BROCK v. MERRELL DOW PHARMACEUTICALS, INC.

GARZA, Circuit Judge:

Mr. & Mrs. Floyd Brock filed suit in federal district court on behalf of their minor child, Rachel Brock, to recover damages for birth defects that allegedly resulted from Mrs. Brock's ingestion during her pregnancy of the anti-nausea drug Bendectin, which is manufactured by Merrell-Dow Pharmaceuticals, Inc. ("Merrell-Dow"). The Brocks obtained a jury verdict in the amount of $550,000 against Merrell-Dow, representing $240,000 in compensatory damages and $310,000 in punitive damages. Merrell-Dow appeals that verdict here, arguing that the Brocks did not present sufficient evidence to allow the jury to conclude that Bendectin caused Rachel Brock's birth defect. After reviewing the record and decisions of other courts confronted with similar suits regarding Bendectin, we hold that Merrell-Dow was entitled to judgment notwithstanding the verdict, and the judgment in favor of the Brocks is therefore reversed and the case will be dismissed.

Background

Mrs. Brock conceived Rachel Brock on or around July 2, 1981. On July 28, 1981, Mrs. Brock began to experience morning sickness, and she began to take Bendectin, a prescription drug manufactured by Defendant, Merrell-Dow.1 Rachel Brock was born on March 19, 1982 with a limb reduction defect known as Poland's Syndrome, which is recognized by a shortening or absence of fingers with a decrease in the corresponding pectoralis muscle on one side.

Mr. and Mrs. Brock filed a diversity suit against Merrell-Dow on behalf of their daughter in the U.S. District Court for the Eastern District of Texas. The complaint alleged theories of improper inspection, design defect, and failure to warn. Causation was a hotly contested issue, with both sides presenting expert testimony and studies regarding the possible teratogenicity2 of Bendectin. At the end of trial, Merrell-Dow moved for a directed verdict, arguing that there was no credible evidence tending to show that Bendectin causes birth defects. Merrell-Dow's motion was denied, and the issue of whether Bendectin caused Rachel Brock's birth defect was given to the jury. The jury found for the Brocks, and awarded both compensatory and punitive damages. Merrell-Dow then moved for judgment notwithstanding the verdict, and that motion was denied. Merrell-Dow here appeals the denial of its motions for directed verdict and for judgment notwithstanding the verdict.3

Standard for Determining Sufficiency of the Evidence

The standard for granting a judgment notwithstanding the verdict is the same as that governing rulings on directed verdicts: judgment notwithstanding the verdict is proper only when there can be only one reasonable conclusion drawn from the evidence. Dun & Bradstreet, Inc. v. Miller, 398 F.2d 218, 224 (5th Cir.1968). It is generally accepted that the court, in determining whether the evidence is sufficient to present a question for the jury, is not free to weigh the evidence, pass on the credibility of witnesses, or substitute its judgment of the facts for that of the jury. See Glazer v. Glazer, 374 F.2d 390, 400 (5th Cir.1967), cert. denied 389 U.S. 831, 88 S.Ct. 100, 19 L.Ed.2d 90; Alman Bros. Farms & Feed Mill, Inc. v. Diamond Lab, Inc., 437 F.2d 1295, 1298 (5th Cir.1971); Cardwell v. U.S., 186 F.2d 382 (1951); see generally 9 Wright & Miller, Federal Practice and Procedure Sec. 2524 (1971). Viewing the evidence in the light most favorable to the party against whom the motion is made, the court must give that party the benefit of all reasonable inferences from the evidence. Boeing Co. v. Shipman, 411 F.2d 365, 375 (1969).

These general and abstract formulations lose much of their usefulness, however, when we attempt to apply them to the concrete factual situation at hand. One certainly might infer from the evidence in the case that Bendectin causes birth defects, and further that Bendectin caused Rachel Brock's limb reduction defect — in fact, the jury concluded that this very thing occurred. However, the court must determine whether this is a reasonable inference to be drawn from the evidence presented, and the formulae provide us with little guidance as to what constitutes a reasonable, as opposed to unreasonable, inference that a jury could draw from the evidence.4 Ultimately, the "correctness" of our decision that there was insufficient evidence presented by plaintiff on the issue of whether Bendectin caused Rachel Brock's limb reduction defect to enable a jury to draw a reasonable inference may be just a matter of opinion, but hopefully the reasoning below will persuade others of the insights of our perspective.

