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In re Testosterone Replacement Therapy Products Liability Litigation Coordinated Pretrial Proceedings

United States District Court, N.D. Illinois, Eastern Division

October 23, 2017

In re Testosterone Replacement Therapy Products Liability Litigation Coordinated Pretrial Proceedings This document applies to all cases

          CASE MANAGEMENT ORDER NO. 76 (RULINGS ON AUXILIUM'S MOTIONS TO EXCLUDE EXPERT TESTIMONY AND FOR SUMMARY JUDGMENT - DKT. 34, 38, & 39 IN HOLTSCLAW V. AUXILIUM, CASE NO. 15 C 3941, AND DKT. 29, 33, & 34 IN OWENS V. AUXILIUM, CASE NO. 14 C 5180)

          MATTHEW F. KENNELLY, DISTRICT JUDGE.

         Plaintiffs in this multidistrict litigation (MDL) proceeding allege that they suffered either arterial cardiovascular injuries or injuries related to blood clots in the veins (venous thromboembolisms, or VTEs) as a result of taking prescription testosterone replacement therapy (TRT) drugs. Defendants Auxilium Pharmaceuticals, LLC (formerly known as Auxilium Pharmaceuticals, Inc.) and Endo Pharmaceuticals Inc. (collectively, Auxilium) manufacture and sell Testim, [1] one of the TRT drugs at issue in this litigation. Two cases in which Auxilium is a defendant have been selected for "bellwether" trials. In each of those cases, Auxilium has moved to exclude the testimony of a number of plaintiffs' expert witnesses under Federal Rules of Evidence 702 and 403 and Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579 (1993), and for summary judgment. This Court has already ruled on motions raising similar issues in cases brought against AbbVie, another of the defendants in this proceeding, concerning its TRT drug Androgel. See In re Testosterone Replacement Therapy Prod. Liab. Litig. Coordinated Pretrial Proceedings ("In re: TRT"), No. 14 C 1748, 2017 WL 1833173, at *1 (N.D. Ill. May 8, 2017) (ruling on motions to exclude expert testimony and for summary judgment on issue of causation); In re: TRT, No. 14 C 1748, 2017 WL 1836435, at *1 (N.D. Ill. May 8, 2017) (ruling on motion for summary judgment on failure-to-warn claims); In re: TRT, No. 14 C 1748, 2017 WL 1836443, at *1 (N.D. Ill. May 8, 2017) (ruling on motions to exclude expert testimony and for summary judgment on claims concerning "off-label" marketing). In this opinion, the Court assumes familiarity with those rulings.

         Isaac Owens and Steve Holtsclaw are the plaintiffs in the two bellwether cases against Auxilium. Owens alleges that his use of Testim caused him to suffer a deep vein thrombosis (DVT)[2] in July 2013. Holtsclaw alleges that his Testim use caused him to suffer a heart attack in July 2014. Both plaintiffs contend that Auxilium marketed Testim "off label"-that is, for uses other than that for which the Food and Drug Administration (FDA) approved the drug-and that Auxilium misrepresented the safety and efficacy of Testim for off-label use. They also contend that Auxilium failed to adequately warn that Testim could cause users to suffer DVTs and heart attacks. Owens has brought claims against Auxilium under the state laws of Kentucky. Holtsclaw has sued Auxilium and Endo, [3] asserting claims under Tennessee law.

         Auxilium seeks to exclude the testimony of a number of plaintiffs' expert witnesses. According to Auxilium, the opinions of Drs. Peggy Pence, Steven Woloshin, and David Handelsman, concerning Auxilium's alleged off-label marketing of Testim, are inadmissible because they are based on speculation about Auxilium's intent or are otherwise irrelevant. Auxilium also moves to exclude testimony from plaintiffs' experts concerning whether Testim caused the plaintiffs' injuries. Auxilium maintains that Dr. Hossein Ardehali has no reasonable basis for concluding that Testim, as opposed another potential risk factor, caused Holtsclaw's heart attack. Similarly, Auxilium argues that Dr. Jihad Abbas has no reasonable basis to conclude that Testim caused Owens's heart attack; Auxilium also contends that Dr. Abbas' opinion is based on inaccurate assumptions about Owens's use of Testim. Finally, Auxilium contends that the opinions of Owens's treating physicians, Drs. Ardel Cagata and Martin Ozor, that Testim is capable of causing DVTs are not based on any reliable methodology and are therefore inadmissible.

