A 12-year-old boy suffered from inflammatory bowel disease. For many years he was treated with a combination of drugs that included mercaptopurine (6–MP), an immunosuppressant, and one of a class of drugs known as thiopurines, and the tumor necrosis factor alfa antagonist (anti-TNF) drug infliximab, marketed as Remicade. Anti–TNF drugs are approved to treat various autoimmune disorders, such as Crohn’s disease and rheumatoid arthritis. Eight years after he was diagnosed with inflammatory bowel disease, the boy received his last dose of Remicade and his IBD went into remission.
Two months after the boy received his last dose of Remicade, the FDA approved a new label for the drug. The label included a warning reporting postmarketing cases of Hepatosplenic T-cell lymphoma (HSTCL), an exceedingly rare and aggressive form of cancer, in young male patients with Crohn’s disease treated with both Remicade and a thiopurine such as 6–MP.
When the boy’s symptoms returned, his doctor prescribed another anti-TNF drug, Humira. At the time, Humira’s label did not warn of the risk of HSTCL.
The boy developed HSTCL, the non-Hodgkin’s lymphoma that is exceedingly rare and aggressive. HSTCL has low responses to chemotherapy, frequent relapses after contemporary treatments and the inability of the majority of the patients to undergo bone marrow transplantation. Most patients die within the first year of diagnosis. Only a very small fraction of patients diagnosed with HSTCL achieve long-term survival. He died at the age of 21, six months after he was diagnosed.
His parents sued the manufacturers and distributors of the drugs used to treat their son’s inflammatory bowel disease. The complaint asserted claims under California law for negligence and strict liability. Specifically, the complaint alleged that the drugs caused the man to develop HSTCL and the manufacturers and distributors did not give adequate warnings about the risks associated with the drugs.
The case was removed to federal court. The parents settled their claims against some of the drug manufacturers. The United States District Court for the Northern District of California granted summary judgment to the manufacturer of 6-MP. The district court found the testimony of the parents’ causation experts was not reliable and therefore not admissible. The district court first focused on the fact that the experts developed their opinions specifically for litigation, and had never conducted independent research on the relationship between 6–MP and anti-TNF drugs and the development of HSTCL. The district court also noted that both doctors conceded that although their opinions were based on a reasonable degree of medical certainty, they would not satisfy the standards required for publication in peer-reviewed medical journals. The district court determined that the lack of animal or epidemiological studies showing a causal link between HSTCL and the combination of 6MP and anti-TNF drugs also undermined the experts’ methodology. The court reasoned that without some reliable evidence of the positive link between the drugs at issue and HSTCL, the experts could not reasonably eliminate other potential causes of the boy’s HSTCL. The district court concluded that the parents did not present admissible expert testimony of causation and did not show that their son’s prescribing physician relied on the warning labels.
The Ninth Circuit United States Court of Appeals reversed. The court held that the district court erred by excluding the experts’ testimony and the district court erred in finding that that the parents did not produce any evidence to suggest that the boy’s prescribing physician actually relied on the manufacturer’s warning labels before prescribing the 6-MP.
The district court erred by excluding the experts’ testimony. The district court looked too narrowly at each individual consideration, without taking into account the broader picture of the experts’ overall methodology. It improperly ignored the experts’ experience, reliance on a variety of literature and studies, and review of the boy’s medical records and history, as well as the fundamental importance of differential diagnosis by experienced doctors treating troubled patients. The district court also overemphasized the facts that (1) the experts did not develop their opinions based on independent research and (2) the experts did not cite epidemiological studies. The court concluded that the proposed testimony was sufficiently reliable that the parents’ experts should have been allowed to testify under Daubert.
The district court erred in finding that that the parents did not produce any evidence to suggest that the boy’s prescribing physician actually relied on the manufacturer’s warning labels before prescribing the 6-MP. The court held that, viewing the evidence in the light most favorable to the parents, there was a genuine dispute of material fact as to whether the prescribing physician’s conduct would have changed with warnings from the manufacturer. The doctor changed from one anti-TNF to another based on his belief that the second anti-TNF had a better safety profile due to its lack of a black box warning. The court reasoned that this change in prescribing practices, which could reasonably be attributed to the lack of a warning on the second anti-TNF, created a question of material fact as to whether the presence of a warning on the 6-MP would have changed the prescribing physician’s practices with regard to the boy. The court also noted that the parents presented evidence that the prescribing physician changed his prescribing practices generally after he learned of incidents of HSTCL in patients taking both 6–MP and anti-TNF agents.
The Ninth Circuit United States Court of Appeals reversed the district court’s grant of summary judgment in favor of the drug manufacturer.
See: Wendell v. GlaxoSmithKline LLC, 2017 WL 2381122 (9th Cir., June 2, 2017) (not designated for publication).
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