Court Opinion

ID: 857137
Source: CourtListenerOpinion
Date Created: 2013-04-03 19:36:39.257491+00
Date Added: 2024-06-11T09:06:34.772997
License: Public Domain

United States Court of Appeals
                        For the First Circuit

Nos. 11-1904, 11-2096

    IN RE: NEURONTIN MARKETING AND SALES PRACTICES LITIGATION

KAISER FOUNDATION HEALTH PLAN, INC.; KAISER FOUNDATION HOSPITALS;
   KAISER FOUNDATION HEALTH PLAN OF COLORADO; KAISER FOUNDATION
 HEALTH PLAN OF GEORGIA, INC.; KAISER FOUNDATION HEALTH PLAN OF
 THE MID-ATLANTIC STATES, INC.; KAISER FOUNDATION HEALTH PLAN OF
        NORTHWEST; KAISER FOUNDATION HEALTH PLAN OF OHIO,

                        Plaintiffs, Appellees,

                                  v.

           PFIZER, INC.; WARNER-LAMBERT COMPANY, LLC,

                        Defendants, Appellants.

          APPEALS FROM THE UNITED STATES DISTRICT COURT
                FOR THE DISTRICT OF MASSACHUSETTS

           [Hon. Patti B. Saris, U.S. District Judge]

                                Before

                       Lynch, Chief Judge,
                   Souter,* Associate Justice,
                    and Lipez, Circuit Judge.

     Kathleen Sullivan, with whom Mark S. Cheffo, Katherine A.
Armstrong, Quinn Emanuel Urquhart Oliver & Hedges LLP, and Skadden,
Arps, Slate, Meagher & Flom LLP were on brief, for appellants.
     David C. Frederick, with whom Scott K. Attaway, W. Joss
Nichols, Caitlin S. Hall, Linda P. Nussbaum, Kellogg, Huber,

     *
       Hon. David H. Souter, Associate Justice (Ret.) of the
Supreme Court of the United States, sitting by designation.
Hansen, Todd, Evans & Figel, P.L.L.C. and Grant & Eisenhofer, P.A.
were on brief, for appellees.

                          April 3, 2013
            LYNCH, Chief Judge.      This is an appeal from verdicts of

over $140 million, reached by both a jury and a court, compensating

Kaiser, a major health plan provider and insurer, for the injury

Kaiser suffered by its payment for four categories of off-label

Neurontin prescriptions which had been induced by a fraudulent

scheme by Pfizer, the manufacturer of Neurontin.              These verdicts

followed a settlement that Warner-Lambert, a subdivision of Pfizer,

had reached in a criminal case brought by the United States, in

which Warner-Lambert pled guilty to two counts and agreed to pay a

$240 million criminal fine concerning the off-label marketing of

Neurontin; Pfizer agreed to pay an additional $190 million in civil

fines. This is one of several related appeals regarding Neurontin,

which result in separate opinions, of which this is the lead.               We

affirm the verdicts for Kaiser.

                                      I.

            On February 1, 2005, Kaiser Foundation Health Plan, Inc.

and Kaiser Foundation Hospitals (together, "Kaiser"), Aetna, Inc.

("Aetna"), and The Guardian Life Insurance Company of America

("Guardian") filed a coordinated complaint in the U.S. District

Court in Massachusetts against Pfizer, Inc. and Warner-Lambert

Company (together, "Pfizer"), asserting injury from the fraudulent

marketing    of   Neurontin   for   off-label   uses.     The     coordinated

plaintiffs    asserted   violations    of,   inter    alia,   the   Racketeer

Influenced   and   Corrupt    Organizations     Act   ("RICO"),     18   U.S.C.

                                     -3-
§ 1962, and the California Unfair Competition Law ("UCL"), Cal Bus.

& Prof. Code § 17200.     Ultimately, Kaiser prevailed, but Aetna and

Guardian's claims were dismissed on summary judgment, and Aetna's

dismissal is the subject of a separate appeal.

           In a related case in which we issue a separate opinion,

Harden Manufacturing Corporation ("Harden") filed a class action

complaint on May 14, 2004, in the same court, against Pfizer and

Parke-Davis (as a division of Warner-Lambert) on behalf of a broad

purported class consisting of "[a]ll entities throughout the United

States and its territories who, for purposes other than resale,

purchased, reimbursed and/or paid for Neurontin for indications not

approved by the FDA ('the Class') during the period from January 1,

1994 through the present ('the Class Period')."             Harden asserted

claims under RICO, as well as state-law claims for common law

fraud,   violation   of   consumer      protection   statutes,   and   unjust

enrichment.

           Both the class complaint and the coordinated complaint

were part of a larger multidistrict litigation ("MDL") concerning

the marketing and sale of Neurontin, which was consolidated in the

District of Massachusetts in November 2004.             In each case, the

defendants moved for summary judgment.            On January 8, 2010, on

defendants' motion the district court dismissed the claims of

Guardian and   Aetna;     the   court    denied   summary   judgment   as   to

Kaiser's claims.     See In re Neurontin Mktg. & Sales Practices

                                     -4-
Litig. (Neurontin Coordinated SJ), 677 F. Supp. 2d 479 (D. Mass.

2010).   On December 10, 2010, the court granted summary judgment

against all of the Harden purported class plaintiffs except two,

whose claims are not relevant to this appeal.   See In re Neurontin

Mktg. & Sales Practices Litig. (Neurontin Class SJ), 754 F. Supp.
2d 293, 311 & n.4 (D. Mass. 2010).

          Beginning on February 22, 2010, the district court held

a jury trial on Kaiser's RICO claims against the defendants.    On

March 25, 2010, after a five-week trial, the jury concluded that

"Kaiser prove[d] that Pfizer violated RICO with respect to its

promotion of Neurontin for" bipolar disorder, migraine, neuropathic

pain,1 and dosages exceeding 1800 mg per day, and that these

"violation[s] of RICO cause[d] Kaiser injury." See In re Neurontin

Mktg. & Sales Practices Litig. (Kaiser Findings), No. 04-cv-10739-

PBS, 2011 WL 3852254, at *1 (D. Mass. Aug. 31, 2011).     The jury

awarded Kaiser damages in the amount of $47,363,092, which the

court trebled to $142,089,276.     Id.   The jury also rendered an

advisory verdict in favor of Kaiser on its state UCL claim, finding

that Pfizer had engaged in fraudulent business acts or practices

which caused Kaiser damages with respect to bipolar disorder,

     1
       Neuropathic pain is pain caused by damage to the nerves, as
opposed to nociceptive pain, which is pain caused by an injury. In
re Neurontin Mktg. & Sales Practices Litig. (Kaiser Findings), No.
04-cv-10739-PBS, 2011 WL 3852254, at *38, *1 n.1 (D. Mass. Aug.
31, 2011).

                                 -5-
migraine,    neuropathic    pain,    and    doses   over   1800   mg,   but   no

liability with respect to nociceptive pain.

            On November 3, 2010, the district court found in Kaiser's

favor on its claims under the UCL, issuing extensive findings of

fact and conclusions of law.            In re Neurontin Mktg. & Sales

Practices Litig., 748 F. Supp. 2d 34 (D. Mass. 2010), amended and

superseded by Kaiser Findings, 2011 WL 3852254. The district court

ordered   defendants   to   pay     $95,286,518     in   restitution,   Kaiser

Findings, 2011 WL 3852254, at *2, but because this figure reflected

the same damage claims encompassed by the jury verdict on Kaiser's

RICO claim, the court did not add it to the jury award, id. at *60

n.25. On February 22, 2011, the court entered judgment in favor of

Kaiser on its RICO and UCL claims, and on July 27, 2011, the court

denied Pfizer's motion for a new trial or, in the alternative, to

alter or amend judgment.

            On September 20, 2011, Pfizer filed a notice of appeal as

to the court's entry of judgment in favor of Kaiser on its RICO and

UCL claims, and as to the court's denial of Pfizer's motion for a

new trial.    This opinion concerns only that appeal.

                                      II.

            We review de novo defendants' contention that Kaiser's

RICO and UCL claims failed as a matter of law, taking the evidence

in the light most favorable to the verdict.                Tuli v. Brigham &

Women's Hosp., 656 F.3d 33, 38 (1st Cir. 2011).             Where defendants

                                      -6-
challenge the district court's findings of fact, we review these

findings for clear error.     Fed. R. Civ. P. 52(a)(6).   We begin by

setting out the district court's findings of fact and the jury's

conclusions.

A.        The Defendants' Fraudulent Marketing Campaign

          Parke-Davis, an operating division of Warner-Lambert

Company, developed Neurontin2 during the 1980s and early 1990s as

an anti-epileptic drug.     Kaiser Findings, 2011 WL 3852254, at *5.

To secure approval from the Food and Drug Administration ("FDA")

for a drug for a particular indication, a drug manufacturer must

submit two favorable double-blind randomized controlled trials

("DBRCTs").    Id.   On December 30, 1993, the FDA approved Neurontin

as an adjunctive therapy in the treatment of partial seizures in

adults with epilepsy, setting the maximum dose at 1800 mg/day. Id.

The FDA found that certain patients taking Neurontin experienced

depressive side effects, and the FDA issued a warning to physicians

in January 2008 to "[b]e aware of the possibility of the emergence

or worsening of depression, suicidality, or any unusual changes in

behavior" resulting from the use of anti-epileptic drugs including

Neurontin.    Id. (alteration in original) (internal quotation marks

omitted). In 1996, Parke-Davis applied to the FDA for approval of

Neurontin as a monotherapy for the treatment of seizures, and

     2
       Neurontin's generic name is gabapentin.      Kaiser Findings,
2011 WL 3852254, at *5.

                                  -7-
sought an increase in Neurontin's effective dose range and maximum

recommended dose; the FDA rejected this application.    Id. at *6.

          Pfizer acquired Warner-Lambert in 2000.    Id. at *5.   In

2001, Pfizer filed an application with the FDA seeking approval of

Neurontin for the broad indication of neuropathic pain; after

receiving negative feedback from the FDA and non-FDA experts,

Pfizer withdrew its application.   Id. at *10.   The FDA did approve

Neurontin for the treatment of post-herpetic neuralgia ("PHN"), a

type of neuropathic pain associated with shingles, in 2002.    Id.

          In 1994, Parke-Davis had estimated that Neurontin would

generate $500 million in profits over the duration of its patent.

Id. at *6.   In order to increase Neurontin's earning potential,

Parke-Davis began in 1995 to develop strategies to market Neurontin

for off-label conditions -- that is, conditions not included on the

official label approved by the FDA.      Id.     As Parke-Davis was

implementing these strategies, Pfizer acquired Warner-Lambert, and

so, Parke-Davis. Id. at *5. These marketing strategies apparently

worked; in the year 2003, Neurontin sales exceeded $2 billion. Id.

at *6.   Pfizer's Neurontin team estimated that only about ten

percent of Neurontin prescriptions that year were for the FDA-

approved on-label uses for epilepsy or PHN, and that more than a

third of prescriptions were for the off-label uses of neuropathic

pain, migraine or headache, or bipolar disorder.

