Grimes v. Hoffman-Laroche CV-92-54-B 09/28/95 P UNITED STATES DISTRICT COURT FOR THE DISTRICT OF NEW HAMPSHIRE

Rhonda Grimes

v. Civil No. 92-cv-54-B

Hoffmann-LaRoche, Inc. and Dr. Pierre G. Labrecque

MEMORANDUM AND ORDER

Rhonda Grimes sued Hoffmann-LaRoche ("Hoffmann") and her

doctor, Pierre G. Labrecque, after developing cataracts which she

claims were caused by taking Accutane, a prescription drug

manufactured by Hoffmann. She contends that Dr. Labrecque

negligently failed to warn her that Accutane could cause

cataracts and negligently failed to use less obtrusive treatments

before prescribing Accutane. She claims that Hoffmann is

strictly liable for defectively designing Accutane and failing to

warn her adequately of Accutane's side effects. She also claims

that Hoffmann is liable based on a negligent failure-to-warn

theory. Both defendants deny that Accutane caused Grimes'

cataracts.

Grimes attempts to prove causation through the testimony of

Dr. Sidney Herman, an ophthalmologist with a recognized expertise in evaluating photochemical effects on the eye. Defendants have

moved pursuant to Federal Rule of Evidence 7 02 to exclude Dr.

Lerman's testimony on the ground that it is unreliable when

judged by the standard established by the Supreme Court in

Daubert v. Merrell Dow Pharmaceuticals, Inc., 113 S. C t . 2786,

2796 (1993). Anticipating success with this motion, defendants

also move for summary judgment, claiming that Grimes cannot prove

causation without Dr. Lerman's testimony. For the reasons that

follow, I grant both motions.

DISCUSSION

I. MOTIONS TO EXCLUDE

A. The Legal Standard

After Daubert, expert testimony must satisfy three

reguirements in order to survive a Rule 702 objection: first,

the expert must be gualified; second, the expert's testimony must

be reliable; and third, it must "fit" the facts of the case.

United States v. Shay,

, (1st Cir. 1995).

Qualifications alone are insufficient to satisfy the rule's

reguirements if the expert's testimony is based on unreliable

methodology or if it cannot reliably be applied to the facts in

issue. Daubert v. Merrell Dow Pharmaceuticals, Inc.,

1311, 1319 (9th Cir. 1995) (expert's qualifications, conclusions,

and assurances of reliability are not enough to satisfy

requirements), petition for cert, filed (Aug. 1, 1995); Porter v.

Whitehall Lab., Inc.,

(S.D. Ind. 1992),

a f f 'd ,

(7th Cir. 1993) ("expert is a conduit of facts

and not merely a subjective speculator relying on stature

alone").

Rule 7 0 2 's reliability requirement demands that "the

expert's opinion be based on the 'methods and procedures of

science1 rather than on 'subjective belief or unsupported

speculation1; the expert must have 'good grounds' for his or her

belief." In re Paoli R.R. Yard PCB Litiq.,

(3d

Cir. 1994) (quoting Daubert, 113 S. C t . at 2795) . Among the

factors that a court should consider in determining the

reliability of scientific testimony are: (1) whether the opinion

can be or has been tested; (2) whether the theory or technique on

which the opinion is based has been subjected to peer review and

publication; (3) the technique's known or potential error rate;

(4) the existence and maintenance of standards controlling the

3 technique's operations; and (5) "general acceptance."1 Daubert,

113 S. Ct. at 2 1 9 6 - 9 1 ; In re Paoli,

. In

evaluating these factors, the focus "must be solely on principles

and methodology, not on the conclusions that they generate."

Daubert, 113 S. C t . at 2797.

The rule's "fit" requirement refers to the necessity of a

connection between the expert's testimony and the facts of the

case. Daubert, 113 S. C t . at 2795-96. For example, if a

plaintiff offers scientific testimony that a particular chemical

causes cancer in rats in order to prove that the chemical also

causes cancer in humans, the testimony will not fit the facts of

the case and must be excluded unless the plaintiff also

establishes that the expert can reliably extrapolate from rats to

humans. In re Paoli,

. Thus, the results of a

scientifically reliable experiment or study will fail Daubert's

fit requirement and be excluded unless the results can be linked

1 The concept of general acceptance was first applied to expert testimony in Frye v. United States,

(D.C. Cir. 1923). There, the court stated that "while courts will go a long way in admitting expert testimony deduced from a well-recognized scientific principle or discovery, the thing from which the deduction is made must be sufficiently established to have gained general acceptance in the particular field in which it belongs." I d . at 1014.

4 through scientifically reliable means to the expert opinion it

purports to support. See In re Paoli,

, 744-45

n.12, 745 (Daubert's reliability requirement applies to each step

in the expert's analysis) .

