United States Court of Appeals 

For the First Circuit 

Nos. 18-1146, 18-1147 

IN RE: CELEXA AND LEXAPRO MARKETING AND 

SALES PRACTICES LITIGATION 

PAINTERS AND ALLIED TRADES DISTRICT COUNCIL 82 HEALTH CARE FUND; 

DELANA S. KIOSSOVSKI; RENEE RAMIREZ, on behalf of herself and 

all others similarly situated; MARLENE T. LOCONTE, 

Plaintiffs, Appellants, 

MARTHA PALUMBO, individually and on behalf of all other persons 

similarly situated; PETER PALUMBO, individually and on behalf of 

all other persons similarly situated; JAYNE EHRLICH, 

individually and on behalf of all other persons similarly 

situated; ANNA MURRET, individually and on behalf of all other 

persons similarly situated; UNIVERSAL CARE, INC.; ANGELA 

JAECKEL; MELVIN M. FULLMER, on behalf of himself and all others 

similarly situated; NEW MEXICO UFCW UNION'S AND EMPLOYER'S 

HEALTH AND WELFARE TRUST FUND, on behalf of itself and all 

others similarly situated; ALLIED SERVICES DIVISION WELFARE 

FUND, on behalf of itself and all others similarly situated; 

TARA JOHNDROW, individually and on behalf of all others 

similarly situated; BRIAN ANSON, individually and on behalf of 

all others similarly situated; SCOTT A. WILCOX, on behalf of 

himself and all others similarly situated; MUNICIPAL REINSURANCE 

HEALTH INSURANCE FUND; RANDY MARCUS; BONNIE MARCUS; RUTH DUNHAM; 

TANYA SHIPPY; JILL POWELL, 

Plaintiffs, 

v. 

FOREST PHARMACEUTICALS, INC.; FOREST LABORATORIES, INC.; FOREST 

LABORATORIES, LLC, successor in interest to Forest Laboratories, 

Inc., 

Defendants, Appellees, 

PFIZER, INC.; WARNER LAMBERT COMPANY, 
Defendants. 

APPEALS FROM THE UNITED STATES DISTRICT COURT 

FOR THE DISTRICT OF MASSACHUSETTS 

[Hon. Nathaniel M. Gorton, U.S. District Judge] 

Before 

Howard, Chief Judge, 

Torruella and Kayatta, Circuit Judges. 

R. Brent Wisner, with whom Michael L. Baum, Baum, Hedlund, 

Aristei & Goldman, P.C., Christopher L. Coffin, and Pendley, Baudin 

& Coffin, LLP were on brief, for appellants. 

 Andrew J. Ceresney, with whom Edwin G. Shallert, Kristin D. 

Kiehn, J. Robert Abraham, Debevoise & Plimpton LLP, John G. 

O'Neill, and Sugarman, Rogers, Barshak & Cohen, P.C. were on brief, 

for appellees. 

January 30, 2019 
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KAYATTA, Circuit Judge. These consolidated appeals 

arise out of two so-called "off-label" prescription-drug-marketing 

cases aggregated for pretrial proceedings in the District of 

Massachusetts by order of the multidistrict litigation panel. 

Plaintiffs claim that the defendants, Forest Pharmaceuticals, Inc. 

and Forest Laboratories, Inc. (collectively "Forest"), engaged in 

fraud to push their antidepressant drugs on unsuspecting minors 

for whom the FDA had not approved the use of these medications. 

As we will explain, we reverse the dismissal of the claims brought 

by two of the four plaintiffs, and we vacate the denial of 

plaintiffs' motion to compel the production of additional 

documents by Forest. We otherwise affirm the challenged districtcourt rulings, including the denial of class certification. 

I. 

We begin by summarizing the relevant statutory and 

regulatory framework and by reciting the facts relevant to the 

plaintiffs' summary-judgment appeal in the light most favorable to 

the plaintiffs. See Boudreau v. Lussier, 901 F.3d 65, 71 (1st 

Cir. 2018). 

A. 

The Federal Food, Drug, and Cosmetic Act ("FDCA") 

requires drug manufacturers to obtain approval from the U.S. Food 

and Drug Administration ("FDA") before marketing a drug for a 

particular medical use. 21 U.S.C. § 355(a); see also Mut. Pharm. 
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Co., Inc. v. Bartlett, 570 U.S. 472, 476 (2013). To secure that 

approval, the drug manufacturer must submit to the FDA either a 

new-drug application ("NDA") or a supplemental new-drug 

application ("sNDA"), and the manufacturer must demonstrate the 

drug's efficacy for the indicated use in at least two doubleblind, randomized-controlled trials ("DBRCTs"). See In re 

Neurontin Mktg. & Sales Practices Litig. (Kaiser), No. 04-cv10739-PBS, 2011 WL 3852254, at *5 (D. Mass. Aug. 31, 2011), aff'd, 

712 F.3d 21 (1st. Cir. 2013); see generally 21 C.F.R. § 314.105. 

The FDCA creates both civil and criminal penalties for drug 

manufacturers that promote the use of approved drugs for unapproved 

uses (referred to here as "off-label" uses). See 21 U.S.C. 

§§ 331(d), 333(a), 355(a); Lawton ex rel. United States v. Takeda 

Pharm. Co., 842 F.3d 125, 128 n.4 (1st Cir. 2016). The FDCA, 

however, does not prohibit doctors from prescribing drugs for offlabel uses. Lawton ex rel. United States, 842 F.3d at 128 n.4. 

B. 

Forest manufactures and markets prescription drugs, 

including the antidepressant medications Celexa and Lexapro. 

Celexa and Lexapro are chemically similar selective serotonin 

reuptake inhibitors ("SSRIs"), a class of antidepressants that 

affect a patient's mood by blocking the reabsorption of the 

neurotransmitter serotonin in the brain, Eli Lilly & Co. v. Teva 

Pharm. USA, Inc., No. 05-1044, 2005 WL 1635262, at *1 (Fed. Cir. 
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July 13, 2005). The FDA approved Celexa and Lexapro for the 

treatment of major depressive disorder ("MDD") in adults (i.e., 

individuals aged eighteen or over) in 1998 and 2002, respectively. 

