, though the framework I propose here is simplistic, we have to start somewhere. To be sure, there is a more nuanced approach to this beast, but generally, one will not go wrong by asking these questions before committing huge resources to a project, particularly if the answer to question 2 or 3 is a resounding "no." So, even in health economics it behooves one to know the Zilberberg rule of thirds: choose the right population where the diagnostic/therapeutic advance and its costs can be justified by a substantial gain in the outcomes.

And that is your one thing for today.    

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Evidence and profit: An unhealthy alliance

My JAMA Commentary came out this week, and I am getting e-mail about it. It seems to have resonated with many docs who feel that the research enterprise is broken and its output fails them at the office. But what I want to do is tie a few ideas together, ideas that I have been exploring on this blog and elsewhere, ideas that may hold the key to our devastating healthcare safety problem.

The last four decades can be viewed as a nexus between the growth of evidence-based medicine (EBM) on the one hand, and the unbridled proliferation of the biopharmaceutical industry and its technologies. The result has been rapid development, maximization of profit, and a juggernaut of poorly thought-out and completely uncoordinated research geared initially at regulatory approval and subsequently to market growth. It is not that the clinical research has been of poor quality, no. It is that our research tools are primitive and allow us to see only slivers of reality. And these slivers are prone to many of our cognitive biases to boot. So, the drive to produce evidence and the drive to grow business colluded to bring us to where we are today: inundated with evidence of unclear validity, unbalanced with regard to where the biggest difference to public health can be made. Yet we are constantly poked and prodded by the eager bureaucracy to do better at implementing this evidence, while the system continues to perform in a devastatingly suboptimal fashion, causing more deaths every year than strokes.

A byproduct of this technological and financial race has been the rapid escalation of healthcare spending, with the consequent drive to contain it. The containment measures have, of course, had the "unintended consequence" of increased patient volume for providers and of the incredible shrinking appointment, all just to make a living. The end-result for clinicians and patients is the relentless pressure of time and the straight jacket of "evidence-based" interventions in the name of quality improvement. And in this mad race against the clock and demoralization, very few have had the opportunity to think rationally and holistically about the root causes of our status quo. The reality is that we are now madly spinning our wheels at the margins, getting bogged down in infinitesimal details and losing the forest for the trees (pardon all of the metaphor mixing). Our evidence-based quality improvement efforts, while commendable, are like trying to plug holes in a ship's hull with bandainds: costly and overall making little if any difference.

But if we step back and stop squinting, we can see the big picture: stagnated and outdated research enterprise still rewarding spending over substance, embattled clinicians trying to stay afloat, and a $2.5 trillion healthcare gorilla feeding the economy at the expense of human lives. Will technology fix this mess? Not by itself, no. Will more "evidence" be the answer? No, not if we continue to generate it as usual. Is throwing more money at the HHS the solution? I doubt it. A radical change of course is in order. Take profit out of evidence generation, or at least blunt its influence (this will reduce the clutter of marginal, hair-splitting technologies occupying clinicians' collective consciousness), develop new tools for better patient care rather than for maximizing the bottom line, give clinicians more time to think about their patients' needs rather than about how to maintain enough income to pay for the overhead, these are some of the obvious yet challenging solutions to the current crisis. Challenging because there needs to be political will to implement them. And because we are currently so invested in the path we are on that it is difficult and perhaps impossible to stray without losing face. But what is the alternative?

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