In re Mirena Ius Levonorgestrel-Related Prods. Liab. Litig. (No. II)
This text of 387 F. Supp. 3d 323 (In re Mirena Ius Levonorgestrel-Related Prods. Liab. Litig. (No. II)) is published on Counsel Stack Legal Research, covering District Court, S.D. Illinois primary law. Counsel Stack provides free access to over 12 million legal documents including statutes, case law, regulations, and constitutions.
Opinion
PAUL A. ENGELMAYER, United States District Judge
This multi-district products liability litigation involves a contraceptive product: the Mirena intrauterine device ("IUD") developed, manufactured, and distributed by defendants Bayer HealthCare Pharmaceuticals, Inc., Bayer Pharma AG and Bayer Oy (together, "Bayer"). The Mirena IUD is implanted in the uterus and functions by releasing a synthetic steroid hormone known as levonorgestrel ("LNG"). Plaintiffs claim that the hormonal component of Mirena caused them to suffer from a disease known as idiopathic intracranial hypertension ("IIH"), also known as pseudotumor cerebri ("PTC"). IIH is an uncommon disease marked by increased cerebrospinal fluid ("CSF") pressure in the skull.
This decision resolves a defense motion for entry of summary judgment based on the limited issue of general causation. Bayer disputes that there is competent evidence to establish that the use of Mirena is a cause of IIH. And this Court, heeding the guidance of the United States Judicial Panel on Multi-District Litigation ("JPML"), prioritized discovery on that question: whether Mirena's release of LNG is capable of causing IIH. On October 24, 2018, with fact and expert discovery complete on that issue, the Court granted defense motions under Daubert v. Merrell Dow Pharmaceuticals, Inc. ,
After the Daubert ruling, with leave of the Court, Bayer filed the present motion for summary judgment. Bayer argues that plaintiffs lack evidence sufficient to establish general causation, and that such is fatal to their claims. Bayer argues, first, as a categorical matter, that expert testimony is required to establish general causation in a products liability case involving a pharmaceutical product such as Mirena. Alternatively, Bayer argues that even if lay testimony (e.g., admissions by a product's manufacturer) could in theory establish general causation, the non-expert evidence in the record of this case is insufficient to so establish. Plaintiffs counter with a range of arguments, including that general causation is not a required element of proof, that expert evidence is not required to establish general causation, that a factfinder considering together disparate elements of non-expert evidence could reliably find general causation by Mirena of IIH, and that granting Bayer summary judgment on this element-with discovery not having been taken as to the individual cases of the approximately 920 plaintiffs comprising this MDL-would violate the Seventh Amendment and be unconstitutional.
For the reasons that follow, the Court grants Bayer's motion for summary judgment.
I. Pertinent History of This Litigation
The Court incorporates by reference its decision on the Daubert motions, which sets out the background to plaintiffs' claims, and the procedural history of this litigation, in considerable detail. See Mirena IIH/Daubert ,
A. The JPML's Centralization of Mirena/IIH Cases Before This Court
On April 6, 2017, the JPML centralized in this District pretrial proceedings in the 113 cases then pending across 17 districts nationwide in which plaintiffs had alleged IIH injuries caused by the hormonal component of the Mirena IUD. Most of these cases were at a relatively early stage of discovery or at the pleading stage, although fact and expert discovery had closed in the 10 longest pending actions. See generally Dkt. 1 at 2-3 (JPML Transfer Order). The JPML had earlier, in July 2014, denied a motion to centralize the Mirena/IIH actions, at a time when nine such actions, spanning six districts, were pending. Explaining, in 2017, its decision to centralize the pending cases, the JPML emphasized several factors that made centralized proceedings more efficient. Two are relevant here.
First, the JPML noted the heightened difficulty coordinating discovery and other pretrial proceedings given the increased number and dispersal of pending actions and of participating law firms. Id. at 2. "The record," the JPML stated, "demonstrates that centralization is necessary to facilitate the efficient conduct of common discovery." Id. at 3.
Second, general causation had emerged as an important issue common to all proceedings. "[T]he records in the many actions filed since [2014] demonstrate that discovery and pretrial motions concerning the issue of general causation have been, or will be, at the center of all actions-that is, whether the hormonal component in *329Mirena is capable of causing intracranial hypertension." Dkt. 1 at 3; see also id. at 4 ("Issues concerning general causation [and] the background science ... will be common to all actions.").
B. Organization of This MDL
In overseeing this action, this Court has given priority to the matters that led the JPML to centralize the Mirena/IIH actions.
Specifically, on June 21, 2017, after appointing plaintiffs' leadership team and reviewing written submissions and eliciting counsel's input at an initial conference, see generally Dkt. 51 (transcript of June 13, 2017 hearing), the Court issued an order stating that priority would be given to: (1) "the process of providing common fact discovery to plaintiffs from Bayer," and (2) "resolving whether plaintiffs have admissible evidence sufficient to establish general causation" by Mirena of IIH. Dkt. 40 at 1 (June 21, 2017 Order). The Court has done so as follows.
Outgoing discovery from Bayer : On July 27, 2017, after receiving submissions delineating the 14 discovery disputes identified by the parties and inquiring about them at a hearing, the Court resolved these disputes in a series of bench rulings. See generally Dkt. 51 at 10-59 (transcript of July 27, 2017 hearing). The Court ordered that Bayer broadly produce written discovery on all common issues, including electronic records from more than 50 Bayer custodians, and including broad production from Bayer's adverse-events database.
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PAUL A. ENGELMAYER, United States District Judge
This multi-district products liability litigation involves a contraceptive product: the Mirena intrauterine device ("IUD") developed, manufactured, and distributed by defendants Bayer HealthCare Pharmaceuticals, Inc., Bayer Pharma AG and Bayer Oy (together, "Bayer"). The Mirena IUD is implanted in the uterus and functions by releasing a synthetic steroid hormone known as levonorgestrel ("LNG"). Plaintiffs claim that the hormonal component of Mirena caused them to suffer from a disease known as idiopathic intracranial hypertension ("IIH"), also known as pseudotumor cerebri ("PTC"). IIH is an uncommon disease marked by increased cerebrospinal fluid ("CSF") pressure in the skull.
This decision resolves a defense motion for entry of summary judgment based on the limited issue of general causation. Bayer disputes that there is competent evidence to establish that the use of Mirena is a cause of IIH. And this Court, heeding the guidance of the United States Judicial Panel on Multi-District Litigation ("JPML"), prioritized discovery on that question: whether Mirena's release of LNG is capable of causing IIH. On October 24, 2018, with fact and expert discovery complete on that issue, the Court granted defense motions under Daubert v. Merrell Dow Pharmaceuticals, Inc. ,
After the Daubert ruling, with leave of the Court, Bayer filed the present motion for summary judgment. Bayer argues that plaintiffs lack evidence sufficient to establish general causation, and that such is fatal to their claims. Bayer argues, first, as a categorical matter, that expert testimony is required to establish general causation in a products liability case involving a pharmaceutical product such as Mirena. Alternatively, Bayer argues that even if lay testimony (e.g., admissions by a product's manufacturer) could in theory establish general causation, the non-expert evidence in the record of this case is insufficient to so establish. Plaintiffs counter with a range of arguments, including that general causation is not a required element of proof, that expert evidence is not required to establish general causation, that a factfinder considering together disparate elements of non-expert evidence could reliably find general causation by Mirena of IIH, and that granting Bayer summary judgment on this element-with discovery not having been taken as to the individual cases of the approximately 920 plaintiffs comprising this MDL-would violate the Seventh Amendment and be unconstitutional.
For the reasons that follow, the Court grants Bayer's motion for summary judgment.