This case is one of a series of many cases filed against Merrell-Dow by parents of children with birth defects allegedly caused by the ingestion of Bendectin during pregnancy. Academic commentators have dubbed this case and others like it "mass toxic torts."5 This represents a growing realization among academics, lawyers, and judges that cases such as this present special problems and challenges to traditional ideas regarding the role of the jury as a decisionmaker.

The first problem is that there is often no consensus in the medical community regarding whether a given substance is teratogenic; this is the case with Bendectin. Moreover, while we now recognize some of the many factors which can cause birth defects, medical science is now unable, and will undoubtedly remain unable for the foreseeable future, to trace a known birth defect back to its precipitating cause.6 The second problem, in addition to the problem of unknowability, is that juries are asked to resolve these questions, upon which even our brightest medical minds disagree, in order to resolve the case at hand and decide whether the plaintiff is entitled to recovery, and in so doing must necessarily resort to speculation.

Under the traditional approach to scientific evidence, courts would not peer beneath the reasoning of medical experts to question their reasoning.7 Confronted, as we now are, with difficult medical questions, courts must critically evaluate the reasoning process by which the experts connect data to their conclusions in order for courts to consistently and rationally resolve the disputes before them. Moreover, in mass torts the same issue is often presented over and over to juries in different cases, and the juries often split both ways on the issue.8 The effect of this is to create a state of uncertainty among manufacturers contemplating the research and development of new, and potentially lifesaving drugs.9 Appellate courts, if they take the lead in resolving those questions upon which juries will go both ways, can reduce some of the uncertainty which can tend to produce a sub-optimal amount of new drug development.

We are not without precedent in our approach to this problem. The case before us parallels in many respects the recently conducted Agent Orange Litigation.10 In those cases, plaintiffs attempted to prove that exposure to Agent Orange, a defoliant used during the Vietnam War, had caused them adverse health effects. Judge Weinstein granted summary judgment against opt-out plaintiffs on the basis that they had been unable to prove that exposure to low levels of dioxin caused their health problems. Although plaintiffs had provided the affidavits of experts indicating that exposure to Agent Orange had caused their health problems, the court attacked the reasoning of the experts and found it to be inadequate.11

Courts have not always been so willing to analyze the reasoning employed by experts to reach their conclusions. In Ferebee v. Chevron Chemical Co., 736 F.2d 1529 (D.C.Cir.1984), cert. denied 469 U.S. 1062, 105 S.Ct. 545, 83 L.Ed.2d 432 (1984), the District of Columbia Circuit considered the question of whether a fatal lung disease contracted by an agricultural worker was caused by his exposure to paraquat, a defoliant. Plaintiff presented two experts who expressed the opinion that paraquat had caused his illness, even though they admitted that cases like the plaintiff's were rare. The court denied defendant's motion for judgment notwithstanding the verdict, and in so holding, noted that "[j]udges ... have no special competence to resolve the complex and refractory causal issues raised by the attempt to link low level exposure to toxic chemicals with human disease. On questions such as these, which stand at the frontier of current medical and epidemiological inquiry, if experts are willing to testify that such a link exists, it is for the jury to decide whether to credit such testimony." Id. at 1534.