                               -8-
             Both the jury and the district court found that Parke-

Davis, Warner-Lambert, and Pfizer had "engaged in the fraudulent

marketing of Neurontin" for the treatment of bipolar disorder,

beginning     in   July   1998,   id.    at    *17;    for    the    treatment   of

neuropathic pain, beginning in November 1997, id. at *23; for the

treatment of migraines, beginning in April 1999, id. at *25; and

for doses greater than 1800 mg/day, beginning in November 1997, id.

at *28.3     This fraudulent marketing included, but was not limited

to, three strategies, each of which included subcomponents: (1)

direct marketing (or "detailing") to doctors, which misrepresented

Neurontin's effectiveness for off-label indications; (2) sponsoring

misleading     informational      supplements         and    continuing    medical

education      ("CME")    programs;      and    (3)     suppressing       negative

information about Neurontin while publishing articles in medical

journals that reported positive information about Neurontin's off-

label effectiveness.       See id. at *12, *17, *18, *25, *28.

             The   defendants'    fraudulent      marketing         campaign   also

targeted third-party payors ("TPPs"), including Kaiser, a non-

profit healthcare provider which is also one of the largest health

maintenance organizations ("HMOs") in the United States.                   Id. at

*2.       As to these targets, additional mechanisms were used to

influence both formulary decisions and prescribing decisions.                    In

      3
       The court and the jury found that Kaiser had not proven that
Pfizer fraudulently marketed Neurontin for nociceptive pain. Kaiser
Findings, 2011 WL 3852254, at *26.

                                        -9-
1994, in a memo discussing the promotion of Neurontin as an anti-

convulsant, Parke-Davis's marketing team listed Kaiser as second on

its list of "Top 10 HMOs Targeted for Neurontin."                Id. at *11.          In

2004, Pfizer developed an "Operating Plan" for marketing a number

of drugs, including Neurontin, to Kaiser; tellingly, the plan

featured,     as    a   strategy,       "develop[ing]      relationships            with

[decisionmakers affiliated with Kaiser] who are not considered

whistle blowers."       Id. (emphasis added) (internal quotation marks

omitted).    Pfizer also employed physicians associated with Kaiser

to serve on speakers' bureaus and publish misleading articles about

Neurontin.    Id.

B.          Kaiser's Management of Neurontin on Its Formularies

            Kaiser is composed of two separate corporations: the

Kaiser Foundation Health Plan, which owns six regional health plans

and   directly      provides    medical       coverage    to   beneficiaries          in

California and Hawaii, providing medical insurance to about 8.6

million members; and Kaiser Foundation Hospitals, which operates

health care facilities and pharmacies.               Id. at *2.            The Kaiser

Foundation    Health     Plan     and   its     subsidiaries     do    not     employ

physicians themselves, but have exclusive contractual relationships

with regional Permanente Medical Groups ("PMGs").                Id. at *3.

            Each PMG has its own Pharmacy and Therapeutics ("P & T")

Committee     which     manages    each    PMG's    formulary,        or     list     of

medications      that   treating    physicians      may    prescribe.           Id.

                                        -10-
Representatives from both entities sit on the P & T Committees and

participate in formulary management.         Kaiser Foundation Hospitals

has   a    Drug   Information   Service    ("DIS")    that   researches   and

communicates information about drugs, including monographs about

new drugs or new drug uses, to physicians and P & T Committees.

Id.       DIS monographs summarize available evidence -- including

publicly available evidence and unpublished information obtained

from pharmaceutical manufacturers -- on drug safety and efficacy,

and P & T Committees rely heavily on these monographs in making

formulary decisions.      Id.

             PMG formularies may list drugs (1) without restrictions;

(2) with restrictions limiting prescribing to a particular group of

physicians; or (3) with guidelines for appropriate prescribing.

Id. at *4.     Kaiser will pay for off-formulary prescriptions and no

prior authorization is required for any prescription. Nonetheless,

an internal Kaiser study found that 95% of prescriptions written by

PMG physicians comply with formularies.         Id.

             After the FDA approved Neurontin for epilepsy in 1993,

the P & T Committee of each regional PMG added Neurontin to its

formulary, with one regional PMG -- Hawaii -- not adding Neurontin

to its formulary until 2000.         Id.    The Southern California PMG

initially restricted prescribing of Neurontin to neurologists. Id.

In September of 1997, however, its P & T Committee permitted

anesthesiologists to prescribe Neurontin for reflex sympathetic

                                    -11-
dystrophy, a particular pain syndrome.        Id.    In June of 1999, the

Committee removed prescribing restrictions on Neurontin and added

guidelines reserving its use for neuropathic pain patients who were

unresponsive to or intolerant of other treatments.           Id.   Then, in

September of 1999, the P & T Committee removed all remaining

formulary restrictions on Neurontin. Id. at *5.            Prescriptions of

Neurontin increased dramatically thereafter.         Id. at *31.

           The district court found that "Kaiser relied on Pfizer's

misrepresentations and omissions during the development of drug

monographs in both June and September 1999," id. at *29, and that

Pfizer's misrepresentations "directly affected decisions about

Neurontin's placement on formulary without restrictions," id. at

*30.

C.         Physicians' Prescribing Behavior as to Neurontin

           The   jury   and   court   found   that   the   prescribing   of

Neurontin had in fact been causally affected by the fraudulent

marketing scheme, which included the sponsorship of CME events

attended by physicians and direct marketing to physicians.           Id. at

*12.   Defendants stress that no physician in this case, or in the

Neurontin MDL as a whole, testified that he or she prescribed

Neurontin because of defendants' fraudulent off-label marketing.

Id. at *32.   But Kaiser presented other evidence as to causation,

and evidence as to why such individual testimony was unreliable.

                                  -12-
          The primary evidence was the expert testimony of Dr.

Meredith Rosenthal, who holds a Ph.D. in health economics from

Harvard University and is a professor at the Harvard School of

Public Health.    Id.   Dr. Rosenthal "use[d] aggregate data and

statistical approaches to link patterns in promotional spending[4]

to patterns in prescribing for the drug."    Id. (internal quotation

mark omitted).   Her regression analysis found a causal connection

between the fraudulent marketing and the quantity of prescriptions

written for off-label indications.    She also testified as to why

Pfizer's proposed physician-by-physician analysis of causation was

not a scientifically valid approach to causation.

          Dr. Rosenthal used "gold standard" national data on

Neurontin prescriptions, and employed the assumptions that (1)

"Kaiser's patient population and physician distribution are similar

to the national mix," and (2) "promotional spending on off-label

marketing was the same as the promotional spending on fraudulent

off-label marketing."   Id. at *32-33.      The district court found

both assumptions to be reasonable.    Id. at *32-33.

          As is customary for such experts, Dr. Rosenthal testified

that she "assumed that the allegations in the complaint are true"

for purposes of conducting her analysis, but offered no view as to

     4
      Dr. Rosenthal's promotional spending data included "spending
on detailing of doctors, advertisements in professional journals,
and the retail value of samples."       Kaiser Findings, 2011 WL
3852254, at *32 n.19.

                               -13-
whether or not there had been a fraudulent marketing scheme.                  She

further explained that her assignment was only to calculate the

percentage of prescriptions caused by Pfizer's fraudulent off-label

marketing and not to convert that percentage into a damages number

for Kaiser, which was the task of another expert witness, Dr.

Raymond Hartman, Ph.D.

           Dr.    Rosenthal      explained     the     difference       between

correlation and causation and stated that her analysis established

causation by performing a regression analysis on sales information

against promotional spending on detailing, professional journal

advertising, and the retail value of samples, while controlling for

other   variables.      Her    analysis    excluded    the    many    off-label

prescriptions    by    physicians   who    received    legitimate      on-label

promotion.    She concluded that the "percentage[s] of Neurontin

prescriptions that were caused by Pfizer's fraudulent marketing of

Neurontin" were, by off-label indication, as follows: 99.4% of

prescriptions    for   bipolar   disorder;    70%     of   prescriptions      for

neuropathic pain; 27.9% of prescriptions for migraine; and 37.5% of

prescriptions for doses over 1800 mg/day.        Id. at *33.         Thus, three

out of ten Neurontin prescriptions written by neurologists for

migraine would not have been written or filled but for the alleged

misconduct.       As     for   Neurontin     prescriptions       written       by

psychiatrists    for   bipolar   disorder    between       November    1995   and

December 2004, 99.4% would not have been written had there been no

                                    -14-
fraud.       Dr. Rosenthal testified that it was her opinion "to a

reasonable degree of scientific certainty that these calculations

are the best way to estimate the number of prescriptions and the

share      of    prescriptions   that     were      affected   by    the   alleged

misconduct."5

                Turning to Pfizer's insistence that only doctor-by-doctor

evidence could prove causation, Dr. Rosenthal testified as to the

well-recognized unreliability in the field of healthcare economics

of asking doctors individually whether they were influenced by the

many methods of off-label marketing.             She said that self-reporting

from       physicians    about   patterns      of     practice      that   may   be

controversial shows both conscious reluctance and unconscious bias,

which lead them to deny being influenced.                  As a result, it is

preferable "[t]o examine objectively the causal association between

promotion and sales using . . . econometric models." Dr. Rosenthal

utilized the standard practice of using "aggregate data and . . .

statistical approaches to link patterns in promotional spending to

patterns in prescribing for the drug."                Dr. Rosenthal testified

that it was "neither standard nor appropriate to look physician by

physician."

                In opposition to Dr. Rosenthal's expert testimony, Pfizer

introduced the expert testimony of Dr. Michael C. Keeley, Ph.D.,

       5
       These calculations applied to Kaiser as well as to other
payors across the country.

                                        -15-
who testified as to alleged flaws in Dr. Rosenthal's methodology.

Dr. Keeley testified that when he re-ran Dr. Rosenthal's regression

analysis     with     different      assumptions,     he     did      not    find    a

statistically significant relationship between Pfizer's promotion

of Neurontin and prescriptions of Neurontin.                Dr. Keeley did not

present his own causation or damages model, however.                        The court

rejected Dr. Keeley's criticisms and accepted Dr. Rosenthal's

calculations.       Id. at *58.

            The court also found that subsidiary evidence tended to

show   a   causal     link.      For    example,    PMG    physicians        attended

conferences where Neurontin was promoted for off-label uses, and

after one such conference, in May 1999, new starts of Neurontin

increased by 62%.         Id. at *30.

D.          Criminal Proceedings and Related Proceedings Against the
            Defendants Concerning Neurontin

            Dr. David Franklin was employed as a medical liaison at

Parke-Davis for about five months in 1996; on August 13, 1996, he

filed a sealed qui tam action against Parke-Davis under the False

Claims Act ("FCA"), 31 U.S.C. §§ 3729-3733.               United States ex rel.

Franklin v. Parke-Davis, Div. of Warner-Lambert Co., 147 F. Supp.
2d 39, 43-44, 46 (D. Mass. 2001).               Franklin alleged that Parke-

Davis engaged in a fraudulent scheme to promote off-label uses of

Neurontin,    and    that     this   campaign   caused     false      claims    to   be

submitted    to     the   Veterans     Administration      and   to    the     federal

government for Medicaid reimbursement. Id. at 43. Franklin's suit

                                        -16-
remained under seal for more than three years, as the government

considered whether to intervene, and was then unsealed on December

21, 1999, with the government participating only as an amicus

curiae.     Id. at 46.      On June 16, 2004, Franklin, Parke-Davis,

Pfizer, and     the   United   States    entered    into      a    stipulation   of

dismissal, under which Franklin received a relator's share of

$24,640,000.

            On May 13, 2004, the U.S. Department of Justice filed a

criminal information charging Warner-Lambert with illegal off-label

promotion of Neurontin. Kaiser Findings, 2011 WL 3852254, at *11.

