McDarby v. Merck, 401 N.J. Super. 10 (App. Div. 2008) slide show - the Vioxx case from the...

7/27/2019 McDarby v. Merck, 401 N.J. Super. 10 (App. Div. 2008) slide show - the Vioxx case from the plaintiff's point of view

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McDarby v. Merck 1

The Vioxx Story

McDarby v. Merck401 N.J. Super 10 (App. Div. 2008)

Vioxx May 20, 1999-September 30,

2004


2/104

Standards of review on appeal

Questions of law - de novo review

Questions of fact:

- defer to jury if there is more than ascintilla of evidence

- review facts in light most favorable

to prevailing party below Questions of admissibility of evidence

- abuse of discretion

McDarby v. Merck 2


3/104

Elements of a failure to warn

claim

Plaintiff was a foreseeable user

Product was not being misused by plaintiff

Product defect: Seller/mfr failed to provideadequate warning of risks

Product defect was a proximate cause ofharm

McDarby v. Merck 3


4/104

Framing the counterfactual hypothetical

What was Mercks tortious conduct?

If Mercks conduct had not been

tortious what harm would have been

avoided?

McDarby v. Merck 4


5/104

Did Merck behave reasonably toward

three constituencies?

FDA - with which the seller contends

for the widest possible marketing range

Physicians - the primary targets of

intensive marketing campaigns, and

Patients - the object of push-marketing

to create demand for the drug

McDarby v. Merck 5


6/104

Stating the theme

The record discloses the tension thatexisted between Merck's scientists and itsmarketers and, in plaintiffs' view, thepressure on Merck's employees to

preserve market share and concomitantprofits arising from the sale of Vioxx -- adrug envisioned as re-establishing Merck

as preeminent in the field ofpharmaceutical development andmanufacture -- regardless of thecardiovascular risks posed by the drug.

McDarby v. Merck 6


7/104McDarby v. Merck 7

Dr. Scolnicks lament

The pain is truly awful. Not financialbut personal.... The Timessaid this wasmarketing triumphing over science.

When science dominated in the pastwe won over and over again.

It will take a new CEO to help Merckbecome reborn...


8/104McDarby v. Merck 8

Product launch a superstarAt the 3 day June 1999 launch party

David Anstice, Merck's President forHuman Health Products in North

America, described

Vioxx as a "superstar" that wouldmake Merck "own" the rheumatologymarket "once again.

McDarby v. Merck (NJAD 2008)


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McDarby v. Merck 9

Vioxx for lunch -Targeting MDs

The largest sales force ever deployed Sales incentives targeting over 10,000

physiciansMDs pitching VIOXX

"Health Education Liaison" - $ 3million/month

17 million free samples in 1st 6 months

Ds who resisted Vioxx sales entreatieswere to beneutralized or discredited


10/104

McDarby v. Merck 10

A blockbuster

Merck SEC 8 K filing January 23, 2001

"Our five key products - VIOXX. ZOCOR.COZAAR, FOSAMAX and SINGULAIR droveMerck's performance for the year and createda powerful platform for growth."

VlOXX has become the worlds fastestgrowing branded prescription arthritis

medicine.

VIOXX achieved $2.2 billion in sales for theyear 2000


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McDarby v. Merck 11

Hard sell

Mass marketing to the elderly


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McDarby v. Merck 12

Targeting Dr. Braun

Vioxx sales reps visited at leasttwice a week

One acknowledged, the doctor wastargeted because of the high volumeof his prescriptions for pain relievers

Braun relied on sales reps forinformation, as well as on label itself

Would this affect your view of thecase?


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McDarby v. Merck 13

Post-VIGOR Safer than Placebo

Dr. Braun was also shown Merck's

"CV Card," entitled Chemical Profile,

Osteoarthritis Studies" that indicated

no elevated risk of heart attackand,

according to Dr. Braun, showed Vioxx

to be safer than a placebo.


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Dr. Braun

Q. If you had been told by Merck thatVioxx could increase the risk of a heartattack, would you have prescribed Vioxxto Mr. McDarby?