I. Pertinent History of This Litigation
The Court incorporates by reference its decision on the Daubert motions, which sets out the background to plaintiffs' claims, and the procedural history of this litigation, in considerable detail. See Mirena IIH/Daubert ,
A. The JPML's Centralization of Mirena/IIH Cases Before This Court
On April 6, 2017, the JPML centralized in this District pretrial proceedings in the 113 cases then pending across 17 districts nationwide in which plaintiffs had alleged IIH injuries caused by the hormonal component of the Mirena IUD. Most of these cases were at a relatively early stage of discovery or at the pleading stage, although fact and expert discovery had closed in the 10 longest pending actions. See generally Dkt. 1 at 2-3 (JPML Transfer Order). The JPML had earlier, in July 2014, denied a motion to centralize the Mirena/IIH actions, at a time when nine such actions, spanning six districts, were pending. Explaining, in 2017, its decision to centralize the pending cases, the JPML emphasized several factors that made centralized proceedings more efficient. Two are relevant here.
First, the JPML noted the heightened difficulty coordinating discovery and other pretrial proceedings given the increased number and dispersal of pending actions and of participating law firms. Id. at 2. "The record," the JPML stated, "demonstrates that centralization is necessary to facilitate the efficient conduct of common discovery." Id. at 3.
Second, general causation had emerged as an important issue common to all proceedings. "[T]he records in the many actions filed since [2014] demonstrate that discovery and pretrial motions concerning the issue of general causation have been, or will be, at the center of all actions-that is, whether the hormonal component in *329Mirena is capable of causing intracranial hypertension." Dkt. 1 at 3; see also id. at 4 ("Issues concerning general causation [and] the background science ... will be common to all actions.").
B. Organization of This MDL
In overseeing this action, this Court has given priority to the matters that led the JPML to centralize the Mirena/IIH actions.
Specifically, on June 21, 2017, after appointing plaintiffs' leadership team and reviewing written submissions and eliciting counsel's input at an initial conference, see generally Dkt. 51 (transcript of June 13, 2017 hearing), the Court issued an order stating that priority would be given to: (1) "the process of providing common fact discovery to plaintiffs from Bayer," and (2) "resolving whether plaintiffs have admissible evidence sufficient to establish general causation" by Mirena of IIH. Dkt. 40 at 1 (June 21, 2017 Order). The Court has done so as follows.
Outgoing discovery from Bayer : On July 27, 2017, after receiving submissions delineating the 14 discovery disputes identified by the parties and inquiring about them at a hearing, the Court resolved these disputes in a series of bench rulings. See generally Dkt. 51 at 10-59 (transcript of July 27, 2017 hearing). The Court ordered that Bayer broadly produce written discovery on all common issues, including electronic records from more than 50 Bayer custodians, and including broad production from Bayer's adverse-events database. Both as to custodians and as to search parameters, the common discovery ordered from Bayer extended well beyond the parameters then used in the individual cases comprising the MDL. It also substantially exceeded the discovery that Bayer had produced in an immediately prior MDL also relating to the Mirena IUD. See MDL No. 2434 (the "Perforation MDL"). In that case, overseen by the Hon. Cathy Seibel of this District, the plaintiffs had alleged different injuries: that the hormone-release feature of Mirena had caused the IUD to migrate within the uterus after its insertion, leading to uterine perforation and related migration injuries.
General causation : The Court directed that the issue of general causation be litigated in the MDL as a threshold issue. To facilitate that issue's prompt resolution, the Court ordered that all fact discovery relating to general causation-including all document and deposition discovery-be completed by December 8, 2017. Dkt. 62. Alerted by counsel that each side expected to make Daubert challenges to the admissibility of each other's experts on general causation, the Court set deadlines spanning late December 2017 through late March 2018 for the submission of all expert reports on general causation, depositions of general causation experts, and reciprocal Daubert briefing. The Court set for the week of April 9, 2018 a "Science Day" tutorial for the Court on the background scientific issues in the case, followed by a Daubert hearing as to expert testimony on general causation. Id.
In prioritizing general causation, the Court was informed by, in addition to the guidance of the JPML, the representations of counsel in this case that the issue of general causation would be common and identical to all potential Mirena/IIH plaintiffs so as to make it an appropriate issue for this transferee court to resolve at the threshold. See, e.g. , Dkt. 51 at 29. The Court was also informed by the experience of the Perforation MDL. There, Judge Seibel held that plaintiffs' proposed expert testimony as to the general causation proposition at issue-that the Mirena IUD's release of the hormone LNG was capable of causing the Mirena IUD to *330migrate after insertion and cause uterine perforation-was not reliable under Daubert . See In re Mirena IUD Prods. Liab. Litig. ,
C. The Daubert Motions as to General Causation Experts
Plaintiffs proposed to call seven expert witnesses as to general causation. Each opined that using the Mirena IUD can cause a woman to develop IIH. The seven experts were: (1) Dr. Lemuel A. Moyé, an epidemiologist; (2) Dr. Laura M. Plunkett, a pharmacologist and toxicologist; (3) Dr. James M. Wheeler, an OB/GYN; (4) Dr. Frederick W. Fraunfelder, an ophthalmologist; (5) Dr. Philip Darney, an OB/GYN; (6) Dr. Conrad E. Johanson, a neuroscientist; and (7) Dr. Vincent Salpietro, a pediatric neurologist. Bayer, in turn, proposed to call 12 expert witnesses. Each opined that existing evidence and scholarship does not permit this conclusion.
Each expert authored a report and was deposed. Each side thereafter moved to exclude the others' experts. Each of the combined 19 experts was the subject of individualized Daubert briefing and oral argument.
D. The Court's Ruling
On October 24, 2018, the Court issued a lengthy (156-page) decision excluding plaintiffs' seven expert witnesses. For each witness, the Court analyzed in detail the witness's stated bases for claiming general causation of IIH by Mirena and evaluated the witness' methodology against the standards set by Daubert and its progeny. While a top-line summary inherently is incapable of capturing the Court's witness-specific analyses, the following brief overview is provided with the goal of enabling understanding of arguments made on summary judgment.
Characteristics of Mirena : The Court began by reviewing salient characteristics of Mirena, an IUD that releases LNG, a synthetic progestin. Mirena was approved by the FDA in 2000; some 45.4 million Mirena devices have been inserted worldwide, equating to 142 woman-years of use. In contrast to combined oral contraceptives, which contain progestin and estrogen and whose effectiveness among obese women has been questioned, Mirena is believed to be effective among obese women. Also commending its use among obese women, studies indicate that Mirena does not increase the risk of weight loss and blood clots and does not expose the user to potential risks associated with estrogen-containing contraceptives.
LNG : The Court next summarized LNG, the hormone Mirena releases. It mimics the effects of the naturally occurring sex hormone progesterone. LNG is widely used in gynecology, with a primary use in numerous contraceptives. These uses include LNG-releasing IUDs like Mirena ;
*331LNG-releasing subdermal implants such as Norplant, which was marketed in the United States from 1991 to 2002, and Jadelle, which is currently marketed in Europe; the single-dose hormone contraceptive known as Plan B; and as the progestin component of numerous combined oral contraceptives (which usually contain both LNG and an estrogen component).
IIH : The Court next reviewed IIH. It is a rare disease marked by intracranial pressure derived not from a tumor or lesion but from the excessive buildup of CSF. The Court noted that IIH is more likely to afflict obese or overweight women, and that scholars are divided as to the cause of IIH, with some theorizing that IIH is caused by an increase in the production of CSF, but a greater number theorizing that IIH is caused by the impaired absorption of CSF.
Existing scholarship-the Etminan and Valenzuela epidemiological studies : The Court then reviewed in detail existing scholarship as to the question whether use of Mirena is a cause of IIH, as well as other writings bearing on the subject. The Court did so because plaintiffs' seven experts, to varying degrees, drew on this literature in their reports. "[O]utside of this litigation," the Court summarized, "no medical organization, regulatory agency, article in peer-reviewed scientific literature, or other research has found that use of Mirena is a cause of IIH."
The Court noted that two published epidemiological studies had addressed the possibility of a causal connection between the use of Mirena and IIH.
