Nobody who reads our blog can have any doubt that we’re four-square in favor of allowing drug and device manufacturers (our clients) to engage in the truthful promotion of off label uses. It’s not just that we think the restrictions are unconstitutional (although we do); it’s that we think that off-label use saves lives and alleviates suffering.

That’s why we we’ve been profoundly conflicted about the ongoing litigation seeking to establish a constitutional right for terminally ill patients to have access to entirely unapproved drugs that might save their lives. On the one hand, it bears some resemblance to off-label use. On the other hand, we’re old enough to remember Laetrile – a supposed “miracle cure” for cancer that had people flocking to Mexico back in the 1970s. Laetrile turned out to be entirely useless, dangerous (if not prepared properly, it could contain cyanide), and oversold by those with a financial interest in it. The FDA quite rightly put its foot down over Laetrile, and was rewarded with landmark precedent supporting deference to administrative agency (the FDA, of course) decisions regarding statutory interpretation. United States v. Rutherford, 442 U.S. 544 (1979).

But as we’ve said repeatedly, we’re lawyers representing FDA-regulated manufacturers. So when Abigail Alliance for Better Access to Developmental Drugs v. Eschenbach, ___ F.3d ___, 2007 WL 2238914 (D.C. Cir. Aug. 7, 2007), was decided earlier this week, and rejected any constitutional right of access to totally FDA-unapproved drugs, we were mostly relieved. Our clients dodged another bullet.

There’s already been a lot of comment about Abigail Alliance in the blogosphere. The Law Professors quite predictably have an excellent thumbnail sketch of the decision. Our favorite FDA specialists quite understandably dive into the implications of the decision on the Agency’s pending initiatives. Other drug law gurus had a field day with the court’s really long regulatory history discussion. Volokh also has a lot to say, especially about the nature of the constitutional right that the plaintiffs asserted. The interesting ideological split and, of course, prospects for further appeal, are on the menu at Scotusblog. The appellate mavens over at How Appealing even found an appellate procedure twist.

We’ll leave the constitutional and administrative implications of the decisions to the professors and other scholars who specialize in that sort of stuff. We’re tort lawyers. We’re not even sure we can count as high as the Tenth Amendment. Our perspective is different and, not surprisingly, practical. We’d like to pose the question, if the decision had gone the other way, just what our clients would have been expected to do?

In Abigail Alliance terminally ill people were suing the FDA. They were represented, interestingly enough, by the Washington Legal Foundation, folks that we ordinarily think of as friends of the pharmaceutical and medical device industries. But that’s really more of an alliance of convenience. Those guys are ideologically in favor of less government. We’re not ideological about much of anything. We just want government (especially the FDA) to do right by our clients. “Cough … preemption … cough.” When it doesn’t, the WLF is a great bunch to work with. Our biggest problem with this sort of suit over access to experimental drugs is that, if the FDA had lost, our industry clients probably would have been the next defendants.

Essentially, the plaintiffs in Abigail Alliance sought to overturn the FDA’s ability to prohibit access to new drugs before they had been approved for anything. The FDA’s clinical trial process is nothing if not fiendishly complicated, but in a nutshell, it requires manufacturers who wish to test a new drug (or device, but this controversy is almost solely about drugs) to contract with a group of doctors (“investigators”) and hospitals (“institutions”), and restrict availability of the drug under study to those enrolled in research studies conducted under elaborate, FDA-approved written protocols. If a patient doesn’t qualify for the study, that patient cannot get the drug – not legally, anyway.

The new drug must then run the gauntlet of several phases of study, from animal testing all the way to (if the drug continues to show promise) double-blinded experiments involving hundreds or thousands of research subjects. The Abigail Alliance opinion describes this laborious process in detail. 2007 WL 2238914, at *1-2.

One overwhelming, unfortunate fact: most potential drugs don’t make the cut, and for those that do, the entire process can take quite a few years. The Abigail Alliance decision says the average is seven years. Id. at *1. We believe it.

The FDA already has an exception for terminally ill patients, involving so-called “compassionate use.” 21 C.F.R. §312.34(a-b). That program is rather limited, though, because: (1) there can’t be any alternative, approved therapy; (2) research into the drug must be sufficiently advanced for there to be ongoing clinical trials, and (3) the would-be manufacturer must be “actively pursuing” FDA approval. Nor is compassionate use particularly attractive to our clients, since they’re not allowed to make any profit at all from such use. 21 C.F.R. §312.7(d)(3).