The District of Columbia Circuit retreated from this approach recently when it considered, in a Bendectin case, the very same issue we are addressing here. In Richardson by Richardson v. Richardson-Merrell, Inc., 857 F.2d 823 (D.C.Cir. 1988), the D.C. Circuit affirmed the lower court's grant of judgment notwithstanding the verdict to defendant. In its discussion of its approach to resolving the conflicting expert testimony in favor of defendant, the court opined that "[e]xpert witnesses are indispensible in a case such as this. But that is not to say that the court's hands are inexorably tied, or that it must accept uncritically any sort of opinion espoused by an expert merely because his credentials render him qualified to testify." Id. at 829. The court then proceeded to look behind the conclusion of plaintiff's expert and found his reasoning inadequate. In distinguishing Ferebee, the court narrowly interpreted the case to apply only where the causation issue is novel and "stands at the frontier of current medical and epidemilogical inquiry." Id. at 832. The Bendectin cases are different, opined the D.C. Circuit, in that there is a wealth of published epidemiological data, none of which has concluded that the drug is teratogenic. Thus, in Richardson, the court affirmed its willingness to look behind the conclusions of experts, at least in cases which are not at the frontier of epidemiological inquiry.12 We too, have chosen to take the same approach as the Richardson court, and in the next section we will present our analysis of the reasoning employed by the expert witnesses in this case.

Sufficiency of the Evidence Presented

Undoubtedly, the most useful and conclusive type of evidence in a case such as this is epidemiological studies. Epidemiology attempts to define a relationship between a disease and a factor suspected of causing it — in this case, ingestion of Bendectin during pregnancy. To define that relationship, the epidemiologist examines the general population, comparing the incidence of the disease among those people exposed to the factor in question to those not exposed. The epidemiologist then uses statistical methods and reasoning to allow her to draw a biological inference between the factor being studied and the disease's etiology.13

One difficulty with epidemiologic studies is that often several factors can cause the same disease. Birth defects are known to be caused by mercury, nicotine, alcohol, radiation, and viruses, among other factors. When epidemiologists compare the birth defect rates for women who took Bendectin during pregnancy against those who did not take Bendectin during pregnancy, there is a chance that the distribution of the other causal factors may not be even between the two groups. Ususally, the larger the size of the sample, the more likely that random chance will lead to an even distribution of these factors among the two comparison groups, unless there is a dependence between some of the other factors and the factor being studied. For example, there would be a dependence between variables if women who took Bendectin during pregnancy were more or less likely to smoke than women who did not take Bendectin. Another source of error in epidemiological studies is selective recall — i.e., women who have children with birth defects may be more likely to remember taking Bendectin during pregnancy than those women with normal children. Fortunately, we do not have to resolve any of the above questions, since the studies presented to us incorporate the possibility of these factors by use of a confidence interval. The purpose of our mentioning these sources of error is to provide some background regarding the importance of confidence intervals.

In this case, the parties described the results of epidemiologic studies in terms of two numbers: a relative risk and a confidence interval. The relative risk is a number which describes the increased or decreased incidence of the disease in question in the population exposed to the factor as compared to the control population not exposed to the factor. In this case, the relative risk describes the increased or decreased incidence of birth defects in the group of women who took Bendectin versus women who did not take Bendectin. A relative risk of 1.0 means that the incidence of birth defects in the two groups were the same. A relative risk greater than 1.0 means that there were more birth defects in the group of women who took Bendectin.

Just because an epidemiological study concludes that a relative risk is greater than 1.0 does not establish that the factor caused the disease. If the confidence interval is so great that it includes the number 1.0, then the study will be said to show no statistically significant association between the factor and the disease. For example, if a study concluded that the relative risk for Bendectin was 1.30, which is consistent with a 30% elevated risk of harm, but the confidence interval was from 0.95 to 1.82, then no statistically significant conclusions could be drawn from this study because the relative risk, when adjusted by the confidence interval, includes 1.0. Again, it is important to remember that the confidence interval attempts to express mathematically the magnitude of possible error, due to the above mentioned sources as well as others, and therefore a study with a relative risk of greater than 1.0 must always be considered in light of its confidence interval before one can draw conclusions from it.

