Sometimes there are decisions that we begin to read with an expectation—perhaps based on a thumbnail from Bexis—that we will have a strong impression.  Not surprisingly, the expected impression is usually negative.  This was the case with Apter v. HHS, No. 22-40802, 2023 U.S. App. LEXIS 23401 (5th Cir. Sept. 1, 2023), which concerned an APA-based challenge to FDA public statements on the use of ivermectin to treat or prevent COVID-19 in humans.  Over the last three years or so, we have written plenty on ivermectin, hydroxychloroquine, and government measures to combat the COVID-19 pandemic.  For much longer, we have written more than plenty on issues relating to FDA’s authority, such as preemption, limits on FDA’s enforcement authority, and APA challenges to its actions.  One particularly long-standing and road-winding issue has been FDA’s authority to discourage, prevent, and discourage the promotion of off-label use of FDA-regulated medical products.  Based on that history, just hearing that the Fifth Circuit reversed the dismissal of claims against FDA by three Texas physicians who favored the off-label use of ivermectin to treat or prevent COVID-19 in humans made us think the decision must be flawed.  Based on the opinion itself, the flaws in reasoning are not so egregious.  Without diving into the appellate record, let alone trying to determine what the appellees could have done differently, we can only say so much, but there is still something fundamentally off about the result.

Jumping ahead a bit, the core of the Apter decision is the panel’s conclusion that FDA lacks express authority to discourage off-label use.  Phrased too broadly, “FDA is not a physician. It has authority to inform, announce, and apprise—but not to endorse, denounce, or advise.”  Id. at *29-30.  We agree with that to a degree.  As we have pointed out many times, FDA does not regulate the practice of medicine.  States have that authority.  However, FDA does plenty to “denounce” and “advise” on all sorts of issues related to the practice of medicine.  Sticking with drugs, there are scores of FDA public statements about who should not take a drug because FDA believes there is an unacceptable risk or simply because FDA has not approved or otherwise recognized the benefit of a particular use.  The whole concept of a use in a particular patient for a particular purpose being on-label or off-label relates to this.  What is off-label can relate to how old the patient is and how long the drug can be used continuously, for instance.  FDA requires the labels for generic drugs to match the labels for branded drugs, including various statements “denouncing” certain uses.  FDA issues monographs for certain categories of over-the-counter drugs that will invariably include at least one “DO NOT USE” statement.  FDA has issued many statements about class-wide issues that “endorse,” “denounce,” and/or “advise” by just about any reckoning.  We could go on.  Surely, FDA has some authority to do all of this.  The distinction cannot be as simple as FDA having authority to tell drug companies what they can and cannot do, but having no such authority to say anything directly to doctors and patients.  After all, access to the FDA website is not limited to manufacturers and wannabe manufacturers.  Many statements by FDA are intended to be read by doctors and patient to relay FDA’s thinking on the safety and efficacy of drugs, including who should use them, for what purpose they should be used, and when to stop them.  It would be hard to fulfill the broad public health charge FDA has from Congress if FDA could only communicate its decisions and thinking to the entities that it directly regulates.  (Extended to food, precluding FDA from telling consumers not to eat spinach recalled because of E. coli contamination would be pretty dumb.)

Were the FDA’s statements about the off-label use of ivermectin to treat or prevent COVID-19 in humans really that unusual as to be categorically different than all the statements from FDA nobody would argue are beyond its purview?  Some of them were via social media, which, like texting, can be criticized for deteriorating the quality and clarity of, to say nothing of the importance of punctuation in, written communications.  We might cut FDA at least a little slack for using social media to convey information during a pandemic that FDA clearly felt related to its overall public health mission.  The Fifth Circuit did not cut FDA any slack when it came to social media or view its communications collectively.  Finally turning to the facts of the case, the plaintiffs complained that FDA statements ranging from “You are not a horse.  Stop it with #ivermectin.  It’s not authorized for treating #COVID” to a comprehensive “Consumer Update” on “Why You Should Not Use Ivermectin to Treat or Prevent COVID-19” interfered with their medical practices (favoring the off-label use of the anthelmintic drug) and harmed their reputations.  The court below concluded that the suit was barred by sovereign immunity because the APA did not cover plaintiff’s claims, but it did not address standing.  Plaintiffs appealed.  This is where our a priori impressions enter the picture.  We would not have thought the APA covered challenges to FDA public statements about an approved drug (in the middle of a pandemic) or that a few individual physicians had standing to make those challenges.  A manufacturer with an NDA, ANDA, etc., for the drug in question, maybe, but not some doctors who prescribed it to their patients anyway.  The Fifth Circuit disagreed.  Of course, this was an appeal of a 12(b) motion, so all the allegation in the complaint were accepted as true.  (We note that the Fifth Circuit cited a pre-TwIqbal decision for this standard, so only factual allegations that were plausible and not conclusory should have been credited.)