So the plaintiffs in Abigail Alliance sought a broad constitutional right, unfettered by FDA red tape, for access to possibly life-saving unapproved drugs at just about any stage in the research and approval process. Their argument was very simple and powerful. It’s our lives at stake. We can make the choice to assume the risk that the drugs won’t work or might cause other injuries. 2007 WL 2238914, at *4, 10-11. To this assertion of personal autonomy, they added an argument by analogy – the constitution extends protection to private matters like education, travel, abortion, and consensual sex. If the constitution affords people the right to refuse lifesaving therapy, how can it not extend its protection to people seeking to save their own lives? Id. at *11 n.19, *14 (dissenting opinion).

The en banc Court of Appeals for the District of Columbia Circuit said “no” anyway. The plaintiffs’ notion of some “legal tradition” in favor of free access to drugs failed when the long history of regulation of drug safety was considered:

[Plaintiff’s] effort to focus on efficacy regulation ignores one simple fact: it is unlawful for [anyone] to procure experimental drugs not only because they have not been proven effective, but because they have not been proven safe. Although [plaintiff] contends that it only wants drugs that “are safe and promising enough for substantial human testing,” i.e., drugs that have passed Phase I testing, current law bans access to an experimental drug on safety grounds until it has successfully completed all phases of testing.

2007 WL 2238914, at *6.

OK, we suppose that’s right, but just exactly how relevant is it in this context? We’re the first to admit that drug safety is of paramount importance, but this case is about people who are going to die anyway – unless some miracle happens. It sort of reminds us of Heckler v. Chaney, 470 U.S. 821 (1985), in which a bunch of death row inmates sued because the use of drugs for lethal injections wasn’t a use that the FDA had been approved as “safe and effective.” Needless to say, they lost.

If a terminal cancer patient has six weeks to live, does it really matter if a potentially lifesaving drug might increase the risk of heart attack or diabetes? We think there are just some extreme situations in which drug safety doesn’t count for all that much. This is one of them.

Like we say, we’re conflicted. We like the result, but some of the reasoning the court employs to get there is rather hard to defend.

The court next went into excruciating detail concerning the history of governmental control over the safety of drugs going all the way back to 1447. Id. at *6-8. The net result of all this history is that the court finds plenty of legal basis for the FDA’s role in regulating experimental drugs.

However, once again the rhetoric gets a little over the top. The court finds no tort-based justification for “a constitutional right to override the collective judgment of the scientific and medical communities expressed through the FDA’s clinical testing process.” Id. at *9. While we agree with the sentiment about tort law – strip away the constitutional overlay and the court gave a pretty good description of conflict preemption – the notion of FDA approval as expressing “collective” medical and scientific judgment is questionable when a very large percentage of all prescriptions written in this country are for off-label uses. E.g., David C. Radley, et al., Off-Label Prescribing Among Office-Based Physicians, 166 Arch. Internal Med. 1021, 1023 (2006) (over 20% of all prescriptions off-label; 46% of cardio-vascular prescriptions off-label); Shane M. Ward, WLF & the Two-Click Rule: The First Amendment Inequity of the Food & Drug Administration’s Regulation of Off-Label Drug Use Information on the Internet, 56 Food & Drug L.J. 41, 45-46 (2001) (off-label use over 30% for cancer, 40% for AIDS, 80% for children, and 90% for patients with rare diseases). While the FDA certainly has a big role to play, the importance of that role can be exaggerated, and we think the DC Circuit did so here. This is another reason for our conflicted attitude towards the Abigail Alliance litigation.

In the end, however, it was the Supreme Court precedent upholding the FDCA against similar, but sometimes non-constitutional, challenges that proved dispositive. In Gonzales v. Raich, 545 U.S. 1, 28 (2005), and United States v. Oakland Cannabis Buyers’ Co-op., 532 U.S. 483, 490 (2001), the Court considered a variety of arguments and rejected claimed constitutional and non-constitutional grounds for allowing the medicinal use of marijuana. In Rutherford, 442 U.S. at 552, the Court had refused to resort to “statutory interpretation” to create an implied “medical necessity” exception that would have permitted access to supposedly curative drugs by the terminally ill.