The first was by Mahyar Etminan. See Mayhar Etminan, et al., Risk of intracranial hypertension with intrauterine levonorgestrel, 6 Therapeutic Advances in Drug Safety 110 (2015) ("Etminan" or the "Etminan study"); see also
The second study was by Reuben M. Valenzuela. See Reuben M. Valenzuela, et al., An examination of the risk of pseudotumor cerebri among users of the levonorgestrel intrauterine device, 41 Neuro-Opthalmology 192 (2019) ("Valenzuela" or the "Valenzuela study"). A retrospective case-control study, it addressed the risk of IIH among certain patients in Utah and Denmark. The Valenzuela study found a statistically significant correlation between a patient's use of an LNG-releasing IUD and the patient's having IIH. But the authors emphasized that they had not found causation of IIH by use of an IUD, but merely a correlation between the two. See
Case and adverse event reports : The Court next summarized two published case reports, one from 2010 and one from 2017. Each reviewed the experience of an individual patient who had used an LNG-based IUD and developed symptoms consistent, or asserted to be consistent, with IIH.
Studies of other LNG-based contraceptive devices : The Court next reviewed writings regarding other contraceptives using LNG. As to combined oral contraceptives (those containing both estrogen and progestin) and IIH, which contain a substantially higher amount of LNG (some 20 to 30 times more) than does Mirena, five epidemiological studies have been done. All failed to find a causal link; two of plaintiffs' experts acknowledged the science has largely disproven a link between IIH and combined oral contraceptives.
Overall state of existing research : Summarizing-as the backdrop for plaintiffs' experts' reports-the state of research as to whether Mirena can cause IIH, the Court wrote:
The state of research outside of this litigation as to the general causation proposition here-that using the Mirena IUD can cause a woman to develop IIH-presents a challenge for an expert witness here who would so testify.
As the above review reflects, to date, no prospective experiments have been undertaken that sought to address that question. Two epidemiological studies have examined that question but neither has found such causation. One such study, Etminan, has been retracted to the extent that it-based on its DPA analysis of reports in the FAERS database-had initially found an increased IIH risk among Mirena users. And the surviving half of the Etminan study (which compared Mirena with oral contraceptives) did not find any such increased risk. The other epidemiological study (Valenzuela) found a correlation between Mirena use and IIH. But it found only that. In language that warned against conflating correlation with causation, the Valenzuela study emphasized that its finding of such a correlation "does not indicate" that an LNG-based IUD such as Mirena is an "independent risk factor" for IIH. Rather, as Valenzuela recognized, alternative explanations for the correlation between Mirena and IIH are apparent-notably, the confounding factors of overweightness and obesity among reproductive-age women. As to the other contraceptive products using LNG, five studies of combined oral contraceptives have affirmatively found that these products, which contain notably higher amounts of LNG than Mirena, do not cause IIH. And no study has established a causal link between IIH and Norplant, which also contained substantially more LNG than Mirena.
In the face of this assembled historical record, with no medical organization or regulator or peer-reviewed scientific literature having found that Mirena or any contraceptive product using LNG is a cause of IIH, an expert witness who would so opine as to Mirena necessarily would break new ground in this litigation.
Assessments of plaintiffs' expert witnesses : The Court then assessed the reports of plaintiffs' seven experts opining that the use of Mirena is a cause of IIH. None, the Court noted, reached this conclusion "through an experiment, laboratory work, or a new epidemiological study of his or her own."
Instead, four experts-Drs. Moyé, Plunkett, Wheeler, and Fraunfelder-arrived at this result largely by drawing upon existing sources. "These include the Valenzuela study plus, depending on the witness, some or all of the following: the repudiated portion of the Etminan study; case reports regarding Mirena; case reports regarding Norplant and other subdural implants; and Norplant's warning label. These experts also draw upon a newly available source of data: the case reports regarding Mirena first added in Bayer's 2017 signal investigation, which was made available to plaintiffs in discovery. To varying degrees, each of these four experts also articulates a theory as to a biological mechanism by which Mirena might cause IIH."
Plaintiffs' remaining three expert witnesses (Drs. Darney, Johanson, and Salpietro) were predominantly "mechanism" experts. Their reports each developed a thesis as to how, biologically, use of Mirena may cause IIH. The Court found the methodology of these experts, too, to fall short of Daubert 's standards. See
In light of the exclusion of the general-causation testimony of all of plaintiffs' expert witnesses, the Court elected not to resolve plaintiffs' motions to exclude the testimony of Bayer's responsive general causation experts. Rather, the Court stated, it anticipated that the litigation, tracking the Perforation MDL, would likely next move to a defense motion for summary judgment on the issue of general causation. The Court accordingly denied as potentially moot, and without prejudice, plaintiffs' Daubert motions aimed at Bayer's general causation experts.
E. Bayer's Present Motion for Summary Judgment
Following the Daubert ruling, the Court directed counsel to confer as to next steps in the case, including whether, as in the Perforation MDL, to proceed to summary judgment on the limited issue of general causation. Dkt. 321. After receiving the parties' views, Dkt. 322, the Court decided on that course and, on November 19, 2018, set a briefing schedule, with Bayer's opening brief in support of summary judgment due in December. Dkt. 325.
The Court recognized that, in the absence of expert evidence, plaintiffs might argue-as plaintiffs in the Perforation MDL had in opposing summary judgment after Judge Seibel's adverse Daubert ruling-that there had been admissions by Bayer that established general causation by Mirena of the condition at issue (here, IIH). Accordingly, to facilitate informed briefing, the Court directed plaintiffs' counsel to file, by December 3, 2018, a letter "identifying the alleged admissions as to general causation, made by Bayer or its experts, on which plaintiffs intend to rely in opposing summary judgment." Dkt. 325 (Order of November 19, 2018). The Court emphasized that plaintiffs' letter "will not limit the range of materials on which plaintiffs may rely in their briefing," but stated its expectation that plaintiffs would "make a good-faith effort to thoroughly canvas the materials and disclose, with specificity, the evidence on which they expect to rely in opposing a motion for summary judgment."
On December 14, 2018, Bayer filed its motion for summary judgment, Dkt. 328, and, in support, a memorandum of law, Dkt. 329 ("Bayer Mem."), the declaration of Paul W. Schmidt, Dkt. 331 ("Schmidt Decl.") and accompanying exhibits, and a Rule 56.1 statement, Dkt. 332, ("Bayer 56.1").
On January 18, 2019, plaintiffs filed a memorandum of law in opposition to Bayer's motion, Dkt. 333 ("Pl. Mem."), an opposition to Bayer's Rule 56.1 statement and counter statement of facts, Dkt. 334 ("Pl. 56.1"), and a document styled as a declaration pursuant to Federal Rule of Civil Procedure 56(d) in opposition to Bayer's *335motion for summary judgment, Dkt. 335.
On February 11, 2019, Bayer submitted a reply memorandum of law in support of its motion, Dkt. 340 ("Bayer Reply"), an opposition to plaintiffs' Rule 56.1 statement, Dkt. 341, and a response to plaintiffs' Rule 56(d) declaration, Dkt. 342.
II. Discussion
The Court's resolution of Bayer's Daubert motions has left plaintiffs without any expert testimony as to general causation, to wit, that Mirena can cause IIH. Bayer therefore moves for summary judgment.
Bayer makes three arguments. First, it argues, summary judgment for the defense in a pharmaceutical product liability case is, categorically, required where the plaintiff lacks expert evidence as to general causation. Second, it argues, to the extent the case law leaves open the theoretical alternative in which corporate admissions of general causation can substitute for expert evidence, plaintiffs lack any such admissions here. Third, Bayer argues, the alternative non-expert materials on which plaintiffs rely in opposing summary judgment (e.g., adverse event reports; the label on a different contraceptive product, Jadelle; inferences drawn from scientific literature largely addressed by plaintiffs' experts in their excluded reports; theories of possible biological mechanisms of causation; and regulatory documents) cannot support a finding of general causation. Bayer argues that, in seeking to base general causation on these materials, plaintiffs improperly seek to substitute the arguments and inferences of counsel for the expert evidence (or corporate admissions) that are required.
