Parker v. Merck & Co., Inc.

1 2 3 4 5 6 7 8 9 UNITED STATES DISTRICT COURT 10 SOUTHERN DISTRICT OF CALIFORNIA 11 12 RICHARD PARKER, an individual Case No.: 3:24-cv-00916-H-BLM 13 Plaintiff, ORDER: 14 v. (1) GRANTING DEFENDANTS’ 15 MERCK & CO., INC., a New Jersey MOTION FOR SUMMARY Corporation; MERCK SHARP & 16 JUDGMENT; DOHME CORP., a New Jersey 17 Corporation; ORGANON & CO., a (2) DENYING AS MOOT Delaware Corporation; ORGANON LLC, 18 DEFENDANTS’ MOTION TO a Delaware Limited Liability Company; EXCLUDE OR LIMIT 19 and DOES 1-10, inclusive, OPINION TESTIMONY OF 20 Defendants. DAVID HEALY; AND 21 (3) DENYING AS MOOT 22 DEFENDANTS’ MOTION TO EXCLUDE OPINIONS OF 23 DIMA MAZEN QATO 24 [Doc. Nos. 9, 10, 11.] 25 26 27 28 1 On May 30, 2024, Defendants Merck & Co., Inc. (“Merck”), Merck Sharp & Dohme 2 Corp. LLC (“MSD”), Organon & Co., and Organon LLC (“Defendants”) filed a motion 3 for summary judgment, or in the alternative, partial summary judgment. (Doc. No. 11.) 4 Defendants also filed a motion to exclude or limit the opinion testimony of David Healy 5 (Doc. No. 9), and a motion to exclude the opinions of Dima Mazen Qato, MPH, PhD (Doc. 6 No. 10) (collectively, the “Daubert motions”). On July 9, 2024, Plaintiff Richard Parker 7 (“Parker” or “Plaintiff”) filed a response in opposition to Defendants’ motion for summary 8 judgment (Doc. Nos. 24, 25), and responses in opposition to Defendants’ Daubert motions 9 (Doc. Nos. 26, 27). On July 22, 2024, Defendants filed reply briefs in support of their 10 Daubert motions. (Doc. Nos. 30, 31.) Defendants also filed objections to and motions to 11 strike the individual declarations of David Healy (Doc. No. 30-2), and Dima Qato (Doc. 12 No. 31-5), submitted by Plaintiff in opposition to Defendants’ Daubert motions. On July 13 23, 2024, Defendants filed a reply in support of their motion for summary judgment or, in 14 the alternative, partial summary judgment. (Doc. No. 32.) On July 30, 2024, Plaintiff filed 15 his response to Defendants’ statement of undisputed facts. (Doc. No. 33.)1 16 The Court held a hearing on Defendants’ motion for summary judgment and Daubert 17 motions on August 19, 2024. (Doc. No. 46.) Kimberly L. Beck, Lynne M. Kizis, and 18 Shehnaz M. Bhujwala appeared telephonically for Plaintiff. Paul R. Johnson and Susan V. 19 Vargas appeared for Defendants. (Id.) For the reasons below, the Court grants Defendants’ 20 motion for summary judgment and denies Defendants’ Daubert motions and motions to 21 strike as moot. 22 / / / 23 / / / 24 25 1 Docket Entry No. 33 is Plaintiff’s Response to Defendants’ Statement of Undisputed Facts. On August 13, 2024, Defendants filed an objection to Plaintiff’s response on the 26 grounds that the response was not timely filed. (Doc. No. 39.) Defendants have failed to 27 demonstrate how they have been prejudiced by the untimeliness of the filing. Thus, the Court overrules Defendants’ objections to Plaintiff’s Response to Defendants’ Statement 28 1 BACKGROUND 2 A. Singulair’s Regulatory Background 3 Defendants Merck and MSD (the “Merck Defendants”) are New Jersey corporations 4 that manufacture and sell pharmaceutical drugs. (Doc. No. 1, Compl. ¶ 11.) One of these 5 drugs is Singulair, which includes the active ingredient montelukast. (Id. ¶ 2; Doc. No. 11- 6 6, Defs.’ Ex. 3, at 13 ¶ 11.) Singulair is prescribed for the treatment of asthma, the 7 prevention of exercise-induced bronchoconstriction, and relief of symptoms of allergic 8 rhinitis (also called hay fever). (Doc. No. 1, Compl. ¶ 1.) Merck patented Singulair in 9 1996 and the Merck Defendants began selling Singulair in 1998 after it was approved by 10 the United States Food and Drug Administration (FDA). (Id. ¶¶ 2, 27; Doc. No. 11-4, 11 Defs.’ Ex. 1; Doc. No. 11-5, Defs.’ Ex. 2.) The Merck Defendants were the exclusive 12 manufacturers, distributors, and sellers of Singulair from 1998 to mid-2012. (Doc. No. 1, 13 Compl. ¶ 12.) On August 3, 2012, Merck’s patent expired and generic montelukast drugs 14 entered the market. (Id. ¶ 27.) At some point after March 4, 2020, the Merck Defendants 15 assigned some unspecified rights, liabilities, or control over Singulair to their subsidiary, 16 Organon & Co., and its subsidiary, Organon LLC (the “Organon Defendants”). (Id. ¶ 13.) 17 The Organon Defendants are organized under the laws of Delaware and have their principal 18 places of business in New Jersey. (Id.) 19 Originally, the Singulair label contained no warnings regarding neuropsychiatric 20 events. (Id. ¶ 3.) Since its introduction, however, Defendants have added warnings to 21 Singulair’s product label regarding neuropsychiatric events. (Id.; see Doc. No. 33 ¶¶ 1– 22 156.) On March 4, 2020, the FDA required Defendants to add the strongest type of warning 23 (a “black box warning”) to Singulair’s label regarding neuropsychiatric events. (Doc. No. 24 33 ¶ 125; Doc. No. 11-87, Defs.’ Ex. 83.1.) 25 B. Factual Background regarding Plaintiff’s Use of Montelukast 26 Plaintiff Richard Parker (“Parker”) is a citizen and resident of San Diego County, 27 California. (Doc. No. 1, Compl. ¶ 7.) Parker’s medical records indicate that he was 28 prescribed montelukast from January 2016 to August 2021. (Doc. No. 33 ¶¶ 150, 159, 171, 1 177, 180, 186, 192, 204, 207, 227.) 2 1. Singulair Warnings in Effect When Parker Was Prescribed Montelukast 3 4 It is undisputed that, at the time Parker was first prescribed montelukast in 2016, the 5 Singulair label included the following information. 6 The HIGHLIGHTS OF PRESCRIBING INFORMATION section on the first page 7 of the November 2014 label, in effect on January 1, 2016, included the following warning: 8 Neuropsychiatric events have been reported with SINGULAIR. Instruct patients to be alert for neuropsychiatric events. Evaluate the risks and 9 benefits of continuing treatment with SINGULAIR if such events occur (5.4 10 and 6.2). 11 (Id. ¶ 151; Doc. No. 11-90, Defs.’ Ex. 86 at 2.) 12 The WARNINGS AND PRECAUTIONS section of the label stated the following: 13 5.4 Neuropsychiatric Events 14 Neuropsychiatric events have been reported in adult, adolescent, and 15 pediatric patients taking SINGULAIR. Post-marketing reports with 16 SINGULAIR use include agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream 17 abnormalities, hallucinations, insomnia, irritability, memory impairment, 18 restlessness, somnambulism, suicidal thinking and behavior (including suicide), and tremor. The clinical details of some post-marketing reports 19 involving SINGULAIR appear consistent with a drug-induced effect. 20 Patients and prescribers should be alert for neuropsychiatric events. Patients should be instructed to notify their prescriber if these changes occur. 21 Prescribers should carefully evaluate the risks and benefits of continuing 22 treatment with SINGULAIR if such events occur [see Adverse Reactions (6.2)]. 23 24 (Doc. No. 33 ¶ 152; Doc. No. 11-90, Defs.’ Ex. 86 at 4–5.) 25 Under ADVERSE REACTIONS, Section 6.2 Post-Marketing Experience of the 26 November 2014 label included the statement: 27 The following adverse reactions have been identified during post-approval 28 use of SINGULAIR. Because these reactions are reported voluntarily from 1 ath peiorp furelaqtuioenn coyf ourn ecsetratbailnis hsi az ec,a iut siasl nreolta atilownasyhsip p toos sdirbulge etox proelsiuarbel y. .e .s t.i mate 2 3 Psychiatric disorders: agitation including aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream 4 abnormalities, hallucinations, insomnia, irritability, memory impairment, 5 restlessness, somnambulism, suicidal thinking and behavior (including suicide), and tremor [see Warnings and Precautions (5.4)]. 