Drug manufacturers, including Forest, had difficulty demonstrating 

that SSRIs were also effective in treating depression in children 

and adolescents. As of 2005, only Fluoxetine -- commercially known 

as Prozac -- had gained FDA approval for the treatment of pediatric 

depression. In 2009, the FDA approved Lexapro for the treatment 

of depression in adolescents (i.e., individuals of ages twelve 

through seventeen). The FDA has never approved Celexa for any 

pediatric use nor has it approved Lexapro as a treatment for 

depression in children (i.e., individuals under the age of twelve). 

The record in this case nevertheless strongly suggests 

that Forest engaged in a comprehensive off-label marketing scheme 

from 1998 through 2009 aimed at fraudulently inducing doctors to 

write pediatric prescriptions of Celexa and Lexapro when Forest 

had insufficient reason to think that these drugs were effective 

for the treatment of depression in children and adolescents. 

Plaintiffs have pointed to substantial evidence that Forest sought 

to achieve this illicit aim by: (1) promoting Celexa's efficacy 

for the treatment of pediatric depression at medical conferences, 

at continuing-medical-education programs, and in press releases; 

(2) concealing negative clinical studies concerning Celexa's 

efficacy and safety; and (3) directly encouraging physicians to 
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prescribe Celexa and Lexapro for the treatment of pediatric 

depression. 

For years, Forest nevertheless denied that it was 

engaged in the off-label promotion of these drugs. Forest 

Laboratories' Executive Vice President, Dr. Lawrence Olanoff, 

testified before Congress in 2004 that "because the FDA has not 

approved pediatric labeling for our products, Forest has always 

been scrupulous about not promoting the pediatric use of our 

antidepressant drugs, Celexa and Lexapro. That is the law, and we 

follow it." Publication and Disclosure Issues in Antidepressant 

Pediatric Clinical Trials: Hearing Before the Subcomm. on 

Oversight & Investigations of the Comm. on Energy & Commerce, 108th 

Cong. 82 (2004) (statement of Dr. Lawrence Olanoff). 

Even before Dr. Olanoff assured Congress of Forest's 

scrupulousness, a whistleblower had commenced a qui tam action, 

alleging that Forest had violated the False Claims Act ("FCA"), 31 

U.S.C. § 3729(a), by fraudulently marketing and promoting Celexa 

and Lexapro for the off-label treatment of depression in pediatric 

patients. Complaint, Gobble v. Forest Labs., Inc., No. 03-10395-

NMG (D. Mass. Mar. 4, 2003), ECF No. 1. The United States later 

intervened in that suit, and, in February 2009, the district court 

unsealed the United States' complaint. Order Granting Motion to 

Unseal, United States ex rel. Gobble, No. 03-10395-NMG (D. Mass. 

Feb. 24, 2009), ECF No. 64. The evidence belying Dr. Olanoff's 
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assurances to Congress turned out to be quite substantial. 

Ultimately, in September 2010, Forest paid a $39 million fine in 

connection with pleading guilty to criminal violations of the FDCA 

for its off-label promotion of Celexa between 1998 and 2002 and an 

additional $149 million to the United States to settle civil claims 

that Forest illegally promoted Celexa and Lexapro for pediatric 

use in 2002 through 2005. 

C. 

Within the following four years, over a dozen consumers 

and entities who paid for prescription drugs filed the lawsuits 

that led to this appeal. Initially, four plaintiffs joined in the 

notice of appeal. Only two, Renee Ramirez and the Painters and 

Allied Trades District Council 82 Health Care Fund ("Painters") 

have presented any argument on appeal. We refer to these two 

collectively as "plaintiffs."1 Ramirez purchased Celexa and 

Lexapro for her young son from February 2003 through March 2010 on 

the recommendation of her son's neurologist. Painters has 

reimbursed its pediatric insureds for off-label prescriptions of 

Celexa and Lexapro since early 1999. Plaintiffs together seek 

 1 Marlene LoConte and Delena Kiossovski joined in the notice 

of appeal but subsequently filed no brief, and the single brief 

filed by the other parties contains no argument at all for 

questioning the grounds upon which the district court dismissed 

the claims of LoConte and Kiossovski. We therefore deem their 

appeal of the judgments against them to be waived. See VázquezRivera v. Figueroa, 759 F.3d 44, 46-47 (1st Cir. 2014). 
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recovery under the Racketeer Influenced and Corrupt Organizations 

Act ("RICO"), 18 U.S.C. § 1962(c)–(d), the Minnesota Consumer 

Fraud Act, Minn. Stat. § 325F.69, and the Minnesota Unfair Trade 

Practices Act, Minn. Stat. § 325D.13, and for unjust enrichment.

In June 2016, the district court denied Painters' motion 

to certify two nationwide classes of similarly situated healthinsurance companies and health plans that had paid for or 

reimbursed off-label pediatric prescriptions of Celexa or Lexapro. 

In re Celexa & Lexapro Mktg. & Sales Practices Litig. (Painters I), 

315 F.R.D. 116, 131 (D. Mass. 2016).2 In rejecting class 

certification, the court reasoned that while Painters had 

satisfied the Rule 23(a) numerosity, commonality, typicality, and 

adequacy requirements, Painters had failed to establish that 

common questions of fact or law predominated over individual issues 

as required by Rule 23(b)(3). Id. at 123–31.

Subsequently, in March 2017, a dispute arose as a result 

of Forest's apparently belated production of two internal 

memoranda in advance of a deposition conducted by agreement after 

discovery had otherwise closed. The two documents contained 

 2 Painters' motion for class certification provided no time 

period for the proposed Celexa class. At oral argument, however, 

plaintiffs' counsel clarified that plaintiffs only seek to 

challenge manufacturer-induced prescriptions for off-label uses 

made prior to the FDA's approval of Lexapro for adolescent use in 

March 2009. Thus, we construe Painters' appeal in accordance with 

this statement. 
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details regarding a study of Celexa's effectiveness. Forest 

revealed that it had not sought any responsive documents from its 

Clinical Supply Group in responding to Painters' discovery 

requests. The district court nevertheless denied Painters' motion 

to compel Forest's supplemental production of documents from this 

group, concluding that any such production would be cumulative. 