I begin my review of defendants' challenge to the

admissibility of Dr. Lerman's testimony by describing his opinion

on causation and the methodology he used in reaching that

opinion. I then review his methodology in light of Rule 7 0 2 's

requirements. In doing so, I am mindful that the burden lies

with Grimes to demonstrate by a preponderance of the evidence

that the rule's requirements have been met. Daubert, 113 S. C t .

at 2796 n.10.

B. Dr. Lerman's Testimony

Dr. Lerman proposes to testify that Accutane "played a role"

in the development of Grimes' cataracts. In reaching this

ultimate conclusion. Dr. Lerman necessarily must also conclude

that therapeutic doses of Accutane will cause cataracts in

certain humans under certain conditions. Stated differently. Dr.

Lerman's conclusion that Accutane was the specific cause of

Grimes' cataracts is necessarily based, in part, upon his opinion

that Accutane is a general cause of cataracts when it is taken in

therapeutic doses. See, e.g., Wade-Greaux v. Whitehall Lab., 874

, 1448 (D.V.I. 1994) (discussing concepts of

specific and general causation), aff'd without op.,

(3d Cir. 1994).

Rather than relying on epidemiological data. Dr. Lerman

bases his general causation opinion primarily on scientific

theory, an in vitro experiment, and what he considers certain

"generally accepted" scientific facts.2 Simply stated, his

theory is that: (1) Accutane is a "photosensitive" drug; (2)

that gets into the lens when taken in therapeutic doses; (3)

becomes "photobound" to normally transparent lens protein after

being exposed to normal levels of ultraviolet radiation; and (4)

alters the lens protein in such a way as to produce opacities in

the lens, otherwise known as cataracts. Dr. Lerman defines a

photosensitive drug as "a compound whose chemical structure

endows it with the ability to absorb optical radiation (UV and

visible) and undergo a primary photochemical reaction resulting

in the generation of highly reactive and relatively long-lived

2 Dr. Lerman also bases his opinion in part on the fact that there have been anecdotal reports of cataracts in patients who have taken Accutane. However, no epidemiological studies have been done which establish any relationship between Accutane and cataracts and Dr. Lerman does not contend that causation can be proved by anecdotal evidence alone.

6 intermediates (triplets, radicals and ions) that can cause

chemical modifications in other (nearby) molecules of the

biologic system." Sidney Lerman, "Photosensitizing Drugs and

their Possible Role in Enhancing Ocular Toxicity," Ophthalmology,

Vol. 93, No. 3, (March 1986). According to Dr. Lerman,

photobinding occurs when a photosensitive drug is exposed to

ultraviolet light and becomes "cross linked" or bound to

surrounding tissue. This process is potentially significant in

the development of cataracts, according to Dr. Lerman, because

when a photosensitive chemical becomes photobound with lens

protein, it remains in the lens rather than diffusing out and its

phototoxic effect is exacerbated.3

The research Dr. Lerman conducted to test his theory

involved the use of ultraviolet spectroscopy and high performance

liguid chromatography ("HPLC") to compare various samples of lens

protein.4 The samples used during the tests were taken from

3 The lens is surrounded by a thin membrane called the agueous humor. The membrane allows compounds of a certain size, weight, and chemical structure to diffuse in and out of the lens. Molecules that are too large or that become bound to lens protein molecules cannot diffuse out of the lens.

4 Ultraviolet spectroscopy is a method of identifying an unknown compound by comparing the freguency of ultraviolet light absorbed by that compound with the freguency absorbed by a known

7 (1) Grimes and another patient who had developed cataracts after

taking Accutane; (2) age-matched5 normal lenses; (3) age-matched

cataractous lenses from patients who had not taken Accutane; (4)

age-matched normal lenses that were incubated in Accutane,

exposed to ultraviolet radiation, and dialyzed;6 and (5) age-

compound. See 13 Encyclopedia Britannica 527-28 (Phillip Goeth ed.) (1991). Ultraviolet spectroscopy can also be used to measure the amount of a compound known to absorb a specific freguency of ultraviolet light present in a sample by measuring the amount of ultraviolet light absorbed at the known freguency. High performance liguid chromatography is another method of identifying unknown compounds by comparing them with known compounds. See Van Nostrand Reinhold Encyclopedia of Chemistry 252-54 (Douglas M. Considine, ed.) (1984). During this process, different compounds will move through a thin tube filled with solid supports and liguid at different rates. By comparing the rate at which an unknown compound moves through the tube with the movement rate of known compounds, the unknown compound may be identified. See i d .

Age-matched lenses are used for comparison purposes because the lens changes as a person ages.