Pfizer caused Warner-Lambert to plead guilty to two felony counts

of marketing Neurontin for unapproved uses, with Warner-Lambert

"expressly and unequivocally admit[ting]" that it promoted the sale

and use of Neurontin for neuropathic pain, bipolar disorder, and

migraine.    Id.   To be clear, this plea did not admit to fraudulent

marketing.     Warner-Lambert agreed to pay a $240 million criminal

fine, and Pfizer paid $190 million in additional civil fines.                  Id.

News of this action, plea, and settlement caused Kaiser to take

certain steps, as described below.

E.          Kaiser's Actions To Reduce Neurontin Prescriptions

            Neurontin    prescriptions         written   by       PMG    physicians

increased    dramatically      after    September    1999         (the   fraudulent

marketing campaign began in 1997).            This notable increase led some

Kaiser regions to "examine their members' use of Neurontin" and

                                       -17-
make efforts to limit it.     Id. at *31.   By the spring of 2002, the

Northern California PMG had barred Pfizer drug representatives from

detailing its physicians regarding Neurontin, and the same PMG's

Drug Utilization Group ("DRUG") began a campaign to promote only

the appropriate use of Neurontin, which other regional PMGs joined.

Id.

          In late 2002, Kaiser learned about Franklin's qui tam

action and escalated its efforts to limit prescribing of Neurontin

for neuropathic pain, bipolar disorder, migraine, and nociceptive

pain.   Id.   Kaiser shared materials about Neurontin produced by

DRUG and the Southern California PMG's Drug Utilization Action Team

("DUAT") with all regional PMGs.        The district court found that

though Neurontin use continued to increase nationally, Kaiser's

efforts to limit its use "result[ed] in a 33-34% decrease in new

starts of Neurontin."   Id.

          The P & T Committees did not remove Neurontin from their

formularies or impose restrictions on its use after learning about

the allegations of defendants' fraudulent off-label marketing of

Neurontin.    Favorable information about using Neurontin to treat

neuropathic pain remained on Kaiser's website until the eve of

trial. Id. at *30.   The district court found, however, that Kaiser

employees did not know about the full scope of defendants' fraud.

Rather, they learned of the full scope of the fraud through (1)

discovery in this suit, and (2) the publication, in November of

                                 -18-
2009,    of    an    article    in    the    New    England   Journal    of   Medicine

reporting defendants' use of scholarly publications to disseminate

misleading information about Neurontin.                  Id. at *31, *7 & n.4.

F.             Injury and Damages Sustained by Kaiser Due to Defendants'
               Fraud

               The court and the jury found that Kaiser had suffered

both injury and quantifiable damages as a result of defendants'

actions.

               After reviewing the evidence at trial -- including the

results of DBRCTs and other clinical trials, anecdotal accounts of

clinical success, regulatory approval in other countries, and

expert opinions, id. at *34-45 -- the district court found that

"there    is    no    reliable       scientific     evidence   that     Neurontin   is

effective for bipolar disorder, migraine, or at high doses," and

that although there was evidence that Neurontin was effective in

treating some kinds of neuropathic pain, "there is no reliable

scientific evidence to support a broad indication of neuropathic

pain," id. at *34.        The court also found that "PMG physicians would

have almost certainly prescribed alternative medication to their

patients had they not prescribed Neurontin."                   Id. at *33.

               In    addition    to    Dr.    Rosenthal's     expert    testimony   on

causation and injury, Kaiser presented testimony by a second

expert, Dr. Hartman, who provided evidence as to the damages

                                             -19-
incurred by Kaiser.       His analysis used a list6 of alternative drugs

that "were more appropriate for each off-label indication than

Neurontin"     in    order   to    determine       the    average   cost   of   the

alternative medications that would have been prescribed in the

absence of defendants' fraud. Id. Dr. Hartman then multiplied the

quantity of affected prescriptions (as determined by Dr. Rosenthal)

by the average excess cost of each Neurontin prescription as

compared to alternative medications.                 Id.     He concluded that

Kaiser's damages from defendants' fraud totaled $62,457,082, with

Kaiser   sustaining       the     following    damages      from    fraud-induced

prescriptions       for   each    off-label    indication:       $17,822,647     for

bipolar disorder; $39,774,623 for neuropathic pain; $1,260,464 for

migraine; and $3,599,348 for doses over 1800 mg/day.                 Id. at *34.

In fact, the total awarded by the jury was less than this sum.

          Dr. Keeley, Pfizer's expert, testified that Dr. Hartman's

calculations    were      flawed    because    he   did    not   have   data    that

permitted him to determine which alternative drugs would have been

prescribed in place of Neurontin.             Dr. Keeley did not present his

own estimate of Kaiser's damages, however.

          Pfizer argued to the jury that Neurontin was effective

for the off-label uses at issue, and that as a result, (1) Pfizer's

promotional     campaign         involved     no    misrepresentations         about

     6
       This list had been developed by the chairperson of Kaiser's
DIS, Dr. Marta Millares. Kaiser Findings, 2011 WL 3852254, at *33.

                                       -20-
Neurontin's       effectiveness;          (2)      even     if         Pfizer      made

misrepresentations, Kaiser doctors prescribed Neurontin for off-

label uses because it was effective in their clinical experience,

not    because   of     Pfizer's   misrepresentations;           and    (3)     because

Kaiser's      damages     theory   was     based    on    Neurontin's         complete

ineffectiveness for off-label uses, Kaiser's damages calculations

were invalid if Neurontin was sometimes effective for these uses.

The jury rejected Pfizer's arguments and awarded Kaiser $47,363,092

in damages, which the court trebled to $142,089,276.                     Id. at *1.

              Pfizer argued to the district court that since doctors

consider      "multiple    sources,      types,    and    levels   of     scientific

evidence" in making treatment decisions, and the effectiveness of

a drug is a patient-specific inquiry, the court should not confine

its analysis of Neurontin's effectiveness for off-label uses to

whether DBRCTs demonstrated efficacy. Kaiser responded that DBRCTs

were    the    "gold-standard      for    determining      efficacy"       and     that

"[l]ower-tier evidence is insufficient, especially in place of

existing DBRCTs."

              Pfizer further argued to the court that because Neurontin

was not "completely and categorically ineffective" for off-label

uses, Pfizer had not misled Kaiser about Neurontin's efficacy and

Kaiser had not proved that it suffered economic injury.                          Pfizer

also argued that Dr. Rosenthal's and Dr. Hartman's testimony was

flawed and hence not probative of causation or damages.                    The court

                                         -21-
rejected Pfizer's arguments and accepted Dr. Rosenthal's and Dr.

Hartman's calculations as the basis for its own damages award of

$95,286,518.   Id. at *58-60.

                                 III.

          Pfizer seeks to vacate the court and jury findings of

liability and damages on a number of theories.      It argues that

Kaiser's claims fail as a matter of law, that the evidence was

insufficient, and that there were trial errors.     At the heart of

the appeal is the claim that, as a matter of law, Kaiser cannot

meet the RICO or UCL causation requirements, and so Pfizer was

entitled to a directed verdict.         On appeal, Pfizer does not

challenge the conclusions of the jury and district court that it

engaged in a fraudulent scheme with respect to its promotion of

Neurontin for off-label uses.7

A.        RICO Causation

          The civil damages provision of RICO provides that "[a]ny

person injured in his business or property by reason of a violation

of section 1962 of this chapter may sue therefor . . . and shall

     7
       As noted, Pfizer argued to the jury and the district court
that Neurontin was effective for off-label uses and that Pfizer
therefore made no material misrepresentations. It does not make
this argument on appeal. Instead, it argues on appeal only that
Neurontin's effectiveness means Kaiser did not prove that it
suffered economic injury from paying for off-label prescriptions of
Neurontin. Pfizer does state on appeal, in passing, that Kaiser
"presented no evidence of fraudulent detailing (sales calls) to PMG
doctors," but it does not squarely challenge the district court's
contrary finding and, in any event, makes this argument only to
attack the "fit" of Kaiser's expert testimony.

                                 -22-
recover threefold the damages he sustains and the cost of the suit,

including a reasonable attorney's fee."        18 U.S.C. § 1964(c).    In

relevant part, section 1962 prohibits "any person employed by or

associated with any enterprise engaged in, or the activities of

which affect, interstate or foreign commerce" from "conduct[ing] or

participat[ing], directly or indirectly, in the conduct of such

enterprise's affairs through a pattern of racketeering activity."

Id. § 1962(c).    A "racketeering activity" can consist of a wide

range of predicate offenses, including, as alleged in this case,

mail and wire fraud, see id. § 1961(1), and a "pattern" of such

activity requires at least two racketeering acts, id. § 1961(5).

           Our RICO causation analysis is controlled by the Supreme

Court's decisions in Holmes v. Securities Investor Protection

Corp., 503 U.S. 258 (1992), and its progeny.8        See Anza v. Ideal

Steel Supply Corp., 547 U.S. 451 (2006); Bridge v. Phoenix Bond &

Indem. Co., 128 S. Ct. 2131 (2008); Hemi Grp., LLC v. City of New

York, 130 S. Ct. 983 (2010).        In Holmes, the Supreme Court held

that the civil RICO provision's "by reason of" language contains

both but-for causation and proximate causation requirements.          503

U.S. at 268.   In our view, these are two quite distinct questions.

Here,    the   harm   to   Kaiser    plainly   was   foreseeable,     and

foreseeability is needed for, but does not end the inquiry as to,

     8
       The parties apply the same analysis on the proximate
causation questions to both Kaiser's RICO claim and its UCL claim,
so we proceed on the assumption that this approach is correct.

                                    -23-
proximate causation.        The proximate causation question in this

appeal concerns whether the chain of events between Pfizer's

misrepresentations and Kaiser's payment for the prescriptions is so

attenuated that, for legal and policy reasons, Kaiser's claim for

recovery should be denied.            The but-for causation question, in

contrast, is whether, absent Pfizer's fraud, Kaiser would have paid

for fewer off-label Neurontin prescriptions.

             Pfizer's primary argument is that, as a matter of law,

there is no proximate causation in this case because there are too

many steps in the causal chain connecting its misrepresentations to

the injury to Kaiser, particularly because that injury rests on the

actions of independent actors -- the prescribing doctors.                  As to

but-for     causation,    Pfizer   argues    that   its   evidence    at   trial

"falsified" Kaiser's theories of causation, and that some of the

evidence     Kaiser   presented       to   prove    but-for   causation      was

inadmissible.     We take these arguments in sequence.

B.           Proximate Causation

             In Holmes, the Supreme Court upheld entry of summary

judgment for the defendant on RICO claims brought by a plaintiff

who   was    subrogated    to   the   rights   of   others,   based    on    the

plaintiff's failure to meet the proximate cause requirement.                 Id.

at 262-64, 271-74. The Holmes plaintiff alleged that the defendant

had engaged in an enterprise to manipulate the prices of certain

stocks, id. at 261, and complained that this conduct caused the

                                      -24-
plaintiff to have to pay the claims of customers of two broker-

dealers that had become insolvent once the fraud was revealed, see

id. at 262-63.   The Court determined that, even if this plaintiff

were allowed to stand in the shoes of a better-situated plaintiff

(namely, the customers), the link was too remote between the

alleged stock manipulation scheme and the harm to the customers,

because that harm was itself contingent on the harm suffered by the

broker-dealers who had purchased the manipulated stock. See id. at

271.   The only connection between the RICO conduct and the claimed

harm was the broker-dealers' insolvency.    Id.

