There was a time when we paid quite a bit of attention to the circumstances under which a participant in a clinical trial could impose liability on the sponsor of the clinical trial. We even tried a case to a defense verdict for the sponsor of a clinical trial in a case where the plaintiff claimed, as to our client and the investigator defendant, that his HIV misdiagnosis should have been reversed during the clinical trial, which involved a medication switch for patients well controlled under an existing treatment regimen. Leading up to that trial and after it, we gained a pretty good understanding of the law on liability related to clinical trials. For instance, cases have looked at whether the learned intermediary doctrine is somehow disrupted when the prescription is written by a clinical trial investigator.  (Like here and here)  Cases have also looked at whether participants in a clinical trial can compel the sponsor to continue providing them the study drug after the trial ends.  (Like here and here)  (Legislative efforts to encourage drug manufacturers to sponsor clinical trials for rare conditions have been discussed before, like here.)

For some reason, and with one recent exception, it seems like there have been fewer of these cases in the last few years. There are certainly lots of clinical trials going on and, presumably, patients in them who might claim some injury, physical or otherwise, from their participation. Could it be that the putative plaintiffs have backed off of trying to sue clinical trial sponsors? Could it be that the plaintiff lawyers have read the rulings and decided these cases are not worth bringing? Could it be that the cases still exist, but we are not seeing decisions from them caught in the net Bexis uses to find blogworthy decisions?

We may never know the real answer, but we did see an appellate decision from New York last week in Wholey v. Amgen, Inc., — N.Y.S.3d –, 2018 WL 4866993 (N.Y. App. Div. Oct. 9, 2018). Wholey involved claims of injury from the use of a well-known and often-studied FDA-approved prescription drug both during and after a clinical trial. The defendants filed motions to dismiss, which were granted in part and denied in part, and an appeal ensued. This is the part we care about:

As the sponsors of a clinical trial, defendants owed no duty to the plaintiff Lauren Wholey, as enrollee in the trial (see Sykes v. United States, 507 Fed. Appx. 455, 462 (6th Cir. 2012); Abney v. Amgen, Inc., 443 F.3d 540, 550 (6th Cir. 2006)). Thus, her claims concerning the drug Enbrel must be limited to those that allegedly arose after she stopped participating in the trial and was prescribed the drug as a patient.

Id. at *1. When we said that was the part we care about, we meant it. That is the full discussion of the issue of liability for the sponsors of a clinical trial. No duty means no liability. We appreciate the finality and brevity of the analysis. We emulate the brevity here.

 

In Looney v. Moore, 2018 WL 1547260 (11th Circuit Mar. 30, 2018), the Eleventh Circuit confirmed Alabama law’s rejection of an “increased risk of harm causation standard and established that lack of informed consent plaintiffs must have a physical injury.

Looney is a clinical trial case. Parents of several infants who were born prematurely claimed that the infants suffered injuries as a result of their participation in a clinical trial aimed at analyzing the effects of differing oxygen saturation levels on premature infants. Plaintiffs made negligence, negligence per se, product liability, breach of fiduciary duty and lack of informed consent claims, and they sued the doctors involved in the study, as well as the independent review board and the company that made the medical equipment for the study. Defendants won at the summary judgment stage, and the Eleventh Circuit affirmed.

The simplest issue was causation. The Eleventh Circuit applied Alabama’s strict requirement that a plaintiff making a negligence claim must show that the negligence more than likely caused plaintiff’s injury. An “increase risk of harm” is insufficient:

The Alabama Supreme Court has made clear that, “to present a jury question, the plaintiff in a medical-malpractice action must adduce some evidence indicating that the alleged negligence (the breach of the appropriate standard of care) probably caused the injury. A mere possibility is insufficient. . . . . An alleged “increased risk of harm” is not sufficient to survive summary judgment under Alabama law, which requires proof that the alleged negligence probably caused the injury.

Id. at *3.

Confirming this standard turned out to be the end of plaintiffs’ negligence claims. That’s because no expert, whether it be for plaintiffs or defendants, was willing to say that the defendants’ negligence during the clinical trial probably caused any of the infants’ injuries. At their depositions, defendants’ experts said that the infants’ premature births probably caused their injuries, not participation in the study. Id. Plaintiffs’ own expert could only manage to say that the clinical trial “increased the risk of harm” to the infants, not that it more likely than not injured them. Id. This testimony gave a jury no basis to find for plaintiffs, and the Eleventh Circuit affirmed defendants’ summary judgment victory. Id. at *4.