In re Celexa & Lexapro Mktg. & Sales Practices Litig. 

(Painters II), 288 F. Supp. 3d 483, 486–87 (D. Mass. 2018).

In due course, after deeming discovery complete and 

ruling on various interim motions, the district court entered 

summary judgment for Forest on plaintiffs' RICO claims, holding 

that neither Painters nor Ramirez could demonstrate injury. In re 

Celexa & Lexapro Mktg. & Sales Practices Litig. (Painters III), 

289 F. Supp. 3d 247, 253–56 (D. Mass. 2018). The court then 

proceeded to dismiss plaintiffs’ state-based allegations as 

deriving from their noncognizable RICO claims. Id. at 258–59. 

This appeal by Painters and Ramirez followed. 

II. 

Summary judgment is appropriate "if the movant shows 

that there is no genuine dispute as to any material fact and the 

movant is entitled to judgment as a matter of law." Fed. R. Civ. 

P. 56(a). In granting summary judgment dismissing all of 

plaintiffs' claims, the district court concluded that plaintiffs 

had no competent proof that either Celexa or Lexapro was 
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ineffective for treating depression in children or adolescents. 

We review this conclusion de novo. Martinez v. Petrenko, 792 F.3d 

173, 179 (1st Cir. 2015). 

A. 

Prevailing on a RICO claim requires proof of an economic 

injury. See 18 U.S.C. § 1964(c) ("Any person injured in his 

business or property by reason of a violation of section 1962 of 

this chapter may sue therefor."). Plaintiffs allege injury in the 

form of payments made for ineffective drugs.3 The district court 

therefore turned its attention to determining whether plaintiffs 

had enough evidence to allow a jury to find Celexa and/or Lexapro 

ineffective for treating pediatric depression. See Painters III, 

289 F. Supp. 3d at 253–56. Four clinical trials and the FDA's 

2009 approval of Lexapro for adolescents informed the district 

court's decision. 

Starting in 1997, Lundbeck -- the developer of Celexa -

- began conducting Study 94404, which focused on Celexa's efficacy 

in treating depression in adolescents. The study produced acrossthe-board negative results. Forest then conducted Study MD-18 in 

an attempt to demonstrate Celexa's effectiveness in both children 

 3 In its opposition to Forest's motion for summary judgment, 

Painters argued that it need not demonstrate that Celexa and 

Lexapro are ineffective in treating pediatric depression to 

establish RICO injury. The district court rejected this argument 

in its order granting Forest's motion, and Painters has not 

developed any challenge to that ruling on this appeal. 
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and adolescents. The efficacy results of MD-18 are difficult to 

assess because Forest bungled the study: Some participants 

randomized into the active treatment group were dispensed 

nongeneric, pink tablets in one portion of the trial, potentially 

unblinding both the individuals who received these pills and the 

researchers conducting the study. The MD-18 study only 

demonstrated statistically positive results when these potentially 

unblinded participants were included. Finally, in 2002–2004 and 

2005-2007, Forest conducted two additional clinical trials. Study 

MD-15 examined Lexapro's efficacy in children and adolescents and 

achieved negative results. Study MD-32 set out to test Lexapro's 

effectiveness in treating only adolescents and achieved 

statistically significant positive results. 

Based upon the results of MD-32 and the Celexa MD-18 

study, Forest submitted an sNDA to the FDA in 2008. In 2009, the 

FDA approved the application, allowing Forest to market Lexapro 

for use in adolescents. Forest did not seek such approval for 

Celexa. 

Plaintiffs' evidence that Celexa and Lexapro were 

ineffective for the pertinent indications consisted of the 

following: The FDA has neither approved Celexa for treating 

depression in children or adolescents nor has it approved Lexapro 

for use in children; Study 94404 demonstrated only a detrimental 

effect of Celexa in treating depression in adolescents; Study MD-
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18 was corrupted and showed no beneficial effect in children and 

adolescents unless the potentially unblinded participants are 

included in the results; and Study MD-15 produced uniformly 

negative results in testing Lexapro's efficacy in children and 

adolescents. In addition, plaintiffs produced expert testimony 

opining that the positive results in MD-32 were not of clinical 

significance and that MD-18 should properly be considered a 

negative trial. Plaintiffs also provided the results of a 

2016 meta-analysis study that found that neither Celexa nor 

Lexapro had any more beneficial effect than a placebo in treating 

pediatric depression. 

There is also evidence in the record before us, however, 

that cuts the other way. In September 2002, the FDA accepted 

Study MD-18 as a positive trial that would support a determination 

of Celexa's effectiveness for the treatment of MDD in adolescent 

patients. And in January 2003, the FDA also stated that MD-18 

could be employed to support an application for FDA approval "for 

both Celexa and Lexapro, in pediatric patients with [MDD]." The 

FDA relied in part on these findings in approving Lexapro for the 

treatment of depression in adolescents in March 2009. Further, 

Forest points out that neither Painters nor Prime Therapeutics 

("Prime"), Painters' pharmacy-benefits manager, has taken any 

effort to limit or remove from its formulary pediatric 

prescriptions of Celexa and Lexapro. 
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This record raises two questions. First, do the FDA's 

various pronouncements or actions close the door on any effort to 

convince a jury that either Celexa or Lexapro was ineffective? 

Second, to the extent that the FDA's pronouncements and actions 

are not preclusive, is the evidence in this case nevertheless 

insufficient to support a jury finding of ineffectiveness? 

1. 

Forest claims that two of our recent decisions -- 

D'Agostino v. ev3, Inc., 845 F.3d 1 (1st Cir. 2016), and In re 

Celexa & Lexapro Mktg. & Sales Practices Litig. (Marcus), 779 F.3d 

34 (1st Cir. 2015) -- answer the first question in the affirmative 

by deeming FDA approval dispositive. Even were we to find it 

convincing, this argument would not cover all the challenged uses 

at issue in this appeal. The FDA has never approved Celexa for 

any of the off-label uses for which Forest promoted it. Nor has 

it approved Lexapro for the treatment of MDD in children under the 

age of twelve. So Forest's reliance on actual FDA approval to 

foreclose a jury determination of inefficacy must be limited to 

Forest's marketing of Lexapro for adolescent use and, perhaps as 

well, to the question of how to construe MD-18. 

