Medicine: The art of applied science

I read this NPR article this morning and had to do a post in response. The gist is that the military is turning to what we might call the less conventional (for us in the West) medical modalities to deal with the injuries sustained by the current crop of vets. Instead of getting them hooked on pain meds for life (we saw plenty of this in the VAs in the '80s and '90s among Vietnam vets), they are turning to stuff like massage and acupuncture. And, predictably, it is stirring up controversy.

The story that is told is of a Sgt. Rick Remalia who fractured his back and pelvis in Afghanistan:

Remalia broke his back, hip and pelvis during a rollover caused by a pair of rocket-propelled grenades in Afghanistan. He still walks with a cane and suffers from mild traumatic brain injury. Pain is an everyday occurrence, which is where the needles come in.

And lately he has been receiving acupuncture treatments, with this result:

"I've had a lot of treatment, and this is the first treatment that I've had where I've been like, OK, wow, I've actually seen a really big difference," he says.

And incidentally, her gets these treatments from a military physician, who, herself a skeptic, admits to perceiving a personal benefit from her own exposure to it:

"I actually had a demonstration of acupuncture on me, and I'm not a spring chicken," she says, "and it didn't make me 16 again, but it certainly did make me feel better than I had, so I figured, hey ... let's give it a shot with our soldiers here."

So, all good so far, right? Well, Harriet Hall is quoted in the same article, and to her this falls right into what she likes to call "quack-ademic" medicine. She says,

"The military has led the way on trauma care and things like that, but the idea that putting needles in somebody's ear is going to substitute for things like morphine is just ridiculous," Hall says.

Now, as you know, I have had some debates with the SBM crowd in the past, and as it turns out, we agree on the science more than we disagree. However, I am thinking that this argument is not about science, but about politics.

I am well aware that a group of anecdotes does not amount to science. And I am also well aware that what we are hearing here are anecdotes. But here is the thing: when your kid tells you that she likes chocolate ice cream better than vanilla, do you ask for evidence that chocolate is better than vanilla at the population level? No, that's absurd! OK, you say, but this is a strawman: nobody is going for a claim of superiority of chocolate ice cream over vanilla. That is true, but is this about the science or about being able to make a claim? If my kid likes chocolate, why not let her have that when ice cream is on the menu? If acupuncture seems to provide some relief to Sgt. Remalia, why not let him have that relief? After all, whose opinion about what works counts in this individual example, ours or the patient's? And if the ethics of using placebo are the concern, there is nothing wrong with letting him know that in large clinical trials the evidence is equivocal, which means that it may work for some and not for others. In fact, this might be a good disclaimer to make before commencing any treatment, one with the right to claims and one without.

Another argument is that there is no way that insurance (or our taxes) should pay for this unproven treatment. Still about science? Do any of you want to stand up and tell Sgt. Remalia, who fought for our freedom, that we will not pay for the only thing that seems to help him, that is pretty cheap and safe and that has very few, if any, long-term adverse effects, in stark contrast to pain killers? Yes, I understand that this is not science, but is there no room for humanism in the practice of medicine? After all we have throaty debates as to whether or not it is ethical to deny a $100,000 payment for a treatment that, on average, prolongs life by 2 weeks. Surely, denying Sgt. Remalia access to this relief would diminish our humanity. And what about the costs of treating addiction to pain killers?

So, here are my points:
1. I completely agree that that acupuncture "works" for Sgt. Remalia, does not mean that "acupuncture works" in the scientific sense. It may or may not work; furthermore, our current models of the universe do not allow us to have an adequate mechanistic explanation. But that is not the point -- it works for this young man whose life will never be the same because he signed up to defend his country. To this extent his "claim" has all kinds of internal validity.
2. Making claims is subject to legal and regulatory frameworks that have very little to do with science. I have done much blogging on clinical vs. statistical considerations in clinical research that feeds regulatory approvals and hence claims, and I remain of the opinion that a lot of the acceptable claims are specious. I know, I know, this is a "tu quoque" argument, but if we are talking about the goose and the gander, well...
3. Whether or not a treatment should be paid for is more prone to political than evidence-based decisions. Given that most medicines work in a minority of patients, and none comes without adverse events, the extent of which remains largely unknown because of our negligence to build real regulatory systems to quantify them, we are spending a lot of dollars on stuff that does not work at the individual level.

Medicine has to be part science and part art; in fact the art is in how and when to apply the science. That latter portion must be about humanism.

   

Side effects: The subject must become the scientist

A few weeks ago someone I know, a normally robust and energetic woman, began to feel fatigued and listless, and had some strange sensations in her chest. She presented to her primary care MD, who obtained an EKG and a full panel of blood tests. The former showed some non-specific changes, while the latter was entirely normal. Although reassured, she continued to experience malaise. When she fetched her EKG, she received a copy with the computer interpretation indicating that, in its wisdom, the program could not rule out a heart attack. Given that her symptoms continued, and now anxiety was piled on top, she presented to the ED, where a heart attack was excluded, and she was scheduled for a stress test. In the subsequent weeks the symptoms continued off and on, and the stress test turned out to be negative for coronary disease. Great, mazel tov!

What I failed to mention was that just prior to the onset of her symptoms, she had been started on 5-fluorouracil cream for a basal cell skin cancer. And while she did not commit my current device of omission with her doctors (including the dermatologist who prescribed the drug), all denied her constellation of symptoms as a potential side effect. And granted, when I looked it up, there was no mention of anything like fatigue and listlessness. So, does it mean that it is not within the realm of the possible that this drug was responsible?

Not at all. And here is why. Our adverse event reporting is essentially a discretionary system. Here is what the FDA says about their Adverse Event Reporting System (AERS):

Reporting of adverse events from the point of care is voluntary in the United States. FDA receives some adverse event and medication error reports directly from health care professionals (such as physicians, pharmacists, nurses and others) and consumers (such as patients, family members, lawyers and others). Healthcare professionals and consumers may also report these events to the products’ manufacturers. If a manufacturer receives an adverse event report, it is required to send the report to FDA as specified by regulations. 

What this means is that, when a patient complains to a doctor of a symptom, even when its onset is in obvious proximity to a particular medication, the doctor is not compelled to report it. The most an average physician will do is look up the known AE profile of the drug and at best look up its interactions with other medications. But one is not generally inclined to use one's imagination (and the constraints of the shrinking appointments spread across exponentially growing cognitive loads conspire against it too) to entertain the possibility that the current problem is related. And yet since many AEs are particularly rare, the knowledge about them must necessarily rely on scrupulous reporting by the prescribers into a central repository. This is what is missing: not the repository, but the impetus to report.

So, when we go looking up side effects of a given medication, we must take the information for what it is: a woefully incomplete list of what has been experienced by other patients. And when someone asks "Do statins make you stupid," instead of denying the possibility, we should just admit that we don't know. Because once drugs are released by the FDA into the wild of our modern healthcare, by relying on others' reports of AEs we become inadvertent enablers of our ignorance about them.

My friend's symptoms abated after she finished the course of the 5-FU cream. None of the MDs bothered to report her symptoms to the AERS, and nor did she. I am not even sure that any of the players were aware of the possibility. Oh, well, an opportunity lost. We need to feel responsible for gathering this knowledge. The subject must be empowered to become the scientist; this is the only way we can get the full picture of the harm-benefit balance of our considerable and unruly pharmacopeia.

If you want to report a possible side effect of a medication, this FDA web page will guide you through the process.