Plaintiffs’ informed consent claim was a bit trickier. Plaintiffs argued that they did not need a physical injury to make this claim, something that Alabama law had not directly addressed. Id. The Eleventh Circuit sought help on this, certifying a question to the Alabama Supreme Court. But the Alabama Supreme Court declined to answer. Id. This left the Eleventh Circuit in the position of having to predict how Alabama law would decide the issue. Id.

To do this, the Eleventh Circuit first considered the Alabama Medical Liability Act. It required an injury. The Eleventh Circuit also considered Alabama Supreme Court informed consent decisions. In each instance, the court laid out the elements of any informed consent claim, but they did not explicitly include injury. The Eleventh Circuit was not troubled by this because, in each case, the plaintiff not only suffered an injury, but a serious one. Id. at *5.

Left looking for any support for their theory of a claim without physical injury, plaintiffs pointed to battery claims, in particular medical battery claims, which in Alabama do not require physical injury. Id. at *7. The Eleventh Circuit distinguished these claims. Battery claims are not based in negligence, but instead on a lack of any consent at all. Id. On the other hand, plaintiffs in lack of informed consent claims actually give consent to the procedure. They just claim that their consent was ill informed. Id. at *8. In other words, their claims are based on the negligence of the medical providers. And that brings us back to the strict requirement under Alabama law that a plaintiff making a negligence claim must establish that the negligence probably caused an injury. With that, the Eleventh Circuit upheld summary judgment against plaintiffs’ informed consent claims. Id. at *9.

Last week, we took a short Western Caribbean cruise to celebrate a jarringly-advanced birthday. While the weather wasn’t an asset (it was 43 degrees when we departed Fort Lauderdale, and hovered in the 60s for most of the trip), we left behind record cold and treacherous ice in Philadelphia, so we had no climatic complaints.  We were slightly apprehensive, however, because we were sailing on the very ship that had been in the news a few weeks earlier for a norovirus outbreak that sickened a couple hundred passengers.  But we convinced ourselves that the adverse publicity surrounding the recent outbreak would ensure that pre-sailing sanitation and onboard precautions were at an all-time high.  And we were correct:  the entrance to every venue on the ship was blocked by crew members bearing giant bottles of hand sanitizer, application of which was required for passage.  Even at the 24-hour soft-serve frozen yogurt machine (if we were assured this would be operational at all times, we could happily exist without dining rooms), the crew member manning the controls would not hand over a cone to anyone who did not sanitize first.  It apparently worked:  we came through unscathed and heard of no reports of illness on the ship.  (We also had a blast — played round after round of trivia, “clear kayaked” off the coast of Cozumel, drank many glasses of wine, and spent hours and hours motionless except for turning the pages of our book.)  Bottom line was that the cruise line did all that it was supposed to do to protect its passengers.  Beyond that, people had to be smart and careful, because the ship’s duty only extended so far.

Today’s case also involves questions of duty and of whether the defendant’s duty extended as far as the plaintiff said it did.   In Liu v. Janssen Research & Development, LLC, No. B269318, 2018 WL 272219 (Cal. Ct. App. Jan. 3, 2018), an unpublished decision from the California Court of Appeal, the plaintiff’s son and decedent died after briefly participating in a clinical trial for a long-acting injectable form of the defendant’s antipsychotic medication.  The decedent had begun treatment for mental illness nine years earlier, and had been taking another antipsychotic medication for five of those years.  His treating psychiatrist was the doctor selected to be the principal physician/investigator for the defendant’s clinical trial, and it was she who invited the decedent to participate in the study.

The decedent underwent a screening EKG, which revealed several abnormalities, and a blood test, which revealed slightly elevated liver enzymes. The treater concluded that the results were not clinically significant, and “based on [the decedent’s] otherwise normal physical examination and denial of a family history of cardiac disease,” she admitted him to the study. Liu, 2018 WL 272219 at *1.