That was enough to kill the notion of terminally ill patients’ right as a protected constitutional right. The Abigail Alliance court then went through the motions of applying the “rational basis” test (otherwise known as the “plaintiff always loses” test), to the FDA’s restrictions upon the use of unapproved drugs. Not surprisingly, those restrictions passed that test with flying colors:

Although terminally ill patients desperately need curative treatments, as Rutherford holds, their deaths can certainly be hastened by the use of a potentially toxic drug with no proven therapeutic benefit. Thus, we must conclude that, prior to distribution of a drug outside of controlled studies, the Government has a rational basis for ensuring that there is a scientifically and medically acceptable level of knowledge about the risks and benefits of such a drug.

2007 WL 2238914, at *12.

So back to the beginning: Why, oh great defenders of off-label use, is this not analogous to the therapeutic use of drugs for unapproved uses? It is, sort of, but then it isn’t. The main differences are:

  • Off-label use involves a drug that’s had its basic safety thoroughly reviewed and found sufficient for at least some human use. Completely unapproved drugs have had little if any safety screening.
  • Drugs used off-label are manufactured in this country (or at least up to prevailing FDA standards), in accordance with accepted good manufacturing practices. (We’re assuming legality here.) Totally unapproved drugs, the sale of which is illegal, could come from anywhere, be manufactured in somebody’s basement, and have handwritten labeling.
  • Unlike off-label use, there’s no procedure for reporting and categorizing adverse reactions to drugs lacking any FDA approval whatsoever.
  • Drugs used off-label are nevertheless dependably on the market for their approved uses. Most unapproved drugs are at best in the process of being investigated. Such investigations might fail, or the owner of the drug might decide not to proceed for any number of reasons, some of which might be economic in nature.

For these reasons, when push comes to shove, we have to agree with the FDA on the basic point. If the FDA can’t at least require that a drug be approved as safe and effective for some purpose before it can be sold, then there wouldn’t be much left of the FDA’s regulatory authority. Add to that the practical problems in dealing with drugs that aren’t necessarily being made by anyone we’d feel comfortable buying them from, and we don’t find the off-label use analogy all that compelling.
But as lawyers representing clients, we can’t pretend that there isn’t more at work here (well, we could, but that wouldn’t be very persuasive, and you’d stop reading our blog). If the Abigail Alliance plaintiffs had succeeded against the FDA today, they’d be suing our clients tomorrow.
Why?
Well, who’s got the drugs that those plaintiffs want?
Our clients, the drug manufacturers, that’s who.
Even without a constitutional right to give them momentum, some desperate, terminally ill participants in FDA-approved clinical trials have sued manufacturers demanding that they continue supplying them with experimental drugs after the manufacturer has made the decision not to continue with trial. See Abney v. Amgen, Inc., 443 F.3d 540 (6th Cir. 2006). The Sixth Circuit described the claims in Abney thusly:

The plaintiffs in this case are eight individuals involved in a clinical drug trial sponsored by [defendant]. When the study was terminated, the plaintiffs sued claiming that [defendant] was legally required to continue providing them with the drug.

Id. at 542.
The study-subject plaintiffs in Abney lost, because nothing in the informed consent forms they signed or in the study materials they received amounted to a contractual promise to keep giving them the medication after the manufacturer decided not to continue with the study. Id. at 548-49. The court also determined that the manufacturer had done nothing that amounted to a promissory estoppel (a fancy legal term for a promise not meeting the standards for a contract, but that the court decides to enforce anyway), id. at 549-50, and had not formed a fiduciary relationship with any of the study subjects. Id. at 550-51.
Chillingly, while the claims against the manufacturer failed in Abney, the court suggested that the plaintiffs might have been on firmer ground suing the hospital at which the study was being conducted. Id. at 551. In making that suggestion, the court forgot one little detail – the suit was for a preliminary injunction to continue supplying certain medications. If enjoined, the hospital would have had to get the medication from somewhere. We repeat, who’s got the drugs that those plaintiffs want? The manufacturer, of course. The plaintiffs in Abney weren’t dumb, they went right to the source.
Abney is just the tip of the iceberg. A nifty little biotech blog we just discovered lists five examples of similar litigation that haven’t yet matured into any published opinions. We can just imagine how Abney and similar cases might turn out if, instead of having to argue contracts and estoppels, the plaintiffs are able to point to a newly-minted “fundamental” constitutional right as the basis for seeking an injunction. That’s why we’re more relieved than anything else at the result in Abigail Alliance.
Think about it, just what would our clients be required to do if there were a constitutional right of access to unapproved and experimental drugs? What warnings would our clients have to put on the totally unapproved drugs that they’d be required to supply? There are no standards – by definition there can’t be. From our perspective as tort lawyers we’d probably advise our clients to give the ultimate warning:

WARNING: This drug ain’t approved for nuthin. If you take it, there’s a good chance it’ll kill you – but we don’t know how. Don’t expect it to work either. We really don’t know what this stuff’ll do, and we ain’t gonna try to find out. Take this entirely at your own risk.

Trouble is, if a manufacturer did put a warning like that on an unapproved drug, it would go to jail. If a manufacturer put any warning at all on an unapproved drug, it would go to jail. The FDA simply doesn’t let manufacturers from making any statements at all about unapproved uses, let alone entirely unapproved drugs. It’s called “promotion,” and it’s illegal.
The recognition of a constitutional right of access to entirely unapproved drugs would create a Catch-22 legal environment where, on the one hand a company definitely should provide warnings – if only to protect itself from liability – but the law absolutely forbids giving them.
Plainly, in addressing the claim of a broad, vague new constitutional right, neither side in Abigail Alliance gave much thought to the practicalities of the situation. In order to satisfy that right, would the manufacturer of an experimental drug be forever locked into providing it, even after it had decided not to proceed with commercialization? FDA good manufacturing practices are pretty strict. Unless manufacturing is turned over to some fly-by-night foreign operation (which nobody advocates), to keep a production process going for a minuscule population claiming constitutional entitlement is not a cheap proposition. So from a purely monetary standpoint, we’re pleased that no new constitutional right is going to interfere with our clients’ ability to allocate their limited resources available for research in favor of those drugs in the pipeline that appear to have the most promise.
Isn’t that putting the crass commercial interests of drug companies ahead of the needs of desperately ill people? Well, if it is, then we’re in good company – eight of ten DC circuit court judges agree with us. Not bad for a couple of tort lawyers whose only real familiarity with constitutional law is limited to preemption and the First Amendment.
Further, we don’t think so, for two reasons: (1) forcing an uneconomic reallocation of research dollars will ultimately result in fewer FDA approvable “safe and effective” drugs being discovered, something that would wind up hurting many more people than a few unapproved drugs could possibly help; and (2) creating an uncertain, litigation-charged environment around experimental drugs that might cure fatal diseases would have any number of unintended consequences – from making enrollment in clinical trials more difficult, to driving the conduct of such trials out of the country altogether.
Nor does it hurt that we’re defense lawyers, and this kind of pejorative rhetoric is something we’ve had thrown at us in practically every case we have to defend.
All of this is why, in the end, we think that notwithstanding some questionable reasoning, the court got it right. These plaintiffs, like so many others, have fallen prey to judicial triumphalism – the notion that litigation and court decisions are the best way to solve any and all societal problems. The solution isn’t for courts to create another undefined constitutional right enforceable through amorphous litigation. Rather, Congress should legislate, and the FDA should regulate to create an environment in which experimental drugs can be available for terminally ill patients under rational and economically sensible criteria, and in which drug companies can provide such drugs without the risk of being sued or being subject to administrative sanction.
That’s precisely what the majority said towards the end of their opinion:

The [plaintiffs’] arguments about morality, quality of life, and acceptable levels of medical risk are certainly ones that can be aired in the democratic branches, without injecting the courts into unknown questions of science and medicine. Our Nation’s history and traditions have consistently demonstrated that the democratic branches are better suited to decide the proper balance between the uncertain risks and benefits of medical technology, and are entitled to deference in doing so. . . . [O]ur holding today ensures that this debate among the Alliance, the FDA, the scientific and medical communities, and the public may continue through the democratic process.

2007 WL 2238914, at *12-13 (emphasis added). That’s something with which we agree whole-heartedly.