In any event, even as thus limited, we do not find 

Forest's reliance on D'Agostino convincing. The claim in 

D'Agostino concerned the sale of medical devices after the FDA had 

approved the devices for the uses for which they were sold. 
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D'Agostino, 845 F.3d at 3, 7–9. In rejecting a challenge to those 

post-approval sales under the False Claims Act based on alleged 

pre-approval fraud on the FDA, we reasoned that "[t]o rule 

otherwise would be to turn the FCA into a tool with which a jury 

of six people could retroactively eliminate the value of FDA 

approval and effectively require that a product largely be 

withdrawn from the market even when the FDA itself sees no reason 

to do so." Id. at 8. Here, by contrast, plaintiffs challenge 

only the promotion of Celexa and Lexapro for uses that were offlabel (i.e., not FDA-approved) at the time Forest promoted and 

sold the drugs.4 When Forest is said to have made those marketing 

efforts, it could not have pleaded reliance on FDA approval. If 

a jury were to hold Forest liable for such pre-approval marketing, 

it would simply be telling Forest that it should not have marketed 

that which Congress under the FDCA does not want it to market: 

drugs for unapproved uses. We therefore see no reason to accord 

to Forest the preclusive protection for pre-approval promotion 

that FDA approval provided the medical-device manufacturer for 

post-approval conduct in D'Agostino.5 

 4 Though plaintiffs' complaints do not explicitly limit their 

RICO and state-law claims to the period prior to FDA's March 2009 

approval of Lexapro, plaintiffs' counsel indicated at oral 

argument that plaintiffs do not challenge Forest's post-approval 

marketing of Celexa and Lexapro. 

5 For similar reasons, Forest's reliance on Buckman Co. v. 

Plaintiffs' Legal Comm., 531 U.S. 341, 348 (2001), in which the 

Supreme Court rejected as preempted state fraud-on-the-FDA claims, 
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Nor does our opinion in Marcus aid Forest in this case. 

In Marcus, we rejected a challenge to a drug label based on 

information that was "plainly known to the FDA prior to approving 

the label." 779 F.3d at 43. We made clear in doing so, however, 

that we were merely applying the state-law preemption principles 

the U.S. Supreme Court laid out in PLIVA, Inc. v. Mensing, 564 

U.S. 604 (2011), and Wyeth v. Levine, 555 U.S. 555 (2009). See 

Marcus, 779 F.3d at 40–43 (explaining that a drug manufacturer can 

only be held liable under state law for inadequate warning in an 

FDA-approved label when the drug manufacturer can, "of its own 

volition, . . . strengthen its label in compliance with its state 

tort duty" (quoting PLIVA, Inc., 564 U.S. at 624)). Marcus, 

accordingly, is inapposite. 

This is not to say that the FDA's 2009 approval of 

Forest's sNDA for Lexapro is irrelevant to this case. Certainly 

the approval and the FDA's reliance on MD-18 provide what many 

jurors may view as strong evidence confirming that Lexapro, and 

perhaps Celexa as well, have always been efficacious in treating 

pediatric depression. The common law has long recognized that 

agency approval of this type is relevant in tort suits. See 

Restatement (Third) of Torts: Prod. Liab. § 4 (Am. Law Inst. 1998) 

 

and its progeny is misplaced. Plaintiffs question the efficacy of 

Celexa and Lexapro only for off-label uses; their claims, 

accordingly, are not predicated on a fraud-on-the-FDA theory of 

liability. 
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("[C]ompliance with an applicable product safety statute . . . is 

properly considered in [a product defect case]."). But the common 

law also recognizes that such evidence is not always preclusive. 

Id. ("[S]uch compliance does not preclude as a matter of law a 

finding of product defect."). And while there are strong reasons 

for treating such evidence as preclusive when the challenged sales 

are made in reliance on agency approval, those same reasons cut 

the other way when the sales are made without approval, and 

certainly when made unlawfully, as we must assume they were here. 

2. 

Having decided that the FDA's subsequent approval of 

Lexapro does not preclude proving that pre-approval uses of these 

drugs were ineffective, we turn to addressing whether plaintiffs 

may proceed with a claim based on product ineffectiveness when the 

evidence of efficacy is conflicting. This is more or less the 

question we left unanswered in Kaiser. See Kaiser, 712 F.3d at 49 

(declining to address what evidentiary standard would be needed to 

demonstrate efficacy "if the results of DBRCTs were equivocal" or 

"if there were a different mix of DBRCT and non-DBRCT evidence").6 

 6 To advance its preferred interpretation of the term 

"equivocal" in Kaiser, each party dedicates a significant portion 

of its brief to sparring over whether the DBRCT evidence in the 

Neurontin cases was, in fact, mixed. We need not address this 

question because, as we explain, Painters' RICO claim survives 

summary judgment even though the evidence of inefficacy is mixed. 

We note, however, that the DBRCTs in the Neurontin case were not 

uniformly negative as Forest would have us believe. Rather, the 
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Generally speaking, "conflicting evidence" is the 

hallmark of an issue that calls for factfinding, not summary 

judgment. See, e.g., Adria Int'l Grp. v. Ferre Dev., Inc., 241 

F.3d 103, 111 (1st Cir. 2001) (finding summary judgment 

inappropriate when evidence presented was "contested and 

contradictory"); see also 10A Charles Alan Wright et al., Federal 

Practice and Procedure § 2712 (4th ed. 2018) ("[S]ummary judgment 

is not a substitute for the trial of disputed fact issues."). We 

see no reason to deviate from that general rule merely because the 

product marketed illegally is one that was later approved for 

lawful sales.7 In short, why should we forgo customary factfinding by the jury so as to reward unlawful conduct aimed at 

getting children to consume unapproved drugs? 

