US Pharm. 32(11):44-46.

It should not be a surprise to practicing pharmacists in the United States that diethylstilbestrol (DES) should never be dispensed to pregnant women because of the risks of cancer and other debilitating diseases to adults who were exposed to the drug while still in the womb. Although this knowledge has been available for the past three decades, it continues to be relevant today because the adult DES sons and daughters continue to develop teratogenic effects and now even some adult DES grandsons and granddaughters are developing medical conditions linked to the use of DES.

DES was first prescribed in the 1940s by physicians as an off-label treatment to prevent miscarriages in women who had experienced previous miscarriages. On July 1, 1947, the FDA approved the first supplemental new drug application, adding the prevention of miscarriage as an indication and approving 25-mg tablets for this indication.1

It has been estimated that between 1938 and 1971 as many as 4 million women in the U.S. took DES.2 As early as 1953 it was known that DES did not prevent miscarriage and other pregnancy complications. Despite this knowledge, it was common for physicians in the U.S. to prescribe DES to pregnant women for this reason. In 1971, a correlation was recognized between in utero DES exposure and the development of clear cell adenocarcinoma of the vagina and cervix in the daughters of women who had taken DES during pregnancy.3 In that same year, the FDA issued a warning against the use of DES in pregnant women. Notably, DES continued to be used in various European countries until the early 1980s.4

Over the past few decades, courts have been asked to rule on the liability of the manufacturers of the drug to DES children and grandchildren. Not surprisingly, inquiries on these issues require going back into medical and pharmacy records from the 1940s and 1950s. Another complication is that DES was never patented, and as many as 200 manufacturers produced several different dosage regimens. Combined, these factors make it fairly difficult for the injured offspring to pick exactly which manufacturer made the formulation consumed by the mother or grandmother. Many cases were dismissed almost automatically for this reason.5 A recent case, however, sets the stage for a much different outcome.6

Facts of the Case
The plaintiff, born in August 1965, claimed that while her mother was pregnant with her, the mother was prescribed and consumed DES made by the defendant drug manufacturer, Eli Lilly, and that she suffered damages as a result of her exposure to DES in utero, including pregnancy complications, pregnancy losses, and infertility. The plaintiff stated that she was born in Chanute, Kansas, and has lived her entire life in Kansas. Her mother testified that from the second month of her pregnancy in 1964 until her daughter was born, she took DES as prescribed by Dr. Reuben Burkman. The mother said she always bought DES from the Baker and Burkman Pharmacy. The pharmacy was attached to the clinic building where Dr. Burkman practiced, and Dr. Burkman also owned the pharmacy. (An odd arrangement from today's perspective, but it was not uncommon four or five decades ago.) The mother said she took one small, round, red tablet four times a day.

In 1964 and 1965, Eli Lilly made and sold DES in a 25-mg strength in round, red, enteric-coated tablets. During those same years, Lilly's product information recommended a dosage of 25 to 100 mg per day for the prevention of "accidents of pregnancy." As noted above, it was common in that era to prescribe DES for the prevention of miscarriage. There was evidence that Dr. Burkman often prescribed the drug for such purposes.

In the spring of 1965, Dr. Burkman hired Joan Augustine as a full-time nurse in his clinic. She testified that she went into the pharmacy occasionally to "fix up" a prescription when the pharmacist was not present. She could not recall when she began helping with prescriptions, but knew she engaged in this activity for some prescriptions in 1965. While she could not recall preparing a prescription for the plaintiff's mother, or any other specific DES prescriptions for other patients in 1965, she did remember that the pharmacy stocked Lilly DES in little, red, enteric-coated tablets in 1965. She indicated that the pharmacy carried DES only from Lilly and that the pharmacy carried a lot of Lilly products. She could not recall specifically what dosage the Lilly DES tablet came in.

Ms. Augustine also remembered that Dr. Burkman always had a Physicians' Desk Reference (PDR) in each examining room. The court took judicial notice that the PDRs for 1964 and 1965 contained only Lilly's DES listing and did not mention any risk related to DES during pregnancy, either to the mother or the fetus.

Trial Court Proceedings
Eli Lilly asked the trial judge to dismiss the case for various reasons. The first was that the plaintiff could not prove that Eli Lilly was the manufacturer of the DES that her mother took. It offered evidence that in 1964 and 1965, there were at least 95 other American manufacturers of DES that made dosages in small, red, enteric-coated tablets. The court ruled that even if this was true, it was not relevant because the only credible evidence, provided by Ms. Augustine, was that the pharmacy stocked only Eli Lilly's brand of DES. The court noted that Ms. Augustine testified that Dr. Burkman commonly prescribed DES in 1965, that the pharmacy stocked Lilly's DES in 1965, and that the pharmacy carried a lot of Lilly products.

Eli Lilly next argued that there was no evidence that the pharmacy stocked its 25-mg DES product. The court disagreed and stated that while Ms. Augustine cannot recall specifically what dosage the Lilly DES tablet came in, her testimony did not exclude the possibility that Lilly's DES was available at the pharmacy in other dosages. The judge also noted that despite the nurse's uncertainty about the precise dosages of DES that the pharmacy dispensed, she recalls only Lilly DES on the pharmacy shelf, and she believes that the pharmacy carried DES only from Lilly. The judge concluded that with this testimony, combined with that of the plaintiff's mother that she took a red DES tablet in a 25-mg strength obtained from the Baker and Burkman Pharmacy, a reasonable jury could conclude that Lilly manufactured the DES that the plaintiff's mother ingested in 1965. The court therefore overruled this portion of the defendant's motion for summary judgment.

