DeLUCA BY DeLUCA v. Merrell Dow Pharmaceuticals

• Decision Date: 11 May 1992
• Docket Number: Civ. No. 87-226 (GEB).
• Citation: 791 F. Supp. 1042
• Parties: Amy DeLUCA, an infant by her guardian ad litem, Cindy DeLUCA, and Cindy DeLuca and Ronald DeLuca, Plaintiffs, v. MERRELL DOW PHARMACEUTICALS, INC., et al., Defendants.
• Court: U.S. District Court — District of New Jersey

791 F. Supp. 1042

Amy DeLUCA, an infant by her guardian ad litem, Cindy DeLUCA, and Cindy DeLuca and Ronald DeLuca, Plaintiffs, v. MERRELL DOW PHARMACEUTICALS, INC., et al., Defendants.

Civ. No. 87-226 (GEB).

United States District Court, D. New Jersey.

April 29, 1992.

As Amended May 11, 1992.

Susan Scott, Riker, Danzig, Scherer, Hyland & Perretti, Morristown, N.J., Frank C. Woodside, III, Dinsmore & Shohl, Cincinnati, Ohio, for defendant Merrell Dow Pharmaceuticals, Inc.

John R. Connelly, Jr., Drazin and Warsaw, P.C., Red Bank, N.J., for plaintiffs.

OPINION

GARRETT E. BROWN, Jr., District Judge.

This action arises out of birth defects suffered by the plaintiff Amy DeLuca. Amy DeLuca brought suit through her mother and guardian ad litem, Cindy DeLuca, who with her husband, joined as plaintiffs in their individuals capacities. Plaintiffs allege that the birth defects (limb reduction) suffered by Amy DeLuca were caused by her mother's exposure to Bendectin, an anti-nausea drug produced by the Defendant Merrell Dow Pharmaceuticals, Inc. ("Merrell Dow").

PROCEDURAL HISTORY

By Memorandum and Order dated June 7, 1990, this Court granted defendant Merrell Dow's motion for summary judgment.¹ This Court held that the testimony of Dr. Alan Done, who was offered as an expert in pediatric pharmacology, was inadmissible because it was not based on data of a type reasonably relied upon by experts in the relevant fields as is required by Federal Rule of Evidence 703. Because Dr. Done's testimony was the only evidence offered by plaintiffs to show a causal link between Bendectin exposure and birth defects, the Court entered summary judgment in favor of Merrell Dow. DeLuca v. Merrell Dow Pharmaceuticals, Inc., 131 F.R.D. 71 (D.N.J.1990).

Plaintiffs appealed and the Court of Appeals reversed and remanded the action for further proceedings. DeLuca by DeLuca v. Merrell Dow Pharmaceuticals, Inc., 911 F.2d 941 (3d Cir.1990). The issues presently before this Court are three: (1) whether Dr. Done's testimony should be excluded under Rule 703 because the data upon which he relies are not of a type that experts in the field of epidemiology would rely upon, id. at 952-54; (2) whether Dr. Done's testimony should be excluded from evidence under Rule 702 on the grounds that (a) his methodology is unreliable, or (b) it would overwhelm, confuse or mislead the jury, id. at 954-57; and (3) if Dr. Done's testimony is admissible, whether under applicable New Jersey law the evidence relevant to causation would permit a jury finding that Amy DeLuca's birth defects were caused by her mother's exposure to Bendectin. Id. at 957-59.

Consistent with that opinion, this Court conducted a hearing held on five separate days, followed by extensive post-hearing submissions of the parties, in order to determine whether Dr. Done's testimony is admissible under the criteria set forth in United States v. Downing, 753 F.2d 1224 (3d Cir.1985). The record before this Court consists of written direct testimony submitted by the parties and oral cross-examination and re-direct examination of the witnesses. Plaintiffs' experts were Dr. Alan K. Done, M.D. and Dr. Shanna Swan, Ph.D. Defendants submitted the expert testimony of Dr. Richard R. Monson, M.D., Sc.D, Dr. Nicholas H. Wright, M.D., M.P.H., Dr. Steven H. Lamm, M.D., Dr. Gerald A. Faich, M.D., M.P.H., Dr. Pauline Brenholz, M.D. and Dr. Paul Stanley Lietman, M.D., Ph.D. This Opinion constitutes my Findings of Fact and Conclusions of Law.

FACTUAL FINDINGS

I. Causes and Incidence of Birth Defects

A. Causes of Birth Defects

1. The majority (approximately 65%) of birth defects in general are of unknown origin. Brenholz Direct at 3; Done Test., Tr. 7/10/91, at 29.

2. Possible causes of birth defects include genetic factors (chromosomal abnormalities or mutant genes) and environmental factors (diet, drug exposure, infections, x-rays and the like). Malformations may be multifactorial, meaning they are likely caused by a combination of genetic and environmental factors. Brenholz Direct at 4.

3. Genetic factors are etiological agents that initiate mechanisms of malformation by biochemical or other means at the sub-cellular level. Genetic factors typically are inherited or arise as a new gene mutation or new chromosomal abnormality, but do not necessarily manifest themselves in each pregnancy or in every generation. Brenholz Direct at 4.