Plaintiffs counter with a series of arguments. First, they argue, general causation is not a required element of the state-law causes of action on which plaintiffs in this MDL have sued. An individual plaintiff may prevail as to the element of causation they argue, solely by means of individual (i.e. , plaintiff-specific) causation, a subject as to which there has not been discovery. Second, plaintiffs argue, other forms of evidence, taken together, could permissibly lead a factfinder to find general causation of IIH by Mirena. These building blocks include alleged admissions by Bayer, components of the witness reports by Bayer's and plaintiffs' experts; portions of the Valenzuela study; adverse event reports; viable theories of a biological mechanism by which Mirena might cause IIH; and statements by the FDA. Taken together, plaintiffs argue, these materials give rise to a material dispute of fact as to general causation. Fourth, plaintiffs argue, the Court procedurally erred in directing plaintiffs, prior to Bayer's filing of its summary judgment motion, informally to identify the purported admissions by Bayer on which plaintiffs then anticipated relying. Fifth and finally, plaintiffs claim that granting summary judgment to Bayer on the issue of general causation, without any discovery having been taken as to individual plaintiffs, is unconstitutional-a breach of the Seventh Amendment.
The Court addresses these arguments in turn, after first reviewing the governing legal standards.
A. Applicable Legal Standards
The Court's review of Bayer's motion has been governed by familiar standards. As movant, Bayer must show, on one or more required elements of plaintiffs' claims, "that there is no genuine dispute as to any material fact and [that it] is entitled to judgment as a matter of law." Fed. R. Civ. P. 56(a). The movant bears the burden of demonstrating the absence of a question of material fact. In making this determination, the Court must view all facts "in the *336light most favorable" to plaintiffs, as the non-moving parties. Celotex Corp. v. Catrett ,
If the moving party meets its burden, the burden shifts to the nonmoving party to come forward with specific facts showing that there is a genuine issue for trial. A plaintiff must establish a genuine issue of fact by "citing to particular parts of materials in the record." Fed. R. Civ. P. 56(c)(1)(A) ; see also Wright v. Goord ,
B. The Requirement of Competent Evidence of General Causation
The Court considers first the parties' dispute whether, as Bayer argues and plaintiffs contest, a plaintiff in a products-liability case must establish general causation.
It is black-letter law that a plaintiff, seeking to prevail on a personal injury claim, must show causation, meaning that the defendant's conduct "was the proximate cause of [her] injuries." Mirena Perforation/SJ ,
Bayer argues that, in order to show causation, plaintiffs must produce evidence of both "general" and "specific" causation. Plaintiffs argue that Bayer has failed to articulate a clear definition of general causation. But the definition, as articulated in numerous products liability cases including the earlier Mirena MDL, is straightforward: " 'General causation is whether a substance is capable of causing a particular injury or condition in the general population, while specific causation is whether a substance caused a particular individual's injury.' " Mirena Perforation/Daubert ,
Plaintiffs have not adduced any contrary case authority, i.e. , products liability cases disclaiming a need to prove general causation. Instead, plaintiffs, noting that the claims of the individual plaintiffs comprising this MDL arise under state law, fault Bayer for assertedly asking the Court to "graft a federal 'general causation' element onto state substantive tort law" that the pertinent state tort laws do not require. Pl. Mem. at 2. Plaintiffs are correct that the question presented is one of state law: Because the cases comprising this MDL are before the Court by virtue of diversity jurisdiction, the Court "appl[ies] state substantive law and federal procedural law." Gasperini v. Ctr. for Humanities ,
As Bayer has comprehensively demonstrated in its submissions to this Court on summary judgment, all relevant jurisdictions require some evidence of general causation in products liability cases involving complex products liability (or medical) issues.2 See, e.g. , *338Earl v. Cryovac ,
Further, as the assembled case authority reflects, there is good reason for requiring such proof. As a federal district court in Ohio, supervising a products liability MDL in which the use of an anti-obesity medication was alleged to cause certain cardiovascular and cerebrovascular injuries, aptly observed, proof of general causation plays a vital role in complex cases where the capacity of a product to cause a species of injury is not intuitively obvious-where the causation inquiry "is more complicated because the injuries themselves are usually not immediately obvious and the connection between exposure and injury is not a matter of common sense or everyday experience." In re Meridia Prods. Liab. Litig. ,
Tellingly, plaintiffs' bold present claim that the law does not require proof of general causation in cases such as this is of recent vintage. Plaintiffs only made that argument after the Court, in its October 2018 Daubert decision, excluded plaintiffs' proposed expert witnesses on general causation as unreliable. Plaintiffs earlier had effectively acknowledged the opposite. When plaintiffs asked the JPML to consolidate the pending cases in an MDL, for example, they stated that the foundational issue of general causation was common to all member cases and that this common issue supported consolidation of these cases for pretrial proceedings. See Dkt. 331-2 (Pl. Mot. for Transfer) at 7 (noting that plaintiffs all alleged that their "injuries were caused by levonorgestrel released from the Mirena LNG-IUS through the exact same mechanism of action" and representing "there are common questions of science that will be presented in each of these cases"). Heeding this point, the JPML determined that "[i]ssues concerning general causation , the background science, and Mirena's labeling and regulatory history with respect to the alleged injury will be common to all actions." Dkt. 1 at 4. Later, after consolidation, plaintiffs' counsel, in a letter to this Court, "agree[d] that 'general causation' refers to the question of whether or not Mirena can cause [IIH]." Dkt. 96 at 2. It was based on the JPML's guidance and the parties' identification of general causation as a gating issue that the Court, as noted, prioritized fact and expert discovery, and Daubert litigation, *340on this issue. Before the adverse Daubert ruling, plaintiffs had never suggested that it was unnecessary to show general causation.
The Court holds, therefore, that to withstand Bayer's motion for summary judgment, plaintiffs must produce admissible evidence from which a jury could reliably conclude that Mirena is capable of causing IIH.
Finally, as to this point, the Court rejects an argument by plaintiffs that is tantamount to a claim that proof of general causation is unnecessary. Plaintiffs argue that Bayer's motion for summary judgment is premature because, although discovery as to general causation is closed, there has not yet been discovery as to the individualized circumstances of the approximately 920 plaintiffs. Plaintiffs represent that "[m]any Plaintiffs have had their own doctors determine, through differential diagnosis, that the Mirena was the cause of their intracranial hypertension and that other plaintiffs could obtain expert witness testimony of the same." Pl. Mem. at 18. The premises of this argument are that (1) general causation is not an element of plaintiffs' claims, and (2) the causation element could be established through the testimony of an individual patient's physician to the effect that, after excluding other potential causes for IIH symptoms, the doctor was left with the conclusion that the patient's Mirena use must be the cause.
There is of course a proper place for testimony about the causes of an individual plaintiff's symptoms. That is the essence of the specific causation inquiry undertaken if there is competent evidence of general causation. But plaintiffs' bid here to erase the threshold general causation requirement is at odds with the uniform holdings of the cases canvassed above that general and specific causation present separate inquiries, and that in complex medical products liability cases, the cause of an individual plaintiff's injuries is properly reached only where a plaintiff can first adduce competent evidence that the product is capable of causing the condition at issue. See, e.g. , Norris v. Baxter Healthcare Corp. ,
*341See Soldo ,
C. The Evidence That Plaintiffs Claim Can Establish General Causation
The Court accordingly turns to consider whether, with plaintiffs' expert testimony on general causation having been excluded as unreliable under Daubert , the evidence that plaintiffs have mustered is sufficient to establish general causation. At the threshold, the Court considers whether, as Bayer argues, a plaintiff is required to establish general causation in a medical products liability case such as this through expert testimony, or whether, as plaintiffs argue, alternative forms of evidence, for example, a corporate admission, can establish general causation. The Court declines to hold that expert testimony is categorically required. The Court therefore considers whether the alternative evidence to which plaintiffs point here is sufficient to establish general causation. In considering these questions, the Court is mindful that these are questions of state law. As the Second Circuit emphasized in upholding the entry of summary judgment in the Mirena Perforation MDL, "state law controls on the question of what evidence is necessary to prove an element of a state law claim, such as general causation." In re Mirena IUD Prods. Liab. Litig. ,
1. Is Expert Testimony Required to Establish General Causation?
Bayer argues that expert testimony is legally required to prove general causation in medical products liability cases such as this, and therefore, here, that Mirena is capable of causing IIH. Thus, Bayer argues, because the Court has excluded plaintiffs' proposed general causation experts, the Court must enter summary judgment for the defense. Plaintiffs respond that the law does not rigidly require proof of general causation by expert testimony. And here, plaintiffs argue, general causation can be established through a collection of lay evidence. This largely consists of items on which plaintiffs' excluded experts relied: inferences drawn from scientific literature (e.g., the Valenzuela study); the label used on a different LNG-based contraceptive product, Jadelle; adverse event reports; theories of possible biological mechanisms of causation; and regulatory documents.