           The Holmes Court stated that, "[a]t bottom, the notion of

proximate cause reflects 'ideas of what justice demands, or of what

is administratively possible and convenient.'" Id. at 268 (quoting

W. Keeton, et al., Prosser & Keeton on Law of Torts § 41, at 264

(5th ed. 1984)). As a result, the Court explained, it was "us[ing]

'proximate cause' to label generically the judicial tools used to

limit a person's responsibility for the consequences of that

person's own acts."   Id.

           Because of "the infinite variety of claims that may

arise" in which a court must analyze proximate causation, it is

"virtually impossible to announce a black-letter rule that will

dictate the result in every case."       Id. at 272 n.20 (quoting

Associated Gen. Contractors of Cal., Inc. v. Cal. State Council of

Carpenters, 459 U.S. 519, 536 (1983)) (internal quotation marks

                                -25-
omitted).    Instead, the Court set out certain principles, derived

from the common law and from interpretations of analogous statutes,

to govern the proximate cause inquiry under RICO.

            The Court noted that RICO's civil provision drew its

language directly from the Clayton and Sherman Acts, which had for

decades     been   interpreted   as   incorporating   proximate   cause

requirements.      Id. at 267-68; see Associated Gen. Contractors, 459

U.S. at 531-34. In the antitrust context, the Court had identified

a number of factors that bear on the proximate cause question,

including whether the injury was of the sort that the statutes

sought to redress, Associated Gen. Contractors, 459 U.S. at 538;

the "directness or indirectness of the asserted injury," including

whether the "links" in the "chain of causation" were clear or were

only "vaguely defined," id. at 540; the identity of the "immediate

victims" of the antitrust conduct, id. at 541; whether the injuries

complained of may have been caused by "independent factors," id. at

542; and whether the plaintiffs were part of "an identifiable class

of persons whose self-interest would normally motivate them to

vindicate the public interest in antitrust enforcement," id.

            The Holmes Court used various phrases to define what it

takes to meet RICO's proximate cause standard, such as "some direct

relation between the injury asserted and the injurious conduct

alleged," 503 U.S. at 268, and whether "the link is too remote"

between the conduct and the harm suffered, id. at 271.       The Court

                                  -26-
noted that       the    proximate     cause   analysis           at    common    law    often

included such       a   "demand      for   some direct           relation";       that is,

proximate cause would be lacking if, as in Holmes, the plaintiff

"complained of harm flowing merely from the misfortunes visited

upon a third person by the defendant's acts."                         Id. at 268.      Later,

in Anza v. Ideal Steel Supply Corp., 547 U.S. 451, the Court

similarly found proximate cause lacking where the RICO conduct

alleged had directly harmed a party other than the plaintiff and

the plaintiff's alleged injury was only a collateral result of the

direct harm.       In that case, the defendant's scheme to underpay

sales taxes had directly injured the state by depriving it of tax

revenue, whereas the plaintiff's alleged harm related to the

competitive effects of the defendant charging lower prices without

sales tax.       See id. at 458.

            Importantly,       the     Holmes      Court         also    provided       three

functional factors with which to assess whether proximate cause

exists under RICO.         First, the Court noted concerns about proof,

reasoning that "the less direct an injury is, the more difficult it

becomes     to    ascertain     the    amount      of        a   plaintiff's        damages

attributable to the violation, as distinct from other, independent,

factors."         503   U.S.   at     269.        Second         were    concerns       about

administrability         and   the    avoidance         of       multiple       recoveries:

"[R]ecognizing claims of the indirectly injured would force courts

to adopt complicated rules apportioning damages among plaintiffs

                                           -27-
removed at different levels of injury from the violative acts, to

obviate the risk of multiple recoveries."              Id.   Third, the Court

focused on the societal interest in deterring illegal conduct and

whether that interest would be served in a particular case: "[T]he

need to grapple with [the previous two] problems [may be] simply

unjustified by the general interest in deterring injurious conduct,

since directly injured victims can generally be counted on to

vindicate the law as private attorneys general, without any of the

problems attendant upon suits by plaintiffs injured more remotely."

Id. at 269-70.

            Holmes makes it clear that both the directness concern

and the three functional factors are part of the proximate cause

inquiry.    See id. at 271-74.        Indeed, the Court warned that its

"use   of   the    term   'direct'   should   merely    be   understood   as   a

reference to the proximate-cause enquiry that is informed by the

concerns" of justice and administrability.             Id. at 272 n.20; see

id. at 268.       Holmes and its successor, Anza, both found a lack of

proximate cause when examining the attenuated relationship between

the plaintiffs and the direct victim or victims of the alleged

fraud.

            In Bridge v. Phoenix Bond & Indemnity Co., 128 S. Ct.
2131, the Court considered the RICO claims of such direct victims.

It also relatedly addressed the question of whether first-party

                                      -28-
reliance on a defendant's misrepresentations is required under

RICO, and answered that question "no."9

           In Bridge, the plaintiffs alleged that the defendants had

engaged in a scheme to make misrepresentations to county tax

authorities in order to win more bids at tax lien auctions than

they would have been able to win absent the fraud.       See id. at

2135-36.   The plaintiffs were other bidders at the auctions whose

bids had tied with defendants' bids, and whose claimed injury was

the deprivation of their fair share of winning bids.   Id. at 2136.

           A unanimous Court held that first-party reliance is not

an element of proximate cause in a private RICO claim predicated on

mail fraud.   Id. at 2134.   Thus, even where the plaintiffs did not

receive the misrepresentations at issue -- the county was the party

that had relied on the misrepresentations -- the plaintiffs had

sufficiently alleged proximate causation under RICO.    Id. at 2138,

     9
       We disagree with Pfizer's argument that "attempting to prove
non-party doctors' reliance through inferences from aggregate sales
data invokes the 'fraud on the market' doctrine."               The
fraud-on-the-market doctrine, utilized in securities law, "relieves
the plaintiff of the burden of proving individualized reliance on
a defendant's misstatement, by permitting a rebuttable presumption
that the plaintiff relied on the 'integrity of the market price'
which reflected that misstatement." In re PolyMedica Corp. Sec.
Litig., 432 F.3d 1, 7 (1st Cir. 2005) (discussing Basic Inc. v.
Levinson, 485 U.S. 224 (1988)). While reliance "is an essential
element of the § 10(b) private cause of action," Amgen Inc. v.
Conn. Retirement Plans & Trust Funds, ___ S. Ct. ___, 2013 WL
691001, at *4 (2013) (internal quotation marks omitted),
first-party reliance is not an element of a private RICO claim
predicated on mail fraud, Bridge, 128 S. Ct. at 2134, so the
analogy is inapt.

                                 -29-
2143-44.    Here, like the defendants in Bridge, Pfizer argues that

its supposed misrepresentations went to prescribing doctors, and so

the causal link to Kaiser must have been broken.               Even putting

aside the evidence of Pfizer's direct communications to Kaiser, we

think Bridge forecloses this argument.         The Bridge Court rejected

the attempt to impose a direct reliance requirement on top of the

statutory language providing a private right of action under RICO,

finding no support for it in the common law.           See id. at 2139-41.

We likewise find none here.

            Bridge also supports the conclusion that Kaiser meets the

proximate cause requirement for several additional reasons. First,

Bridge held that the plaintiffs there "clearly were injured by

[defendants'] scheme," as they lost valuable property they would

not otherwise have lost.        Id. at 2139.    In so holding, the Court

analogized to a business being harmed by misrepresentations made by

a rival to its suppliers and competitors but not to the business

itself.    See id.    The Court rejected the argument that no RICO

injury    could   exist   in   such   circumstances.     In   doing   so,   it

commented on the fact that a business so injured would be "the

primary and intended victim[] of the scheme to defraud."                Id.

Here, Kaiser was likewise a "primary and intended victim[] of

[Pfizer's] scheme to defraud."10        Its injury was a "foreseeable and

     10
       In using this language, we do not suggest that a defendant
can escape RICO liability to a foreseeably and actually injured
plaintiff by saying it did not "intend" such a result.     Pfizer

                                      -30-
natural consequence" of Pfizer's scheme, id. at 2144 -- a scheme

that was designed to fraudulently inflate the number of Neurontin

prescriptions for which TPPs paid.          The evidence that Pfizer had

specifically     targeted   Kaiser    for   Neurontin     sales    in   general

supports   the   conclusion    that   Kaiser's      injury   was    a   natural

consequence of Pfizer's fraudulent scheme, but such evidence was

not required, given the mechanisms by which Pfizer's marketing plan

operated. As Judge Posner stated in the Bridge case, after remand:

"The doctrine of proximate cause . . . protects the ability of

primary victims of wrongful conduct to obtain compensation . . . ."

BCS Servs., Inc. v. Heartwood 88, LLC, 637 F.3d 750, 756 (7th Cir.

2011).   Here Kaiser was a primary victim.

           Further,   the   Bridge    Court   saw    no   risk     of   multiple

recoveries or other policy reasons to limit recovery.               See 128 S.

Ct. at 2144 (citing Holmes, 530 U.S. 258; Anza, 547 U.S. 451).               Nor

did it see a "more immediate victim . . . better situated to sue."

Id.   So too here: none of the three functional problems that the

Holmes test is meant to avoid are present in this case.                  To the

contrary, the functional interests in justice and administrability

work in Kaiser's favor.       Because Kaiser was both the natural and

foreseeable victim of the fraud and the intended victim of the

fraud, there is no risk of duplicative recovery.             See id.    Neither

the individual physicians, nor the DIS members, nor the P & T

could not plausibly make such a claim here in any event.

                                     -31-
Committee members -- the parties to whom Pfizer directly made its

misrepresentations       --   ever   paid   anything   toward   a   Neurontin

prescription, so there is no risk of multiple recoveries due to a

suit by another of those actors.11          See Holmes, 503 U.S. at 269.

Kaiser is also in the best position to enforce the law because

Kaiser is the party that directly suffered economic injury from

Pfizer's scheme.     See id. at 269-70.         And, as we explain below,

Kaiser was able to present sufficient evidence to ascertain the

amount of its damages attributable to Pfizer's conduct. See id. at

269.

            In our view, Kaiser has met both the direct relationship

and functional tests articulated in Holmes and its progeny.                We

reject Pfizer's core defense that there are too many steps in the

causal chain between its misrepresentations and Kaiser's alleged

injury to meet the proximate cause "direct relation" requirement as

a matter of law.   Pfizer characterizes this causal relationship as

involving   at   least    four   steps:     Pfizer   communicating    tainted

information about Neurontin to Kaiser's DIS; the DIS producing

monographs that rely on the misrepresentations; those monographs

       11
       There are, of course, other potential victims of Pfizer's
scheme, such as uninsured individuals who paid for their own
prescriptions. But any such injury would be different in kind from
Kaiser's injury and could not be considered "multiple" in that
respect.   At oral argument, Pfizer raised the possibility that
premium payers might also sue as victims of Pfizer's scheme, but
the question of whether any injury to such payers was proximately
caused by this scheme is not before us in this case.