Forest also argues that plaintiffs' evidence of 

ineffectiveness falls short of proving injury because Painters has 

not produced "individualized" proof that Celexa or Lexapro was 

ineffective for any particular insured. By "individualized" 

proof, Forest appears to mean testimony from a patient (or from a 

 

district court noted both positive and negative clinical studies 

in reviewing the parties' evidence of Neurontin's efficacy for the 

at-issue off-label conditions. See Kaiser, 2011 WL 3852254, at 

*34–46 (reviewing mixed DBRCT results). 

7 Nor is summary judgment for Forest warranted due to the fact 

that Painters has not directed the removal of Celexa and Lexapro 

for pediatric uses from its drug formulary. As we held in Kaiser, 

it is "within the factfinder's province to weigh this evidence." 

Kaiser, 712 F.3d at 41. 
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doctor concerning that patient) that the patient experienced no 

beneficial effects from the drug. While evidence of that type 

could be probative, certainly it is not the only way to prove that 

a drug is ineffective. Indeed, given that (1) an ineffective drug 

may trigger a placebo effect in a given individual and (2) an 

effective drug may not benefit all users, individualized proof 

might well be less probative than the type of expert, study-based 

testimony that plaintiffs have offered. In any event, as we 

already held, such individualized proof is certainly not required. 

See In re Neurontin Mtkg. & Sales Practices Litig. (Harden), 712 

F.3d 60, 69 (1st Cir. 2013) ("[W]e reject Pfizer's position that 

these plaintiffs must prove the individual, subjective 

ineffectiveness of each off-label prescription in order to 

establish injury. . . . The Harden plaintiffs have proffered 

clinical trial evidence that Neurontin is ineffective . . ., which 

is certainly enough to raise a genuine issue of fact on the 

effectiveness issue." (citation omitted)); In re Neurontin Mtkg. 

& Sales Practices Litig. (Aetna), 712 F.3d 51, 59–60 (1st Cir. 

2013). 

In sum, we hold that the FDA's 2009 approval of Lexapro 

does not preclude a jury from concluding that the off-label uses 

of Celexa and Lexapro at issue in this case were ineffective in 

treating pediatric depression. Moreover, plaintiffs have provided 

competent and sufficient evidence -- through DBRCTs, expert 
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testimony, and peer-reviewed literature -- to raise a genuine issue 

of material fact as to the efficacy of these drugs for pediatric 

use. Accordingly, the district court erred in granting summary 

judgment for Forest on plaintiffs' RICO and state-law claims on 

this basis. 

B. 

In addition to demonstrating economic injury, a RICO 

plaintiff must prove that the defendant's racketeering conduct 

caused her injury. 18 U.S.C. § 1964(c); Holmes v. Sec. Inv'r Prot. 

Corp., 503 U.S. 258, 268 (1992) (interpreting section 1964(c)'s 

language to mean that a RICO plaintiff must show both but-for and 

proximate causation to establish standing). As we have already 

noted, physicians can -- and do -- lawfully prescribe prescription 

drugs for off-label uses, even though the manufacturer is barred 

by law from promoting such prescriptions. See Lawton ex rel. 

United States, 842 F.3d at 128 n.4. So for any given prescription 

in this case, one would reasonably ask whether Forest's efforts to 

profit by illegally marketing drugs for pediatric use caused a 

particular prescription to be made, or whether, instead, the doctor 

wrote a given prescription based on his or her own professional 

medical judgment (perhaps reasoning that what works for an adult 

patient might also work for a younger patient). 

Forest therefore urges that, even if we disagree with 

the district court on the issue of injury/efficacy, we should still 
- 20 - 

affirm the entry of summary judgment due to Painters' lack of proof 

of but-for causation. While the district court did not consider 

the issue of causation in its summary-judgment ruling, it did 

earlier assay Painters' causation evidence in ruling on Painters' 

motion for class certification. The district court labeled the 

proof so "insubstantial" and "fundamentally flawed" "as to 

preclude class certification." Painters I, 315 F.R.D. at 126–28. 

Forest would have us interpret these pronouncements as a finding 

that the evidence was insufficient as a matter of law to prove 

but-for causation. 

We disagree. In the first place, it is unclear why the 

district court gauged the substantiality or merit of plaintiffs' 

proof in the context of a Rule 23 motion. The central issue in 

that context is not whether the method of proof would or could 

prevail. Rather, it is whether the method of proof would apply in 

common to all class members. See, e.g., Tyson Foods, Inc. v. 

Bouaphakeo, 136 S. Ct. 1036, 1047 (2016) ("When . . . 'the concern 

about the proposed class is not . . . some fatal dissimilarity 

but, rather, a fatal similarity -- [an alleged] failure of proof 

as to an element of the plaintiffs' cause of action -- courts 

should engage that question as a matter of summary judgment, not 

class certification.'" (alteration in original) (quoting Richard 

A. Nagareda, Class Certification in the Age of Aggregate Proof, 84 

N.Y.U. L. Rev. 97, 107 (2009))). 
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More substantively, Painters' evidence does not seem 

clearly insufficient. There is ample evidence that Forest spent 

money inducing doctors to prescribe its drugs to pediatric patients 

and that it would not have done so had the effort not been worth 

the money. Two experts, Dr. Meredith Rosenthal and 

Dr. Christopher Baum, also opined that Forest's spending on 

promotions in general correlated positively with sales. As the 

district court pointed out, Painters' experts then assumed that 

this same approximate correlation applied to off-label promotional 

spending and off-label sales. Painters I, 315 F.R.D. at 127. The 

district court thought this assumption to be a "fundamental flaw" 

in the analysis. Id. Why, exactly, we are not sure. After all, 

why would Forest, which knew its markets better than anyone, have 

spent money on off-label marketing over the long term if it 

generated lower returns than would additional spending on less 

risky, lawful marketing? Certainly there is room for reasonable 

disagreement on the merits of Dr. Rosenthal and Dr. Baum's 

assumption. 