There is much force to Bayer's argument. It is well established that "expert testimony is required to establish causation" where the issue of causation is "beyond the knowledge of lay jurors." Wills v. Amerada Hess Corp. ,
To be sure, courts have applied this principle with sensitivity to the precise *342circumstances at hand. As a general proposition, expert testimony is not generally required in tort cases where a lay juror can "infer causation from common knowledge and lay experience"-such as when there is "an immediate onset of symptoms that naturally follow from an accident or a complete lack of any other possible cause." In re Lipitor Litig. ,
However, as Judge Seibel observed in the preceding Mirena MDL, generally in products liability cases involving complex causation issues, including cases involving pharmaceuticals or medical devices, " 'to establish causation, plaintiffs must offer admissible expert testimony regarding both general causation and specific causation.' " Mirena Perforation/SJ ,
Summary judgment is therefore commonly granted for the defense in pharmaceutical product liability or toxic tort cases where plaintiffs fail to adduce reliable expert testimony establishing general causation. See, e.g. , C.W. ex rel. Wood v. Textron, Inc. ,
In the end, however, courts-including, controlling here, the Second Circuit-have left open the possibility that, even in cases involving complex issues of whether a medical problem was the cause of a physical injury, lay evidence could possibly substitute for expert testimony. Such cases have given as an example of non-expert proof that could potentially establish general causation a corporate defendant's express admission that its product was capable of causing the condition at issue. See In re Mirena IUD Prods. Liab. Litig. ,
The Court has no occasion here to push this doctrinal envelope. For purposes of this decision, the Court assumes arguendo , following the Second Circuit's lead, that it is possible for general causation in complex medical products liability cases to be established other than by expert evidence. And, insofar as plaintiffs here (although suggesting otherwise) do not identify any admission by Bayer that Mirena use is a cause of IIH, the Court further assumes arguendo that other forms of lay evidence could in theory establish general causation. The Court therefore turns to consider whether the particular evidence offered by plaintiffs-much of which the Court addressed in its Daubert decision-is, considered separately or together, equal to that task.
2. Previously-Excluded Testimony from Plaintiffs' Proposed Expert Witnesses Regarding the Cause of IIH
Plaintiffs first propose that although the Court has excluded their expert witnesses as to general causation and although "no definitive mechanism for PTC/IIH has been established," Pl. Mem. at 37, they can draw on aspects of their proposed experts' excluded testimony to "establish 'pieces of the larger specific causation puzzle.' " Pl. Mem. at 27 (quoting Ferguson v. Riverside Sch. Dist. No. 416 , No. CS-00-0097-FVS,
*344The Court, however, has excluded as unreliable plaintiffs' general causation witnesses. The Court did not carve out, and hold admissible, snippets of these experts' proposed testimony. And, even assuming arguendo that various scientific propositions nestled within plaintiffs' experts' reports were, largely, scientifically uncontested, the Court did not hold that these stray propositions could be revived as fodder from which a lay jury could speculate about and derive a theory of general causation. Yet plaintiffs, having failed to put forward reliable expert testimony consistent with Daubert , now propose just that. They propose to put shards of its various experts' reports before the jury, to serve as the basis for a lay conclusion as to a highly complex proposition of general causation as to which no expert has yet reliably opined.
This end-run around Rule 702-and this Court's Daubert ruling-is unsustainable. Even assuming that some species of lay evidence (e.g., an explicit corporate admission that its product is a cause of a disease) could theoretically establish general causation, the propositions here that plaintiffs propose to use as building blocks for a lay finding as to Mirena's capacity to cause IIH are complex, scientific in nature, and highly technical. They patently require expertise to decode and apply. Unguided lay judgments about pharmacokinetics and neuroscience have no place under Rule 702. See, e.g. , Wills v. Amerada Hess Corp. ,
This conclusion follows especially clearly here, where plaintiffs' earlier attempts to formulate a reliable expert conclusion as to general causation drawing on these same (and other) propositions were rejected by the Court after a painstaking review finding serious shortcomings in each expert's methodology. At root, plaintiffs seek to exhume excluded testimony of an intrinsically expert nature and to invite a lay jury to derive from it the very proposition that the Court precluded plaintiffs' experts from offering. The Federal Rules of Evidence do not afford any charter for such a venture.
Plaintiffs' bid to establish general causation by mixing and matching from the reports of their excluded experts instead is properly viewed as, sub silentio , a backdoor means to revive the excluded expert analyses themselves. In its Daubert decision, the Court found that plaintiffs' proposed experts, notwithstanding their qualifications in their respective fields, did not *345articulate a methodologically rigorous and reliable theory of how Mirena causes IIH. The Court so held after performing the role that Daubert , applying Rule 702, envisioned for a trial court: to serve as a "gatekeep[er]" charged with "ensuring that an expert's testimony both rests on a reliable foundation and is relevant to the task at hand." Daubert ,
Plaintiffs' notion that a jury examine and draw conclusions from subsets of excluded expert testimony is all the more problematic in that the testimony on which plaintiffs now rely largely concerns biological mechanisms by which Mirena, theoretically, might cause IIH. This includes Dr. Plunkett's and Dr. Darney's pharmacology and pharmacokinetics opinions and Dr. Johanson's opinions regarding cerebrospinal fluid regulation and the interactions of hormones in the relevant regions of the brain. Pl. Mem. at 26-27. It is hard to imagine topics and disciplines as to which a lay jury would be more in need of reliable expert guidance before it could reliably "find[ ] general causation more likely than not." In re Mirena ,
One example illustrates the point. Plaintiffs envision putting before the jury portions of the opinion of Dr. Plunkett as to the pharmacokinetics of LNG. The Court has summarized this testimony, including as follows:
Dr. Plunkett discusses the difference between "free" LNG and total LNG. She asserts that free LNG levels should be used to access a patient's exposure and response to the hormone. The vast majority of LNG in the blood stream is not "free" floating. Instead, she states, upwards of 98% of LNG is bound to plasma proteins (specifically albumin and a carrier protein called steroid hormone binding globulin). However, she states, LNG's effects are not generally created by such bound LNG. Rather, they are created by "free" LNG activating nuclear hormone receptors.
Mirena IIH/Daubert ,
A final non-starter is plaintiffs' proposal to use testimony at trial from their Science Day experts as a basis for a finding of general causation. Consistent with common practice in MDLs implicating complex medical issues, the Court set aside April 9, 2018, prior to argument on the Daubert motions, as a day on which scientists other than the parties' general causation experts could give the Court a tutorial on background scientific concepts. These included the nature and history of the IIH disease, the chemistry of LNG and its use in various contraceptives, and the history and operation of the Mirena IUD. Dkt. 250 (March 30, 2018 Order) ¶ 1. As directed by the Court, the tutorial by these scientists pointedly avoided issues of general causation. See id. ¶ 2. Even if these tutorials had been admissible,4 these tutorials would therefore not have any bearing on that issue. To the extent that plaintiffs now envision these scientists addressing general causation at trial, the deadline for disclosing general causation experts expired in 2017, pursuant to the schedule set by the Court for resolving, at the threshold, whether there was competent evidence of general causation. See Dkt. 118 ("[T]he ongoing phase of discovery relating to general causation is intended to capture all general causation discovery. The Court agrees with counsel that, if plaintiffs fail to adduce evidence as to general causation sufficient to withstand the defense's anticipated Daubert motion, plaintiffs will not be permitted to come forward with additional evidence as to general causation.").