6 7 (Doc. No. 33 ¶¶ 153–54; Doc. No. 11-90, Defs.’ Ex. 86 at 7.) 8 Section 17, Patient Counseling Information, stated: “Patients should be instructed to 9 notify their physician if neuropsychiatric events occur while using SINGULAIR.” (Doc. 10 No. 33 ¶ 155; Doc. No. 11-90, Defs.’ Ex. 86 at 20.) 11 The Patient Information leaflet, that comes with Singulair, directs patients to read it 12 “before you start taking [Singulair] and each time you get a refill.” (Doc. No. 11-90, Defs.’ 13 Ex. 86 at 22.) The leaflet identifies the following side effects: 14 Behavior and mood-related changes. Tell your healthcare provider right 15 away if you or your child have any of these symptoms while taking SINGULAIR: 16 • agitation including aggressive • irritability 17 behavior or hostility • memory problems • attention problems • restlessness 18 • bad or vivid dreams • sleep walking 19 • depression • suicidal thoughts and actions • disorientation (confusion) (including suicide) 20 • feeling anxious • tremor 21 • hallucinations (seeing or hearing • trouble sleeping things that are not really there) 22 23 (Doc. No. 33 ¶ 156; Doc. No. 11-90, Defs.’ Ex. 86 at 24.) 24 2. Healthcare Professionals Who Prescribed Parker Montelukast 25 In September 2017, Parker established care with allergist and immunologist, Dr. 26 Reddy, because Parker’s asthma and allergies had increased in severity over the previous 27 28 1 five to six years. (Doc. No. 33 ¶ 184.) According to Dr. Reddy, at Parker’s initial 2 treatment date, Parker indicated that one month prior, in August 2017, he had an asthma 3 exacerbation (Doc. No. 11-96, Defs.’ Ex. 92 [Reddy Dep.] at 5:8-13, 10:15-22), but that 4 he “was doing well” while taking montelukast, along with his other medications (id. at 5 7:19-22; Doc. No. 33 ¶ 185). Parker also shared that he had depression and anxiety. (Doc. 6 No. 11-96, Defs.’ Ex. 92 [Reddy Dep.] at 14:4-8.) Dr. Reddy continued his prescription 7 for montelukast and testified that she did not want to titrate any medications down when 8 Parker’s asthma was unstable. (Id. at 16:23-25–17:1-9.) She also testified that at the time 9 she prescribed montelukast to Parker, she was familiar with the risks and benefits of the 10 medication. (Id. at 51:6-14.) 11 Parker saw Dr. Reddy again in October 2017, November 2017, December 2017, 12 April 2018, and November 2018. (Doc. No. 33 ¶¶ 193, 198, 200, 202.) During this time, 13 Parker continued taking montelukast. (Id. ¶ 199.) In November 2018, Dr. Reddy noted 14 that Parker had been under tremendous stress because he lost his job because of his back 15 problems, but that his asthma was “much improved on the current regimen,” so she 16 continued Parker on montelukast. (Id. ¶¶ 203–04.) Parker saw Dr. Reddy again in May 17 2019, December 2019, and June 2021. (Id. ¶¶ 205, 208, 211.) During this time, Parker 18 never told Dr. Reddy that he had experienced panic attacks (id. ¶ 196), took opiates and 19 used other illicit drugs (id. ¶ 197), that he had been hospitalized because he believed his 20 parents were poisoning him, that his uncle had kicked him out of the house, that he was 21 living out of a car, or that he had suicidal ideations (id. ¶ 206). It was not until June 2021, 22 after the black box warning appeared on montelukast’s label, that Dr. Reddy did not restart 23 24 2 Between 2016 and 2021, Parker was evaluated by six individuals who prescribed 25 him montelukast. (Doc. No. 33 ¶¶ 159, 171, 177, 180, 186, 227.) But, in opposing Defendants’ motion for summary judgment, Plaintiff relies solely on Plaintiff’s treatment 26 by Dr. Reddy to support his remaining claims. (Doc No. 24 at 15–16.) As such, the Court 27 will focus on Plaintiff’s treatment by Dr. Reddy and one subsequent provider in this Background section. 28 1 Parker on montelukast because of his history of depression and the recent emphasis of 2 neuropsychiatric adverse effects associated with montelukast. (Id. ¶ 214.) 3 In August 2020, Parker was referred to an internist, Dr. Michael, for asthma and 4 chronic neck trauma. (Id. ¶ 219.) Parker also saw Dr. Michael in June 2021 and August 5 2021, which was his last visit with Dr. Michael. (Id. ¶¶ 222, 227.) Unaware of Dr. Reddy’s 6 decision to stop Parker’s montelukast prescription, at the August 2021 visit, Dr. Michael 7 prescribed Parker montelukast. (Id. ¶¶ 227, 231.) Had Parker told Dr. Michael that Dr. 8 Reddy stopped Parker’s montelukast prescription in June 2021, Dr. Michael would have 9 discontinued the prescription (id. ¶ 231), but Parker never shared that information with Dr. 10 Michael (id.). Dr. Michael testified that at the time he treated Parker in August 2021, he 11 was aware of montelukast’s black box warning and with the risks and benefits of 12 montelukast. (Doc. No. 11-98, Defs.’ Ex. 94 [Michael Dep.] at 22:6-9, 25:2-5.) 13 Additionally, Dr. Michael testified that since 2014, he has considered the warnings 14 contained in montelukast’s label regarding potential neuropsychiatric events whenever he 15 prescribed it. (Id. at 26:13-17.) 16 3. Plaintiff’s Additional Medical History 17 The record before the Court also reflects that at various points, Parker may have 18 been diagnosed with cannabis-induced psychosis (Doc. No. 11-98, Defs.’ Ex. 94 [Michael 19 Dep.] at 18:12-16), complex post-traumatic stress disorder (PTSD) (id. at 16:25–17:1-19), 20 religious trauma syndrome (id.), and schizophrenia (id.; Doc. No. 33 ¶ 225), amongst other 21 neurologic disorders (Doc. No. 25-38, Pl.’s Ex. 27 at 15). The record also reflects that on 22 October 2, 2020, Parker may have attempted suicide. (Doc. No. 33 ¶ 224; Doc. No. 11-98, 23 Defs.’ Ex. 94 [Michael Dep.] at 16:20-24.) Dr. Reddy was never informed about Parker’s 24 medical history regarding these conditions, Parker’s hospitalizations affiliated with 25 neuropsychiatric events, or of any suicidal ideations during her treatment of him. (Doc. 26 No. 33 ¶¶ 195, 218, 221.) 27 / / / 28 / / / 1 C. Procedural Background 2 On May 23, 2024, Richard Parker filed a complaint in this Court. (Doc. No. 1.)3 3 The complaint asserts three causes of action: (1) strict liability—failure to warn (Count I); 4 (2) negligence (Count II); and (3) negligent misrepresentation (Count III). (Doc. 5 No. 1 ¶¶ 103–155.) 6 By the present motion, Defendants move for summary judgment on all of Parker’s 7 claims. (Doc. No. 11.) In response to Defendants’ motion for summary judgment, Parker 8 dismissed his claim for strict liability—failure to warn. (Doc. No. 24 at 5.) Parker now 9 has two remaining claims for (1) negligence and (2) negligent misrepresentation. 10 DISCUSSION 11 I. Legal Standards Governing Summary Judgment 12 Summary judgment is appropriate under Federal Rule of Civil Procedure 56 if the 13 moving party demonstrates “that there is no genuine dispute as to any material fact and the 14 movant is entitled to judgment as a matter of law.” Fed. R. Civ. P. 56(a); Celotex Corp. v. 15 Catrett, 477 U.S. 317, 322 (1986). Material facts are facts that, under the governing 16 substantive law, may affect the outcome of the case. Anderson v. Liberty Lobby, Inc., 477 17 U.S. 242, 248 (1986). A dispute as to a material fact is genuine if there is sufficient 18 evidence for a reasonable jury to return a verdict for the non-moving party. Id. “Disputes 19 over irrelevant or unnecessary facts will not preclude a grant of summary judgment.” T.W. 20 Elec. Serv., Inc. v. Pac. Elec. Contractors Ass’n, 809 F.2d 626, 630 (9th Cir. 1987). 