                                     -32-
influencing   the   PMGs   in   their   formulary   decisions;   and   the

prescribing physicians (who exercise independent medical judgment)

acting within the formulary to issue the prescriptions.          We think

this characterization misconstrues the way in which the Court has

framed the    direct   relation   test.    Moreover, the    adoption    of

Pfizer's view would undercut the core proximate causation principle

of allowing compensation for those who are directly injured, whose

injury was plainly foreseeable and was in fact foreseen, and who

were the intended victims of a defendant's wrongful conduct.12

     12
        The Supreme Court's recent decision in Hemi Group, LLC v.
City of New York, 130 S. Ct. 983, does not, as Pfizer argues, lead
to a contrary conclusion. As an initial matter, that case produced
a 4-1-3 decision with no majority on the proximate cause question.
See id. at 995 (Ginsburg, J., concurring in part and concurring in
the judgment) (providing fifth vote to overturn the decision below,
"[w]ithout subscribing to the broader range of the Court's
proximate cause analysis").      But in any event, the factual
situation here is easily distinguished.
     In Hemi Group, the defendant's alleged RICO conduct was using
the mails to violate the federal Jenkins Act, which requires out-
of-state cigarette vendors to report customer information to the
customers' states of residence.       See id. at 987 (plurality
opinion). Thus, if the defendant's scheme could even be said to
have a foreseen or intended victim, it was New York State (to whom
Hemi Group owed the Jenkins Act reports), not the plaintiff New
York City. Cf. id. at 990 (identifying the state as a "better
situated" plaintiff).
     Further, Hemi Group raised a policy problem not at issue here:
in that case, allowing the city to bring what was essentially a
Jenkins Act claim under the rubric of RICO would have risked
"turning RICO into a tax collection statute." Id. at 993 n.2; see
id. at 995 (Ginsburg, J., concurring in part and concurring in the
judgment) (stating that Justice Ginsburg would have rejected the
city's claim because it was an attempt to make an "end-run" around
the scope of the Jenkins Act).     Kaiser's case involves no such
unusual policy risk.    If anything, the risk cuts in the other
direction: accepting Pfizer's argument on proximate cause as a
matter of law would effectively preclude TPPs from bringing suit

                                  -33-
           In fact, the causal chain in this case is anything but

attenuated. Pfizer has always known that, because of the structure

of the American health care system, physicians would not be the

ones paying for the drugs they prescribed.           Pfizer's fraudulent

marketing plan, meant to increase its revenues and profits, only

became successful once Pfizer received payments for the additional

Neurontin prescriptions it induced.          Those payments came from

Kaiser and other TPPs.    See Bridge, 128 S. Ct. at 2144 (noting that

other auction bidders, not the county officials who immediately

relied on defendants' misrepresentations, were the intended victims

of defendants' RICO conduct); BCS Servs., 637 F.3d at 756.        Kaiser

sought only economic recovery in this case, and its economic injury

occurred   when    it   paid   for    fraudulently   induced   Neurontin

prescriptions.13

under RICO as the primary victims of fraudulent off-label drug
marketing, and from recovering for their economic injuries. That
could mean that no viable plaintiffs would remain to "vindicate the
law as private attorneys general." Holmes, 503 U.S. at 269-70.
Given the high costs imposed by fraud in our health care system,
and Kaiser's status as a primary victim, this result would not be
in the service of either justice or accountability.
     13
       While first-party reliance was not needed, the evidence as
to   Kaiser's   reliance   on   Pfizer's   misrepresentations   was
particularly strong, and it came directly from Pfizer itself.
Pfizer had specifically identified Kaiser as a potential target for
increased Neurontin sales and had developed a five-point plan for
promoting Neurontin to Kaiser. That plan included making contact
with members of the DIS and the P & T Committees. Kaiser Findings,
2011 WL 3852254, at *11. This strategy shows that Pfizer did not
view the various arms within Kaiser as "third and even fourth
parties," Hemi Grp., 130 S. Ct. at 992 (plurality opinion); rather,
it viewed the Kaiser organization as a single entity to which

                                     -34-
               With respect to the mechanisms by which Pfizer marketed

Neurontin      to     PMG   doctors   through    detailing     and   educational

programs, Pfizer fraudulently marketed to physicians with the

intent that those physicians would write prescriptions paid for by

Kaiser.    The fraudulent scheme worked as intended, inducing a huge

increase in Neurontin prescriptions for off-label uses. Pfizer now

argues that because doctors exercise independent medical judgment

in making decisions about prescriptions, the actions of these

doctors are independent intervening causes.                But Pfizer's scheme

relied    on    the    expectation    that    physicians     would   base   their

prescribing decisions in part on Pfizer's fraudulent marketing.

The fact that some physicians may have considered factors other

than Pfizer's detailing materials in making their prescribing

decisions does not add such attenuation to the causal chain as to

eliminate proximate cause. Rather than showing a lack of proximate

causation, this argument presents a question of proof regarding the

total number of prescriptions that were attributable to Pfizer's

actions.       This is a damages question.         Cf. Anza, 547 U.S. at 466

(Thomas, J., concurring in part and dissenting in part) ("Proximate

cause    and    certainty     of   damages,     while   both   related   to   the

plaintiff's responsibility to prove that the amount of damages he

Pfizer could pitch Neurontin in order to create effects that would
reach prescribing physicians.

                                       -35-
seeks   is    fairly   attributable    to    the   defendant,    are   distinct

requirements for recovery in tort.").

             The doctrine of proximate cause, as Judge Posner has

noted, "does its work" in situations where

             too many unexpected things had to happen
             between the defendant's wrongdoing and the
             plaintiff's injury, in order for the injury to
             occur -- so many unexpected things that the
             defendant couldn't have foreseen the effect of
             his wrongdoing and therefore couldn't have
             been influenced, in deciding how much care to
             employ in the activity that produced the
             wrongful act, by the prospect of inflicting
             such an injury as occurred.

BCS Servs., 637 F.3d at 754.           That is not the situation here.

Holding Pfizer liable will have an effect in deterring wrongful

conduct.      And the effect of that wrongful conduct was clear in

foresight, not hindsight.        See id. at 755.         Upholding the finding

of proximate cause here will "protect[] the ability of primary

victims of wrongful conduct to obtain compensation; simplif[y]

litigation; recognize[] the limitations of deterrence . . . and

eliminate[] some actual or possible but probably minor causes as

grounds of legal liability."           Id. at 756.         The district court

correctly     concluded   that   Kaiser      met   the    proximate    causation

requirement.

C.           But-For Causation

             Kaiser introduced several categories of evidence at trial

which clearly demonstrated but-for causation. It produced evidence

that    (1)     its     employees      directly      relied     on      Pfizer's

                                      -36-
misrepresentations in preparing monographs and formularies, which,

in   turn,   influenced         doctors'    prescribing   decisions;   and   (2)

Pfizer's fraudulent off-label marketing directed to physicians

caused PMG doctors to issue more Neurontin prescriptions than they

would have absent such marketing. The latter type of evidence came

from Dr. Rosenthal's report14 as well as inferences from other data.

Pfizer has argued both that the direct reliance evidence was

insufficient      and    that    Dr.   Rosenthal's   aggregate   evidence    was

inadmissible and insufficient.             Pfizer's insufficiency claims rest

on the argument that certain evidence, introduced at trial and

considered by the jury and district court, "falsified" Kaiser's

theories of causation.           We reject both of Pfizer's arguments.

             1.         But-For Reliance Evidence

             Kaiser presented ample evidence of the ways in which its

reliance on Pfizer's misrepresentations regarding the effectiveness

      14
       Kaiser has argued that the district court did not actually
use the Rosenthal report as evidence of causation, but rather used
it only to quantify damages. The district court's findings are not
clear on this point. Compare Kaiser Findings, 2011 WL 3852254, at
*32 ("To meet its burden of proving causation, plaintiffs offered
the testimony of Professor Meredith Rosenthal . . . ."), with id.
at *54 (describing causation question as "what misrepresentations
and omissions Kaiser and DIS relied on[,] . . . whether that
reliance caused Kaiser to suffer injury[, and] . . . whether or not
PMG physicians would have nonetheless prescribed Neurontin to their
patients if DIS had not published monographs recommending Neurontin
or if the P & T Committees had added guidelines or restrictions to
Neurontin's formulary status"). The jury charge on causation and
damages did not mention the aggregate evidence one way or another.
We will proceed on the understanding that the aggregate evidence
both went to causation and set the basis for damages.

                                        -37-
of Neurontin for the four relevant off-label uses met the but-for

causation requirement. Kaiser received Pfizer's misrepresentations

through Pfizer's contacts with Kaiser's DIS, which disseminated

information    throughout    the   Kaiser    organization.        See    Kaiser

Findings, 2011 WL 3852254, at *3-4.             The DIS also relied on

publicly available information about Neurontin, id. at *3, which,

because   of   Pfizer's     publication     strategy,   omitted     important

information about negative study results, see id. at *7-8.                     A

reasonable factfinder could readily conclude that misinformation

received by the DIS would be widely disseminated, utilized, and

relied upon throughout the Kaiser organization to cause but-for

injury.

           Kaiser   specifically    presented evidence       that       the   DIS

shared with all regions at least two monographs that recommended

Neurontin for bipolar disorder and that recommended removal of any

formulary restrictions on Neurontin.           See id. at *28-29.         These

monographs were compiled without Pfizer having disclosed certain

adverse material information. Id. "In making formulary decisions,

P & T Committees rely heavily on DIS's monographs," id. at *3, and

PMG physicians comply with the formulary at a 95 percent rate, id.

at *4.

           There was also evidence that PMG physicians received and

acted upon Pfizer's misrepresentations, both through information

sent through the DIS and information provided to them at Pfizer-

                                   -38-
sponsored events. For one, when DIS answered physicians' questions

through its inquiry service, DIS relied on half-truths communicated

to it by Pfizer.     See id. at *29.         Second, after PMG physicians

attended a medical education conference in May 1999, new Neurontin

prescriptions    increased   by   62    percent.        Id.   at   *30.     And

significantly, when Kaiser conducted the DRUG and DUAT campaigns to

reduce   Neurontin   usage   after     the   negative    information      about

Neurontin came to light, new prescriptions of Neurontin fell by

about 33 percent.    At the same time, such prescriptions continued

to rise nationally.    Id. at *31.

           From this evidence, the district court concluded that

           [t]he publication strategies and the other
           communications between Pfizer and Kaiser
           directly affected decisions about Neurontin's
           placement on formulary without restrictions.
           In addition, the direct communications to PMG
           physicians caused Kaiser injury because it
           reimbursed for Neurontin rather than less
           costly alternatives. Because Kaiser has a 95%
           compliance rate with its formulary, formulary
           restrictions necessarily affect the number of
           prescriptions written for any given drug. I
           find that Kaiser was injured as a result of
           its   reliance    on   Pfizer's   intentional
           misrepresentations and omissions.

Id. at *30.     This finding was not clearly erroneous.            Further, a

reasonable jury could have reached the same conclusion.

           Pfizer argues that Kaiser's DRUG and DUAT campaigns to

reduce prescriptions of Neurontin were not evidence of but-for

causation because they were motivated by the desire to contain

costs, not by concerns about Neurontin's efficacy for off-label

                                  -39-
uses.   Pfizer also argues that once evidence of the DRUG and DUAT

campaigns is properly discounted, there is no evidence that the

Kaiser PMGs took steps to restrict Neurontin on their formularies,

which "falsifies" Kaiser's causal theory of direct reliance.

           Pfizer did present evidence that Kaiser continued to

permit and even recommend the prescription of Neurontin for certain

off-label uses after it became aware of Pfizer's fraud, as well as

evidence that Kaiser's efforts to limit Neurontin prescriptions

were driven in part by its cost.          But Kaiser presented evidence

that it did not learn the full scope of Pfizer's fraud until

November 2009, Kaiser Findings, 2011 WL 3852254, at *31, and that

its efforts to limit Neurontin prescriptions were motivated by

concerns about its efficacy for off-label uses.         It was within the

factfinder's province to weigh this evidence.           Pfizer's evidence

did not, as a matter of law or of evidence, "falsify" Kaiser's

theory of reliance upon Pfizer's misrepresentations.