         In addition to seeking exclusion of expert testimony, Auxilium has moved for summary judgment against both plaintiffs, contending, among other things, that their failure-to-warn and design-defect claims are preempted by federal law and that plaintiffs otherwise lack sufficient evidence to support their claims that Auxilium's marketing and inadequate warning labels caused them to take Testim or that Testim caused their injuries. Endo has also moved for summary judgment on all of Holtsclaw's claims because it did not acquire Auxilium until after Holtsclaw suffered his heart attack. For the following reasons, the Court grants Auxilium's motion to exclude the opinions of Drs. Abbas and Cagata and its motion for summary judgment in Owens's case. The Court also grants Endo's motion for summary judgment in Holtsclaw's. The Court otherwise denies Auxilium's motions, except with respect to certain expert testimony as discussed below. This leaves for trial Holtsclaw's claims against Auxilium.

         Background

         As with the other TRT products in this litigation, the FDA has approved Testim for the treatment of male hypogonadism. The term "hypogonadism" refers generally to a disorder characterized by abnormally low levels of testosterone in the blood and associated signs and symptoms including reduced libido, fatigue, infertility, depressed mood, and reduced muscle mass. Plaintiffs maintain that Testim has been proven safe and effective only for the treatment of so-called "classical" or "pathological" hypogonadism-that is, hypogonadism that results from certain recognized medical conditions, such as Klinefelter syndrome or injury to the testicles. According to plaintiffs, Auxilium and other TRT manufacturers have inappropriately marketed TRT products beyond the use for which they were approved by targeting users who suffer from symptoms associated with the normal male aging process. Plaintiffs assert that "age-related hypogonadism, " also referred to as "andropause" or "Low T, " is a fictitious condition, created by Auxilium and other manufacturers of TRT and for which TRT use has never been proven safe or effective. According to plaintiffs, Testim and other TRT drugs do not appreciably improve the symptoms of aging but do increase the risk that users will suffer cardiovascular injuries (namely, heart attacks and strokes) or VTE injuries (DVTs and pulmonary embolisms).

         The Court need not elaborate on the purported mechanisms by which TRT allegedly causes cardiovascular and VTE injuries, having already discussed those mechanisms in prior rulings. In general, plaintiffs and their experts posit that TRT increases the risks of cardiovascular and VTE injuries because of its pro-thrombotic nature-that is, because of its tendency to increase the risk of clotting in the blood. According to plaintiffs and their experts, TRT is pro-thrombotic because of its tendency to increase (1) estradiol, a metabolite of testosterone and a form of estrogen, which has been connected to increased risk of clot formation; (2) thromboxane A2 receptors, which can promote abnormal platelet function and an increased risk of clotting; and (3) hematocrit (the ratio of the volume of red blood cells to the total volume of blood), which can increase blood viscosity, leading to a higher incidence of clotting.

         The FDA has, at various times, considered requiring TRT manufacturers and sellers, including Auxilium, to warn about the risk of cardiovascular and VTE injuries that might accompany TRT use. The Court focuses here on the regulatory history regarding warnings for cardiovascular injuries because that history is more relevant for the issues discussed below. In January 2010, the FDA received notice that a clinical trial studying the effects of TRT on elderly men (the TOM-testosterone in older men-trial) had been stopped prematurely because of an increase in adverse cardiovascular events among study participants treated with testosterone compared to placebo. In response to the discontinued study, the FDA undertook a qualitative review of available information regarding adverse events associated with testosterone therapy in men. After reviewing the results of the TOM trial and other published studies on the topic, the FDA noted the limitations of the TOM trial and, in January 2011, ultimately concluded that the evidence from that trial and other studies available at the time did not support an association between TRT and increased risk of cardiovascular events in men. The FDA noted that larger safety trials designed to evaluate cardiovascular outcomes were necessary to provide a more conclusive answer on the relationship between TRT and adverse cardiovascular events.