21 / / / 22 23 3 This case is related to Bueno v. Merck & Co., Inc. et al., United States District Court, 24 Southern District of California, Case No. 3:22-cv-00522-H-BLM (“Bueno”). On March 3, 25 2022, Richard Parker and Spencer Bueno filed a complaint in the Superior Court of the State of California, County of San Diego, which was subsequently removed to this Court 26 based on diversity jurisdiction. (Bueno, 22-cv-522-Doc. Nos. 1, 7.) On May 20, 2024, the 27 Court granted a joint motion to sever the claims of Plaintiff Richard Parker, and Plaintiff Parker was severed from the Bueno litigation. (Bueno, 22-cv-522-Doc. No. 84.) Parker 28 1 A party seeking summary judgment always bears the initial burden of demonstrating 2 that there is no genuine dispute as to any material fact. Celotex, 477 U.S. at 323. A moving 3 party without the ultimate burden of proof at trial can satisfy its burden in two ways: (1) 4 by presenting “evidence negating an essential element of the nonmoving party’s claim or 5 defense;” or (2) by demonstrating “that the nonmoving party does not have enough 6 evidence of an essential element to carry its ultimate burden of persuasion at trial.” Nissan 7 Fire & Marine Ins. Co. v. Fritz Companies, Inc., 210 F.3d 1099, 1102 (9th Cir. 2000). 8 Once the moving party establishes the absence of a genuine dispute as to any 9 material fact, the burden shifts to the nonmoving party to “set forth, by affidavit or as 10 otherwise provided in Rule 56, ‘specific facts showing that there is a genuine issue for 11 trial.’” T.W. Elec. Serv., 809 F.2d at 630 (quoting former Fed. R. Civ. P. 56(e)); accord 12 Horphag Research Ltd. v. Garcia, 475 F.3d 1029, 1035 (9th Cir. 2007). To carry this 13 burden, the non-moving party “may not rest upon mere allegation or denials of his 14 pleadings.” Anderson, 477 U.S. at 256; see also Behrens v. Pelletier, 516 U.S. 299, 309 15 (1996) (“On summary judgment, . . . the plaintiff can no longer rest on the pleadings.”). 16 Rather, the nonmoving party “must present affirmative evidence . . . from which a jury 17 might return a verdict in his favor.” Anderson, 477 U.S. at 256. 18 When ruling on a summary judgment motion, the court must view the facts and draw 19 all reasonable inferences in the light most favorable to the non-moving party. Scott v. 20 Harris, 550 U.S. 372, 378 (2007). The court should not weigh the evidence or make 21 credibility determinations. See Anderson, 477 U.S. at 255. “The evidence of the non- 22 movant is to be believed.” Id. Further, the court may consider other materials in the record 23 not cited to by the parties, but it is not required to do so. See Fed. R. Civ. P. 56(c)(3); see 24 also Simmons v. Navajo Cnty., 609 F.3d 1011, 1017 (9th Cir. 2010) (“[A] district court 25 has no independent duty ‘to scour the record in search of a genuine issue of triable fact.’”). 26 II. Plaintiff’s Negligent Failure to Warn Claims 27 California’s learned intermediary doctrine applies to negligent failure-to-warn 28 claims. Himes v. Somatics, LLC, 16 Cal. 5th 209, 221 (2024); see also Thomas v. Abbott 1 Lab’ys, 2014 WL 4197494, at *5 (C.D. Cal. July 29, 2014). “The learned intermediary 2 doctrine provides that manufacturers have a duty to warn physicians, but not the 3 physicians’ patients, about certain risks accompanying use of their prescription drugs and 4 many medical devices.” Himes, 16 Cal. 5th at 221; see also Carlin v. Superior Ct., 13 Cal. 5 4th 1104, 1116 (1996) (“[I]n the case of prescription drugs, the duty to warn runs to the 6 physician, not to the patient.” (emphasis in original)). “The doctrine’s rationale is that 7 warnings pertaining to prescription drugs and medical devices should be relayed to patients 8 by their physicians—rather than by the manufacturer—because physicians are in a better 9 position to assist patients in deciphering and evaluating the warnings.” Himes, 16 Cal. 5th 10 at 227. In other words, “[a]s long as the manufacturer has adequately warned the patient’s 11 physician of the non-negligible risks of its prescription drug or medical device, the 12 manufacturer has fulfilled its duty to warn.” Id. at 221. Under California law, a drug 13 manufacturer’s duty to warn by providing an adequate label extends to the generic 14 equivalent version of a brand-name drug because “[g]eneric drug manufacturers are 15 required to follow the brand-name manufacturer’s label to the letter.” T.H. v. Novartis 16 Pharms. Corp., 4 Cal. 5th 145, 155 (2017). 17 The determination as to whether a warning for a prescription medication is adequate 18 “depends on ‘how a prescribing doctor would understand the label.’” Rodman v. Otsuka 19 Am. Pharm., Inc., 564 F. Supp. 3d 879, 891 (N.D. Cal. 2020), aff’d, No. 20-16646, 2021 20 WL 5850914 (9th Cir. Dec. 9, 2021) (citing Hexum v. Eli Lilly & Co., 2015 WL 5008263 21 at *7 (C.D. Cal. 2015)). “There can be no genuine dispute about the adequacy of a warning 22 that directly warns in plain and explicit terms of the specific risk that has caused injury to 23 the plaintiff.” Id. (internal quotation marks omitted). 24 “‘A plaintiff asserting causes of action based on a failure to warn must prove not 25 only that no warning was provided or the warning was inadequate, but also that the 26 27 4 The parties agree that California law applies to Parker’s claims. (See Doc. No. 11- 28 1 inadequacy or absence of the warning caused the plaintiff’s injury.’” Himes v. Somatics, 2 LLC, 29 F.4th 1125, 1126 (9th Cir. 2022), certified question answered, 16 Cal. 5th 209, 3 (2024) (quoting Motus v. Pfizer Inc., 196 F. Supp. 2d 984, 991 (C.D. Cal. 2001), aff’d, 358 4 F.3d 659 (9th Cir. 2004)); see also Rodman, 564 F. Supp. 3d at 892 (“[E]ven if a warning 5 was inadequate, ‘a product defect claim based on insufficient warnings cannot survive 6 summary judgment if stronger warnings would not have altered the conduct of the 7 prescribing physician.’” (quoting Motus v. Pfizer Inc. (Roerig Div.), 358 F.3d 659, 661 8 (9th Cir. 2004))). To prove causation, the plaintiff must prove that a failure to warn was a 9 “substantial factor” in causing the injury. See Himes, 16 Cal. 5th at 222. Additionally, 10 “[w]here the evidence shows that the physician would have continued to recommend the 11 treatment notwithstanding the stronger warning,” a plaintiff can also prove causation by 12 proving “that an objectively prudent person in the patient’s position would have declined 13 treatment despite the physician’s assessment that the benefits of the treatment for the 14 patient would still outweigh any risks disclosed by a stronger warning.” Id. at 219. 15 A. Duty to Adequately Warn Physicians 16 It is undisputed that at the time Plaintiff was first prescribed montelukast in 2016, 17 the Singulair label contained warnings regarding neuropsychiatric events and psychiatric 18 disorders in the Highlights of Prescribing Information section on the first page of the label 19 (Doc. No. 33 ¶ 151), in the Warnings and Precautions section (id. ¶ 152), in the Post- 20 Marketing Experience section (id. ¶¶ 153, 154), in the Patient Counseling Information 21 section (id. ¶ 155), and as side effects in the Patient Information sheet (id. ¶ 156). Despite 22 the plain warnings regarding neuropsychiatric events and Dr. Reddy’s testimony that, at 23 the time she prescribed montelukast to Parker, she was familiar with its risks and benefits 24 (Doc. No. 11-96, Defs.’ Ex. 92 [Reddy Dep.] at 51:6-14), Plaintiff argues that the warnings 25 in the montelukast label were inadequate (Doc. No. 24 at 5), and disputes whether Dr. 26 / / / 27 / / / 28 / / / 1 Reddy was adequately warned of the risks of Singulair (Doc. No. 33 ¶ 186). Specifically, 2 Plaintiff asserts that Merck breached its duty to adequately warn physicians of the 3 neuropsychiatric conditions affiliated with montelukast by failing to take the following 4 three actions: 5 (1) Changing the Language of the Prescriber’s Information regarding Adverse 6 Events - First, Plaintiff argues that Merck could have accepted FDA’s suggestion 7 to warn that the adverse event reports “are consistent with a drug-induced effect,” 8 instead of “convinc[ing] the FDA to allow Merck to say some post-marketing 9 reports involving Singulair ‘appear consistent with a drug-induced effect’.” 10 (Doc. No. 24 at 6; see also id. at 11, 18-19, 33.) 11 (2) Adding a Contraindication - Second, Plaintiff asserts that “Merck could have 12 added a contraindication for people who were prescribed Singulair for allergic 13 rhinitis and experienced suicidality while taking Singulair.” (Id. at 6; see also 14 id. at 18, 33.) 15 (3) Sending a “Dear doctor” letter following 2020 “black box” warning - Third, 16 Plaintiff asserts that Merck “could have also sent out a ‘Dear Doctor’ letter to let 17 prescribers know that the black box warning was added to the label in 18 March/April 2020, as that was the height of the Covid health crisis and many 19 20 21 5 Plaintiff does not argue that Defendants could have or should have unilaterally added 22 a black box warning to montelukast’s label before 2020. At the August 19, 2024, hearing, 23 Plaintiff conceded that Defendants could not have unilaterally added a black box warning. See also Rosewolf v. Merck., 4:22-cv-02072-JSW, slip op. at 15 (N.D. Cal. Dec. 2, 2022) 24 (Plaintiff’s counsel stating in a related case: “Plaintiffs agree that Defendants could not 25 have unilaterally added the Black Box Warning.”). “A black box warning is the strongest type of warning allowed in drug labeling, and to ensure their significance is undiluted, use 26 of a black box warning is permitted only where specifically required by the FDA.” Amos 27 v. Biogen Idec Inc., 249 F. Supp. 3d 690, 694 (W.D.N.Y. 2017). 28 1 practitioners were consumed with addressing Covid-related concerns.” (Id. at 6; 2 see also id. at 14, 19, 33.) 3 Plaintiff does not offer any evidence in support of his argument that Defendants were 4 negligent by not taking these three recommended actions. 6 (Doc. No. 24 at 18–19.) The 5 expert report of Plaintiff’s expert, Dr. Dima Mazen Qato, PharmD, MPH, PhD, does not 6 mention, let alone explain, how the language in montelukast’s warning label about 7 “marketing reports that ‘appear consistent’ with a drug-induced effect” differs in meaning 8 from, or is inadequate to, the language, “marketing reports that ‘are consistent’ with a drug- 9 induced effect.” (See generally Doc. No. 11-100, Defs.’ Ex. 96.) She also does not offer 10 any opinion or evidence on contraindications for individuals experiencing suicidal 11 ideations or suicidality, or “Dear doctor” letters. (Id.) Furthermore, Plaintiff does not 12 challenge Defendants’ argument that the labeling critiques that appear in Dr. Qato’s report 13 concerning recommended warnings to “pediatric populations,” modified instructions in 14 dosage and administration for “adolescents,” and the “food effects” on levels of 15 montelukast (see id. at 14–15), have no relevance to Parker, who was an adult when he was 16 first prescribed montelukast and has never alleged an inadequacy of montelukast’s label 17 with respect to “food effects” (Doc. No. 11-1 at 21).7 While Dr. Qato’s report generally 18 indicates that “the manufacturer (Merck) should have anticipated, monitored, and/or 19 warned about . . . neuropsychiatric risks” (Doc. No. 10-4 at 14), she does not explain how 20 the neuropsychiatric warnings that existed on the montelukast label were inadequate. See 21 Oregon v. Bos. Sci. Corp., 2022 WL 1607960, at *4 (E.D. Cal. May 20, 2022) (“‘[M]erely 22 stating that the Defendants failed to ‘adequately warn’ of [the alleged injury] is a bare legal 23 24 25 6 Plaintiff does not dispute that prior to Defendants’ filing their motion for summary judgment, Plaintiff withdrew his “warnings expert,” Jack E. Fincham, PhD., R.Ph. (Doc. 26 No. 11-1 at 20.) 27 7 At the August 19, 2024, hearing, Plaintiff’s counsel conceded that the sections of Dr. Qato’s report regarding inadequate warnings for children, adolescents, and the “food 28 1 conclusion’ and would be insufficient to state a cognizable failure to warn claim.” (quoting 2 Marroquin v. Pfizer, Inc., 367 F. Supp. 3d 1152, 1161 (E.D. Cal. 2019))). 3 The same is true of the report written by Plaintiff’s other expert, Dr. David Healy. 4 (Doc. No. 25-38, Pl.’s Ex 27.) Dr. Healy does not discuss any specific inadequacies in the 5 Singulair or montelukast label.8 (See generally id.) 6 Because no evidence has been proffered to prove how Singulair’s label was 7 inadequate for physicians prescribing montelukast to adults like Parker, Plaintiff has failed 8 to carry his burden of demonstrating that he has sufficient evidence to allow a jury to 9 determine that the warnings on the Singulair label were inadequate. Thus, Defendants are 10 entitled to summary judgment of Plaintiff’s remaining claims on this basis. See Garber v. 11 United States, 2017 WL 797096, at *8 (C.D. Cal. Feb. 27, 2017), aff’d, 709 F. App’x 485 12 (9th Cir. 2018) (“[T]he adequacy of defendant’s warnings [is] beyond the common 13 knowledge of a layperson. Accordingly, [it] must be established through expert 14 testimony.”); Rodman, 564 F. Supp. 3d. at 891 (granting summary judgment on failure-to- 15 warn claim after excluding plaintiff’s expert’s labeling opinions because “[w]hether a 16 warning is adequate depends on how a prescribing doctor would understand the label” 17 (internal quotation marks and citations omitted)); Kamerik v. Depuy Orthopedics, Inc., 18 2013 WL 12322041, *4 (C.D. Cal. Jan. 28, 2013) (granting summary judgment on 19 negligence and warnings-based claims in the absence of expert testimony as the standard 20 of care for manufacturer of complex medical device was “‘beyond the common knowledge 21 of [laypeople]’” (quoting Torres v. Taser Int’l, Inc., 277 F. App’x 684, 687 (9th Cir. 22 2008))); see also Anderson, 477 U.S. at 257 (explaining that “in order to defeat a properly 23 supported motion for summary judgment,” a plaintiff must present “affirmative evidence” 24 “from which a jury might return a verdict in his favor”). 25 / / / 26 27 8 At the August 19, 2024 hearing, Plaintiff conceded that Plaintiff does not rely on Dr. 28 1 B. Causation 2 Since Plaintiff does not prevail on demonstrating the inadequacy of the Singulair 3 warning label, causation is rendered moot. Nevertheless, the Court will address causation. 4 Plaintiff bears the burden of proving that any inadequacies by Defendants in warning 5 Plaintiff’s physicians of the risks associated with Singulair caused his injuries. See Himes, 6 16 Cal. 5th at 222–23. To prove causation, the plaintiff must prove that a failure to warn 7 was a “substantial factor” in causing the injury. Id. at 222. 