           2.      Regression Analysis Aggregate Evidence

           Pfizer relies heavily on its argument that the aggregate

statistical     evidence    presented     by   Dr.   Rosenthal   was    also

insufficient to show causation (or injury) as a matter of law, and

was inadmissible as well.

                   a.      Admissibility of Rosenthal Testimony

           We review a district court's ruling on the admissibility

of an expert witness's testimony for abuse of discretion.              In re

                                   -40-
Pharm. Indus. Average Wholesale Price Litig. (AWP), 582 F.3d 156,

198 (1st Cir. 2009). Under Daubert v. Merrell Dow Pharmaceuticals,

Inc., 509 U.S. 579 (1993), expert testimony must have a "reasoning

or methodology" that is "scientifically valid," id. at 592-93, and

that methodology must also have a "valid scientific connection to

the pertinent inquiry" -- that is, a proper "fit" with the facts of

the case, id. at 591-92.           Admissibility does not turn on a

determination by the trial court of "which of several competing

scientific theories has the best provenance," nor does it turn on

convincing the trial court that the proffered expert is correct.

Milward v. Acuity Specialty Prods. Grp., Inc., 639 F.3d 11, 15 (1st

Cir. 2011) (quoting Ruiz-Troche v. Pepsi Cola of P.R. Bottling Co.,

161 F.3d 77, 85 (1st Cir. 1998)) (internal quotation mark omitted).

           It is clear that Dr. Rosenthal's evidence met several

requirements of Federal Rule of Evidence 702.                 Dr. Rosenthal is a

witness with the requisite "knowledge, skill, experience, training,

or education," Fed. R. Evid. 702, and her opinion would assist the

trier of fact to understand the evidence or to determine a fact in

issue,   Fed.   R.    Evid.   702(a).        Yet    Pfizer     argues   that   Dr.

Rosenthal's testimony should have been excluded, attacking both the

methodology and the "fit" of the Rosenthal report.

           As to the methodology, regression analysis is a well

recognized   and     scientifically     valid      approach    to   understanding

statistical data, and courts have long permitted parties to use

                                      -41-
statistical data to establish causal relationships.                     See, e.g.,

Wards Cove Packing Co., Inc. v. Atonio, 490 U.S. 642, 657-58 (1989)

(holding that under Title VII of the Civil Rights Act of 1964,

"specific   causation"   is    shown      and   a   "prima      facie    case"   is

"establish[ed]" when plaintiff identifies a specific employment

practice linked to a statistical disparity); Watson v. Fort Worth

Bank & Trust, 487 U.S. 977, 994 (1988) (opinion of O'Connor, J.)

(explaining that, to establish a prima facie case under Title VII,

"[o]nce the employment practice at issue has been identified,

causation   must be   proved;      that   is,   the    plaintiff        must   offer

statistical evidence of a kind and degree sufficient to show that

the practice in question has caused the exclusion of applicants for

jobs or promotions because of their membership in a protected

group"); Duren v. Missouri, 439 U.S. 357, 366-67 (1979) (permitting

petitioner to establish prima facie violation of fair cross-section

requirement of Sixth and Fourteenth Amendments by using "statistics

and other evidence" to show that "the underrepresentation of women,

generally and on his venire, was due to their systematic exclusion

in the jury-selection process"); Times-Picayune Pub. Co. v. United

States, 345 U.S. 594, 621 (1953) (in antitrust case, looking to

"economic    statistics"      to    determine         whether     "demonstrably

deleterious effects on competition may be inferred"); In re High

Fructose Corn Syrup Antitrust Litig., 295 F.3d 651, 660-61 (7th

Cir. 2002) (permitting use of regression analysis to show causation

                                    -42-
in antitrust case); Conwood Co., L.P. v. U.S. Tobacco Co., 290 F.3d
768, 794 (6th Cir. 2002) (finding regression analysis "to be

admissible on the issue of causation" in antitrust case (emphasis

omitted) (quoting Jahn v. Equine Servs., PSC, 233 F.3d 382, 390

(6th Cir. 2000))).

            Pfizer    argues     that   Dr.    Rosenthal's    analysis    is

nonetheless unreliable in this instance because it did not account

for other factors that may have led a doctor to prescribe Neurontin

for off-label use, particularly because the model did not include

a "time trend."15     Pfizer also argues that the methodology must be

unsound because the data contradict the results of Dr. Rosenthal's

regression in three ways: (1) gabapentin prescriptions continued to

grow after October 2004, when marketing spending plummeted as

Neurontin    lost    patent    protection;    (2)   the   model   improperly

controlled for a spike in promotional spending in 2003, when

Neurontin prescriptions remained relatively flat; and (3) the model

attributed 85% of Neurontin prescriptions for nociceptive pain to

alleged fraudulent marketing, but the factfinders found that there

was no fraudulent marketing for that indication.

            The district court acted well within its discretion in

concluding that Dr. Rosenthal's methods met the scientific validity

     15
        Dr. Rosenthal described a "time trend" as a variable that
is "introduced to capture some conglomeration of variables believed
to have a pattern over time . . . . [I]t's a hypothetical based on
the idea that there are some things [other than promotional
spending] over time that drive sales."

                                    -43-
standard under Rule 702.        "So long as an expert's scientific

testimony rests upon 'good grounds, based on what is known,' it

should be tested by the adversarial process, rather than excluded

for fear that jurors will not be able to handle the scientific

complexities." Milward, 639 F.3d at 15 (citation omitted) (quoting

Daubert, 509 U.S. at 590).      Pfizer's own expert witness admitted

that peer-reviewed, published studies do not always contain time

trends. Moreover, Dr. Rosenthal explained her reason for declining

to use a time trend: because the case involved only a single drug

(as opposed to other studies involving multiple drugs), the time

trend would likely be a confounding variable, because its inclusion

would produce results showing that promotional spending had no

statistically significant effect on prescriptions -- a conclusion

that would not comport with basic economics.        Indeed, Pfizer's own

documents and testimony show that it expected and believed that

off-label     marketing   of   Neurontin   would     increase    off-label

prescriptions, and that its marketing had that result.           The choice

not to use a time trend did not make Dr. Rosenthal's methodology

unreliable.

            Pfizer's   objections    regarding     data   that   allegedly

contradict the reliability of the model also do not show that the

district court abused its discretion.      These objections presented

a question for the jury.         The post-October 2004 increase in

gabapentin prescriptions does not render the regression analysis

                                    -44-
inadmissible.       Indeed, the increase can be explained by the fact

that gabapentin became a generic drug at that time, and the

generic's lower price would be expected to increase gabapentin

sales even though marketing efforts for Neurontin had ceased. This

change in circumstances does not negate the causal relationship

between marketing and prescriptions that the model revealed for the

pre-October 2004 period.

            There was also nothing methodologically suspect about Dr.

Rosenthal's controlling for a spike in promotional spending in

2003, because that spike was likely the result of "strategic

interaction" between the marketing efforts for Neurontin and for

Pfizer's launch of a new anti-epileptic drug, Lyrica.                        As Dr.

Rosenthal    explained,      this    was    the     most   plausible   reason      why

promotional spending for Neurontin would increase even as it neared

the end of its patent life.

            Finally, Pfizer's argument about the 85% figure for

nociceptive pain misunderstands the structure of the model.                         In

conducting    her    analysis,       Dr.    Rosenthal       assumed    --   at     the

plaintiffs'     direction     --     that     all      off-label    marketing      was

fraudulent,16 then analyzed the relationship between marketing and

prescriptions.        Such   an     approach      to   proving     injury   from    an

underlying assumption of unlawful behavior (to be proven to the

fact-finder) is well accepted in the antitrust context from which

     16
          Her analysis excluded the marketing for on-label uses.

                                       -45-
RICO has drawn many of its causation principles.                See, e.g.,

Associated Gen. Contractors, 459 U.S. at 528, 535-46 (noting that

appellate court had "properly assumed" that defendant's alleged

conduct "might violate the antitrust laws," id. at 528, then going

on   to   separately   evaluate   whether    plaintiff   had   sufficiently

alleged antitrust injury).         Ultimately, Pfizer's attacks on Dr.

Rosenthal's methodology were all grist for the trier of fact; they

warranted    "test[ing]   by    the   adversarial   process,   rather   than

exclu[sion]."    Milward, 639 F.3d at 15.

            As to the "fit" between Dr. Rosenthal's model and the

facts at issue in the case, Pfizer objects that: (1) Dr. Rosenthal

did not analyze the effect of the distorted studies or educational

events on prescriptions, but rather the effect of promotional

spending on prescriptions; (2) she did not analyze the effect of

formulary expansion on the number of prescriptions written; (3) the

analysis used national drug utilization data, as opposed to drug

utilization data of Kaiser; (4) the analysis assumes all off-label

marketing expenditures for Neurontin were for fraudulent marketing;

and (5) the diagnostic codes used to determine what condition the

drug was prescribed for indicate a patient's primary condition, so

Neurontin could have been prescribed for an on-label use, but

appear to be off-label.        The basic thrust of Pfizer's argument is

that Dr. Rosenthal's analysis does not provide insight into the

                                      -46-
quantity of prescriptions written as a result of Pfizer's alleged

fraudulent marketing.

            None of these arguments demonstrate that the district

court abused its discretion under the "fit" criterion in admitting

Dr. Rosenthal's testimony.        The use of promotional spending as a

variable was a reasonable "fit" to represent Pfizer's fraud because

Pfizer targeted its promotional activities toward PMG physicians

and toward Kaiser itself, and the money it spent on promotion

helped to implement its fraudulent publication strategy.                      See

Kaiser Findings, 2011 WL 3852254, at *11-28.              The analysis did not

require Kaiser to quantify the "publication strategy" as distinct

from other promotional activities in order to effectively model the

causal relationship.       In fact, if publications and CME events did

exert an effect independent of detailing (for instance, an effect

on    decisions   about     the   formulary),       the    model   would   have

underestimated the impact of the fraud.

            Next, the use of national drug data was reasonable, and

the district court did not abuse its discretion in so holding.                See

id.   at   *32.   Dr.     Rosenthal   used   data    that    was   prepared   by

independent consulting companies, and this type of data is used by

Pfizer itself in its own strategic planning and marketing efforts.

Kaiser did not independently keep track of the usage for which each

prescription was written, so Dr. Rosenthal used what she considered

the best alternative, derived from national databases that the

                                      -47-
district court described as the "gold standard."        Id.     Pfizer does

not challenge the district court's determination that it was

reasonable to assume that Kaiser's patient population and physician

distribution are similar to the national mix.             See id.      The

district court also permissibly found a "fit" in Dr. Rosenthal's

use of the databases' diagnostic codes (particularly with respect

to bipolar disorder) to determine the percentage of prescriptions

written for each indication.      Indeed, Pfizer's own estimate was

that bipolar disorder accounted for 14.7 percent of Neurontin

prescriptions, which is "quite close" to Dr. Rosenthal's estimate

of 16 percent.   See id. at *32 n.20.

          Finally, that Dr. Rosenthal's report assumed all of

Pfizer's off-label marketing was fraudulent marketing is not a

basis to find that the district court erred in admitting the

report.   Pfizer is incorrect that this assumption means that Dr.

