Cooper v. Takeda Pharmaceuticals America, Inc.

Facts

D is a pharmaceutical company headquartered in Japan. It manufactures pioglitazone, a prescription drug used to treat type 2 diabetes, marketed in the United States since 1999 under the brand name Actos®. P was prescribed Actos® to treat his type 2 diabetes. He took Actos® continuously until he was diagnosed with bladder cancer five years later in November 2011. P sued D for negligent failure to warn and strict liability failure to warn, negligent misrepresentation, fraudulent concealment, and loss of consortium, and also sought punitive damages. Dr. Alfred I. Neugut, an epidemiologist and oncologist, testified that to a reasonable degree of medical certainty, “Actos … contribute[s] to or cause[s] the development of bladder cancer.” His opinion was based primarily on his review of 15 epidemiological studies (the same studies relied on by Dr. Norm Smith, the expert whose testimony is in issue in this appeal). When, as here, most studies consistently reach a similar result, an epidemiologist can be confident that the consistent result is correct. Most of the studies gave a positive result and most of the studies with negative results “leaned in the positive direction.” The studies used a “hazard ratio,” which compares the number of cases in which a disease actually occurs to the number of cases in which it was expected to occur. Thus, if the disease occurred in 30 cases when it was expected to occur in only 10, the hazard ratio would be three (30 actual cases divided by 10 expected cases). A hazard ratio of three suggests that in the population studied a person who ingested the drug would be three times more likely to develop the disease than people who did not ingest the drug. The “Mamtani Study,” produced a hazard ratio of 6.97 for people exposed to the drug for five years or more. A risk ratio of seven is “uncommonly high.” Dr. Smith is a urologic oncologist and is the codirector of the urologic oncology section at the University of Chicago. He is certified by the American Board of Urology and was selected to participate in the American Urology Association Leadership Program, designed to train surgeons to be leaders in that organization. Dr. Smith treats patients, 80 percent of his practice being devoted to treating patients with bladder cancer, and he also teaches medical students. When Dr. Smith finished co-writing the Kiriluk paper on bladder cancer risk from occupational and environmental exposures, there was limited data available regarding the association between Actos® use and bladder cancer, and therefore that subject only covered one paragraph in the Kiriluk paper. By the time of his second deposition, Dr. Smith had reviewed 15 epidemiological and clinical studies showing an increased risk of bladder cancer among patients taking Actos® for diabetes. Dr. Smith testified it was his opinion that, to a reasonable degree of medical certainty, Actos® causes bladder cancer. His opinion was based on his review of the 15 epidemiological studies which, particularly when taken as a whole, indicate that Actos® use is associated with a significantly increased risk of bladder cancer. It greatest among long-term users and those with a larger cumulative dose. Asked if the studies on which he relied took into account diabetes and older White male subjects, Dr. Smith answered in the affirmative, saying that many of the studies that found a relationship between Actos® and bladder cancer had “adjusted for sex, race, smoking, hemoglobin[] A1C, et cetera, yes.” D acknowledged to the FDA in an e-mail sent in May 2012 that the potential development of bladder cancer is now an identified risk of Actos®. Dr. Smith based his specific causation opinion on his own paper regarding potential exposure-related causes of bladder cancer; on a particular table from an epidemiology study relating to Actos®; and a combination of all the published literature, the D studies, his experience taking care of bladder cancer patients, and his experience in having written on exposures and risks for bladder cancer. Dr. Smith reviewed about 1,000 pages of P's medical records. P had taken over 50,000 milligrams of Actos® over the course of slightly more than five years. Dr. Smith reviewed Jack Cooper's deposition and had reviewed 15 epidemiological and clinical studies examining the relationship between bladder cancer and ingestion of Actos®. P was generally in good health, with no history of kidney stones. The medical records indicated that P had no family history of bladder cancer and that he was a retired construction supervisor and “has had no occupational exposure.” P did not use alcohol. He was described both as a former smoker and as a “never smoker,” with benign essential hypertension, type 2 diabetes mellitus, and chronic kidney disease, stage 3. He had a history of basal cell carcinoma of the face. P was White, and his date of birth was in August 1933. Dr. Smith considered as factors to rule in P's race, his sex, his smoking history (including secondhand smoke), and his occupation as a construction supervisor. Dr. Smith stated he was not aware of any literature that would indicate a retired Pacific Telephone Company supervisor would have a risk of developing bladder cancer of even half of the risk posed by his Actos® exposure. Dr. Smith ruled out radiation exposure, chemotherapy, infections, immunosuppression, the pain medication phenacetin, Aristolochia fungi, arsenic exposure, HPV, chlorinated or fluoridated water, and vitamin D deficiency. Dr. Smith stated that all of the epidemiological studies he reviewed had adjusted for age, sex, and race. Asked more specifically if the studies on which he relied took into account diabetes and older, White, male subjects, Dr. Smith answered in the affirmative. He said that the studies that found a relationship between Actos® and bladder cancer had “adjusted for sex, race, smoking, hemoglobin[] A1C, et cetera, yes.” Dr. Smith also acknowledged the hypothesis that renal insufficiency and albuminuria directly contribute to the incidence of bladder cancer, but he disagreed with that theory. He also said there was no data to support the association between exposure to electromagnetic power lines and bladder cancer. He considered P's history of smoking, environmental exposures, and occupational exposures. He noted that it was sometimes hard to define a single agent to which a patient might have been exposed. “But if you look once again at all of that, you don't really get hazard ratios out of the ones whereas in the Mamtani article, that seems to fit Mr. Cooper very well with his … 50-plus thousand milligrams cumulative dose greater than five years that has a hazard ratio of almost seven. Dr. Smith definitively stated: “After review of all the potentials, differential diagnosis, ruling in, ruling out, carefully evaluating the occupational, environmental, and smoking, that it's my opinion that the most substantial causative factor for Mr. Cooper was his length of Actos and cumulative dose of Actos.” P got the verdict. The jury returned a verdict for Takeda on the claims for negligent misrepresentation (12 to zero), intentional concealment (11 to one), and punitive damages (12 to zero). The jury awarded P $5 million in compensatory damages and $1.5 million in damages for loss of consortium. D had sought to exclude Dr. Smith's testimony or have it stricken all during the trial. The court felt that without a competent differential diagnosis based on P's history and medical condition that accounted for all potential causes and ruled out each potential cause except Actos®, Dr. Smith's specific causation opinion was unreliable. After the verdict, the court ruled on D's motions. The court concluded that Dr. Smith's differential diagnosis was speculative and unreliable. Therefore, the court struck the testimony on causation and purported to grant D's motion for nonsuit. Later, the court vacated the order granting nonsuit and considered instead D's motions for JNOV and for a new trial. The court concluded that (1) without Dr. Smith's testimony, evidence of causation was lacking, and (2) even if the testimony were not stricken, it did not constitute substantial evidence of causation. Therefore, the court granted JNOV. The court also granted a motion for a new trial. P appealed. 

Issues

Rule of Law

Holding and Decision

Legal Analysis

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