8 Six individuals prescribed Plaintiff montelukast: (1) Dr. Thiel, (2) Dr. Parikh, (3) 9 nurse Milton, (4) nurse Ochoa, (5) Dr. Reddy, and (6) Dr. Michael. (Doc. No. 33 ¶¶ 159, 10 170, 177, 180, 186, 192, 227.) However, Plaintiff does not mention any prescriber besides 11 Dr. Reddy in his opposition to Defendants’ motion for summary judgment. (See generally 12 Doc. No. 24.) In light of this failure to address the other prescribers in his briefing, Plaintiff 13 has failed to demonstrate a triable issue of fact regarding causation as to those other five 14 prescribers. See Hartranft v. Encore Capital Group., Inc., 543 F. Supp. 3d 893, 913 (S.D. 15 Cal. 2021) (“[W]here a non-moving party fails to address an argument raised by the moving 16 party in the opposition brief, the Court may consider any arguments unaddressed by the 17 non-moving party as waived.”); see also Pacific Dawn LLC v. Pritzker, 831 F.3d 1166, 18 1178 n.7 (9th Cir. 2016) (noting that because “plaintiffs did not raise . . . [the] argument 19 to the district court in their . . . opposition to the defendants’ motion for summary judgment. 20 . . the argument was waived”). Accordingly, the Court will only address the extent to which 21 any inadequacies to the montelukast label might have affected Dr. Reddy’s prescribing 22 decision, thereby causing injury to Parker. 23 As to causation, Plaintiff has not raised a triable issue of fact. Plaintiff has not 24 demonstrated that Dr. Reddy would have changed her prescribing decisions had 25 Defendants followed any of Plaintiff’s three proposals to: (1) accept FDA’s suggestion to 26 warn that the adverse event reports “are consistent with a drug-induced effect,” rather than 27 that adverse event reports “appear consistent with a drug-induced effect,” (2) add a 28 contraindication for patients with allergic rhinitis “who experienced suicidality while 1 taking Singulair,” or (3) issue a “Dear doctor” letter to physicians following the addition 2 of the black box warning in 2020. (See Doc. No. 32 at 8.) 3 First, there is no testimony from any expert or Dr. Reddy, that a label change stating 4 that adverse event reports “are consistent” with a drug-induced effect would have changed 5 her decision to prescribe montelukast to Parker compared to the label at the time she 6 prescribed the medication, which stated that adverse event reports “appear consistent” with 7 a drug-induced effect. (See generally Doc. No. 25-39, Pl.’s Ex. 28 [Reddy Dep.].) Without 8 any evidence from Dr. Reddy or an expert, Plaintiff does not meet his burden to prove that 9 changing, “appear consistent” to “are consistent” on the label would materially affect his 10 physician’s prescribing decisions. See Anderson, 477 U.S. at 257 (explaining that “in order 11 to defeat a properly supported motion for summary judgment,” a plaintiff must present 12 “affirmative evidence” “from which a jury might return a verdict in his favor”). 13 Second, Plaintiff’s proposed contraindication for patients prescribed montelukast for 14 allergic rhinitis, or allergies (but not asthma), could not have applied to Dr. Reddy’s 15 prescribing decisions given that the contraindication would only have affected patients 16 prescribed montelukast for allergic rhinitis and nothing else, and it is undisputed that Parker 17 was originally prescribed montelukast for asthma, and then later for asthma and allergies. 18 (Doc. No. 33 ¶¶ 157–59 (undisputed that Dr. Thiel prescribed Singulair after “Parker 19 established care with Dr. Thiel in early January 2016 for asthma”); ¶¶ 176–77 (undisputed 20 that nurse Milton continued his prescription for montelukast after Parker established care 21 with her in part due to “asthma and allergies”); ¶¶ 184–185 (undisputed that “Parker told 22 Dr. Reddy he ‘was doing well’ with respect to the management of his asthma and allergies 23 on medications including montelukast”); ¶¶ 200–01 (undisputed that in April 2018, Parker 24 saw Dr. Reddy “because his cold exacerbated his asthma. . . [h]owever, Parker had 25 continued to take montelukast and his asthma was much more stable”); ¶¶ 222–23, 227 26 (undisputed that Parker saw Dr. Michael in June 2021 for his “asthma and thoracic back 27 pain” and “Dr. Michael again prescribed Parker montelukast in August 2021 during their 28 last visit.”).) Even if Plaintiff recommended a label change to include a contraindication 1 for patients prescribed montelukast for allergic rhinitis and asthma and experienced 2 suicidality while taking Singulair, Plaintiff does not raise a triable issue of fact regarding 3 causation because it is undisputed that Parker never told Dr. Reddy or Dr. Michael that he 4 experienced suicidality. (Id. ¶ 218 (undisputed that “other than Parker’s depression, Dr. 5 Reddy knew of none of his past adverse psychiatric events”); id. ¶ 224 (undisputed that 6 “Parker did not tell Dr. Michael he attempted suicide”).) 7 Third, there is no evidence that a “Dear doctor” letter to Dr. Reddy following the 8 addition of the black box warning to the Singulair label would have changed her 9 prescribing decisions. Plaintiff asserts that Dr. Reddy “was adamant about taking [Parker] 10 off Singulair as soon as she discovered the black box warning.” (Doc. No. 24-1 ¶ 68.) 11 Plaintiff proffers no evidence that a “Dear doctor” letter would have expedited or in any 12 other way altered Dr. Reddy’s decision to take Parker off Singulair. (See generally id.; 13 Doc. No. 24.) 14 Plaintiff’s argument that he can prove causation by showing that had the warnings 15 been stronger, “an objectively prudent person in the patient’s position would have . . . 16 declined the treatment,” regardless of a physician’s recommendation (Doc. No. 24 at 20), 17 fares no better. After the FDA added the black box warning to the montelukast label, Dr. 18 Reddy stopped prescribing Plaintiff montelukast. (Doc. No. 24-1 ¶ 68.) However, Plaintiff 19 did not follow Dr. Reddy’s prescribing recommendation and did not stop taking 20 montelukast. (Doc. No. 33 ¶¶ 220, 223 (undisputed that Parker’s medical records reflected 21 montelukast as “active” before his appointment with Dr. Michael in August 2020 and again 22 in June 2021).) Following Dr. Reddy’s decision to stop Parker’s montelukast prescription, 23 Dr. Michael, who was unaware of Dr. Reddy’s decision, prescribed Parker montelukast 24 again in August 2021 during their last visit. (Id. ¶¶ 227, 231.) It is undisputed that had 25 Parker told Dr. Michael that Dr. Reddy stopped Parker’s montelukast prescription in June 26 2021, Dr. Michael would have discontinued the prescription (id. ¶ 231), but Parker did not 27 share that information with Dr. Michael (id.). 28 1 In sum, Plaintiff has failed to present sufficient evidence as to how Plaintiff’s three 2 suggested enhanced label warnings would have altered the conduct of Plaintiff’s 3 prescribing physicians, or even an objectively reasonable consumer’s decision to ingest 4 montelukast. As such, Defendants are entitled to summary judgment of Plaintiff’s 5 remaining claims on this basis. See Motus v. Pfizer Inc. (Roerig Div.), 358 F.3d 659, 661 6 (9th Cir. 2004) (affirming summary judgment where plaintiff “failed to establish proof that 7 stronger warnings would have changed her husband’s medical treatment or averted his 8 suicide”). 9 IV. Preemption 10 Even though Defendants are entitled to summary judgment as to Plaintiff’s 11 negligence and negligent misrepresentation claims, the Court will nevertheless address 12 preemption. Defendants argue that even if the Singulair warnings were inadequate, 13 Defendants are entitled to summary judgment because Plaintiff’s failure-to-warn claims 14 are preempted by the federal Food, Drug, and Cosmetic Act (“FDCA”). (Doc. No. 11-1 at 15 10, 25.) Specifically, Defendants assert that because a pharmaceutical manufacturer 16 typically cannot change an FDA-approved drug’s label without the FDA’s preapproval of 17 any proposed changes, a state’s product liability law is preempted by the FDCA unless the 18 manufacturer could unilaterally correct the alleged labeling deficiency using the “changes 19 being effected” (“CBE”) regulation. (Id. at 25.) Plaintiff responds that federal law does 20 not preempt California law, which required Merck to provide a stronger warning, and 21 Merck could have strengthened its warnings through the CBE process. (Doc. No. 24 at 22 23–33.) 