THE WITNESS: Of course not.

Q. Why not?

A. My . . . job as a doctor is to try toprevent things from happening, try toprevent strokes, try to prevent heartattacks.

Ch. 5 Cause in fact 14


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McDarby v. Merck 15

Fighting the FDA


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McDarby v. Merck 16

Ugly cubed

October 15 2001 e-mail Dr. Scolnick toAnstice:

David. Be assured we will not accept thislabel. If we need to we will ask to go toan advisory committee meeting.

Anstice replied:

. . . We knew it would be UGLY and it

is. We'll fight back and see where weget.

Scolnick responded:

It is ugly cubed. They are bastards.


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McDarby v. Merck 17

Risks to Sales strength of label


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McDarby v. Merck 18

Dilution:

Burying the bad newsThe FDA-Merck Compromise

of 2002 revised labeling


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McDarby v. Merck 19

2002 FDA-Approved post-VIGOR Vioxx

Label

Precautions Cardiovascular Effects

The information below should be

taken into consideration and caution

should be exercised when VIOXX isused in patients with a medical

history of ischemic heart disease.


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McDarby v. Merck 20

2002 FDA Approved post-VIGOR Vioxx

Label

Precautions

Because of its lack of platelet effects,

VIOXX is not a substitute for aspirinfor cardiovascular prophylaxis.


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McDarby v. Merck 21

Is Naprosyn really better

than aspirin?Or is Vioxx the problem?

The need for study post-VIGOR


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McDarby v. Merck 22

Science vs. marketing

March 9, 2000, Dr. Edward Scolnick, thePresident of Merck's Research Division, in ane-mail about the VIGOR data stated:

"The CV events are clearly thereIt is ashame but it is a low incidence and it ismechanism based as we worried itwas."

McDarby v. Merck (N.J.A.D. 2008)


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McDarby v. Merck 23

Im in minor agony

April 12, 2000 e-mail to Dr. Alise Reicinfrom Dr. Scolnick re CV safety post-VIGOR

I will tell you my worry quotient is high. Iactually am in minor agony. What I reallywant to do is a 10,000 vs. 10,000patient studysafety firstprimaryendpoint and efficacy secondaryor co-primary.


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McDarby v. Merck 24

Vioxx the business

climateBlockbuster drug patent

expirations on the horizon


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McDarby v. Merck 25

Whos in charge here? David Anstice, direct By Mark Lanier 185

12 You're a salesman? 13 A. Yes. I have been involved at Merck

for 32 years. 14 Q. So in 1994, Merck makes you

their new 15 president of health, you, DavidAnstice, the marketing sales guru, right?

17 A. Yes.


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McDarby v. Merck 26

Storm clouds David Anstice, Direct

By Mr. Lanier 15 the storm cloud that's

16 developing is y'all have these six blockbuster drugs,

17 and by that we mean drugs that are bringing in each

18 over a billion dollars in sales a year, that you see

19 that these drugs are coming off patent and that you

20 know that other companies are going to be able to

make generics and drive the price down, true? 22 A. That's right.


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McDarby v. Merck 27

Rush to market

Q. Sir, do you recall in your own speechsaying thatVIOXX was important

because it was through products like

VIOXX that you got your replacement

revenue that y'all woulddesperately

need?A. I may have used the term.


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McDarby v. Merck 28

Compressed and accelerated

Q. This is the same page whereearlier y'all said that "the

development of VIOXX must proceed

aggressively to meet the challenge of

Celebrex."

"The clinical program has, thus, beencompressed and accelerated.

Direct examination of David Anstice, Pres., Merck HumanHealth


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McDarby v. Merck 29

FDA Expedited Approval

May 20, 1999


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McDarby v. Merck 30

Phase IV Mass

marketingThe scarcely controlled human

experiment stage of productdevelopment


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McDarby v. Merck 31

Changes may be needed

If additional information relating tothe safety or effectiveness of thisdrug becomes available, revision ofthe labeling may be required.