The Brocks relied on a reanalysis conducted by Dr. Jay Glasser of the previously conducted Heinonen study. The Heinonen study, which was conducted by Professor O.P. Heinonen under the auspices of the U.S. National Institute of Neurological and Communicative Disorders, was based on over 50,000 pregnancy records collected in the United States. Dr. Heinonen, in analyzing these records, found that approximately 1,000 women had taken Bendectin during the first four months of their pregnancies. 63 of those women had infants with malformations as opposed to 3,200 out of 49,000 who had not taken Bendectin. This yielded a relative risk of 0.97 with confidence limits from 0.75 to 1.26. Therefore, this study does not support the proposition that Bendectin causes birth defects.

The Heinonen study considered as birth defects all malformations, of which limb reduction defects of the type experienced by Rachel Brock are a subset. Dr. Glasser's reanalysis of the data used in the Heinonen study only considered limb reduction defects. That study found a relative risk of 1.49. However, Dr. Glasser admits that the confidence interval was from 0.17 to 3; this renders the study statistically insignificant. The plaintiffs did not offer one statistically significant (one whose confidence interval did not include 1.0) study that concludes that Bendectin is a human teratogen. No published epidemiological study has found a statistically significant increased risk between exposure to Bendectin and birth defects. One of plaintiff's experts, Dr. Snodgrass, conceded that he was not aware of any such studies. Transcript at 198-99. Nor have any such studies been presented to the other two federal appeals courts which have considered this matter.14

Although we find Dr. Glasser's results inconclusive due to the fact that the confidence intervals include 1.0, we further note that Dr. Glasser has not published his study or conclusions for the purposes of peer review. While we do not hold that this failure, in and of itself, renders his conclusions inadmissible, courts must nonetheless be especially skeptical of medical and other scientific evidence that has not been subjected to thorough peer review. Clearly, "the examination of a scientific study by a cadre of lawyers is not the same as its examination by others trained in the field of science or medicine." Richardson, 857 F.2d at 831, n. 55 (quoting Perry v. United States, 755 F.2d 888, 892 (11th Cir. 1985).15

We find, in this case, the lack of conclusive epidemiological proof to be fatal to the Brock's case. While we do not hold that epidemiologic proof is a necessary element in all toxic tort cases, it is certainly a very important element. This is especially true when the only other evidence is in the form of animal studies of questionable applicability to humans. We are not the first court to emphasize the importance of epidemiologic analysis. For instance, in Heyman v. United States, 506 F.Supp. 1145 (S.D.Fl. 1981), which was one of the "swine flu" cases, the plaintiff had contracted Guillan-Barre Syndrome, allegedly caused by a swine flu innoculation under the National Swine Flu Immunization Program. In dismissing plaintiff's action for failure to prove that the swine flu vaccine caused her illness, the court held that "[g]iven the general inability of a physician to make accurate predictions of causation without at least some reference to epidemiological studies, plaintiff's position that her illness was caused by the swine flu shot amounts to nothing more than speculation." Id. at 1149.

The Brocks have also introduced animal studies in order to prove that Bendectin is a teratogen.

This circuit has previously realized the very limited usefulness of animal studies when confronted with questions of toxicity. In Gulf South Insulation v. U.S. Consumer Product Safety Comm., 701 F.2d 1137 (5th Cir.1983), we vacated a urea-formaldehyde ban on foam insulation promulgated by the Consumer Product Safety Commission ("CPSC"). The CPSC, which is prohibited from promulgating a safety rule unless it has substantial evidence that a product poses an unreasonable risk of injury, banned urea-formaldehyde based on a high exposure rat study which showed a heightened risk of cancer. The court noted several methodological flaws which rendered the rat study inconclusive; specifically, the court focused on the small number of rats used in the study, the high (sometimes near-lethal) doses given, and the difficulty of extrapolating those results to humans. Id. at 1146.