While it held that the claims under the APA and common law were still unavailable, the Apter court found that the plaintiffs “can use the APA to assert their ultra vires claims against the defendants,” who can only be sued to the extent their consented to suit via the APA.  If that seems a bit circular, than maybe it is.

For instance, one of the Doctors’ foremost arguments under the ultra vires doctrine is that FDA has statutory authority to share data, facts, and knowledge, but not to recommend treatments or give other medical advice. The argument proceeds along these lines: (1) FDA cannot act without express statutory authority, (2) FDA does not have express authority to recommend against off-label uses of drugs approved for human use, (3) the Posts recommend against ivermectin, therefore (4) the Posts are beyond FDA’s authority. We agree that, at this stage, FDA has not offered even a “colorable basis” for rejecting this argument.

Id. at *13-14 (footnote omitted).  That “colorable basis” phrase, used here to suggest a burden for the defendants that did not exist, is more often seen in the context of the APA applying—and thus sovereign immunity being waived—if the agency had a “colorable basis” to act in the area is acted.  That is what the district court found below.  We can shortcut most of the analysis here by noting that the Fifth Circuit found “Nothing in the [FDCA’s] plain text authorizes FDA to issue medical advice or recommendations.”  Id. at *16.  Despite standard references to the need to confer with health care providers and factually accurate references to what indications were approved and whether veterinary drugs—which ivermectin is also—are approved to be used in people, the communications as a whole were seen as rendering “medical advice and recommendations.”  Clearly, the flippant nature of some of the social media posts weighed heavily in that analysis.  Less so were FDA’s statement about the safety issues in using ivermectin to treat or prevent COVID-19 in humans; safety concerns are the more common touchstone for FDA’s communications with the public about a drug or class of drugs.  This may be because the safety issues with the approved human drug were connected only to “large doses” and were not prominent among the overall FDA messaging, at least as presented by the court in its acceptance of the allegations in the complaint.

As to standing, the plaintiffs offered more than a mere disagreement with the substance and tone  FDA’s statements, as we had expected.  They claimed the FDA’s statements were referenced in medical board referrals for one plaintiff, pharmacies refused to fill their ivermectin prescriptions, and the lost privileges and academic positions because of their own statements.  It may be easy to plead a purported link between FDA’s statements and these “injuries,” but proving it will be another thing entirely.  Nonetheless, the court found these plaintiffs had standing to assert their sole surviving claim because it applied a fairly low bar for standing rarely used in an area like this:  the “zone of interests” test.  (See here, here, and here for some dives on standing.)  Under this test, there is no jurisdiction “’only when a plaintiff’s interests are so marginally related to or inconsistent with the purposes implicit in the statute that it cannot reasonably be assumed that Congress intended to permit the suit.”  Id. at *23 (quoting Texas v. U.S., 50 F.4th 498. 520 (5th Cir. 2022)).  Even with this “not especially demanding” standard, it is hard to see how the FDCA’s purposes anticipated plaintiff’s interests.  Indeed, the nature of the ultra vires claim is that statements from FDA that amounted to medical advice were not part of the FDCA at all.

To get around this, the Fifth Circuit cited a single provision from the FDCA and nothing from its legislative history.  The court characterized that provision, 21 U.S.C. § 396, as having “plain text [that] protects some aspects of the ‘practitioner-patient relationship’ from FDA’s “limit[ation] or interfere[nce].’”  Id. at *23.  Actually, the provision, within the “Miscellaneous” subchapter of the FDCA as enacted, states “Nothing in this chapter shall be construed to limit or interfere with the authority of a health care practitioner to prescribe or administer any legally marketed device to a patient for any condition or disease within a legitimate health care practitioner-patient relationship.”  We do not see how this provision does the trick.  It did for the Fifth Circuit:  “Here, because the Doctors are within the Act’s zone of interests, they can use the APA as a vehicle to assert their ultra vires claims against the Agencies.”  Id. at *24.  Again, this seems off to us, but the FDA will get a chance to contest the merits back down in the district court.

In terms of implications, we return to the issue of FDA’s regulation of truthful statements by drug or device companies about off-label uses of their products. If FDA has no authority to issue any advice or recommendations about the drugs and other medical products it regulates, including anything that amounts to denouncing their off-label use, then can it tell a manufacturer that it cannot offer truthful statements about those off-label uses?  Can it force a manufacturer to actively discourage off-label use simply because it is off-label and adds to sales numbers?  There has been a ton of litigation over the years where manufacturers were targeted even when the off-label use was considered standard of care.  Apter, of course, did not address any issues related to the interaction between FDA and a manufacturer or between a manufacturer and doctors or patients.  It did, however, further something of a trend, particularly in the Fifth Circuit itself, to place limits on FDA’s authority.