Sincerely,Robert J. DeLap, M.D., Ph.D., Director

Office of Drug Evaluation

Food & Drug AdministrationCenterfor Drug Evaluation and Research

May 20, 1999


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McDarby v. Merck 32

Superior to Placebo

Initial label

VIOXX has demonstrated significant

reduction in joint pain compared to

placebo for treatment ofosteoarthritis.


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McDarby v. Merck 33

The scarcely controlled human

experiment FDA medical officer Maria Villalba, MD, May 20, 1999:

With the available data, it is impossible toanswer with complete certainty whetherthe risk of cardiovascular and

thromboembolic events is increased inpatients on [Vioxx].

A larger database will be needed to

answer this and other safety comparisonquestions.

McDarby v. Merck (N.J. App.Div. 2008)


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McDarby v. Merck 34

Hard sell

Mass marketing to the elderly


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McDarby v. Merck 35

DTC Advertising

Throughout the period Vioxx was onthe market

Merck ran magazine advertisementsand television spots featuring iceskater Dorothy Hamill touting the drugand persons able to engage in leisureactivities because of their use of Vioxx

McDarby v. Merck (NJAD 2008)


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McDarby v. Merck

Persuading the jury

McDarby v. Merck 36


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12/13/2003

Only 4 MonthsBefore Heart

Attack

John McDarbys 75th Birthday

It did t h t


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It didnt have tohappen.

What obstacles did

McDarby face inproving Vioxx

caused his heartattack?


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McDarby v. Merck 39

VIGORTHE BEGINNING OF THE END


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McDarby v. Merck 40

Merck failed to tell

the whole truthAnd nothing but the truth


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McDarby v. Merck 41

Di b ti


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McDarby v. Merck 42

0

1

2

3

4

5

6

7

Heart

Attack Risk

Placebo Vioxx

Diabetics

Diabetics

Vioxx= 6.1 x increased risk of heart attack


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McDarby v. Merck 43

Valley Hosp ital

Consul tat ion

HISTORY OF PRESENT ILLNESS:

The patient is a 75- year-old male

with a past history of diabetes

mellitus who was in his normal stateof health when he was in his house

and experienced some weakness.

The patient denies any chest pain

when he had felt weak and possiblyhad some vertigo, fell on his right

side and sustained a fracture.

April 15, 2004

MEDICATIONS:

Micronase and Vioxx


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McDarby v. Merck 44

It didnt have to happen


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McDarby v. Merck 45

You should have knownIn fact, you did

Letter to Merck & Co


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McDarby v. Merck 46

Merck &

Co., Inc.

Potential

cardiovascular

implications of

COX-2

9 September 98

patient groups where

this hypothesis could be

tested patients with

diabetes mellitus

I suggest that it would be inthe best interest of Merck to look

into these issues as quickly and

thoroughly as possible.

Letter to Merck & Co.,

Inc.

C 2 I hibit i b l i th


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McDarby v. Merck 47

Cox-2 Inhibitors - imbalance in the

bloodstream?

Garret Fitzgerald, the [Merck] study'schief investigator hypothesized - ifCOX-2 inhibitors suppressed

prostacyclin generated within bloodvessels without suppressingthromboxane, increased clotting,

leading to heart attacks and strokes,would result.

October 19, 1998

McDarby v. Merck (N.J.A.D.2008)


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McDarby v. Merck 48

Unblinding the VIGOR

DataMarch 2000

2000 03 09


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McDarby v. Merck 49

Dr. EdwardScolnick

Head of MerckResearch

Labs\March 9,2000

The CV events

are clearly there.

12 days later Dr. Braunprescribed John McDarby

his first dose of Vioxx

2000-03-09


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McDarby v. Merck 50

Diabetes Why didntMerck warn?

Age

Low goodcholesterol

Merck Blames No Excuses

Why didntMerck warn?

Why didntMerck warn?