If the jury accepts this assumption as reasonable, and 

if it finds that the prescriptions that Painters paid for were 

typical of those that the experts analyzed, jurors would then have 

a fair path to finding that Forest's off-label marketing caused 

Painters to pay for ineffective drugs. The experts' interpretation 

of the data indicated that Forest's off-label promotions caused 
- 22 - 

76% and 54% of all pediatric prescriptions of Celexa and Lexapro, 

respectively. Dr. Rosenthal estimated that if Painters paid for 

as few as five independent prescriptions, there would be a 98% 

chance that at least one was the result of off-label marketing. 

In fact, Painters likely paid for the Celexa or Lexapro 

prescriptions of more than five different patients.8 So the odds 

that Painters was not harmed if the drugs were, indeed, ineffective 

was likely infinitesimal (assuming the prescriptions were 

independent of one another).9

 8 In its summary judgment order, the district judge observed 

that Painters reimbursed sixteen of its pediatric insureds for 

seventy-two off-label prescriptions of Celexa from 1999 through 

2004, and thirty-one of its pediatric insureds for 234 off-label 

prescriptions of Lexapro from 2002 through early 2015. Painters 

III, 289 F. Supp. 3d at 251. It is not clear from the record how 

many of these Lexapro prescriptions were written prior to March 

2009. Viewing this evidence in the light most favorable to 

Painters, Ellis v. Fidelity Mgmt. Tr. Co., 883 F.3d 1, 3, (1st 

Cir. 2018), and without any counter-argument on this point by 

Forest, we assume for purposes of this appeal only that well more 

than five of the aforementioned Lexapro prescriptions were filled 

prior to the FDA's 2009 approval of Lexapro. 

9 The statistical proof in this instance is being used only 

to prove that a group of prescriptions likely includes at least 

one that a certain activity caused, and it is then being utilized 

to estimate the percentage of such causally connected 

prescriptions in that group. Painters proposes no use of the 

statistical data to prove that Forest's off-label marketing caused 

any particular prescription to be written. See In re Asacol 

Antitrust Litig. (Asacol), 907 F.3d 42, 54 (1st Cir. 2018) (finding 

it "far from self-evident" that expert testimony opining that 

"ninety percent of class members were injured" would be "sufficient 

to prove that any given individual class member was injured"). 
- 23 - 

Nor is Painters' evidence limited to the thrust of its 

statistics. Painters also has evidence that Forest sales 

representatives called or visited at least two physicians who 

subsequently ordered pediatric prescriptions of Celexa and Lexapro 

that Painters reimbursed. In addition, Painters produced evidence 

suggesting that Forest specifically targeted Painters' pharmacybenefits manager, Prime, and that Prime relied upon a misleading 

report by Forest of Study MD-18 in managing Painters' formulary. 

All together, this is surely enough to raise a triable issue of 

fact as to whether Forest's off-label marketing caused Painters to 

pay for a prescription for which it would not have otherwise paid. 

This is not to say that Painters will ultimately prevail 

on the issue of causation. The district court has not conducted 

a Daubert analysis. And there may be other potential bones to 

pick with the sufficiency of Painters' proof of causation. As the 

record now stands, though, we agree with Painters that we cannot 

affirm the summary judgment finding that its causation proof is 

insufficient as a matter of law. 

As for Ramirez, Forest did not challenge her standing on 

the basis of causation in its memorandum in support of its motion 

for summary judgment. Accordingly, we express no opinion as to 

whether Ramirez has raised a triable issue on RICO causation. See 

Rosaura Bldg. Corp. v. Municipality of Mayagüez, 778 F.3d 55, 63 
- 24 - 

(1st Cir. 2015) ("Time and time again we have held that arguments 

not advanced before the district court are waived."). 

As for proximate causation, it is of no moment that 

pediatricians were the immediate target of Forest's fraudulent 

marketing. Here, as in Kaiser, a jury could find that Painters 

and Ramirez were "the primary and intended victims of [Forest's] 

scheme to defraud." Kaiser, 712 F.3d at 37 (quoting Bridge v. 

Phx. Bond & Indem. Co., 553 U.S. 639, 650 (2008)). Moreover, 

Painters' and Ramirez's alleged harm (i.e., reimbursing or 

purchasing more pediatric prescriptions than they otherwise would 

have) was a "foreseeable and natural consequence" of Forest's 

scheme. Bridge, 553 U.S. at 658. Indeed, it was precisely the 

point. 

Accordingly, for the foregoing reasons, we reverse the 

district court's entry of summary judgment for Forest on Painters' 

RICO and state-law claims and on Ramirez's RICO and unjustenrichment claims. 

III. 

Early on in this litigation the district court denied 

Painters' motion to certify this case as a class action under 

Federal Rule of Civil Procedure 23(b)(3). In so ruling, the 

district court reasoned that a variety of important issues, 

including causation and injury, would pose individual questions 

that would need to be answered for each class member. Painters I, 
- 25 - 

315 F.R.D. at 123–30. The presence of these individual questions, 

reasoned the district court, defeated Painters' effort to satisfy 

the requirement of Rule 23(b)(3) that common issues must 

predominate. Id. Painters now appeals that ruling as it applies 

to classes consisting of third-party payors ("TPP") who paid for 

or reimbursed prescriptions of Celexa or Lexapro prior to early 

2009. It is not clear why those issues to which the district court 

pointed would preclude certification of such a class. As we have 

already explained, Painters' clinical and statistical evidence, if 

believed, could establish causation and injury at least for any 

TPP who paid for more than a handful of different patients' 

prescriptions. Nevertheless, as we will explain, it has become 

apparent that the proper application of the statute of limitations, 

while preserving plaintiffs' individual claims, precludes 

Painters' attempt to maintain a class action. 

A. 

The parties agree that the applicable statutory 

limitations period is four years. See Agency Holding Corp. v. 

Malley-Duff & Assocs., Inc., 483 U.S. 143, 156 (1987). That fouryear period began to run "at the time [the] plaintiff knew or 

should have known of his injury." Lares Grp., II v. Tobin, 221 

F.3d 41, 44 (1st Cir. 2000) (citing Rodriguez v. Banco Central, 

917 F.2d 664, 665 (1st Cir. 1990)). The injury here is the payment 

made on account of off-label prescriptions that Forest induced. 
- 26 - 

See Kaiser, 712 F.3d at 39 ("[E]conomic injury occur[s] when 

[plaintiff] paid for fraudulently induced [drug] prescriptions."). 