Rosenthal was "assum[ing] the very conclusion she was attempting to

prove."   Dr. Rosenthal's analysis sought to determine whether

Pfizer's marketing had a causal effect on prescribing behaviors,

not whether   the   marketing   was   in   fact   fraudulent.     Pfizer's

objection does not go to the question of whether Dr. Rosenthal's

regression had a close enough "fit" to satisfy Daubert; rather, it

is a question of damages.

                                 -48-
                     b.    Sufficiency of Aggregate Evidence

            Having    found   that       Dr.    Rosenthal's    testimony     was

admissible, we turn to Pfizer's argument that it was insufficient

evidence to support the jury's and district court's findings of

causation.     We reject the argument, while pointing out that her

testimony was not the only evidence of but-for causation.

            Pfizer insists that Dr. Rosenthal's testimony cannot be

credited because      it   does    not   take   into account      the   patient-

specific,     idiosyncratic       decisions     of   individual    prescribing

physicians.     Thus, according to Pfizer, the report was legally

insufficient proof of causation.          Indeed, Pfizer purports to find

support for its position in the district court's rulings entering

summary judgment against Aetna and Harden. See Neurontin Class SJ,

754 F. Supp. 2d at 310-11; Neurontin Coordinated SJ, 677 F. Supp.
2d at 485, 494-95.

            A tort plaintiff need not "prove a series of negatives;

he doesn't have to 'offer evidence which positively exclude[s]

every other possible cause of the accident.'" BCS Servs., 637 F.3d

at 757 (alteration in original) (quoting Carlson v. Chisholm-Moore

Hoist Corp., 281 F.2d 766, 770 (2d Cir. 1960) (Friendly, J.)).

"Once a plaintiff presents evidence that he suffered the sort of

injury that would be the expected consequence of the defendant's

wrongful conduct," the burden shifts to the defendant to rebut this

causal inference.     Id. at 758.

                                      -49-
           Pfizer's argument is a repetition of its assertion that

there is an intervening cause -- individual physicians' independent

medical judgment -- which precludes a finding of causation based on

aggregate evidence.       But "the burden of proving an 'intervening

cause' -- something which snaps the 'causal chain' (that is,

operates as a 'superseding cause,' wiping out the defendant's

liability) that connects the wrongful act to the defendant's injury

-- is on the defendant."        Id. at 757 (citation omitted).     Pfizer

did offer the testimony of doctors who said that their decisions to

prescribe Neurontin were not influenced by Pfizer's fraudulent

marketing, and the jury and district court, within their powers,

rejected the argument.

           Pfizer also argues that its testimony from doctors who

stated that they prescribed Neurontin for off-label uses without

relying   on   Pfizer's    misrepresentations     "falsified"    Kaiser's

statistical analysis.      Not so.    The existence of some doctors who

purportedly were not influenced by Pfizer's misinformation would

not defeat the inference that this misinformation had a significant

influence on prescribing decisions which injured Kaiser.          Indeed,

Dr.   Rosenthal   noted   the   scientific   invalidity   of   looking   to

physician-by-physician accounts of their prescribing decisions.

Weighing the individual testimony presented by Pfizer against the

aggregate evidence presented by Kaiser was a task for the jury and

district court.

                                     -50-
              Pfizer next argues that the Rosenthal report merely

demonstrated "correlation" and not "causation."                  But if Pfizer's

information could not be expected to affect a single doctor's

decisionmaking, the company's choice to undertake the marketing

campaign would be inexplicable.             Cf. id. at 758 ("The object of

[the defendants'] conspiracies was to obtain liens that would

otherwise go to [the plaintiffs and other] bidders -- there could

be no other reason for wanting to pack the room in violation of the

County's rule. . . . How likely is it that [plaintiffs] lost no

bids to bidders who had 13 arms in the room but should have had

only three?").

              More   generally,    Pfizer    argues    that   Kaiser's   use   of

aggregate evidence is precluded by the decisions of other courts in

pharmaceutical marketing RICO fraud cases.                Pfizer relies on a

series   of    cases   that   it   argues    have     rejected    evidence   like

Kaiser's.      See, e.g., In re Schering Plough Corp. Intron/Temodar

Consumer Class Action, 678 F.3d 235 (3d Cir. 2012); Ironworkers

Local Union 68 v. AstraZeneca Pharm., LP, 634 F.3d 1352 (11th Cir.

2011); UFCW Local 1776 v. Eli Lilly & Co., 620 F.3d 121 (2d Cir.

2010); Se. Laborers Health & Welfare Fund v. Bayer Corp., 655 F.

Supp. 2d 1270 (S.D. Fla. 2009).              But we disagree with Pfizer's

characterization of these cases and find them either supportive of

our result or inapposite.          We see no split in authority.

                                      -51-
            In     particular,    Pfizer    leans   heavily    on   the   Second

Circuit's decision in UFCW Local 1776 v. Eli Lilly & Co., 620 F.3d
121, which reversed a district court's certification of a class of

TPP plaintiffs who claimed that Eli Lilly's fraudulent marketing of

Zyprexa caused them to pay an inflated price for that drug and to

pay for prescriptions that would not have otherwise been written.

Id. at 123, 137. To begin, the district court in Eli Lilly granted

class certification on the former (excess pricing) claim, and the

Second Circuit reversed on that basis.                See id. at 133.          By

contrast, the claimed injury to Kaiser resembles the latter (excess

quantity) theory.        The Second Circuit found a lack of but-for

causation only on the excess pricing theory, because doctors do not

generally consider the price of a drug when they make prescribing

decisions.       Id. at 133-34.      On the other hand, doctors would

certainly consider information about the efficacy of a drug when

deciding whether to prescribe it for their patients.

            As to the excess quantity theory, the Second Circuit

described    the    plaintiffs'    aggregate    evidence      of   causation   as

involving only an extrapolation from the fact that the number of

off-label prescriptions for Zyprexa fell after Eli Lilly's fraud

became known.        See id. at 135.         This does not come close to

resembling Dr. Rosenthal's evidence, which examined contemporaneous

data that reflected what was actually happening with regard to

spending and prescriptions while Pfizer's fraud was ongoing.

                                     -52-
Finally, the Second Circuit specifically noted that, "while [the

excess quantity] theory cannot support class certification, it is

not clear that the theory is not viable with respect to individual

claims by some TPPs."       Id. at 136.       Kaiser's case, of course, is

just such an individual claim by a TPP.

            The   other     cases     on     which      Pfizer   relies     are

distinguishable.      The     Eleventh       Circuit,    addressing     alleged

fraudulent    marketing     claims     involving        the   drug    Seroquel,

specifically declined to decide the case on causation grounds.

Ironworkers, 634 F.3d at 1359-60.            Instead, that court held that

the TPP plaintiffs had failed to show economic injury because the

prescriptions at issue were merely less cost-effective than the

alternatives,     rather    than     being    "medically      unnecessary    or

inappropriate."17    Ironworkers, 634 F.3d at 1360.                  Kaiser, in

contrast, staked much of its case on proving that Neurontin was

ineffective for the promoted off-label uses, and the district court

so found.    See Kaiser Findings, 2011 WL 3852254, at *34-45.

            The Third Circuit addressed the causation question as a

matter of Article III standing rather than RICO doctrine.                 In re

Schering Plough, 678 F.3d at 246.          It also did not address the use

     17
       The Eleventh Circuit also decided that the TPPs had assumed
the risk of paying for all prescriptions of covered drugs, even
those induced by fraud, through the process of setting and
collecting premiums.   Ironworkers, 634 F.3d at 1364.      Without
commenting on such a theory, we note that neither party in this
litigation has raised it.

                                     -53-
of aggregate evidence at all, finding merely that the TPP plaintiff

in that case had not connected the pharmaceutical company's alleged

fraudulent marketing scheme as to two drugs to the TPP's payment

for a third drug owned by the same company.          Id. at 247-48.      The

Ninth     Circuit,   in   an   unpublished   decision,   did   not   mention

aggregate evidence.       United Food & Commercial Workers Cent. Pa. &

Reg'l Health & Welfare Fund v. Amgen, Inc., 400 F. App'x 255, 257-

58 (9th Cir. 2010).18

             Courts' treatment of aggregate evidence is not as Pfizer

represents. Earlier we cited to the use of such aggregate evidence

to show causation under several causes of action.         We see no reason

to reach a different conclusion for the specific subset of RICO

claims based on fraudulent marketing.

                                     IV.

             At trial, Pfizer argued that it had not committed fraud

because Neurontin was effective for the off-label uses at issue.

The jury and court rejected the argument, and on appeal Pfizer does

not contest the finding of fraud.             Nonetheless, it uses the

     18
       Further, some courts appear to have conflated the proximate
and but-for causation inquiries in evaluating aggregate evidence
and the role of doctors' medical judgments.        See, e.g., Se.
Laborers, 655 F. Supp. 2d at 1280-81 (stating that court was
performing proximate cause inquiry, but proceeding to analyze but-
for cause question of whether doctors would have prescribed drug at
issue in the absence of misrepresentations). And to the extent
that some district courts may have endorsed Pfizer's position that
aggregate evidence is legally insufficient to prove but-for
causation, we disagree, at least on the facts of this case.

                                     -54-
question of Neurontin's effectiveness to argue that Kaiser failed

to prove that it suffered economic injury.           Pfizer contends that

because Neurontin was actually effective for the off-label uses at

issue,    Kaiser     suffered   no   economic   injury   from    paying   for

prescriptions for these uses. Pfizer claims that the court applied

an erroneous burden of proof and an erroneous medical standard in

making its findings as to Neurontin's effectiveness.19 We disagree.

            Pfizer    asserts   that   the   district    court   erroneously

shifted the burden of proof to it when the court allowed Kaiser to

prove its economic injury by showing that "there is no reliable

scientific evidence that Neurontin is effective" for the conditions

at issue, Kaiser Findings, 2011 WL 3852254, at *34, rather than

requiring Kaiser to show that Neurontin was actually ineffective

for these conditions in all cases.20            See, e.g., In re Schering

     19
       Pfizer also advances a somewhat confusing argument about the
lack of jury instructions on efficacy. Because we decide that, for
the purpose of proving injury, Kaiser adequately proved Neurontin's
inefficacy for the relevant indications, we need not determine
exactly what standard the jury may have used.
     20
       Pfizer also argues, briefly, that Kaiser presented another
theory of injury: that cheaper, alternative drugs could have been
used even if Neurontin was effective. Pfizer asserts that this
theory has been rejected by numerous courts, citing, for example,
Ironworkers, 634 F.3d at 1360; and Dist. 1199P Health & Welfare
Plan v. Janssen, L.P., 784 F. Supp. 2d 508, 520 (D.N.J. 2011).
Kaiser does not explicitly defend the cheaper alternative drug
theory in any detail, devoting only one footnote in its brief to
the theory and relying on only one case, Desiano v. Warner-Lambert
Co., 326 F.3d 339 (2d Cir. 2003), without delving into the trial
evidence. Because neither party has properly briefed the issue,
and because we can dispose of the damages question on the fully
briefed effectiveness theory instead, we do not pass on the

                                     -55-
Plough       Corp.    Intron/Temodar    Consumer     Class   Action,      No.

2:06-cv-5774, 2010 WL 2346624, at *4 (D.N.J. June 9, 2010) ("[A]

lack of data or evidence affirmatively proving that a Subject Drug

was effective in treating a condition [is] not the same as the

actual ineffectiveness of the Subject Drug.").