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McDarby v. Merck 51

Is Naprosyn really better

than aspirin?Or is Vioxx the problem?The need for study post-VIGOR


52/104

McDarby v. Merck 52

Science vs. marketing

March 9, 2000, Dr. Edward Scolnick, thePresident of Merck's Research Division, in ane-mail about the VIGOR data stated:

"The CV events are clearly thereIt is ashame but it is a low incidence and it ismechanism based as we worried itwas."



53/104

McDarby v. Merck 53

Im in minor agony

April 12, 2000 e-mail to Dr. Alise Reicinfrom Dr. Scolnick re CV safety post-VIGOR

I will tell you my worry quotient is high. Iactually am in minor agony. What I reallywant to do is a 10,000 vs. 10,000patient studysafety firstprimary

endpoint and efficacy secondaryor co-primary.


54/104

P hi h


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McDarby v. Merck 55

Preaching to the

professionThe New England Journal of Medicine

COMPARISON OF UPPERGASTROINTESTINAL TOXICITY OF

ROFECOXIB

AND NAPROXEN IN PATIENTS WITH

RHEUMATOID ARTHRITIS

Pit hi


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McDarby v. Merck 57

Pitching naproxen as

cardioprotective

Testimony of Dr. Braun

I was told Vioxx was a safedrug, but it was notcardioprotective as Naprosyn is.

And I was told to just make sure theydon't stop taking their aspirin. (DaC 4341-4342)


57/104


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McDarby v. Merck 59

SNDA spinning VIGOR to the FDA

Primarily, Merck sought to disclose that

the results ofthe VIGOR study provided

"conclusive evidence of the improved GI

safetyof [Vioxx] compared [Naprosyn]


G d b t N


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McDarby v. Merck 60

Good news about Naprosyn

Naprosyn is better than aspirin?


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McDarby v. Merck 61


an implausible hypothesis

Eric Topol, MD, Case-Western, Cleveland Clinic

you have a randomized trial and

an experimental, a new drugwhich hasntbeen studied extensively Vioxx and

an anchor drug, naproxen, that had been

available for 20 years



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McDarby v. Merck 62


an implausible hypothesis

A comparison shows theres more than

five-fold heart attacks and two-fold

excess of cardiovascular serious events

How could you possibly conclude that

its the naproxen being beneficial?

Eric Topol


62/104

McDarby v. Merck 63

Sullied study

Editorial December 29, 2005

Expression of Concern: Bombardieret al., Comparison of Upper

Gastrointestinal Toxicity of Rofecoxiband Naproxen in Patients withRheumatoid Arthritis,

N Engl J Med 2000;343:1520-8.

Gregory D. Curfman, M.D., StephenMorrissey, Ph.D., and Jeffrey M. Drazen,M.D.


63/104


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McDarby v. Merck 65

Sell, Sell, Sell

2001- 2002

Selling the sales staff:


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McDarby v. Merck 66

Selling the sales staff:

Its the Naprosyn, stupid!

Anstice vmm to sales staff 9/13/2001

To understand VIGOR you must

understand Naproxen is

cardioprotective.

Gung ho marketing


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McDarby v. Merck 67

Gung-ho marketing David Anstice, direct

By Mark Lanier

16 In fact, there's this whole training video.

It is called "Be the Power" where twoMercksalesmen

18 are dressed up like superheroes 23 There's a woman who is acting kind of

whiny,I'm afraid I'm going to get hurt if I

take VIOXX... And in the video the VIOXX superheroes, the

Mercksuperheroes are trained to take thiscard and use it like a ray gun.


67/104

McDarby v. Merck 68

Post-VIGOR Safer than Placebo

Dr. Braun was also shown Merck's

"CV Card," entitled Chemical Profile,

Osteoarthritis Studies" that indicated

no elevated risk of heart attackand,

according to Dr. Braun, showed Vioxx

to be safer than a placebo.

The CV Card Omitting the


68/104

McDarby v. Merck 69

The CV Card Omitting the

Naproxen Comparator


69/104

McDarby v. Merck 70

FDA v. Merck - the

Inside StoryTurmoil and doubt Isscience or marketing in

command?