3. The Testimony of Bayer's Proposed Expert Witnesses
Plaintiffs next argue that "admissions" by Bayer's own experts on general causation-each of whom opined that existing studies and data do not supply a reliable basis on which to find Mirena's capacity to cause IIH-can satisfy their causation burden. Plaintiffs first argue that Bayer's experts provide "admissible expert testimony on the methodology that a jury would use to assess 'general causation,' " to wit, the Bradford Hill methodology which several of plaintiffs' excluded experts purported to apply. Pl. Mem. at 29. As the Court has reviewed, Bradford Hill is a methodological tool used by some epidemiologists to distinguish between causal *347and merely associative relationships. See Mirena IIH/Daubert ,
a. Bradford Hill Factors
Plaintiffs argue that they can use the testimony of Bayer's proposed experts to put before the jury the factors of which the Bradford Hill epidemiological inquiry consists, and thereafter task the jury with applying and weighing those factors. The Court has summarized the Bradford Hill inquiry as follows:
The Bradford Hill criteria derive from a 1965 lecture by a British epidemiologist and statistician, Sir Austin Bradford Hill. See David E. Bernstein, The Admissibility of Scientific Evidence After Daubert v. Merrell Dow Pharmaceuticals, Inc. ,15 Cardozo L. Rev. 2139 , 2167 (1994) ("In a celebrated lecture in 1965, Sir Austin Bradford Hill proposed nine criteria to aid scientists in deciding whether a reported association in an epidemiological study is causal."). "The Bradford Hill criteria are metrics that epidemiologists use to distinguish a causal connection from a mere association." [ In re Zoloft (Sertraline Hydrochloride) Prods. Liab. Litig. ,858 F.3d 787 , 796-800 (3d Cir. 2017) ]. These criteria "start with an association demonstrated by epidemiology and then apply" eight or nine criteria to determine whether that association is causal. In re Breast Implant Litig. ,11 F. Supp. 2d 1217 , 1234 (D. Colo. 1998).
Mirena IIH/Daubert ,
Plaintiffs' suggestion that they can satisfy their burden to show general causation by identifying the Bradford Hill criteria for the jury and then inviting the jury to assess, balance, and apply these factors misunderstands the Bradford Hill methodology. The Bradford Hill factors are the province of epidemiologists. Where reliably applied by a qualified epidemiologist, they may support an expert opinion that a causal *348relationship exists between statistically correlated phenomena. See In re Zoloft ,
As a result, even when the Bradford Hill factors are assessed by an expert epidemiologist, courts insist that the expert's application of these factors itself be "reliable according to the principles articulated in Daubert ." In re Zoloft ,
The Third Circuit has emphasized the need for such methodological rigor: "To ensure that the Bradford Hill/weight of the evidence criteria is truly a methodology, rather than a mere conclusion-oriented selection process ... there must be a scientific method of weighting that is used and explained." In re Zoloft ,
This Court's Daubert decision in this MDL, too, canvassed the uniform case law calling for analytically disciplined applications of Bradford Hill. See, e.g. ,
Dr. Moyé, for instance, purported to apply the Bradford Hill factors and found, explicitly or implicitly, that each of the nine was satisfied. On that basis, he opined that use of the Mirena IUD can cause IIH. See
As for Dr. Plunkett, she reviewed each factor in isolation and "opine[d] or (where unable or unwilling expressly to so state) implie[d] that each has been satisfied."
Dr. Wheeler, too, opined that a Bradford Hill analysis revealed that Mirena causes IIH. To support his application of the Bradford Hill criteria, Dr. Wheeler relied principally on "(1) a dataset of 115 case reports drawn from Bayer's 2015 signal investigation in which patients were diagnosed with IIH after having had Mirena inserted, and (2) the Valenzuela study."
A lay jury without a grounding in science or epidemiology, notified of the nine Bradford Hill factors and invited to assess and weigh these scientific factors, could easily make similar methodological errors-or ones far more egregious. Plaintiffs' notion that a jury, taught by Bayer's experts what the nine criteria are, could then reliably apply them badly misapprehends-indeed, it trivializes-this mode of epidemiological inquiry. If qualified expert epidemiologists can misapply the Bradford Hill factors, a lay jury certainly cannot be counted on to individually evaluate and *350collectively weigh these factors in a suitably scientifically rigorous manner, one that avoids the risk of conflating correlation with causation. Notably, plaintiffs do not supply any examples in which any court has permitted the delegation to a lay audience of the application of a complex epidemiological methodology such as Bradford Hill. The Daubert standard, requiring that inherently expert analyses be conducted with due rigor by qualified experts as determined in advance by a trial judge, does not countenance this approach.
b. Testimony from Bayer's Expert Dr. Langer Regarding Causation
Plaintiffs next cast a Bayer epidemiological expert, Dr. Robert Langer, as supporting their thesis of general causation. Dr. Langer, plaintiffs represent, "opines that the adverse event reporting rates for Mirena and [IIH] are consistent with a causal association." Pl. Mem. at 34 (internal capitalization and quotation marks omitted).
Plaintiffs misleadingly portray Dr. Langer's testimony. Far from concluding that Mirena is a cause of IIH, Dr. Langer opined, inter alia , that Mirena is a safe contraceptive device that is the preferred option for overweight and obese women. Dkt. 127-1 ("Langer Rpt.") at 2-3, 9-12. Dr. Langer further opined that IIH is strongly associated with excess weight and that it has become more prevalent since the 1980s as female obesity rates have increased. Id. at 11-19. Dr. Langer pointedly criticized the methodology of plaintiffs' epidemiology expert, Dr. Moyé, opining that Dr. Moyé ignores existing literature citing body weight as a strong and consistent predictor of IIH, selectively cites literature regarding IIH incidence rates, erroneously relies on the Valenzuela study, and ignores evidence that other products with much higher LNG exposure have no known association with IIH. Id. at 43-50.
In painting Dr. Langer as supporting their thesis of general causation, plaintiffs seize on a small portion of his deposition, in which plaintiffs' counsel questioned Dr. Langer about Bayer's adverse events database6 and about the methods for performing a "disproportionality analysis," i.e. , assessing the extent to which there are a disproportionate number of adverse events in that database associated with IIH for women using Mirena. Plaintiffs' counsel asked whether a "proportional recording ratio" ("PRR") "greater than 40 would suggest or be supportive *351of causal association." Dkt. 171-2 ("Langer Dep.") at 18. In response to this proffered PRR figure, and over an objection that the proffered figure was hypothetical, Dr. Langer responded, "it would not be anything near sufficient evidence for a causal association. It would be one of the triggers to look for additional supporting evidence." Id. Plaintiffs' counsel then clarified, "I don't mean on its own. I mean when you're looking at the totality of the evidence, and if you added to that a PRR greater than 40, would that be supportive of finding a causal association, or would it have no effect, or would it be opposing finding a causal association?" Id. at 188-89. Dr. Langer replied, "[i]t would be consistent, but it would really only serve as a starting point to look for evidence from much cleaner study designs." Id. at 189. And when asked about a hypothetical figure for use in a second method of analyzing disproportionality, Dr. Langer reiterated, "in these hypothetical numbers that you're throwing out here, they would be consistent with a causal association. They would not be any major element of evidence absent more appropriate study designs to assess the question of causation." Id.