We need not address at length the animal studies presented by plaintiffs below, except to note several of the more important studies and their methodological flaws. The plaintiffs presented an in vitro study conducted by Drs. Hassell and Horigan. This study used cells cut from the limbs of mice and chickens which were then exposed to various test compounds, including Bendectin. According to plaintiff's experts, limb bud cells which normally form in six days were reduced if those cells were exposed to Bendectin; these limb bud cells ultimately form the arms and legs. However, Dr. Hassell himself cautioned that the body may break down doxylamine, the active ingredient in Bendectin, into a metabolic product which may differ from the pure test compound. Thus, human limb bud cells in a fetus may not be exposed to doxylamine, but rather the metabolic product of doxylamine. Moreover, extrapolation of these findings to humans cannot be done without knowing the dosage level and the corresponding drug level in the bloodstream of the mother. Transcript at 674. Taking the concept of metabolic products one step further, the plaintiff introduced the testimony of Drs. Snodgrass and Newman, who hypothesized that the human body breaks down doxylamine into less complex molecules called metabolites. These metabolites, some of which are negatively charged, are attracted to the relatively alkaline embryotic fluids, and ultimately bond with the cells in the embryo, producing tissue damage. Transcript at 629-30. However, both experts admitted that different species of animals metabolize chemicals differently, and that there are no studies which show that doxylamine is broken down by humans into toxic metabolites. Transcript at 181. Thus, we must view the limb bud tests as quite speculative.

Other plaintiffs' experts conducted animal tests and reanalyses of previously performed animal tests. Drs. Thiersch and Glauser both reanalyzed results of previous studies on animals. Both admitted that the results of their animal studies are difficult to extrapolate to humans. Dr. Thiersch admitted in his deposition that one must rely, in part, on epidemiological studies to determine whether a substance is toxic in humans. Similarly, Dr. Glauser admitted that the only way to tell whether a substance is teratogenic in humans is to look to the human experience.

Dr. McBride, another expert called by plaintiffs, conducted research in Australia, exposing white rabbits and marmosets to high doses of doxylamine — up to 500 times the normal human dose.16 13 of 18 of the rabbits died due to either the toxic effects of doxylamine or the improper insertion of gavage tubes which were used to administer the doxylamine to the rabbits. Of the marmosets, all four which were given high doses of doxylamine (500 times the human dosage) aborted their fetuses, and it was impossible to tell if those fetuses were malformed since the aborted fetus is generally eaten by the mother. Dr. McBride hypothesized that the abortions were the result of the teratogenic effect of doxylamine, rather than the high dosage. However, the fifth marmoset was given a lesser dose (100 times the human dosage), and two of the three fetuses later examined lacked a hind leg. On the basis of this, Dr. McBride concluded that doxylamine is a teratogen. He hypothesized that Bendectin, an anticholinergic drug, reduces the amount of acetylcholine, a neurotransmitter released by nerve cells, in the embryo. If the amount of acetylcholine in the embryo is diminished, the trophic effect on body growth is interfered with. Essentially, Dr. McBride speculated that the development of body tissue depends on the initial development of the nervous system. He cited another hypothesis, that of Professor Alexander Karczman, as supporting his theory of the anticholinergic action of doxylamine. However, the theory regarding the effects of doxylamine on acetylcholine, the nervous system and, ultimately, tissue development is nothing more than unproven medical speculation lacking any sort of consensus. Assuredly, one day in the future, medical science may have a clearer understanding of the mechanics of tissue development in the fetus. However, that is not the case today, and speculation unconfirmed by epidemiologic proof cannot form the basis for causation in a court of law.

In light of the evidence presented, we are convinced that the Brocks did not present sufficient evidence regarding causation to allow a trier of fact to make a reasonable inference that Bendectin caused Rachel Brock's limb reduction defect. We expect that our decision here will have a precedential effect on other cases pending in this circuit which allege Bendectin as the cause of birth defects. Hopefully, our decision will have the effect of encouraging district judges faced with medical and epidemiologic proof in subsequent toxic tort cases to be especially vigilant in scrutinizing the basis, reasoning, and conclusiveness of studies presented by both sides. However, we do not wish this case to stand as a bar to future Bendectin cases in the event that new and conclusive studies emerge which would give a jury a firmer basis on which to determine the issue of causation.

Accordingly, the judgment below is REVERSED and RENDERED, and the court below will enter an order of dismissal.