70/104

McDarby v. Merck 71

The only Essential study

Dr. Scolnick - September 13, 2001 memo:

I want to give you a list of the onlystudies that I regard as ESSENTIAL.

Essential means just that ESSENTIAL.Not preferred, not useful, not helpful;ESSENTIAL. . . .

1. For Vioxx: Only the CV outcomestudy ONLY ESSENTIAL STUDY!


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McDarby v. Merck 72

Your marketing is misleading

FDA to Merck Warning letter 9/17/2001:

Your promotional campaigndiscounts the fact that in the VIGOR

study, patients on Vioxx wereobserved to have a four to five foldincrease in myocardial infarctions

(MIs) compared to Naprosyn(naproxen).

FDA W i L M k


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McDarby v. Merck 73

FDA Warning Letter to Merck

9/17/2001You fail to disclose thatyour

explanation is

hypothetical has not been demonstrated by

substantial evidence, and

there is another reasonableexplanation,that Vioxx may havepro-thrombotic properties.


73/104

McDarby v. Merck 74

Stonewalling

October 1, 2001 Anstice to sales staff:

Merck continues to stand behind theoverall and cardiovascular safety of

Vioxx."

if you are asked any other questionsabout VIGOR by a health care

professional or a customer,you maynot answer the question.


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McDarby v. Merck 75

The FDA Draft Label

UGLY CUBED

FDAs draft label for Vioxx


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McDarby v. Merck 76

FDA s draft label for Vioxx.

October 15, 2001

Warnings

Cardiovascular Disease

VIOXX should be used with caution inpatients at risk of developing

cardiovascular thrombotic events



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McDarby v. Merck 77


October 15, 2001

The risk of developing myocardial

infarction in the VIGOR study was

five-fold higher in patients treated

with VIOXX50-mg (0.5%) as

compared to patients treated with

naproxen (0.1%)



77/104

McDarby v. Merck 78


October 15, 2001

Prospective, well-powered, long term

studies required to compare the

incidence of serious CV events in

patients taking VIOXX versus NSAID

comparators other than naproxen

have not been performed.

The CV Safety Studys Fate


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McDarby v. Merck 79

The CV Safety Study s Fate

By February 13, 2002, a letter of

intent was sent by Dr. Alan Nies,Senior Vice-President for ClinicalSciences at Merck Research

Laboratories to the Harvard MedicalSchool with respect to the study.Despite Dr. Scolnick's urging, the

study was never performed. McDarby v. Merck (N.J.A.D. 2008)


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McDarby v. Merck 80

Fighting the FDA

Ugly cubed


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McDarby v. Merck 81

Ugly cubed

October 15 2001 e-mail Dr. Scolnick toAnstice:

David. Be assured we will not accept thislabel. If we need to we will ask to go to

an advisory committee meeting.Anstice replied:

. . . We knew it would be UGLY and it

is. We'll fight back and see where weget.

Scolnick responded:

It is ugly cubed. They are bastards.


81/104


82/104

McDarby v. Merck 83

Dilution:

Burying the bad newsThe FDA-Merck Compromise

of 2002 revised labeling

2002 FDA-Approved post-VIGOR Vioxx


83/104

McDarby v. Merck 84

2002 FDA Approved post VIGOR Vioxx

Label

Precautions Cardiovascular Effects

The information below should be

taken into consideration and caution

should be exercised when VIOXX is

used in patients with a medical

history of ischemic heart disease.


84/104


85/104

McDarby v. Merck 86

The charge to the jury

Th l t i d f ti


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The relevant period of time

When deciding whether plaintiff hasproven Merck failed to warn of

potential cardiovascular risks of

VIOXX, that it knew or should have

known, the time frame to consider is

the time before Mr. McDarbys heart

attack.