So, the key question becomes: By what date can we say, as a matter 

of law, that Painters knew or should have known that Forest was 

promoting the off-label, ineffective use of Celexa or Lexapro? 

The district court found that date to be no later than 

March of 2009. In re Celexa & Lexapro Mktg. & Sales Practices 

Litig., 65 F. Supp. 3d 283, 289 (D. Mass. 2014). In February of 

that year, the United States unsealed its complaint against Forest 

in United States ex rel. Gobble, which detailed in thirty-three 

pages how "Forest engaged in a fraudulent scheme to market and 

promote Celexa . . . and Lexapro . . . off-label to treat 

depression and other psychiatric conditions in pediatric 

patients." Complaint at 2, United States ex rel. Gobble, No. 03-

10395-NMG (D. Mass. Feb. 13, 2009), ECF No. 61 [hereinafter United 

States' Complaint]. Within weeks, two private class-action 

complaints followed, one in New York and another in Missouri, each 

also alleging a fraudulent scheme to market Celexa and Lexapro for 

ineffective, off-label uses. See Class Action Complaint, 

Universal Care, Inc. v. Forest Pharm., Inc., No. 09-cv-11518-NMG 

(D. Mass. Mar. 20, 2009), ECF No. 1; Class Action Complaint, N.M. 

UFCW Union's & Emp'rs' Health & Welfare Tr. Fund v. Forest Labs., 

Inc., No. 09-cv-11524-NMG (D. Mass. Mar. 12, 2009), ECF No. 1. 

Painters never argued before the district court that it was unaware 
- 27 - 

of the United States' complaint or the March 2009 lawsuits. Nor 

does it so argue on appeal. Rather, it argues that the lawsuits 

did not provide enough notice that Forest had been promoting the 

off-label use of Celexa and Lexapro. Such notice, Painters says, 

was not available until Forest's own public admission to that 

effect in November 2010, when it both pleaded guilty to criminal 

violations of the FDCA and entered into a civil settlement 

agreement with the United States. 

Not surprisingly, Painters points to no case law holding 

that a statutory limitations period does not start to run until 

the potential defendant first delivers a gift-wrapped admission of 

its alleged wrongdoing. Were that the rule, very few limitations 

periods would ever commence, much less conclude. Instead, as we 

have explained in an analogous context, "[w]e look first to whether 

sufficient facts were available to provoke a reasonable person in 

the plaintiff's circumstances to inquire or investigate 

further. . . . Once a duty to inquire is established, the 

plaintiff is charged with the knowledge of what he or she would 

have uncovered through a reasonably diligent investigation." 

McIntyre v. United States, 367 F.3d 38, 52 (1st Cir. 2004); see 

also Sanchez v. United States, 740 F.3d 47, 52 (1st Cir. 2014) 

("The discovery rule incorporates an objective standard. To delay 

commencement of the running of the statute of limitations, 'the 

factual basis for the cause of action must have been inherently 
- 28 - 

unknowable, [that is, not capable of detection through the exercise 

of reasonable diligence] at the time of injury.'" (alteration in 

original) (quoting Gonzalez v. United States, 284 F.3d 281, 288–

89 (1st Cir. 2002))). The same fundamental principle applies to 

RICO suits. See Rotella v. Wood, 528 U.S. 549, 555 (2000) 

("Federal courts . . . generally apply a discovery accrual rule 

when a statute is silent on the issue, as civil RICO is here. . . . 

[D]iscovery of the injury . . . is what starts the clock." 

(citations omitted)); Koch v. Christie's Int'l PLC, 699 F.3d 141, 

150–51 (2d Cir. 2012) (noting that a RICO claim does not accrue 

until a plaintiff has "actual or inquiry notice of the injury" 

(quoting In re Merrill Lynch Ltd. P'ships Litig., 154 F.3d 56, 60 

(2d Cir. 1998))). 

We agree with the district court that the unsealing of 

the United States' complaint and the subsequent lawsuits filed in 

March 2009 were more than sufficient to put a TPP like Painters on 

notice that Forest had likely been inducing off-label 

prescriptions of Celexa and Lexapro. The United States' complaint 

chronicled how Forest suppressed a negative study on Celexa while 

promoting a positive study (which conveniently neglected to 

mention the earlier, negative study). United States' Complaint at 

3, 14. The complaint quoted internal Forest communications and 

recounted the precise details of Forest's unlawful promotional 

activities. Id. at 15–22. It quoted Forest's physician-call notes 
- 29 - 

reporting on the efforts of Forest's sales representatives to 

promote the pediatric use of the drugs. E.g., id. at 20 ("[F]ocus 

on Lexapro efficacy at just 10 mg., great choice for 

child/adolescents."). It also named Forest marketing executives, 

e.g., id. at 23, and outside physicians involved in the promotion 

campaigns, e.g., id. at 21–22. It is inconceivable that any TPP 

like Painters would not have found in the complaint a very strong 

probability that Forest had systematically and fraudulently pushed 

its drugs on unsuspecting children. 

Nevertheless, we also agree with the district court that 

Painters survived Forest's statute-of-limitations defense because 

the running of the limitations period was stayed for more than 

eight months by the filing of the N.M. UFCW class action in March 

2009. See In re Celexa & Lexapro Mktg. & Sales Practices Litig., 

65 F. Supp. 3d at 291. Painters was a member of the putative RICO 

class action for which the N.M. UFCW complaint sought 

certification. Under American Pipe & Construction Co. v. Utah, 

414 U.S. 538 (1974), the limitations period during which Painters 

might sue on its own behalf was therefore tolled until the N.M. 