Plaintiffs seize on a single line in Dr. Langer's deposition testimony, in which he stated that certain hypothesized adverse reporting rates would be "consistent" with a causal association. Id. Plaintiffs claim that this statement is sufficient record evidence of general causation. But, when read in context, it is clear that Dr. Langer's statement does nothing of the sort. Dr. Langer was explicit that the hypothesized reporting rates would not permit the conclusion that Mirena caused IIH. To the contrary, he testified that the hypothesized reporting rates for Mirena "would not be anything near sufficient evidence for a causal association," and such rates would, at most, "serve as a starting point to look for evidence from much cleaner design studies." Id. at 188-89. In any event, even if plaintiffs' characterization of this excerpt were fair-and it is not-Dr. Langer's statement that hypothetical reporting rates could be "consistent" with a causal association at most supports the bare possibility of general causation. That falls far short of what is necessary for plaintiffs to sustain their burden on this element. Rather, as the Second Circuit observed in the preceding MDL, "acknowledgment of the possibility of causation does not establish that causation is more likely than not." In re Mirena IUD Prods. Liab. Litig. ,
4. The Valenzuela Study
Next, plaintiffs argue that the Valenzuela study evidences a "statistically significant association between a patient's use of an LNG-releasing IUD and the patient having [IIH]." Pl. Mem. at 31. Valenzuela, plaintiffs contend, supplies a basis on which a jury could find general causation, such that the issue of general causation must proceed to a jury.
This argument fails. Plaintiffs wrongly portray the Valenzuela study as if it were affirmative evidence of general causation, when in fact the study stopped well short of drawing such a conclusion. The Court considered the Valenzuela study at length in its Mirena IIH/Daubert opinion, summarizing its design and objective as follows:
The Valenzuela study was published in 2017. See Reuben M. Valenzuela, et al., An estimation of the risk of pseudotumor cerebri among users of the levonorgestrel intrauterine device , 41 Neuro-Ophthalmology 192 (2017) (Dkt. 167-64) ("Valenzuela" or the "Valenzuela study"). A retrospective case-control study, it addressed the risk of IIH
*352among certain patients in Utah and Denmark.
In particular, the study examined whether IIH patients in these populations were using LNG-releasing IUDs (principally Mirena ), whether the use of such IUDs was associated with an increased risk of IIH, and whether IIH patients who used such IUDs had signs or symptoms different from those observed in IIH patients who did not use such IUDs. Id. at 1-2. Towards this end, the study compared the incidence of IIH among reproductive age women who used LNG-releasing IUDs with the incidence of IIH among reproductive age women who were not using LNG-releasing IUDs. Id. at 2.
Mirena IIH/Daubert ,
does not indicate that an LNG-IU[D] [such as Mirena ] can cause PTC, and the number of women with an LNG-IU[D] was too small to determine if an LNG-IU[D] is an independent risk factor for PTC. Although use of an LNG-IU[D] seems [to] be associated with an increased risk of PTC, it is possible that this observation occurred because use of an LNG-IU[D] is also associated with other established risk factors that are known to be associated with PTC (e.g., obesity and recent weight gain). This analysis was also limited by the lack of temporal data to confirm that exposure to LNG-IU[D] occurred prior to PTC symptom onset or diagnosis.
The Valenzuela study noted two possible explanations for the correlation between IIH and use of LNG-based IUDs. One "is that LNG causes increased intracranial pressure, through an as-yet undetermined biological mechanism."
is that LNG does not cause increased intracranial hypertension, but that the PTC is more likely to occur in the same population of women who are more likely to have an LNG-IU[D] recommended to them by their physician. LNG-IU[D] is often, although not exclusively, recommended for women who may have difficulty with other forms of contraception. For instance, women with obesity, headache, and/or polycystic ovarian syndrome are more likely to be intolerant to oral contraceptives. For this group of women, LNG-IU[D] may be better tolerated as a form of contraception. This same group of women, with obesity, headache, and polycystic ovarian syndrome, are also more likely to develop PTC. When interpreting the findings presented here, it is also important to consider that the risk analysis does not account for potential confounders.
Several of plaintiffs' proposed experts relied in part on the Valenzuela study to support their conclusion that Mirena can cause IIH. But, as the Court's discussion of the study in Mirena IIH/Daubert emphasized, the Valenzuela study "pointedly disclaimed any finding that Mirena causes IIH, on account of confounding risk factors prevalent among the dominant population of Mirena users."
In light of the fact that the Valenzuela study, by its own account, did not control for the significant potentially confounding IIH risk factors of obesity and recent weight gain, and in light of the fact that the study explicitly disclaimed any finding that Mirena caused IIH, the Court emphasized that the Valenzuela study showed nothing more than a correlation, subject to identifiable confounders, between Mirena and IIH.7 Accordingly, the Court held, the study was insufficient to support an expert conclusion that Mirena causes IIH, and could not be relied on as proof of general causation by an expert witness. While the Valenzuela study could serve as a starting point for an expert probe into general causation, its observation of a statistical association merely identified, rather than answered, the question of whether Mirena causes IIH. See Mirena IIH/Daubert ,
Under these circumstances, the Court reads plaintiffs' bid now to empower the jury on its own to review the Valenzuela study and to treat it as a basis on which to find general causation as a sub silentio attempt to repudiate the Court's Daubert ruling. But plaintiffs do not offer any basis to understand the Valenzuela study any differently than as presented in the Daubert ruling: as finding an association between the use of Mirena and IIH, but as reaching no conclusion as to whether Mirena causes IIH. Plaintiffs are therefore wrong that the Valenzuela study, if put before the jury, would give rise to a material dispute of fact on the issue of general causation, warranting denial of summary judgment.
5. Bayer's Purported Admissions
Plaintiffs next argue that the scenario identified by the Second Circuit and other courts, in which a corporate defendant's admission might qualify as sufficient evidence to establish general causation, applies here, to wit, that admissions by Bayer give rise to a permissible inference that Mirena can cause IIH. In making this argument, plaintiffs must clear a meaningful bar: Courts have cautioned that if there were cases in which *354complex general causation issues could be proved by corporate admissions, such cases would be "rare indeed." In re Lipitor ,
Here, plaintiffs argue that a string of propositions to which Bayer (or its experts) has ostensibly admitted connect syllogistically to an admission to a biomechanical chain of causation under which Mirena causes IIH. Plaintiffs summarize these as follows:
[T]he Court must accept [that] LNG is a reproductive hormone, reproductive hormones are linked with [IIH], [IIH] can be induced by medications, CSF is produced by the choroid plexus, peer-reviewed literature includes mechanism of PTC involving CSF, LNG reaches the brain, crosses the blood-brain and blood-CSF barriers, is capable of causing changes in the brain, is capable of engaging reproductive hormone receptors for androgens, is capable of causing reproductive hormone side effects, is capable of binding to mineralocorticoid receptors, and that peer-reviewed literature recognizes a potential link between those same receptors, in the same region of the brain (the choroid plexus), and causing [IIH].
Pl. Mem. at 37-38.
This concatenation of scientific propositions from which plaintiffs construct a causal chain falls far short of a "clear, unambiguous, and concrete" corporate admission of general causation, Mirena Perforation/SJ ,
In any event, in asking that the jury stitch the above propositions together to find general causation, plaintiffs gloss over Bayer's dispute as to certain of the component points and as to the bottom line conclusion. To choose one example, although LNG is known to bond with mineralocorticoid receptors ("MR"), as plaintiffs note, it is disputed whether LNG is an MR agonist (meaning it binds to receptors and activates them) or antagonist (meaning it binds to receptors and blocks them). One of plaintiffs' excluded mechanism experts, Dr. Salpietro, opined that "[a]ctivation of the choroid plexus MRs and their downstream *355pathways more likely than not stimulates the generation of Na+ (sodium) / K+ (potassium)-ATPase pumps, leading to greater movement of sodium ions at the choroid plexus epithelial cells (CPEC) apical membrane into the cerebral ventricles, thereby actively creating an osmotic gradient to drive secretion of CSF." Dkt. 98-11 ("Salpietro Rpt.") at 17. His model of causation, therefore, depended on LNG being an MR agonist, because the model was based on "activation of the choroid plexus MRs."
Plaintiffs' proposed causal chain of admissions therefore falls well short of the scenario that courts have posited in which a corporate admission might substitute for reliable expert evidence of general causation. Simply put, defendants have not admitted general causation. And plaintiffs' proposal that a jury reason that a series of purported admitted scientific propositions (some not squarely admitted by Bayer) ineluctably leads to the outcome of general causation (very much disputed by Bayer) is not viable. Like other of plaintiffs' proposals for establishing general causation without expert evidence, it would ultimately task a lay factfinder with an assignment well beyond its competence to resolve unaided and invite impermissible conjecture and unscientific guesswork.