Eli Lilly also argued that its alleged failure to warn Dr. Burkman about the teratogenic effects of DES when taken by a pregnant woman was not the proximate or legal cause of the damages suffered by the plaintiff. The parties agreed that Kansas law would govern the legal proceedings. The products liability law in Kansas does require the plaintiff to provide evidence that a failure to warn was the proximate cause of her injuries. This law also establishes a rebuttable presumption of causation once the plaintiff establishes that a warning is inadequate. Here, said the judge, if the plaintiff proves that Lilly failed to provide a proper warning, Kansas law presumes that a doctor using that product would have heeded a proper warning.

The judge read the law to essentially presume that "but for the inadequate warning, the patient would not have been harmed, since the doctor would have given the patient an adequate warning if the doctor had ever received it, and that the inadequate warning is therefore the cause of the patient's injury." 6 Under this scheme, the defendant is given an opportunity to rebut this presumption by establishing that although the prescribing physician would have read and heeded the warning or additional information, the warning would not have changed the course of treatment. Put another way, the judge determined that if Eli Lilly provides credible evidence to rebut the presumption, the presumption disappears and the burden shifts back to the plaintiff to affirmatively prove causation. In any event, the judge determined that there was enough evidence to let a jury determine whether the information available in 1964 and 1965 was sufficient to have required the defendant to warn against prescribing DES to pregnant women.

Another interesting aspect of the lawsuit was that the plaintiff's husband sued Eli Lilly for his "loss of consortium." This is a legal term that, in essence, recognizes the right of a husband or wife to the company, affection, and help of, and sexual relations with, his or her spouse. Eli Lilly argued that the Kansas product liability law does not permit a loss of consortium claim under the facts of this lawsuit because in 1965, when the plaintiff was exposed to DES in utero, she was not married to her husband. The judge disagreed. He could not see why he should bar the plaintiff's loss of consortium claim when, at the time of marriage, the plaintiff's own claim had not accrued because she had not suffered ascertainable injuries. He also noted that although the plaintiff apparently suffered "substantial injury" in 1965 when she was exposed to DES, she may be able to show that she suffered additional injuries when she attempted to become pregnant after she married her husband.

At the end of the day, the judge denied all of the defendant's motions to dismiss the case and scheduled it for a jury trial. There have not been any reported results of whether a trial did occur or if the parties settled the case before the trial.

Analysis
How about the recall of that nurse from some 40 years ago? Her testimony was the only reason that this case did not get thrown out of court, as has been the outcome for thousands of cases just like this one. How the plaintiff or her attorney found this saving angel and got her fabulous testimony might be a story in itself.

Hindsight is always a wonderful teacher. But how much hindsight should be allowed in a courtroom? It is very easy today to recognize the scientific fact that DES is a teratogen and that giving this drug to pregnant women is wrong. It is much more difficult to accurately state the degree of knowledge about this issue 40 or 50 years ago. Consider for just a moment that none of the DES manufacturers back then knew any of this information and that the science of that era could not have reasonably predicted the harm to the unborn children of mothers who were given this drug. Part of the problem is that when the facts of a case like this are submitted to a jury, the jurors will be asked to forget what we now know and to presume that the medical community was clueless as to the dangers of this drug. Another aspect is that these same jurors are looking at the DES son or daughter or maybe even the grandchild who comes to court broken or diseased and completely innocent of ever having done something to have prevented their medical problems. Compared to the big, well-funded, and highly profitable drug manufacturers, it is not even a close bet on which party is going to get the sympathy vote. You can see the cogs turning in the minds of the jurors. Maybe the facts don't prove that Eli Lilly or any other drug producer knew precisely back then that this drug was a time bomb waiting to explode. Maybe the evidence isn't so great against the defendant, but the maker of this drug now knows it does bad things, and the company has lots of money. Compared to the injured and completely innocent plaintiff, the drug company won't even feel a pinch if the jury gives the plaintiff a few million bucks.

Put this way, it is perhaps a bit more palpable why judges have to be very careful about which claims will be submitted to a jury and which ones should be dismissed. Sympathy may be good for the soul, but it should never usurp legitimate evidence and the rule of law. Otherwise, we deteriorate the validity of the court system that Americans so cherish.

References

1. Dutton DB. Worse Than the Disease: Pitfalls of Medical Progress. Cambridge, MA: Cambridge University Press; 1988.

2. Schrager S, Potter BE. Diethylstilbestrol exposure. Am Fam Physician. 2004;69(10). Available at: www.aafp.org/afp/20040515/2395.html. Accessed October 21, 2007. Stillman RJ. In utero exposure to diethylstilbestrol: adverse effects on the reproductive tract and reproductive performance of male and female offspring. Am J Obstet Gynecol.1982;142:905-921.

3. Id.

4. Id.

5. See, e.g., Galvin v. Eli Lilly & Co., No. 05-7134, US Ct App Columba, 488 F.3d 1026; 2007 U.S. App. Lexis 13295, November 17, 2006. Argued, June 8, 2007, Decided, Rehearing, en banc, denied, by Galvin v. Eli Lilly & Co., 2007 U.S. App. Lexis 21094 (D.C. Cir., Aug. 29, 2007). Rehearing denied by Galvin v. Eli Lilly & Co., 2007 U.S. App. Lexis 21105 (D.C. Cir., Aug. 29, 2007); and Wood v. Eli Lilly & Co., No. 95-4924., US APP 11th Cir, 131 F.3d 1447; 1997 U.S. App. Lexis 36321; CCH Prod. Liab. Rep. P15,138; 11 Fla. L. Weekly Fed. C 892, December 29, 1997, Decided, as Amended January 15, 1998.

6. Baughn v. Eli Lilly, Slip Op No 03-2626-KHV (February 17, 2005), 356 F Supp 2d 1177; 2005 US Dist Lexis 2379.

 

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