Tuesday, May 13, 2008

The Pythagorean Integrity of the Law

We don't know what that title means; we just wanted to draw some mathematicians to our blog.

Well, no.

Actually, we just read United States v. Endotec, No. 6:06-cv-1281-Orl-18KRS, 2008 U.S. Dist. Lexis 35427 (M.D. Fla. Apr. 30, 2008), and two things about the opinion struck us as noteworthy.

This was an enforcement action brought by the FDA seeking to enjoin Endotec and certain of its officers from selling specified medical devices and seeking disgorgement of amounts that Endotec had been paid.

You can almost feel the tension in this decision as a company struggling to market new medical devices -- ankle, knee, and TMJ implants -- kept banging its head against the FDA's regulations. The company had submitted six 510(k) submissions seeking permission to sell its ankle devices. Those submissions had either been withdrawn by the company or rejected by the FDA. The company obtained an Investigational Device Exemption for one of its ankle devices, but the clinical study of the device had reached full enrollment, so patients could no longer be treated by that route. Surgeons, however, still wanted to implant the devices, and the evidence at trial convinced the court that the devices "provided greater benefits to patients than the alternatives available in the United States." Id. at *35-36.

The company should not sell devices illegally, of course. But you can feel in this decision a medical tension underlying the legal analysis.

Anyway, we'll start with the Pythagorean integrity that we noticed.

(The following discussion is phrased in very general terms. We're painting with a broad brush here, so please don't take the details of what we're saying as Gospel.)

Many judicial decisions explain that the Medical Device Amendments of 1976 required companies to conduct clinical studies of new medical devices before the devices could be sold. Companies finish the studies, submit the results to the FDA, and get approval to sell the products. That's the "premarket approval" process.

As of the date the Medical Device Amendments became law, however, those clinical studies had not yet been done. Conducting those studies would take time, and Congress didn't want to yank all existing medical devices off the market while manufacturers studied the devices for a few years. So Congress permitted devices that were already being sold in 1976 to stay on the market.

That posed a problem of its own: If existing devices stayed on the market and competitive devices had to go through the PMA process, the manufacturers of existing devices would have a temporary monopoly. The existing devices could be sold, but new, similar competitive devices would be gummed up in the PMA process.

To solve that problem, Congress created the premarket notification (or "510(k)") process, which allowed manufacturers to notify the FDA that they intended to sell devices that were "substantially equivalent" to predicate devices that had been on the market before 1976.

Presto! Revolutionary new devices would be judged for safety and efficacy; existing devices would remain on the market; and new devices that were similar to existing devices could also be sold, avoiding the monopoly problem.

That's PMA and 510(k).

A fair number of decisions also discuss the "Investigational Device Exemption" process.

That process allows a manufacturer to distribute medical devices for the purpose of conducting a clinical study to seek premarket approval. (Until the device is approved, the manufacturer can't distribute it. There has to be a way to distribute the device for the purpose of running the clinical study and thus seeking approval.)

Those are the big three: PMA, 510(k), and IDEs.

Decisions less frequently discuss "compassionate use" approval and the "custom device" exemption. Endotec nicely fills that void.

Suppose a device is not yet PMA- or 510(k)-approved for sale. A patient needs the device, but the patient is not (or cannot be) enrolled in a clinical study. How does the law permit the device to be supplied for that patient's benefit?

The manufacturer petitions the FDA for compassionate use approval, and the FDA can then authorize use of the device in a particular patient.

That leaves only one situation unaccounted for: What about medical devices that are unique -- manufactured for one specific patient or for use by one particular physician? To conduct a clinical study of a medical device, you need a bunch of devices that are all basically the same. There's no way to run a clinical study of a device that is custom-designed for one particular person.

The "custom design exemption" addresses that situation. Devices that are tailored for individual use, and so can't be studied in clinical trials, can be sold under the custom device exemption.

That's the first thing we liked about Endotec. It nicely describes the routes for selling devices outside of the standard PMA, 510(k), and IDE routes, and thus lets readers see that the law makes sense: If patients need medical devices, the law theoretically allows manufacturers to provide those devices.

We're not sure if that's precisely "Pythagorean integrity," but it's pretty cool.

Here's the second thing we noticed about Endotec: The court that conducted the bench trial tried to be practical and not to punish people who were trying to do some good.

Endotec didn't have PMA or 510(k) approval for its various devices, and its clinical study for an ankle device was fully enrolled. But physicians were still asking for the devices, and the company was still selling them.

At trial, the FDA insisted that the sales were unauthorized and illegal. Endotec responded that all of the sales were permitted, either as custom sales, compassionate uses, minor modifications of approved devices, authorized under certain interpretations of IDE study protocols -- whatever!

Maybe we're wrong -- we weren't there, and we're reading between the lines here -- but we get the sense that the trial judge leaned over backwards to try to do what was right. The evidence showed that Endotec's devices actually helped patients. The FDA did not allege "that Defendants have harmed any individual by manufacturing or distributing medical devices and has not alleged that any of Defendants' devices are dangerous or that their use poses any risk." Id. at *31. The "Government did not present any evidence to indicate that the ankle devices were potentially dangerous." Id. at *33.

In that situation, the court chose not to throw the book at anyone. The court found that the disputed ankle devices were all custom devices, so Endotec did not break the law. But the court did enjoin Endotec from advertising the devices and noted that the devices could be used by prescription only. The court also instructed Endotec to strictly adhere to the FDA's requirements for monitoring clinical trials.

The court found that Endotec did violate the law by selling its knee devices, and the court enjoined further sale of the devices until Endotec obtained PMA, 510(k), or IDE approval.

Endotec did not violate the law by selling its TMJ devices. Two sales were permissible under the IDE's investigational plan and another TMJ device was a custom device.

Finally, the court denied the government's request for an order of disgorgement -- the monetary sanction.

In addition to lecturing Endotec to be more careful and keep better records, the court also lectured the FDA: "[I]n the field of medical devices, the FDA might ask Congress to revise 21 U.S.C. Secs. 360a-360k to speed up procedures, so that citizens of the United States can benefit sooner from the fast-moving technology of the twenty-first century." Id. at *41.

What does Endotec teach?

First, the law makes sense: As a theoretical matter, the Medical Device Amendments permit devices to be distributed to all patients who need them.

Second, the FDA should be cautious: If it looks as though the Agency is acting too slowly and thus keeping helpful medical devices off the market, courts will be less willing to help the Agency in its enforcement efforts.

Third, manufacturers should be smart: They should obey the law. If they're operating near the edge of the law, they'd better be darn sure that the devices they sell help people and do no harm, as was apparently true of Endotec's devices.

Finally, society should get its act together: Let's fund the FDA sufficiently to permit it to do its job, and let's get beneficial drugs and devices on the market as quickly as reasonably possible. That would reduce -- or perhaps eliminate -- the tension between companies struggling to help patients and the letter of the law.

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