4. Environmental factors, or teratogenic agents, may induce congenital malformations when the tissues and organs are developing. Brenholz Direct at 4.

5. The fact that a chromosomal study is normal does not rule out genetic defects. Medical science has not yet developed tests for most genetic defects. Brenholz Test., Tr. 9/19/91, at 78-79.

6. Family history is similarly not determinative, as recessive genes can be inherited from generation to generation, but do not manifest themselves unless there is a union with a partner who also carries the same recessive gene. There is a one in four chance that such a condition will appear. Brenholz Test., Tr. 9/19/91, at 79-80.

B. Incidence of Birth Defects

7. Congenital malformations are as old as recorded medical history. There have been countless instances of similar limb defects reported prior to Bendectin's first having been sold in this country in 1957. Since the time that Merrell Dow ceased the marketing of Bendectin, limb defects of the type suffered by Amy DeLuca have continued to be observed and reported. Brenholz Direct at 8.²

8. An analysis comparing the incidence of birth defects to the sale of Bendectin has shown that there is no association between the two. Lamm Direct at 5-6; Defendant's Ex. 50.³

9. Data collected by the Centers for Disease Control ("CDC") in Atlanta, Georgia show that after Bendectin ceased to be marketed (when Bendectin had been off the market for about three years) there was a slightly greater increase in birth defects than when Bendectin was prescribed in approximately 25% of all pregnancies. Wright Direct at 48; Defendant's Ex. 45.⁴

C. Evaluation of Possible Teratogens

10. Geneticists use the Catalog of Teratogenic Agents, written by Thomas H. Shepard, M.D., as a source of reference when consulting patients as to the probable outcome of a pregnancy. In the Catalog, Dr. Shepard characterizes substances as "proven", "possible" or "unlikely" teratogens. Bendectin is listed as "unlikely" to be a teratogen. Cigarette smoking is listed as a "possible teratogen." The question of whether an induced abortion affects subsequent pregnancies has been debated. Brenholz Direct at 5-6; Defendant's Ex. 51.⁵

11. Geneticists also use Reprotox, a computerized teratogen registry of the Reproductive Toxicology Center in Washington, D.C. Reprotox contains accurate, objective, comprehensive information regarding potential teratogenic agents and offers summaries of relevant and important articles. The registry states that animal and epidemiologic studies demonstrate no association between Bendectin and adverse pregnancy outcomes in general, and limb defects specifically. Brenholz Direct at 7; Defendant's Ex. 53.⁶

12. Dr. Done has offered no materials on teratogenicity which state to the contrary.⁷

13. Dr. Done has failed to explain how he himself ruled out Mrs. DeLuca's prior abortion and cigarette smoking as possible causes of Amy DeLuca's birth defects. Done Aff.; Done Test., Tr. 7/10/91; Brenholz Direct at 6-7.

14. Dr. Brenholz testified that pregnancy and smoking are always factors to be considered in determining the etiology of a birth defect. She also testified that a prior recent abortion and cigarette smoking could not be linked with a definite birth defect. Brenholz Test., Tr. 9/19/91, at 66-69.

II. Epidemiologic Studies on Bendectin

A. Principles of Epidemiology

15. Dr. Done placed emphasis in this case on epidemiologic studies, as there is almost universal agreement that the effects of drugs in human beings can best be evaluated by studying data concerning how those drugs did in fact affect persons who ingested them.

16. Plaintiffs originally relied secondarily on animal studies as well as epidemiologic studies. However, Magistrate Judge John Devine entered an order, which this Court affirmed on appeal, excluding from evidence all in vivo and in vitro animal studies. Plaintiffs have not challenged that ruling. Dr. Done also stated in his affidavit that he relied on structural activity considerations as well. His direct testimony, however, did not address this theory, but instead exclusively treated epidemiologic studies.

17. Epidemiologic studies typically express their results in terms of relative risks or odds ratios. The relative risk or odds ratio compares the rate of disease in the exposed population to the rate of disease in the unexposed population. If the two rates are the same, then the ratio is one. Where there is no association between exposure and disease, one would expect to find studies yielding relative risks grouped around the number 1.0 — some less than 1.0 and some more than 1.0. Monson Direct at 20-22; Wright Direct at 11-12.

18. The size of a study is one measure of its stability and power; thus, other things being equal, the larger the study, the greater its strength. Monson Direct at 22-24.

19. A confidence interval is a statistical calculation which provides information as to the stability of a relative risk calculation. A 95% confidence interval means that there is a 95% probability that the "true" relative risk falls within the interval. Monson Direct at 25; Wright Direct at 18. Most epidemiologists use a 95% interval; some use a 90% interval. Wright Direct at 21.

B. The Bendectin Studies

20. Bendectin is one of the most extensively studied drugs in history. Dr. Done listed forty-two entries on Table 1 included as part of Exhibit B to his affidavit. That list contained thirty-one published studies or reports on Bendectin, six studies that did not address...