6 Dialysis is a technigue which can be used to determine whether a compound has become bound to proteins in a sample. After a compound has been added to the sample, the sample and a small amount of solution are placed in a semi-porous bag through which proteins are too large to diffuse. The bag is then placed in a beaker of the solution. If the compound does not bond with the proteins, it will diffuse out of the bag into the surrounding solution. Conversely, if it does bond with the protein, it will not diffuse into the surrounding solution because the compound protein material is too large to fit through the pores of the bag. matched normal lenses that were incubated in Accutane and

dialyzed without first being exposed to ultraviolet radiation.7

The spectroscopy results revealed that lens material taken

from lenses that had been exposed to Accutane and ultraviolet

radiation showed greater absorbency to ultraviolet radiation

between 330-390 nanometers8 than lens material taken from both

the lenses that had not been exposed to Accutane and the lenses

that had been incubated in Accutane but not exposed to

ultraviolet radiation prior to dialysis. The HPLC results also

revealed an "anomalous peak" which was present only in the

analysis of the lens material taken from the lenses of the

Accutane patients and the lenses incubated in Accutane and

exposed to ultraviolet radiation before dialysis.

Dr. Lerman contends that his experiment proves both that

when Accutane is taken in therapeutic doses it can enter the

7 I cannot determine from Dr. Lerman's deposition testimony whether he conducted spectroscopy and HPLC tests on the samples he obtained from both Grimes and the other Accutane patient. I am also unable to determine from the evidence how many age- matched normal lenses and cataractous lenses Dr. Lerman used in his research. Nevertheless, I assume for purposes of analysis that Dr. Lerman performed spectroscopy tests and HPLC tests on the lens material taken from both Accutane patients. I also assume that he used multiple control samples.

8 A nanometer is a measuring unit for wavelengths of light. lens, and that if Accutane enters the lens and is exposed to

ultraviolet radiation, it becomes photobound to lens protein.

According to Dr. Lerman, the experiment proves the first point

because samples of the lens protein taken from the Accutane

patients showed the same increased absorbency to certain wave

lengths of ultraviolet radiation during spectroscopy and the same

anomalous peak during HPLC testing as was shown by his analysis

of the lens protein that had been incubated in Accutane and

exposed to ultraviolet radiation prior to dialysis. Dr. Lerman

reasons that the only plausible explanation for the anomalous

peak and the increased ultraviolet absorbency seen in the lens

material taken from the Accutane patients is that the Accutane

they were taking, or one of its metabolites, entered their

lenses. He also contends that the experiment proves the second

point because he detected the anomalous peak and increased

ultraviolet absorbency only in the lens material that had been

exposed to both Accutane and ultraviolet radiation before

dialysis. According to Dr. Lerman, the sample that was exposed

to Accutane but not ultraviolet radiation did not exhibit the

anomalous peak and increased ultraviolet absorbency because the

Accutane in the sample did not become bound to the lens protein

and was removed during dialysis. Finally, he concludes that

10 Accutane produces cataracts because, he argues, it is "generally

accepted" that cataracts will result whenever a photosensitive

chemical becomes photobound to lens protein.

C. Analysis

Assuming without deciding that Dr. Lerman's experiment is a

scientifically reliable way of determining that therapeutic doses

of Accutane will enter the lens and become photobound to lens

protein if exposed to ultraviolet radiation, he must still have a

reliable basis for concluding that Accutane will produce

cataracts if it enters the lens and becomes photobound.9

Otherwise, his opinion cannot satisfy Daubert's fit reguirement

because the results of his experiment cannot be linked reliably

to the opinion they purport to support.

In completing the final step in his analysis. Dr. Lerman

relies on what he considers to be the generally accepted

scientific fact that photosensitive chemicals that enter the lens

9 Defendants argue that Dr. Lerman's experiment is flawed because: (1) the sample he took from Grimes' lens was tainted; (2) he failed to use adeguate controls; and (3) he has failed to account for other innocent explanations that are also consistent with his result. I need not consider these contentions because I conclude that Dr. Lerman's testimony should be excluded even if his experiment was methodologically sound.

11 and become photobound to lens protein will produce cataracts.10

In a letter filed with the court after the hearing concluded. Dr.

Lerman explained his view.

It is universally accepted that many forms of radiation can cause cataracts. Two forms of radiation, namely, x-rays and ultraviolet radiation, are well known cataractogenic agents. The role of [U.V. absorbing] photosensitizers in the generation of cataracts is primarily due to the fact that they enhance UV action on the lens in which they are photobound to lens protein. It therefore follows that the demonstration of such photobinding clearly shows that it can and will initiate and enhance the formation of a cataract.

Notwithstanding Dr. Lerman's undeniable expertise, this broad

assertion is insufficient to establish the reliability of his

conclusion on this point for three independent reasons. First,

an expert cannot establish that a fact is generally accepted

merely by saying so. In this case. Dr. Lerman has failed to

identify any authoritative source which recognizes as generally

accepted the proposition that all photosensitive chemicals

10 Grimes does not contend that any of Daubert's alternative criteria can be used to establish the reliability of the final step in Dr. Lerman's opinion. Therefore, I will only consider whether the scientific propositions on which his opinion is based are generally accepted.