UFCW class action was dismissed in June 2010. Forest did not cross 

appeal the district court's application of American Pipe. Rather, 

Forest argues only that the limitations period began running long 

before March of 2009 when plaintiffs first should have suspected 

that Celexa and Lexapro were ineffective for pediatric use. We 
- 30 - 

reject that argument because the injury here is paying for 

unlawfully induced off-label prescriptions, not merely physiciandirected, off-label prescriptions. 

B. 

Even though plaintiffs can sue, thanks to American Pipe, 

Painters cannot parlay that dispensation into the much-delayed 

filing of a class action. See China Agritech, Inc. v. Resh, 138 

S. Ct. 1800 (2018). In American Pipe, the Supreme Court held that 

the "commencement of [a putative class action] tolls the running 

of the statute for all purported members of the class who make 

timely motions to intervene after the court has found the suit 

inappropriate for class action status." 414 U.S. at 552-53. China 

Agritech clarified that this tolling rule has limits: While a 

putative class member may join an existing suit or file an 

individual action upon denial of class certification, a putative 

class member may not commence a class action anew beyond the time 

allowed by the untolled statute of limitations. 138 S. Ct. at 

1807 ("The 'efficiency and economy of litigation' that support 

tolling of individual claims do not support maintenance of untimely 

successive class actions; any additional class filings should be 

made early on, soon after the commencement of the first action 

seeking class certification." (citation omitted) (quoting Am. 

Pipe, 414 U.S. at 553)). 
- 31 - 

Painters argues that China Agritech is distinguishable 

from the case at hand because there was no substantive ruling on 

class certification in N.M. UFCW; the first time any district court 

addressed class certification was in Painters' case. Painters' 

position relies on an impermissibly narrow reading of the Court's 

decision in China Agritech. Though the Supreme Court granted 

certiorari in that case to answer the narrow question of whether 

a putative class member may commence a class action beyond the 

limitations period upon the district court's denial of a request 

for class certification filed within the statute of limitations, 

id. at 1804, the Court proceeded to provide a broader answer: Its 

precedents do not "so much as hint[] that [American Pipe] tolling 

extends to otherwise time-barred class claims," id. at 1806. Thus, 

the Court effectively ruled that the tolling effect of a motion to 

certify a class applies only to individual claims, no matter how 

the motion is ultimately resolved. To hold otherwise would be to 

allow a chain of withdrawn class-action suits to extend the 

limitations period forever. 

For the foregoing reasons, the district court did not 

abuse its discretion in declining to certify Painters' proposed 

nationwide class of TPPs. 

IV. 

Finally, Painters also takes issue with the district 

court's denial of its motion to compel Forest's supplemental 
- 32 - 

production of documents related to the MD-18 Study. This court 

reviews a district court's discovery decision for abuse of 

discretion, intervening "only upon a clear showing of manifest 

injustice, that is, where the lower court's discovery order was 

plainly wrong and resulted in substantial prejudice to the 

aggrieved party." Pina v. Children's Place, 740 F.3d 785, 791 

(1st Cir. 2014) (quoting Dennis v. Osram Sylvania, Inc., 549 F.3d 

851, 859 (1st Cir. 2008)). 

Here, it is undisputed that Forest did not perform an 

exhaustive search in response to Painters' requests for documents 

related to the MD-18 Study: Indeed, Forest acknowledges 

(employing the passive voice) that "files within the custody of 

the Clinical Supply Group were not searched." Forest also does 

not deny that its own preliminary search within this group -- after 

discovery had closed -- produced two responsive memoranda 

regarding the packaging error in the MD-18 Study. The only excuse 

Forest provides is that "[p]laintiffs were fully apprised of the 

scope of document collection and were aware that files within the 

custody of the Clinical Supply Group were not searched." Forest, 

however, points us to nothing in the record demonstrating that 

Painters acquiesced to Forest's limiting the scope of its document 

collection in this way. These admissions notwithstanding, the 

district court denied Painters' Rule 37 motion to compel the 

supplementary production of documents related to the MD-18 Study. 
- 33 - 

It reasoned that the Rule 26(e)(1) duty to supplement only applies 

when "the supplemental material has not been otherwise made known 

to the requesting party" and observed that Painters had already 

received "substantial production of documents related to the 

packaging error" such that any new production would be cumulative. 

Painters II, 288 F. Supp. 3d at 487.

Rule 26(e)(1) requires that a party who has responded to 

a request for production supplement its response in a timely manner 

"if the party learns that in some material respect the . . . 

response is incomplete . . . and if the additional . . . 

information has not otherwise been made known to the other parties 

during the discovery process." Fed. R. Civ. P. 26(e)(1). Whether 

or not "information has not otherwise been made known" -- and, 

thus, whether or not additional production would be cumulative -- 

necessarily hinges on the relevance that the additional production 

might have for the requesting party's claims and the complexity of 

the issue that the factfinder is tasked to resolve; clearly, a 

relatively high degree of granularity in document production is to 

be expected in technical matters of great significance to a party's 

overall claim. 

The district court viewed FDA approval as being 

preclusive as to the validity of Studies MD-18 and MD-32. See 

Painters III, 289 F. Supp. 3d at 255–56. It also viewed the 

validity of those two studies as fatal to plaintiffs' attempt to 
- 34 - 

prove ineffectiveness with the type of evidence used in Neurontin. 

See id. Given those views, the district court understandably 

decided that further evidence on the question of effectiveness was 

cumulative and of no material import. See Painters II, 288 F. 

Supp. 3d at 487. Because we have now explained why the FDA's 

approval of Lexapro for its use in adolescents is not as preclusive 

as the district court might have reasonably thought, and because 

Painters and Ramirez have a live claim on the merits, one might 

reasonably expect Forest to search for responsive files within the 

"Clinical Supply Group." Accordingly, we vacate the district 

court's discovery ruling so that on remand it can consider whether 

further discovery is called for in view of our decision in this 

appeal. 

V. Conclusion 

For the foregoing reasons, we reverse the district 

court's entry of summary judgment for Forest on Painters' and 

Ramirez's RICO and state-law claims and vacate the district court's 

denial of Painters' Rule 37 motion to compel supplemental 

discovery. At the same time, we affirm the district court's denial 

of Painters' motion for class certification. We award no costs to 

any party.