23 Under the Supremacy Clause of the Constitution, “when federal and state law 24 conflict, federal law prevails and state law is preempted.” Knox v. Brnovich, 907 F.3d 25 1167, 1173 (9th Cir. 2018) (quoting New Jersey Thoroughbred Horsemen’s Ass’n v. Nat’l 26 Collegiate Athletic Ass’n, 584 U.S. 453, 471 (2018)). State law includes “state common 27 law or state statutes that require drug manufactures to warn drug consumers of the risks 28 associated with drugs.” Merck Sharp & Dohme Corp. v. Albrecht, 587 U.S. 299, 303 1 (2019). Absent express preemption, state law may be “impliedly pre-empted where it is 2 impossible for a private party to comply with both state and federal requirements.” Mut. 3 Pharm. Co. v. Bartlett, 570 U.S. 472, 480 (2013) (internal quotation marks and citation 4 omitted). The question of preemption is “one for a judge to decide, not a jury.” Albrecht, 5 587 U.S. at 303. 6 The federal law at issue here is the “statutory and regulatory scheme through which 7 the FDA regulates the information that appears on brand-name prescription drug labels.” 8 Id. “Prospective drug manufacturers work with the FDA to develop an appropriate label 9 when they apply for FDA approval of a new drug.” Id. at 304. Because research about 10 drug safety may evolve over time, drug manufacturers “generally seek advance permission 11 from the FDA to make substantive changes to their drug labels.” Id. “In general, the FDA 12 must approve any subsequent label change through a supplemental application process.” 13 Krantz v. Regeneron Pharms., Inc., 2024 WL 1792769, at *6 (C.D. Cal. Apr. 24, 2024) 14 (citing 21 C.F.R. § 314.70b(2)(v)(A)). However, the FDA’s CBE regulation “permits drug 15 manufacturers to change a label to ‘reflect newly acquired information’ if the changes ‘add 16 or strengthen a . . . warning for which there is ‘evidence of a causal association,’ without 17 prior approval from the FDA.” Albrecht, 587 U.S. at 314–15 (citing 21 C.F.R. § 18 314.70(c)(6)(iii)(A)). 19 The CBE regulation defines the term, “newly acquired information,” as: 20 [D]ata, analyses, or other information not previously submitted to the Agency, which may include (but is not limited to) data derived from new 21 clinical studies, reports of adverse events, or new analyses of previously 22 submitted data (e.g., meta-analyses) if the studies, events, or analyses reveal risks of a different type or greater severity or frequency than previously 23 included in submissions to FDA. 24 25 21 C.F.R. § 314.3(b). “Newly acquired information” is not limited to new data, but “also 26 encompasses ‘new analyses of previously submitted data.’” Wyeth v. Levine, 555 U.S. 27 555, 569 (2009) (quoting 73 Fed. Reg. 49603-01, 49604 (Aug. 22, 2008)). This is because 28 “risk information accumulates over time and . . . the same data may take on a different 1 meaning in light of subsequent developments. . . .” Id.; see also id. at 570 (finding that, 2 “[i]n later years, as amputations continued to occur, Wyeth could have analyzed the 3 accumulating data and added a stronger warning about IV-push administration of the 4 drug”). 5 In conducting a preemption analysis in pharmaceutical litigation, “[w]hether federal 6 and state laws irreconcilably conflict entails the threshold inquiry of whether there is 7 ‘newly acquired information’ to support a CBE submission.” In re Incretin-Based 8 Therapies Prod. Liab. Litig., 524 F. Supp. 3d 1007, 1018 (S.D. Cal. 2021), aff’d, 2022 WL 9 898595 (9th Cir. Mar. 28, 2022) (quoting Albrecht, 587 U.S. at 314); see also Krantz v. 10 Regeneron Pharms., Inc., 2024 WL 1792769, at *7 (C.D. Cal. Apr. 24, 2024) (“In the 11 context of preemption by the FDCA of claims of failure-to-warn, the burden is first on the 12 Plaintiffs to allege facts showing that [defendant] could have unilaterally changed [the 13 drugs’] label under the CBE regulation”) (internal quotation marks and citation omitted). 14 “If the answer is no, then the state law claim is preempted.” In re Incretin, 524 F. Supp. 15 3d at 1018; see also Knight v. Boehringer Ingelheim Pharm., Inc., 984 F.3d 329, 332 (4th 16 Cir. 2021) (finding that because the manufacturer did not have “newly acquired 17 information” to unilaterally change its label, the state law claim is preempted). “If the 18 answer is yes, then the Court considers whether there is clear evidence that ‘the drug 19 manufacturer fully informed the FDA of the justifications for the warning required by state 20 law and that the FDA, in turn, informed the drug manufacturer that the FDA would not 21 approve a change to the drug’s label to include that warning.’” In re Incretin, 524 F. Supp. 22 3d at 1018 (quoting Albrecht, 587 U.S at 315). 23 In the context of pharmaceutical litigation, “[i]mpossibility pre-emption is a 24 demanding defense.” Wyeth, 555 U.S. at 573. Because the CBE regulation permits 25 manufacturers to make changes effective immediately while pending FDA review, “a drug 26 manufacturer will not ordinarily be able to show that there is an actual conflict between 27 state and federal law such that it was impossible to comply with both.” Albrecht, 587 U.S. 28 1 at 315. Nevertheless, a drug manufacturer “cannot propose a change that is not based on 2 reasonable evidence.” Id. 3 A. CBE Change Prior to 2008 4 Plaintiff first argues that prior to 2008, before the codification of the “newly acquired 5 information” requirement, Merck “could have submitted a label change based on the many 6 adverse event reports that were piling up” or “could have provided to the FDA the very 7 simply [sic] calculation Dr. Qato provided.” (Doc. No. 24 at 27.) Plaintiff does not cite to 8 any evidence of “the many adverse event reports that were piling up” (id.), nor does 9 Plaintiff cite to the “simpl[e] calculation” to which he refers. (See generally Doc. No. 24.)9 10 Without evidence to substantiate his assertion, Plaintiff does not meet his burden to prove 11 that prior to 2008, Merck could have submitted a CBE label change. See Opara v. Yellen, 12 57 F.4th 709, 728 (9th Cir. 2023) (mere conclusory allegations are insufficient to raise a 13 fact issue that would preclude summary judgment). 14 B. CBE Change Following 2008 “Newly Acquired Information” Requirement 15 16 Following the 2008 addition of the “newly acquired information” requirement in the 17 CBE regulation, 21 C.F.R. § 314.3(b), Plaintiff argues “two forms of ‘newly acquired 18 information,’” could have justified a CBE change to Singulair’s label: (1) “[a]pproximately 19 ten thousand reports regarding neuropsychiatric adverse events [that] were in the FDA 20 database[,]” “any one” of which could have been “sufficient to justify a label change” (Doc. 21 No. 24 at 29), and (2) “the more mathematically rigorous calculations of existing Merck 22 23 9 In Plaintiff’s Statement of Uncontested Facts, Plaintiff refers to a “simple analysis” 24 performed by Dr. Qato that could possibly reference the “simple calculation” to which he 25 refers here. (See Doc. No. 24-1 ¶ 48 (“Merck performed a 400-page analysis of this information, but as Dr. Qato demonstrated, an epidemiologist could perform a simple 26 analysis in five to ten minutes to see this data is flawed.”).) However, it is undisputed that 27 Dr. Qato performed her analysis using data published in 2009 (Doc. No. 33 ¶¶ 238, 239), which would not have been available to Defendants prior to 2008. 