Saturday, February 16, 2008

The N = 1 Trial

[Clink Note: First I put up this post, then Dinah posted over it, then she reposted it at the top of the blog with bookend comments. I've taken out her bookend comments and put them immediately after this post, so please do scroll down to read them or click here. Oy. My Comcast access has been really spotty or non-existant this week so I have to act fast while it's up.]

In the January edition of American Psychiatry News Dr. Glenn Treisman writes a critique of the "fail-first" policies of managed care organizations entitled Promoting The Concept Of The Individual Trial (free registration required to read the article). He begins with a brief case presentation of a patient who was successfully treated as an inpatient with a drug that was nonformulary according to his new insurance company. The patient was discharged and his outpatient doctor, who didn't have access to his previous treatment records, switched him to a different formulary medication which he had previously failed. The patient relapsed and required rehospitalization.

He begins with a critique of the idea of therapeutic equivalence. Therapeutic equivalence refers to the idea that different medications can be shown to be equally effective in treating a given medical condition. Dr. Treisman rightly points out that this evidence is based on treatment response of large groups of patients and may not be predictive for a given individual. For example, SSRI's as a whole may be equally effective in treating depression but a specific patient may find Zoloft more effective than Paxil. There may also be specific individual issues such as co-existing medical conditions that may influence a clinician's choice of medication. (See also Dinah and Roy's posts on How To Choose An Antidepressant, Part 1 and Part 2).

He goes on to attack what he refers to as a perversion of the term "evidence-based medicine". This term originally meant that doctors should base their treatment decisions upon current research, using the best information that is available at the time. He alleges that insurance companies use evidence-based practices as an excuse to deny care and save money:

"At times, evidence-based medicine has come to be used as an excuse to change the equation of medical treatment entirely. The new equation is to start with the premise that treatment should not be used unless it has been 'proven' to work."
The misuse of therapeutic equivalence and evidence-based medicine, according to Treisman, has caused patients to become disillusioned and suspicious of traditional medical care and turn to alternative and homeopathic treatments. And for doctors he feels the nonformulary approval process "wastes the time of busy physicians" and injures patients.

So that's my recap of the article. My reaction to the article is that I agree wholeheartedly with Dr. Treisman that it's good to remember the limitations of large clinical trials when you're treating the individual patient. It's also good to remember that therapeutic equivalence is a regulatory concept not necessarily a clinical truth.

Here's where I disagree:

The nonformulary process and the emphasis upon adherence to treatment guidelines is not solely the fault of the "evil" greedy insurance companies. I think we as physicians need to accept our role in driving these policies.

Health care cost containment is everyone's responsibility. It's easy for doctors to feel bothered by paperwork, to feel threatened by challenges to clinical autonomy, or to be offended by suggestions that one's practice is not up to modern clinical standards. But the fact of the matter is that in psychiatry there are a lot of free-wheeling physicians out there. Indiscriminate use of expensive medications for vague clinical indications (Seroquel for anxiety, anyone?) drives up the cost of health care for everyone. And practice guidelines were not developed by insurance companies. They were created by professional organizations to enhance the overall standard of care and quality of care given by their physician members. The professionals themselves recognized that there were issues with wide variation in patient care, or suboptimal care, long before insurance companies got ahold of these guidelines.

It's a facile sleight-of-hand trick to point to the evil greedy insurance companies for the policies that now nag us. I'd remind folks that we have only ourselves to blame.


Anonymous said...

Aw...I will agree with "misuse" of evidence.

This example is the ecological fallacy

Midwife with a Knife said...

I agree with the agreement and disagreement.

You have to start somewhere. And given roughly equivalent efficacy (as far as you can tell in any group of people), it certainly makes sense to start with the least expensive drug (barring terrible side effects, etc.).

Having said that, I'm a bit of a hypocrite. I'm not really interested in trying the less expensive but more likely to cause side effects sulfsalazine (although who knows, I may have no side effects from it, i've never taken it); my more expensive and side effect free mesalamine will do just nicely. In fact, I've been contemplating asking for the new (and presumably more expensive) once daily dosing, because I have a really tough time with three times daily dosing because of work demands.

If I were going to walk the walk as well as I talk the talk, I would have started with sulfsalazine and then gone on to mesalamine if side effects developed. And I certainly wouldn't be thinking that my insurance should pay for me to take my meds once a day instead of 3 times a day.

Midwife with a Knife said...