         In January 2014, after new published articles suggested a possible increase in adverse cardiovascular events among TRT users, the FDA announced that it was investigating the risk of stroke, heart attack, and death in men taking TRT but had not concluded that TRT drugs increases the risk of those outcomes. Later that year, the FDA requested that the label for Testim and other TRT drugs be updated to warn that TRT use may increase the risk of venous thromboembolic events. Auxilium responded to that request by proposing to include a warning with the more general phrase "embolism and thrombosis" instead of "venous thromboembolic events." Dkt. no. 45-8, Case No. 15 C 3941, at 2. In June 2013, the FDA rejected Auxilium's proposal to use the more general phrase, noting that its "requested labeling changes were based on [its] review of cases of venous thromboembolism (DVT, PE), and not arterial thromboembolism (strokes, heart attacks)" and that the more specific phrase was therefore more accurate "clinically and scientifically, to describe the said warning." Dkt. no. 41-1, Case No. 15 C 3941, at 2 (emphasis in original). Auxilium views the FDA's response to its proposal as a clear indication that the FDA would have rejected an attempt by Auxilium at that time to strengthen the Testim warning label with respect to cardiovascular risk.

         After the FDA announced that it was investigating the risk of stroke, heart attack, and death in men taking TRT, the group Public Citizen submitted a citizen petition asking the FDA to (1) add a "black box" warning to the labels for all drugs containing testosterone highlighting the increased risks of cardiovascular dangers, (2) send "Dear Doctor" letters to warn physicians of the possibility of cardiovascular effects, and (3) require the medication guide for all testosterone products to be updated to reflect this risk. The FDA denied the requests in July 2014, concluding that there was not sufficient evidence of a causal link between TRT and adverse cardiovascular link to support the actions requested in the citizen petition. The agency noted, however, that the studies included in the petition warranted further exploration of a possible safety signal regarding TRT and cardiovascular risk. In September 2014, the FDA convened an advisory committee to consider the issue, and the committee ultimately agreed that a weak signal of cardiovascular risk had emerged from the results of recent epidemiological studies. In May 2015, the FDA required Auxilium to add the following warning to the Testim label:

         5.5 Cardiovascular Risk

Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. To date, epidemiological studies and randomized controlled trials have been inconclusive for determining the risk of major adverse cardiovascular events (MACE), such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of testosterone compared to non-use. Some studies, but not all, have reported an increased risk of MACE in association with use of testosterone replacement therapy in men. Patients should be informed of this possible risk when deciding whether to use or to continue to use Testim.

Dkt. no. 46-5, Case No. 15 C 3941, at 7.

         As the Court noted above, plaintiffs emphasize Auxilium's promotion of Testim for the treatment of aging men who do not have classical hypogonadism. It is undisputed that neither Owens nor Holtsclaw recalls viewing any advertisement or other promotional material for Testim or any other TRT drug before each began using Testim. There is also no evidence in the record that either plaintiff independently asked his doctor about TRT because of promotional material he had seen. Plaintiffs contend, however, that evidence in the record tends to show that plaintiffs' prescribing physicians received false and misleading marketing materials and communications from Auxilium and relied on that misleading information when deciding to prescribe Testim for Owens and Holtsclaw. In response to this contention, Auxilium points out that both Dr. Dennis Smith, Owens's prescribing physician, and Dr. Dean McLaughlin, Holtsclaw's prescribing physician, testified that they never received any information from Auxilium that they believed was false or inaccurate.

         Plaintiffs maintain that the record supports an inference that the physicians relied on Auxilium's misrepresentations. With respect to Dr. McLaughlin, plaintiffs emphasize the frequency with which he interacted with Testim sales representatives. Plaintiffs note that in addition to providing Dr. McLaughlin with promotional materials and brochures, Testim sales representatives called his office at least 95 times and provided him with a meal during a sales presentation at least ten times. During his deposition, Dr. McLaughlin testified that he relied on Auxilium to provide him with accurate information about Testim's risks and benefits. McLaughlin also stated his belief that TRT is effective for treating men with low testosterone who suffer from common symptoms of aging, including fatigue, decreased energy, lack of libido, and muscle loss, and that the benefits of TRT outweigh the risks for those patients, regardless of whether an underlying condition was causing the patient's symptoms or low levels of testosterone in the blood. Plaintiffs maintain that the lack of scientific support for Dr. McLaughlin's beliefs, combined with his frequent communications with Testim sales representatives and willingness to rely on their representations, supports the inference that Auxilium's representations were the source of his belief that TRT can safely and effectively treat age-related hypogonadism.

         With respect to Dr. Smith, plaintiffs also emphasize his belief that TRT is safe and effective for treating many common symptoms of aging, a belief they contend is not supported by the scientific literature. Though Dr. Smith did testify that he relied on the accuracy of information from Auxilium sales representatives, the evidence of Dr. Smith's contact with representatives from Auxilium is less extensive than in Dr. McLaughlin's case. Instead plaintiffs emphasize that Auxilium provided Dr. Smith with the so-called "ADAM" questionnaire, a TRT promotional device designed to assist in diagnosing age-related hypogonadism. Plaintiffs maintain that the device contains misleading information and that Owens's use of the device to diagnose patients with hypogonadism indicates that he relied on Auxilium's alleged misrepresentations.