12 produce cataracts when they become photobound to lens protein.

In the absence of such authority, I find his testimony on the

point to be unpersuasive. Second, even if it were generally

accepted that some photosensitive chemicals will produce

cataracts if they become photobound to lens protein, that general

proposition would not fit the facts of this case unless one could

reliably draw an analogy between those photosensitive chemicals

and Accutane. See, e.g.. Federal Judicial Center, Reference

Manual on Scientific Evidence 83-84 (1994) [hereinafter Reference

Manual1 (suggesting that an expert who bases an opinion on a

proposed analogy that has not been investigated should not be

permitted to testify because he is offering a "hunch" rather than

an "explanatory theory . . ."). In the present case. Dr. Lerman

has failed to identify any scientifically reliable basis for

concluding that Accutane causes cataracts simply because other

photosensitive drugs cause cataracts.11 Finally, even if it

11 In certain circumstances, toxicologists have relied on similarities in the chemical structures of two compounds to draw an analogy between an established toxic effect exhibited by one chemical and an anticipated toxic effect in another. This technigue is referred to as the identification of Structure Activity Relationships ("SAR"). Reference Manual, supra, at 203; but see David E. Bernstein, The Admissibility of Scientific Evidence after Daubert v. Merrell Dow Pharmaceutical, Inc.,

, 2178-79 (1994) ([c]hemical structure

13 could reliably be claimed that all photosensitive chemicals that

become photobound to lens protein will produce cataracts if they

are present in certain concentrations, that proposition would be

irrelevant here unless there were some basis in the record to

conclude that Grimes had taken a sufficient dose of Accutane to

produce cataracts. Dr. Lerman has not attempted to determine the

amount of Accutane that he claims reached Grimes' lenses. Nor

has he stated how much of a photosensitive drug must be present

in the lens to produce a cataract. Without such information, it

would not be possible to reliably opine that therapeutic doses of

Accutane cause cataracts simply because it is generally accepted

that unspecified doses of other photosensitive drugs produce

cataracts when they become photobound. See, e.g.. Reference

Manual, supra, at 201 ("[T]he expert should offer an opinion as

to whether the dose to which the plaintiff was exposed was

sufficient to cause the disease."). See also Turpin v. Merrell

analysis is an example of a scientific technigue that has valid scientific uses but is not properly used to prove causal association, much less individual causation"). Although Dr. Lerman testified about his research into Psoralan, another photosensitive drug which he claims produces cataracts, he did not claim that Accutane has a similar chemical structure to Psoralan. Thus, even if the identification of an SAR between the compounds could in some circumstances provide a reliable basis for drawing an analogy between the compounds, that technigue is inapplicable here.

14 Dow Pharmaceuticals, Inc.,

, 1360 (6th Cir. 1992)

(failure to indicate dose used in studies left analytical gap

between evidence presented and inference to be drawn about

whether therapeutic doses of medication caused the disease),

cert, denied, 113 S. C t . 84 (1992).

In summary, even if I were to assume that Dr. Lerman's

experiment is methodologically sound, I must still exclude his

opinion on general causation because the final essential step in

the formulation of that opinion is based on an untested

assumption which fails Daubert's reliability and fit

reguirements. Since his opinion on specific causation is

necessarily based on his opinion concerning general causation,

that testimony must be excluded as well. Accordingly, I grant

defendants' motions to exclude.

II. SUMMARY JUDGMENT

"Summary judgment is 'mandate[d] . . . against a party who

fails to make a showing sufficient to establish the existence of

an element essential to that party's case and on which that party

will bear the burden of proof at trial.'" Flanders & Mederios,

Inc. v. Boaosian, slip op. at 21-22 (1st Cir. Sept. 13, 1995)

guoting Celotex Corp. v. Catrett,

(1986).

15 Since it is undisputed that causation is an essential element of

Grimes' claims, see, e.g., LeFavor v. Ford,

(1992), and I have excluded the only evidence Grimes points to in

order to prove causation, defendants' summary judgment motion

must be granted.

CONCLUSION

Defendants' Motions in Limine to exclude Dr. Lerman's expert

opinion testimony (document nos. 38, and 41) and defendants'

Motions for Summary Judgment (document nos. 37 and 42) are

granted.12 The clerk shall issue judgment for the defendants.

SO ORDERED.

Paul Barbadoro United States District Judge September 28, 1995

cc: Edward Van Dorn, Esg. Michael Lehman, Esg. John D. Winter, Esg. John E. Friberg, Esg.

12 I did not rely on Dr. Dillon's testimony in reaching these decisions. Therefore, plaintiff's Motion to Exclude Portions of Expert Testimony of Dr. James Dillon (document no. 69) is deemed moot.

16