6. Regulatory History of Other Products Containing LNG
Plaintiffs next argue that the FDA has concluded that LNG can cause IIH, and this conclusion gives rise to a genuine dispute on the material fact of general causation. Pl. Mem. at 39. To support this claim, plaintiffs point to an FDA warning approved in connection with a separate LNG-based contraceptive product, Jadelle.
As the Court reviewed in its Daubert ruling, Jadelle is a contraceptive implant inserted beneath the skin and placed in the arm. It is the successor product to a product called Norplant, which between 1991 and 2002 was marketed in the United States; Jadelle is currently sold in Europe. Mirena IIH/Daubert ,
For multiple reasons, plaintiffs' reliance on the Jadelle label is misplaced. First, plaintiffs wrongly equate Jadelle with Mirena. But the fact that Jadelle contains LNG does not establish it as tantamount to Mirena. Jadelle is a subdermal implant, unlike Mirena, which is inserted into the uterus. And Jadelle produces substantially higher systemic levels of LNG than Mirena. Compare Dkt. 135-6 ("Mirena Label") § 11.1 (total implanted dose of 52 mg) with Jadelle Label at § 2.1 (total implanted dose of 150 mg).
Moreover, Jadelle's label quite clearly does not reflect a determination by the FDA that LNG causes IIH. The warning *356states only that "[IIH] has been reported on rare occasions in users of [LNG] implants." The label encourages women using Jadelle and experiencing IIH symptoms to consider these reports, and directs Jadelle users to discontinue using Jadelle if IIH is diagnosed. See Jadelle Label § 5.9. This Court in its Daubert ruling addressed an analogous argument by one of plaintiffs' experts that the Jadelle label, and a similar label on Norplant, another LNG-releasing contraceptive device, revealed a determination of general causation. Rejecting as baseless the claim that the "Jadelle and Norplant labels bespeak a predicate finding of causation," the Court wrote, "on their face, these labels ... establish nothing of the kind."
In any event, even if the Jadelle label could be read to reflect an FDA determination of Jadelle's or LNG's capacity to cause IIH-and it clearly cannot-"[i]t is widely recognized that, when evaluating pharmaceutical drugs, the FDA often uses a different standard than a court does to evaluate evidence of causation in a products liability action. Entrusted with the responsibility of protecting the public from dangerous drugs, the FDA ... may choose to err on the side of caution and take regulatory action such as revising a product label ... upon a lesser showing of harm to the public than the preponderance-of-the-evidence or more-like[ly]-than-not standard used to assess tort liability." In re Neurontin Mktg., Sales Practices, & Prods. Liab. Litig. ,
7. Overall Assessment of Plaintiffs' Evidence of General Causation
For the reasons above, the items on which plaintiffs rely-following exclusion of their expert witnesses-to establish Mirena's causation of IIH do not do so. None comes remotely close. The Court has separately considered whether this result is different considering these pieces in combination. It is not. Viewing plaintiffs' proffered evidence separately and together, plaintiffs have not come forward with sufficient reliable, non-speculative evidence from which a reasonable factfinder could determine, by a preponderance of the evidence, that Mirena caused plaintiffs' injuries.
D. The Court's November 19, 2018 Order Did Not Alter the Summary Judgment Standard.
Plaintiffs next argue that entry of summary judgment is improper because the *357Court erred in directing plaintiffs, in advance of Bayer's filing of its summary judgment motion, informally to identify the purported admissions by Bayer on which plaintiffs anticipated relying. That argument also fails.
On October 24, 2018, after issuing its Daubert opinion, the Court directed the parties to meet and confer as to next steps in this litigation. Dkt. 321. On November 9, 2018, the parties filed a joint letter setting forth their views. Plaintiffs asked the Court to certify its Daubert ruling for an interlocutory appeal, whereas Bayer argued that the case should proceed to a defense motion for summary judgment on the issue of general causation, as had the Mirena Perforation litigation after Judge Seibel excluded plaintiffs' expert witnesses on that point. Dkt. 322. The Court agreed with Bayer's proposed course as the most efficient, and directed the parties to jointly propose a briefing schedule. Dkt. 323.
On November 16, 2018, the parties submitted a proposed schedule, but stated that they disagreed as to page lengths. Based on plaintiffs' representation that they intended to oppose summary judgment by relying on purported admissions of general causation, Bayer sought an enlargement of its reply brief to address those admissions. Dkt. 324. Bayer noted that in the Perforation MDL, the plaintiffs had agreed to set out the alleged corporate admissions of causation in a letter to the Court, whereas plaintiffs in this case had declined to do so. This, Bayer argued, made it hard for Bayer's opening brief in support of summary judgment to anticipate plaintiffs' concrete bases for asserting that Bayer had admitted general causation, and justified an expanded reply to accommodate purported admissions that plaintiffs' opposition brief had revealed. Id. at 2-3.
To facilitate informed and efficient briefing, the Court, on November 19, 2018, directed plaintiffs' counsel to submit a letter previewing the admissions on which it then intended to rely in opposing Bayer's motion for summary judgment. Dkt. 325. The Court emphasized, however, that while it expected plaintiffs to make a good-faith effort to disclose the specific evidence on which they expected to rely in claiming corporate admissions, plaintiffs' letter to this effect "will not limit the range of materials on which plaintiffs may rely in their briefing." Id. Plaintiffs' counsel thereafter filed such letter, while protesting that the Court's order "turns the summary judgment standard on its head." Dkt. 326.
Plaintiffs are wrong. The Court's approach of attempting informally to identify early the evidence on which a motion for summary judgment would most likely turn was modeled on the Mirena Perforation MDL. This approach did not in any respect relieve Bayer of its burden, as movant, to demonstrate the absence of a question of material fact. It served merely to assure orderly briefing, by enabling the Court to receive, in Bayer's opening brief, a fuller and more informed discussion of the evidence on which plaintiffs expected to rely in opposing summary judgment. The Court's Order did not limit the universe of materials on which plaintiffs were thereafter permitted to rely in opposing Bayer's motion. Plaintiffs cite no authority that this sensible case-management device infringed any legal right of theirs.
E. The Seventh Amendment and Summary Judgment
In a final argument, plaintiffs argue that granting Bayer summary judgment would be unconstitutional. Such an order, plaintiffs claim, would violate the Seventh Amendment right to a jury trial in cases in *358which the value in controversy exceeds $ 20. Although plaintiffs appear to suggest that summary judgment is inherently unconstitutional, see Pl. Mem. at 44, they state that they are not seeking a global ruling that "summary judgment is unconstitutional in all cases," id. at 45. Rather, plaintiffs argue, this case is distinct because Bayer's motion was made after the close of discovery as to general causation, but before plaintiff-specific discovery. Id.
This argument is easily dispatched. It is long established that "summary judgment does not violate the Seventh Amendment." Parklane Hosiery Co., Inc. v. Shore ,
Nor, to the extent plaintiffs imply that the Court has made a factual determination that LNG could not have caused plaintiffs' IIH, has the Court done so. Rather, the Court held in its Daubert ruling, as a legal matter, that plaintiffs' experts have failed to offer reliable, admissible testimony of general causation, consistent with Daubert . And the Court now holds, also as a legal matter, that the remaining evidence also fails to supply a basis on which a jury could reliably find the required element of general causation. In the absence of a genuine dispute of material fact as to causation, summary judgment is appropriate. See McClamrock v. Eli Lilly & Co. ,
CONCLUSION
For the reasons stated above, Bayer's motion for summary judgment is granted. The Clerk of Court is respectfully directed to terminate the pending motion (No. 17 MD 2767, Dkt. 328), and to enter judgment in and close all remaining member cases in this MDL.
SO ORDERED.
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387 F. Supp. 3d 323, Counsel Stack Legal Research, https://law.counselstack.com/opinion/in-re-mirena-ius-levonorgestrel-related-prods-liab-litig-no-ii-ilsd-2019.