Three days later, after a second blood test, the decedent was injected with a non-therapeutic one-milligram dose of the study drug to test for adverse reactions. A second EKG was performed within two hours.  The next day, the results of this EKG and the pre-injection blood test were analyzed, and they indicated worsened cardiac function and much higher liver enzymes than four days earlier.  The decedent was admitted to an acute-care hospital, where he was diagnosed with cardiomyopathy, pneumonia, failing liver function, and altered mental state.  He died two days later.

The plaintiff sued a host of study defendants, including the treater and the drug manufacturer, for negligence, product liability, and negligent failure to warn. After much motion practice, the case proceeded to trial on only the negligence claims and against only the drug manufacturer.  The defendant moved in limine to exclude the plaintiff’s cardiology and pharmacology experts’ opinions that the one-milligram test dose contributed to the decedent’s death, but the trial court admitted the testimony.

At the close of evidence, the trial judge granted a partial directed verdict, finding that the physician/investigator (the treater) was not the agent of the defendant for purposes of finding the defendant vicariously liable for her medical negligence. This left two issues for the jury to consider: 1) whether the defendant manufacturer had an independent duty to intervene in the decedent’s medical care, even if the medical issues “preexisted, or were unrelated to, the study itself,” id. at *5; and 2) the defendant’s duty to monitor the administration of the study drug, including the issue of whether the one-milligram test administration caused the decedent’s death.  The jury found that the defendant was negligent and that its negligence was a substantial factor in causing the decedent’s death, assessing the defendant’s fault at 70% and awarding $5.6 million in damages.

On appeal, the Court of Appeal considered whether the defendant had a duty to intervene in the decedent’s treatment for his preexisting heart disease, and whether there was sufficient evidence that the single one-milligram test dosage was a substantial factor in causing the decedent’s death. With respect to the first question, the court held, “We agree as a matter of law that defendant, as the drug manufacturer/sponsor of a clinical trial, undertook a general duty not to harm the study participants as part of the clinical trial protocols. Administration of the [test dose] fell within the scope of this duty, and we will discuss the sufficiency of the evidence to support liability under this duty of care . . . . But the significant legal question . . . is whether the general duty not to harm study participants encompassed a duty to diagnose or treat [the decedent’s] preexisting, life-threatening heart disease and to intervene in the medical care and decisions precipitated by [the decedent’s] abnormal test results.  . . . [W]e conclude that it did not.”  Id. at *6.

The court’s holding turned on the question of foreseeability. It explained that the general duty FDA regulations impose on study sponsors – to ensure compliance with study protocols and the participants’ safety – is intended to “protect participants generally from foreseeable harm caused by the drug studies themselves, including participants’ adverse reactions to study medications.” Id. at *7.   But it cited state law decisions standing for the proposition that “it is not foreseeable to a study sponsor that study physicians with the primary responsibility for participants’ health and safety will fail to recognize, diagnose, and properly treat preexisting, life-threatening conditions that first manifest during drug studies,” as did the decedent’s heart and other conditions. Id. (citations omitted).  Simply put, “it is not reasonably foreseeable to a drug study sponsor that the response by study physicians . . .  would fall below the standard of care for a medical practitioner.” Id. at *8.

That left the question of medical causation. As noted, the jury’s verdict was based on the testimony of the plaintiff’s cardiology and pharmacology experts. Both experts testified on direct examination that the test dose was a substantial factor in causing the decedent’s death.  But, while the pharmacologist testified that the drug could cause heart arrhythmias, she admitted that there was no evidence that the decedent died from an arrhythmia.  And, while the cardiologist “unequivocally concluded the administration of any amount of the test drug . . . was sufficient to push the decedent ‘over the edge,’ [he] did not provide a reasoned explanation that illuminated for the jury how or why such a low dose of [the drug] could have had such a substantial effect on [the decedent’s] life-threatening heart disease.” Id. As such,  the appeals court found that, “at best, [both] causation experts opined as to a theory that might have contributed to [the decedent’s] death, [they] did not provide the necessary factual basis to qualify that theory as substantial evidence.” Id. at *12.

Judgment for the plaintiff reversed. And though the decision is unpublished and can’t be cited, it reinforces the reality that duties are not unlimited and drug companies aren’t responsible for medical care and aren’t liable for everything that happens to everyone who takes their drugs.  We like this decision and wish it were published – we’ll keep our eyes open for one that is.  And now, we’d gladly use a gallon of hand sanitizer for one more stroll around the deck with a frozen yogurt cone.