               The district court did not place the burden on Pfizer to

show    that    Neurontin   was   effective.   Kaiser    produced    expert

witnesses and evidence showing that Neurontin was no more effective

than placebo for the indications at issue -- i.e., that it was

ineffective.         See Kaiser Findings, 2011 WL 3852254, at *35-45

(reviewing such evidence).        Pfizer then produced its own evidence

to attempt to rebut Kaiser's evidence.

               Pfizer's second argument asserts that the district court

rested its conclusion on the FDA approval standard -- two positive

DBRCTs showing efficacy -- to determine whether Neurontin was

effective, and that this meant the court's conclusion was fatally

flawed.      Pfizer argues that the proper standard was the standard

governing the practice of medicine, not the standard for FDA

approval.21      In clinical practice, Pfizer argues, FDA-type trials

are    not   dispositive;    instead,   physicians    rely   on   their   own

experience, other doctors' positive clinical experiences, and other

"cheaper alternatives" theory.
       21
       We acknowledge the brief of amicus curiae Pharmaceutical
Research and Manufacturers of America on this issue.

                                    -56-
evidence. Relatedly, Pfizer argues that Kaiser's use of "negative"

studies to show ineffectiveness was not legally sufficient because

such studies do not "establish the drug's inefficacy for treating

the condition in all other patients and circumstances."

           Kaiser responds that the district court did not frame the

issue of ineffectiveness only in terms of DBRCTs, but rather

considered a number of different types of evidence, including

clinical trials that did not meet the DBRCT requirements and

reports of clinical judgments such as case studies.            The court was

aware of Pfizer's critique of DBRCTs; it was also aware that, due

to the placebo effect, some patients would report improvements

regardless of whether the drug was scientifically effective for

their conditions, making non-DBRCT evidence less probative of

effectiveness.     Kaiser argues that the court properly chose the

weight to give each type of medical evidence.          Kaiser's is the more

accurate description of the record.          We conclude that the totality

of the evidence supported the district court's ultimate conclusion

that   Kaiser    met   its   burden    of    showing   that   Neurontin   was

ineffective for the four off-label indications.

           Randomized controlled studies like DBRCTs are widely

accepted as "ideally suited" for showing causation and as a "good

measure of the treatment effect." D. Kaye & D. Freedman, Reference

Guide on Statistics, in Federal Judicial Center, Reference Manual

on Scientific Evidence 211, 218, 220 (3d ed. 2011).               Where, as

                                      -57-
here, numerous DBRCTs indicate that a drug is ineffective, that

provides powerful scientific evidence of inefficacy, particularly

as compared to anecdotal experiences, which can be tainted by the

placebo effect.       As one witness in this trial testified, "the

default position [in medical decisionmaking] is that a drug is

ineffective unless it's proven otherwise."      Experiments start with

a null hypothesis that the drug is no more effective than placebo.

In this case, DBRCTs repeatedly showed that there was not enough

evidence to reject the null hypothesis for the indications at

issue.   See Kaiser Findings, 2011 WL 3852254, at *35-45.      Pfizer's

claimed evidence of Neurontin's efficacy came from less convincing

sources.

            Thus, the totality of the evidence strongly supports a

conclusion that Neurontin was not effective for the four off-label

conditions as to which the district court and jury found liability.

We need not address what the standard for efficacy would be if

there were no DBRCTs in existence, or if the results of DBRCTs were

equivocal, or if there were a different mix of DBRCT and non-DBRCT

evidence.

                                   V.

            Because   Kaiser   met both   causation   requirements   with

legally sufficient evidence and proved that it suffered economic

injury from Pfizer's fraudulent scheme, we move to the separate

challenges to the amount of damages awarded. "On that phase of the

                                  -58-
case the plaintiff has a more relaxed burden of proof . . . ,

especially if as in this case the defendants' conduct has made it

difficult for the plaintiff to prove the precise extent of his

damages."     BCS Servs., 637 F.3d at 759; see also Thermo Electron

Corp. v. Schiavone Constr. Co., 958 F.2d 1158, 1166 (1st Cir.

1992).   Under such circumstances, damages do not need to be proven

"with mathematical certainty, provided an award has a rational

basis in the evidence." Thermo Electron, 958 F.2d at 1166 (quoting

Jay Edwards, Inc. v. New Eng. Toyota Distrib., Inc., 708 F.2d 814,

819   (1st   Cir.   1983))   (internal    quotation   mark   omitted);   see

Restatement (Second) of Torts § 912 cmt. a.           "Otherwise 'the more

grievous the wrong done, the less likelihood there would be of a

recovery.'"    BCS Servs., 637 F.3d at 759 (quoting Bigelow v. RKO

Radio Pictures, Inc., 327 U.S. 251, 265 (1946)).

             Pfizer argues that the district court erred in its

calculation of damages, primarily because Dr. Hartman used a list

of alternatives to Neurontin created by Dr. Millares (the chairman

of the DIS) but no expert testified that the drugs on the list were

at least as effective or as well tolerated as Neurontin. Moreover,

Pfizer argues, there was no evidence that PMG doctors would have

prescribed those lower-cost alternative drugs but for Pfizer's

conduct; indeed, those doctors may have prescribed more expensive

drugs instead of Neurontin.      Pfizer claims that these assumptions

made the estimation of damages too speculative.              See Irvine v.

                                   -59-
Murad Skin Research Labs, Inc., 194 F.3d 313, 320 (1st Cir. 1999).

Our review of the district court's admission of Dr. Hartman's

testimony is for abuse of discretion, AWP, 582 F.3d at 197, and

there was none here.

          The burden of proof as to damages is lower than that for

causation, and the factfinder is afforded a greater deal of freedom

to estimate damages where the defendant, as here, has created the

risk of uncertainty. See Ocean Spray Cranberries, Inc. v. PepsiCo,

Inc., 160 F.3d 58, 63 (1st Cir. 1998).   The damages inquiry does

not allow a defendant to benefit from the scope of its wrongdoing;

this is why "[e]ven 'speculation has its place in estimating

damages, and doubts should be resolved against the wrongdoer.'"

BCS Servs., 637 F.3d at 759 (quoting Mid-Am. Tablewares, Inc. v.

Mogi Trading Co., 100 F.3d 1353, 1365 (7th Cir. 1996)).

          The district court did not err in accepting Dr. Hartman's

methodology for calculating damages. In fact, Pfizer never offered

an alternative: it did not provide its own list of substitute

drugs, nor did it offer testimony about the Kaiser list's exclusion

of lamotrigine (the only drug Pfizer names on appeal as improperly

excluded).

                               VI.

          Pfizer raises two other issues on appeal, concerning the

district court's denial of Pfizer's motion to transfer venue before

trial and its denial of Pfizer's motion for a new trial.

                               -60-
A.           Denial of Pfizer's Motion to Transfer Venue

             The coordinated plaintiffs filed their complaint in the

Massachusetts district court on February 1, 2005.          More than four

years later, on December 4, 2009, Pfizer filed a motion to transfer

venue to California pursuant to 28 U.S.C. § 1404.

             Pfizer's   motion   followed   more   than   two   months   of

discussions among the coordinated plaintiffs, the defendants, and

the Massachusetts district court regarding the possibility of

holding a bellwether trial as to one TPP's claims against the

defendants.      The court stated on September 18, 2009, that it

favored holding a trial on Kaiser's claims, a view joined by

plaintiffs on October 2, 2009.22       Defendants opposed, saying that

any bellwether trial should not be on Kaiser's claims because

"Kaiser is the most atypical of the named TPPs."          During none of

these     discussions   did   Pfizer   suggest   that   venue   should   be

transferred to California.

             On November 12, 2009, the district court ordered that

"[t]he trial in the action brought by coordinated plaintiff Kaiser

will begin [before it] on February 22, 2010."       About a month later,

Pfizer moved to transfer venue pursuant to 28 U.S.C. § 1404,

arguing for the first time that transfer was favored by (1)

Kaiser's residence in California, (2) California's greater interest

     22
       While the coordinated plaintiffs represented that they would
prefer to all proceed to trial at one time, they agreed that if the
court were to initially hold only one trial, it should be Kaiser's.

                                   -61-
in the litigation, (3) the greater familiarity of California

federal courts with the California UCL, and (4) the convenience of

witnesses.   The district court, with years of experience in the

case, denied this motion, explaining that (1) Kaiser did not wish

to transfer venue; (2) transfer would result in considerable delay

as any transferee judge familiarized herself with the case; and (3)

defendants would not be prejudiced, since they had access to

videotaped deposition testimony of non-party witnesses.      Kaiser

Findings, 2011 WL 3852254, at *11 n.6.

          On appeal, Pfizer argues that this was error because it

violated the MDL transfer requirements pursuant to 28 U.S.C.

§ 1407(a) and the rule of Lexecon Inc. v. Milberg Weiss Bershad

Hynes & Lerach, 523 U.S. 26 (1998), and because it was an abuse of

discretion, in any event, under 28 U.S.C. § 1404.

          Pfizer is wrong on the law.     Section 1407(a) provides

that an action "transferred to any district for coordinated or

consolidated pretrial proceedings . . . shall be remanded by the

panel at or before the conclusion of such pretrial proceedings to

the district from which it was transferred unless it shall have

been previously terminated."    The Court held in Lexecon that a

district court conducting such pretrial proceedings could not

"invoke § 1404(a) to assign a transferred case to itself for

trial."   523 U.S. at 28.   The coordinated plaintiffs filed their

complaint in the District of Massachusetts; it was not transferred

                               -62-
to this district for pretrial proceedings, and so § 1407(a) and

Lexecon do not govern here.

            There was no abuse of discretion as to § 1404.             See Coady

v. Ashcraft & Gerel, 223 F.3d 1, 11 (1st Cir. 2000).                     Kaiser

opposed defendants' motion to transfer, and coordinated plaintiffs

Aetna and Guardian were domiciled in New York and Connecticut,

respectively.        The Massachusetts district court had considerable

experience with complex claims against defendants arising out of

the fraudulent marketing of Neurontin, and coordinated plaintiffs'

claims were national in scope, not localized to California.

B.          Denial of Pfizer's Motion for New Trial Based on
            Purportedly New Evidence Regarding the Cochrane Review of
            Neuropathic Pain

            There was no abuse of discretion in the district court's

denial of defendants' March 22, 2011 motion for new trial.                   At

trial, Pfizer had presented expert testimony that Neurontin was

effective for the broad treatment of neuropathic pain, which relied

in   part   on   a   2005   review   by   the    Cochrane   Collaboration,   an

independent organization, that concluded that adequate evidence

supported    Neurontin's     efficacy     for    neuropathic   pain.     Kaiser

Findings, 2011 WL 3852254, at *42.              The district court discounted

this testimony because the 2005 Cochrane Review was based on

incomplete information, given defendants' suppression of negative

information about Neurontin's efficacy for the broad treatment of

neuropathic pain.       Id. at *42-43.

                                      -63-
            In 2011, the Cochrane Collaboration published another

review of the effects of gabapentin in treating chronic neuropathic

pain.    This revised review was "updated with the inclusion of

unpublished information made available through litigation" and

concluded that "[g]abapentin provides pain relief of a high level

in about a third of people who take [it] for painful neuropathic

pain."

            The district court denied defendants' motion for a new

trial, explaining that a credible meta-analysis from the Cochrane

Collaboration based on the entirety of the scientific evidence

concerning Neurontin's use in treating broad neuropathic pain was

unavailable to defendants at the time of trial only because "Pfizer

itself did not provide the Cochrane Group with all available

studies prior to the trial because it fraudulently suppressed these

studies."    That reason was sufficient.

                                VII.

            The judgment of the district court is affirmed.

                                -64-