Southern District of Texas Holds Learned Intermediary Doctrine Applies to Clinical Trials

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Does the learned intermediary doctrine apply in the context of a clinical trial?  According to the Southern District of Texas, it does.  The case in question is Butler et al. v. Juno Therapeutics, Inc., a tragic case involving the death of a 19-year-old woman with terminal leukemia who died within days of receiving an experimental cancer drug as a participant in a clinical trial.

In 2015, Juno Therapeutics (Juno) was developing a treatment for advanced blood cancers involving Chimeric Antigen Receptor T-cell (CAR-T) therapy.  CAR-T therapy is designed to modify a patient’s white blood cells to target cancer cells with the goal of improving the patient’s condition so a bone marrow or stem cell transplant can be tolerated.  In October 2015, Juno entered into a Clinical Study Agreement with MD Anderson (and other hospitals) as part of a Phase 2 clinical trial (the “Rocket Study”) of a drug identified as JCAR015, a CAR-T therapy.  Drs. William Wierda and Michael Rytting were the principal investigators of the Rocket Study at MD Anderson.

In May 2016, Maty Holland and her mother, Lisa Butler, met with MD Anderson personnel to explore treatment options for recurrent acute lymphoblastic leukemia.  Following those discussions, Holland enrolled and consented to participate in the Rocket Study.  In the days that followed, before Holland’s first dose of JCAR015, a Rocket Study participant at a different trial site, M.K., developed cerebral edema and died after treatment with JCAR015.  Notably, cerebral edema had not previously been observed with JCAR015.  Juno advised the FDA that the adverse event and M.K.’s death was likely related to the administration of JCAR015 and paused administration of JCAR015.  Juno also discussed the matter with the Rocket Study’s safety monitoring board (the Board) and held biweekly safety calls with the principal investigators, including Dr. Wierda.  The Board recommended resuming the Rocket Study for seven subjects, including Holland, and required principal investigators to inform all enrolled patients of updated safety findings and have patients sign updated consent forms.

Juno communicated the Board’s recommendations to the Rocket Study’s principal investigators.  Shortly thereafter, Holland and Butler met with Dr. Wierda at MD Anderson to discuss Holland’s participation in the Rocket Study.  Holland thereafter verbally consented to continue with the trial, but a new consent form was not signed.  Dr. Wierda’s chart note stated that Holland was told that M.K. experienced fatal cytokine release syndrome and cerebral edema relating to CAR-T treatment.  Butler testified, however, that Dr. Wierda said M.K.’s death was due to a very uncommon high fever that was not related to JCAR015.

On June 23, 2016, Holland received her first infusion of JCAR015.  A week later, she died due to “severe cerebral edema,” “status epilepticus,” and “cytokine release syndrome.”  Holland’s parents sued Juno in the Southern District of Texas alleging claims for wrongful death, failure to warn, strict liability, fraud, negligence, and breach of warranty.  The central feature of the suit, however, alleged that Juno failed to inform Holland of the risks of severe cytokine release syndrome and toxicity relating to JCAR015 and that, had Holland been so informed, she would have chosen a different treatment option.

Juno moved for summary judgment.  The primary question before the Court was whether the learned intermediary doctrine, which serves to immunize prescription-drug manufacturers from liability for failure to warn claims where the manufacturer provides an adequate warning to the prescribing physician, applied in the context of a clinical trial.  Although Texas law clearly recognized the doctrine in Centocor, Inc. v. Hamilton, 372 S.W.3d 140 (Tex. 2012), the Texas Supreme Court had not yet addressed its applicability in the context of a clinical trial.

The plaintiffs argued that the learned intermediary doctrine did not apply because JCAR015 was not a prescription drug.  The Court, however, found that argument untenable given that Texas courts had long applied the doctrine in situations where the product “could not reach their end users except through treating medical professionals[,]” including medical devices, physical therapy bands, and breast implants.  Juno contended that the doctrine applied so long as the intermediary physician exercised independent medical judgment.  The Court disagreed with Juno, noting that Texas law’s application of the doctrine is triggered by the presence of a physician-patient relationship, not the specific conduct of the physician.

With this backdrop, the Court noted that: (1) Holland had a physician-patient relationship with Drs. Wierda and Rytting; (2) Drs. Wierda and Rytting were integrally involved in selecting JCAR015 to treat Holland’s cancer and, in fact, Holland could not have received JCAR015 at MD Anderson without Drs. Wierda and Rytting; and (3) Drs. Wierda and Rytting had a medical understanding of Holland’s condition and further understood the risks associated with JCAR015, including treatment toxicities and cytokine release syndrome.  In light of such findings, the Court reasoned the Texas Supreme Court would likely find the learned intermediary doctrine applicable to the case.

The Court then examined whether Juno’s warning to Drs. Wierda and Rytting was defective.  The plaintiffs needed to show that with a different, adequate warning, Drs. Wierda and Rytting would have recommended a different treatment or that Holland would have refused consent.  The record reflected that Juno repeatedly advised Dr. Wierda that JCAR015 carried a risk of cytokine release syndrome and resulting cerebral edema.  Notwithstanding, Dr. Wierda recommended and treated Holland with JCAR015.  Accordingly, Juno did not fail to warn Dr. Wierda.  The Court further concluded that the plaintiffs could not show that a different warning would have changed the outcome.

This decision is important and should be noted by any drug or device company engaged in a human clinical trial.  Such trials always carry risks, some known and some unknown.  Given the detailed information communicated to investigators, and the extensive informed consent discussions and documentation that accompany participation in such trials, it is logical to extend application of the learned intermediary doctrine to the clinical trial environment.  While this case considered the applicability of the doctrine under Texas law, the Court’s reasoning should prove persuasive to the multitude of other jurisdictions in which the doctrine is recognized.

DISCLAIMER: Because of the generality of this update, the information provided herein may not be applicable in all situations and should not be acted upon without specific legal advice based on particular situations.

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