         During a December 2013 visit, Dr. McLaughlin diagnosed Holtsclaw with hypogonadism based on his complaints of chronic fatigue and laboratory work that revealed a low testosterone level in his blood. Dr. McLaughlin prescribed Testim to treat Holtsclaw's symptoms. Within a month of using the drug, Holtsclaw's testosterone level had returned to the normal range, and he testified during his deposition that he believed that using Testim increased his energy level. In July 2014, roughly seven months after he began taking Testim, Holtsclaw suffered a heart attack at the age of 59. Dr. Ardehali reviewed Holtsclaw's records for this case and noted that his risk factors for atherosclerotic cardiovascular disease prior to the heart attack included dyslipidemia (abnormal amount of lipids in the blood), diabetes, and obesity. According to Dr. Ardehali, the films from the cardiac catheterization performed on Holtsclaw indicate that he experienced a thrombotic event in his coronary arterial system. Based on those films, the preexisting cardiovascular risk factors, and the fact that Holtsclaw suffered his heart attack within a few months of beginning to use Testim, Dr. Ardehali opines that Testim caused Holtsclaw to suffer an acute clotting event that resulted in his July 2014 heart attack.

         Dr. Smith diagnosed Owens with hypogonadism in July 2011 based on complaints of low energy, decreased libido, erectile dysfunction, and a blood test that revealed a below-normal testosterone level. It is undisputed that Owens used Testim sporadically between July 2011 and July 2013, refilling his prescription only three times during that period. There is some dispute about whether the refills were for 30-day or 150-day supplies of the drug, but in either case, Owens would have not have had enough of the drug to take a full dose daily over that time period. Testim, like AndroGel, is a gel that is applied to the skin and enters the blood transdermally. Though the medication guide that accompanies the drug instructs users to apply Testim only to the shoulders and upper arms and not to the abdomen, Owens testified that he would apply the drug to his thighs and stomach. Owens also testified that he did not use the recommended daily dose of Testim. The medication guide instructs users to use daily an entire tube, which contains five grams of gel and fifty milligrams of testosterone. Owens says, however, that when he applied the gel, he used an amount equal to only one-third to one-half of a tube. During a July 2013 appointment, Dr. Smith noted that Owens had "not been using the Testim as diligently as he should" and had "noticed a decrease in his energy level because of this." Dkt. no. 37-7 at 4. Dr. Smith noted that Owens would "get back on the Testim 5g daily" and provided him with a new prescription for a one-month supply with five refills. Id. Nine days after his appointment with Dr. Smith, Owens visited an immediate care center because of pain in his left leg, which had begun two to four days earlier. Doctors at the immediate care center recommended that Owens go to the emergency room, where an ultrasound revealed a DVT in his left leg.

         Owens was 62 years old when he suffered the DVT in July 2013. That DVT was the second that Owens has experienced; his first DVT was in 2005, prior to any TRT use. Owens has also previously suffered a stroke, which left him paralyzed on the left side of his body. Dr. Abbas, who reviewed Owens's medical history and records, acknowledged that Owens's preexisting risk factors for DVT include his prior DVT, paralysis, age, and obesity. Nevertheless, Dr. Abbas opines that Testim was a substantial factor in causing Owens's second DVT. Dr. Abbas testified during his deposition that his opinion that Testim caused Owens's second DVT is based on the assumption that Owens was using the full prescribed dose. With respect to whether Testim use at a less-than-regular dose could cause Owens's injury, Dr. Abbas testified that he does not have an opinion and "would have to investigate it." Dkt. no. 46-4 at 165:5-7. Dr. Smith, for his part, says that Owens never told him that he was taking less than the recommended dose. And Owens, when asked whether it is possible that he would have started using a full tube of Testim after Dr. Smith instructed him to be more diligent about using Testim, said he "do[es]n't recall whether [he] would have or not." Dkt. no. 60-4 at 289:15-20.

         Dr. Cagata, who treated Owens in the hospital for his second DVT, also opines that Testim was a cause of the DVT. This opinion is based on Dr. Cagata's knowledge from medical school that hormone therapy could increase DVT risk and his belief that having ...


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