28 1 clinical trials” (id. at 28). 2 1. Adverse Event Reports in the FDA Database 3 Information previously made available to the FDA does not constitute “newly 4 acquired information.” See In re Incretin, 524 F. Supp. 3d at 1023 (citing 21 C.F.R. § 5 314.3); see also Roshkovan v. Bristol-Myers Squibb Co., No. 221CV08590FWSAGR, 6 2023 WL 6787444, at *7 (C.D. Cal. Sept. 19, 2023) (dismissing failure-to-warn 7 negligence claim on preemption grounds because allegations of adverse-event reports in 8 the FAERS, “a public dashboard maintained by the FDA,” did not sufficiently allege 9 “newly acquired information,” but rather “suggest[ed] that the FDA was aware of the 10 adverse event reports but did not take further action”). Plaintiff concedes that the adverse 11 event reports at issue “were in the FDA database.” (Doc. No. 24 at 29.) These adverse 12 events therefore do not constitute “newly acquired evidence.” See 21 C.F.R. § 314.3(b) 13 (Newly acquired information is “data, analyses, or other information not previously 14 submitted to the Agency. . . .”). 15 Plaintiff also does not attempt to explain how “any one” of the adverse event reports 16 “reveal[ed] risks of a different type or greater severity or frequency than previously 17 included in submissions to FDA.” 21 C.F.R. § 314.3(b). Nor does Plaintiff explain how 18 any of the adverse event reports revealed a causal relationship between montelukast and 19 the adverse event that could justify a CBE change. See Utts v. Bristol-Myers Squibb Co., 20 251 F. Supp. 3d 644, 664 (S.D.N.Y. 2017), aff’d sub nom. Gibbons v. Bristol-Myers 21 Squibb Co., 919 F.3d 699 (2d Cir. 2019) (“[T]he mere existence of reports of adverse 22 events . . . says nothing in and of itself about whether the drug is causing the adverse 23 events.” (quoting Matrixx Initiatives, Inc. v. Siracusano, 563 U.S. 27, 44 (2011)) (applying 24 California law)). Here, Plaintiff’s vague citation to “[a]pproximately ten thousand reports 25 regarding neuropsychiatric adverse events” that “were in the FDA database” (Doc. No. 24 26 at 29), does not constitute “newly acquired information” and does not defeat Defendants’ 27 preemption defense. 28 / / / 1 2. Dr. Qato’s recalculation of Merck’s clinical trial data 2 Plaintiff next asserts that Dr. Qato’s analysis of existing Merck clinical trial data 3 can constitute “newly acquired information.” (Id. at 28–29.) Plaintiff points to Dr. Qato’s 4 analysis of data that Merck had previously submitted to the FDA, and subsequently 5 published in 2009 in the peer-reviewed Journal of Allergy and Clinical Immunology, (“the 6 Philip Paper”). (Doc. No. 11-61, Defs.’ Ex. 58) (Philip, et al., Analysis of behavior-related 7 adverse experiences in clinical trials of montelukast, 124(4) J. Allergy Clin. Immunol. 699 8 (Oct. 2009)). The Philip Paper concluded that “[r]eports of [behavior-related adverse 9 experiences] were infrequent in clinical trials of montelukast. Those leading to study 10 discontinuation or considered serious were rare. Frequencies were similar regardless of 11 treatment group.” (Id. at 2.) Plaintiff’s expert, Dr. Qato, argues that the conclusions in 12 the Philip Paper are “flawed” and that the paper includes “a miscalculation of their 13 statistical analysis that erroneously concludes that montelukast is not significantly 14 associated with such [neuropsychiatric effects] risk.” (Doc. No. 11-100, Defs.’ Ex. 96 at 15 11.) In 2023-2024, Dr. Qato conducted her own calculations, finding that montelukast is 16 significantly associated with behavior-related adverse experiences. (Id. at 12; Doc. No. 17 25-30, Pl.’s Ex. 21 at 52, 54.) 18 The Court rejects Plaintiff’s argument. While “new analyses of previously 19 submitted data” can constitute “newly acquired information” in certain circumstances, 21 20 C.F.R. § 314.3(b), new analyses do not comprise “newly acquired information” when 21 “conducted by an expert in preparation for litigation with the benefit of hindsight.” R.S.B. 22 v. Merck & Co., 2021 WL 6128161, *4 (E.D. Wis. Dec. 28, 2021); see also In re Incretin, 23 524 F. Supp. 3d at 1024–25 (finding “expert report [that] was generated in preparation for 24 litigation and . . . not supported by published research” did not constitute “newly acquired 25 information”); see also In re Zofran (Ondansetron) Prod. Liab. Litig., 57 F.4th 327, 340 26 (1st Cir. 2023) (“[E]xpert report [that] was not prepared, and thus not available to or 27 possessed by [manufacturer], until [after plaintiff filed complaint] . . . cannot serve as 28 newly acquired information that would have triggered an obligation by [manufacturer] to 1 unilaterally amend Zofran’s label . . . .”). Additionally, “asserting that [a] manufacturer 2 could or should have done more studies—i.e., that a manufacturer should have created the 3 ‘newly acquired information’—is insufficient to avoid preemption under the CBE 4 regulation.” Holley v. Gilead Scis., Inc., 2023 WL 6390598, at *8 (N.D. Cal. Sept. 28, 5 2023). 6 Here, Dr. Qato’s “five to ten minute[]” “simple analysis” conducted after Plaintiff 7 filed the complaint, cannot constitute “newly acquired information” that would justify a 8 CBE label change. (See Doc. No. 24 at 12; see also Doc. No. 25-30, Pl.’s Ex. 21 [Qato 9 Dep.] at 55:3-7 (Dr. Qato testifying that her recalculations of Merck’s trial data took “five 10 to ten minutes.”).) Dr. Qato conducted her recalculation analyses after having been 11 retained as an expert for Plaintiffs Parker and Bueno in the related Bueno litigation. (Doc. 12 No. 25-30, Pl.’s Ex. 21 [Qato Dep.] at 52:15-22, 54:7-13.) Because Dr. Qato’s analysis 13 was conducted in preparation for litigation and is unsupported by any published research, 14 it does not constitute “newly acquired information.” See R.S.B. by & through Hammar v. 15 Merck & Co., 2022 WL 3927868, at *4 (E.D. Wis. Aug. 31, 2022) (granting Merck’s 16 motion for summary judgment on preemption grounds in case involving products 17 liability/negligence claims involving Singulair and explaining “even were the Court to 18 consider Dr. Qato’s opinion, her conclusions are litigation-driven and unsupported by any 19 published research, and therefore do not constitute newly acquired information”); see also 20 In re Incretin, 524 F. Supp. 3d at 1024–25 (“Additionally, to the extent Plaintiffs argue 21 that their expert’s re-analysis of the slide images . . . amounts to newly acquired 22 information, the Court disagrees. This expert report was generated in preparation for 23 litigation and is not supported by published research.”) (internal citations omitted); see 24 also R.S.B., 2021 WL 6128161, *4 (“Plaintiffs are not entitled to create their own ‘newly 25 acquired information’ through the use of experts.”). 26 Further, even if the Court were to assume that Dr. Qato’s analysis was timely, her 27 analysis is insufficient to support a CBE label change. “[N]ew analyses of previously 28 submitted data” could only prompt a CBE label change if the new analyses are “based on 1 reasonable evidence.” Albrecht, 587 U.S. at 315. Put simply, the new analyses must 2 provide “reliable evidence of new risks.” Knight, 984 F.3d at 340 (quoting Roberto v. 3 Boehringer Ingelheim Pharms., Inc., 2019 WL 5068452, at *16 (Conn. Super. Ct. Sept. 4 11, 2019)). To evaluate whether new analyses may be “newly acquired information” to 5 support a CBE submission, it is appropriate to consider the information “against the 6 backdrop of the FDA’s year-long attention to, and evaluation of, the [specific safety issue 7 raised by Plaintiff].” In re Incretin, 524 F. Supp. 3d at 1018–19. 