87McDarby v. Merck

The burden of proof


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The burden of proof

To establish a claim of failure to

warn, plaintiff must prove all of the

following elements by a

preponderance (greater weight) of

the credible evidence:

88McDarby v. Merck

Failure to provide adequate warning


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Failure to provide adequate warning

l. That Merck failed to provide an

adequate warning to prescribingdoctors based on what Merck knewor should have known about the risks

of VIOXX in sufficient time before itwas prescribed to the plaintiff toallow for an effective warning to be

given to his prescribing physician.

89McDarby v. Merck

Adequate warning (statutory)


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q g ( y)

In the case of a prescription drug,

the warning must be one that areasonably prudent manufacturerwould have provided to adequately

communicate information on therisks of the product to the prescriber,taking into account the

characteristics of, and the ordinaryknowledge common to, suchprescribing physicians.

90McDarby v. Merck

Adequate warning


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Adequate warning

You should look at the totality of theinformation given to the physiciansabout the drug and its risks,including information given in the

package insert, in the publishedarticles, in the promotional materialsand the information provided by

Mercks sales representatives todoctors.

91McDarby v. Merck

The learned intermediary doctrine


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y

and the extent of the duty

Why the emphasis on Doctors?

Why not direct warning to theconsumer?

Should Merck have compared therisks and benefits of Vioxx to each ofits competitors?

Should a drug companys duty differfrom that of doctors as stated inMastromonaco?

McDarby v. Merck 92

93Elements misuse and


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alteration

2.That when the injury happenedVIOXX was not being misused, or ithad not been substantially altered ina way that was not reasonablyforeseeable.

There is no evidence in this case theproduct was misused by the plaintiff oraltered in a way not reasonablyforeseeable.

93McDarby v. Merck

94Elements reasonably


93/104

y

foreseeable user (or bystander)

3. That the plaintiff was a reasonably

foreseeable user, or a person who

might reasonably be expected to

come in contact with VIOXX.

There is no issue as to this fact.

94McDarby v. Merck

95

Proximate cause


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Proximate cause

4. That VIOXX was a proximate

cause of Mr. McDarbys injury and

damages.

On what aspect of proximate cause

was the jurys finding directed by the

court?

95McDarby v. Merck

Proximate cause


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McDarby v. Merck 96

By proximate cause is meant that the

defect in the product was a substantialfactor which singly, or in combination withanother cause, brought about the illness.

If the product in question, however, does

not add to the risk of the occurrence ofthe particular illness and hence was not acontributing factor in the happening of the

illness then plaintiff has failed to establishthat a particular product defect was aproximate cause of the accident

The heeding presumption


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The heeding presumption

If you find that Merck failed to provide anadequate warning, then the law requiresyou to presume that plaintiffs' doctorswould have heeded that adequate warning

and not have prescribed VIOXX to[plaintiffs]. However, to recover damagesfor their heart attacks, [plaintiffs] must

still prove that their taking VIOXX was aproximate cause of their heart attacks.

Why take this from the jury?

McDarby v. Merck 97


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Overcoming the presumption


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McDarby v. Merck 100

g p p

Judging Merck

Ifyou find that plaintiff has proven

by a preponderance of the evidence

that after a label was approved there

was new information that changed

the known or knowable

cardiovascular risks of VIOXX



100/104


Judging Merck

Then under FDA regulations,

Merck had a duty to warn

physicians of any newly

discovered risks of the drug.


101/104



102/104


Judging Merck

Merck could, if it chooses towithout prior FDA approval, sendletters to physicians, take out

ads, publish in journals, or sendout sales representatives inorder to advise physicians ofnewly known risks of VIOXX.

104



103/104



It is up to you to decidewhat

Merck knew or should have

known about whether therewere potential cardiovascular

risks of VIOXX based upon

reasonable evidence and when.

105

How did plaintiffs overcome thepresumption?


104/104

presumption? It is up to you to then determine

whether Merck acted

reasonably and adequately

warned physicians of any serous

cardiovascular risksbefore the

plaintiff was prescribed VIOXX.

McDarby v. Merck, 401 N.J. Super. 10 (App. Div. 2008) slide show - the Vioxx case from the...

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