Ah... thanks!

sulfsalazine: $99.00/month (at doses equivalent to my current dose)

mesalamine: $470/month (thanks insurance!)

lialda (daily dosing alternative): $560/month.

Heck, if my insurance is paying $470/month (actually more if you count other drugs) for my meds, they can pay another $90, right? Just kidding.

Alison Cummins said...

"The new equation is to start with the premise that treatment should not be used unless it has been 'proven' to work."

Um, that equation looks pretty good to me. At least as a starting point. I would want to elaborate on it.

How about, "If a treatment that has been shown to work for this population is available, a trial of it should be made in preference to a treatment that has not been shown to work for this population."

As in, if we have followed the evidence-based protocol and not reached a satisfactory outcome, we don't stop trying. I'm sure Carrie can weigh in here.

(MWWAK: does Sulfsalazine exist in a one-a-day formulation? How would that change your CBA?)

Midwife with a Knife said...

AC: Nope. No once daily dosing for sulfsalazine. If there was... I would probably at least give it a try. Although, you know, I don't really need once daily dosing. I could deal with twice daily dosing just fine. The three times a day, well, I really struggle to be compliant with it, but I probably make the 80% compliance that is what we sort of expect.

Sarebear said...

This is SO relavant to our just decided major med change - so relevant to the fact that the med we're changing from, while proven to not be efficacious for the population at large, was efficacious for me for things that I get questioned as to whether or not it was - my iatrist is open-minded enough to understand that my individual chemistry and this med may be one of those cases, and if changing to something else doesn't work, he'll go back to the other! Still, he did raise the question that perhaps some of the effect I've been feeling has been anti-anxiety . . . and I'm open-minded enough to consider that, and accept that even, once I get to an end-point in this consideration process.

The evidence for the mood-stabilization properties of the Neurontin in me, though, are unequivocal, and I'm a logical-thought-process person when it comes to analyzing things like that - there is a definite cause-and effect, a definite increase in amplitude of highs and lows, when I'd forget doses, etc. BUT, at the same time, as an online bipolar friend once told me, she said it didn't seem that it was doing for me what a mood stabilizer should - that it wasn't taking me all the way. And I have wondered about that.

Anyway, I bring this up not to consult you three about my particular case, but as, I think, a perfect example of what Clink brings up here.

I'll let y'all know later on my blog what my new med is, should anyone be interested, in a month or two, after I've had time to assess the effects. I'd rather keep it to myself until then.

Still scared to hell, though. Facing the unknown, is a huge, huge nervous/panic thing for me. And that's where, I s'pose, I can think, well, it's not exactly an unknown for the doc, even if there is an element of trial and error as to which particular med works, or works the best, for which particular person . . .!

Anonymous said...

I think it should be a balance be between effectiveness and cost, not an emphasis on one or the other. If there are two equally effective drugs for a person, then the less expensive drug would be a more conscientious choice (granted it doesn't have horrific side effects or potential dangers). On the other hand, if you have two drugs where one is clearly more effective than the other but significantly more expensive, it should be offered as an option. Patients' suffering is real suffering and your job is to help us lead healthy and productive lives. If a doctor is short changing us signifcant improvement for the bottom dollar, they're doing harm.

I think an often overlooked way to reduce costs in the behavioral health field is to encourage psychotherapy. Rather than putting folks on a lifetime course of medication, why not encourage some to learn sets of coping skills. It may be a significant cost and time investment in the short run, but when you consider that many may eventually find they need less medication or no medication at all, it could actually cost less in the longterm.

As far as using only "evidence-based medicince" goes, I sometimes laugh at that. I once briefly worked with a psychiatrist who criticized my neurologist's choices for migraine prevention because none of them were "FDA approved." She worshipped the altar of FDA approval. Well, in the world of migraine treatment, there's very little funding for preventative treatment research. I believe there are about 3 drugs officially "FDA approved" for migraine prevention and they are: Inderal, Depakote, and Topamax. I've failed trials of Inderal and Topamax, having serious side effects on both. Depakote is my last ditch resort when every lesser evil has failed. So, if this woman were treating my migraines with her "evidence-based medicine," I don't know what would happen to me. Would I be forced to stay on a med that makes me suicidally depressed (Inderal)? One that would cause me to lose my job and force me to drop out of school (Topamax)? Or force me on to something that I really don't want to take yet (Depakote) because I know that there are other, albeit non-FDA approved, options. Luckily, she's not treating me, for anything. Between traditional preventatives, some non-traditional preventatives, and some slightly experimental preventatives, my neurologist and I have started to make some headway.