8 Prior to Dr. Qato’s 2023-2024 recalculations of Merck clinical trial data (Doc. No. 9 25-30, Pl.’s Ex. 21 [Qato Dep.] at 52:15-22, 54:7-13), Merck and the FDA had “devoted 10 considerable time and attention” to designing, conducting, implementing, and interpreting 11 clinical trials to evaluate the risk of suicidality (suicidal ideation and behavior) and 12 behavior-related adverse experiences with Singulair, the “specific safety issue raised by 13 plaintiffs.” See In re Incretin, 524 F. Supp. 3d at 1018; (see also Doc. No. 33 ¶¶ 1–66). 14 Specifically, in 2008, Merck, in a months-long collaboration with the FDA, drafted a 15 Statistical Analysis Plan (“SAP”),10 which “intended to be a comprehensive and detailed 16 description of the strategy, rationale, and statistical techniques that will be used for 17 retrospective analysis of adjudicated PSRAEs [‘Possibly Suicide-Related’ Adverse 18 Events] from the montelukast program.” (Doc. No. 33 ¶ 56). The SAP included the 19 generally accepted methodology requested, and approved, by the FDA by which Merck 20 was to conduct its clinical trials. (Id. ¶¶ 53–61; Doc. No. 11-50, Defs.’ Ex. 47 at 10 (SAP 21 identifying the “analysis methods” and “primary method” for Merck to conduct its 22 analyses of individual montelukast trials).) Merck then analyzed data from more than 40 23 clinical trials and submitted its data to the FDA in two separate submissions, each 24 25 10 It is undisputed that on March 27, 2008, the FDA initially requested from Merck a “more thorough evaluation of [Merck’s] controlled clinical trial data.” (Doc. No. 33. ¶¶ 26 43, 44.) Later, on June 19, 2008, the FDA asked Merck to prepare the Statistical Analysis 27 Plan (id. ¶ 53; Doc. No. 11-49, Defs.’ Ex. 46), which Merck first submitted on August 14, 2008 (Doc. No. 33 ¶ 58), and later amended with input from the FDA (id. ¶ 60). 28 1 exceeding 400 pages. (See Doc. No. 11-55, Defs.’ Ex. 52; see also Doc. No. 11-56, Defs.’ 2 Ex. 53 at 18 (“In total, 41 completed (as of 25-Apr-2008) placebo-controlled adult . . . and 3 pediatric . . . studies were included in the adjudication process.”).) In October 2009, 4 Merck published its analyses of suicidality and behavior-related adverse events in the 5 Philip Paper. (Doc. No. 33 ¶ 238; Doc. No. 11-61, Defs.’ Ex. 58.) 6 In her report, Dr. Qato opines that a figure in the Philip Paper “depicts incorrect 7 Odds Ratio (OR) estimates and statistical significance (p-value)” such that when she 8 recalculates the Odds Ratio and corresponding p-value to measure statistical significance, 9 she finds that montelukast is “significantly associated with a 21% increased odds or 10 likelihood of experience a [Behavior Related Adverse Event] . . . and for Psychiatric 11 SOC+Other.” (Doc. No. 11-100, Defs.’ Ex. 96 at 11–12.) Her calculations differ from 12 the findings in Merck’s submission to the FDA and in the Philip Paper, which found no 13 statistically significant risk of neuropsychiatric adverse events. (Id. at 10; Doc. No. 11- 14 61, Defs.’ Ex. 58 at 2.) 15 Dr. Qato’s recalculations of Merck’s clinical trial data cannot constitute “newly 16 acquired information” because Plaintiff has not demonstrated that her calculations are 17 reliable or based on the generally accepted methodology approved by the FDA in the SAP. 18 Indeed, Dr. Qato’s calculations were divorced from the FDA’s requested and 19 generally accepted methodology. Dr. Qato describes her odds-ratio as a “crude” analysis 20 (Doc. 11-99, Defs.’ Ex. 95 [Qato Dep.] at 16:16-21), meaning a “calculation with an 21 unadjusted rate of incidence and odds ratio” (Doc. No. 27 at 8). Her “crude estimates” 22 deviated from the SAP’s methodology that required Merck to make adjustments to the 23 odds ratio calculation “to account for the heterogeneity of the underlying studies.” (Doc. 24 No. 10-1 at 21; Doc. No. 11-50, Defs.’ Ex. 47 at 10–11; see also Doc. No. 33 ¶ 243 25 (undisputed that Dr. Qato did not review the statistical analysis plan, despite testifying 26 that it would be helpful to do so).) “[F]ailing to take account of likely confounders by 27 presenting and relying upon only unadjusted (or minimally adjusted) estimates is a serious 28 methodological concern.” In re Roundup Prod. Liab. Litig., 390 F. Supp. 3d 1102, 1140 1 (N.D. Cal. 2018), aff’d sub nom. Hardeman v. Monsanto Co., 997 F.3d 941 (9th Cir. 2 2021). More than just an oversight, neglecting to account for relevant evidence in 3 conducting her analysis calls into question the reliability of her methods and the 4 reasonableness of her conclusions. See Carnegie Mellon Univ. v. Hoffmann-LaRoche, 5 Inc., 55 F. Supp. 2d 1024, 1039 (N.D. Cal. 1999) (excluding expert’s proposed testimony 6 and noting that he ignored available information and samples); In re Mirena Prods. 7 Liability. Litig. (No. II), 341 F. Supp. 3d 213, 242 (S.D.N.Y. 2018), aff’d sub nom. In re 8 Mirena IUS Levonorgestrel-Related Prod. Liab. Litig. (No. II), 982 F.3d 113 (2d Cir. 9 2020) (explaining that when an expert “ignores evidence that is highly relevant to his 10 conclusion,” exclusion of the expert’s testimony is warranted). 11 Additionally, in Plaintiff’s response to Defendants’ Daubert motion, Plaintiff 12 recognizes, but does not dispute, Defendants’ characterization that Dr. Qato “came to a 13 faulty mathematical conclusion because she used some of the information in one of the 14 table[s] in Dr. Philip’s publication that she should not have used.” (Doc. No. 27 at 16.) 15 While Plaintiff argues, “[i]ncorrectly using a row of numbers in the analysis does not damn 16 an opinion based on solid methodology” (id.), analyses using incorrect data, unsupported 17 by published research, cannot constitute reasonable or reliable evidence. See In re 18 Incretin, 524 F. Supp. 3d at 1025 (“[O]ne unpublished and litigation-driven animal study 19 does not make a risk apparent or otherwise constitute reasonable evidence of association.” 20 (internal quotation marks and citation omitted)). The record before the Court does not 21 support a finding that Dr. Qato’s calculations constitute “reasonable evidence,” Albrecht, 22 587 U.S. at 315, and the Court concludes that Dr. Qato’s analysis does not constitute 23 “newly acquired information.” As such, Defendants are also entitled to summary 24 judgment of Plaintiff’s remaining claims based on preemption. See, e.g., R.S.B., 2022 25 WL 3927868, at *4–*5 (granting Merck’s motion for summary judgment on preemption 26 grounds in case involving products liability/negligence claims involving Singulair). 27 / / / 28 / / / 1 CONCLUSION 2 For the reasons stated above, the Court grants Defendants’ motion for summary 3 ||judgment regarding Plaintiff's remaining claims: Plaintiff's claims for negligence and 4 ||negligent misrepresentation. The Court directs the Clerk of Court to enter a judgment in 5 favor of Defendants and against Plaintiff. 6 In addition, the Court denies Defendants’ motion to exclude the opinions of Dima 7 Mazen Qato and motion to exclude or limit the opinion testimony of David Healy as moot. 8 Court also denies Defendants’ motion to strike the Declaration of David Healy and 9 || motion to strike the Declaration of Dima Qato as moot. 10 IT IS SO ORDERED. 11 |}DATED: August 27, 2024 | | / | | | 2 MARILYN WN. HUFF, Distric e 13 UNITED STATES DISTRICT COURT 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28