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MEDICAL CAUSATION AND RELIABILITY
Recent cases concerning Parlodel, a lactation suppressant, demonstrate the Daubert
issues associated with admission of scientifically reliable medical evidence necessary to provecausation. Some courts have allowed expert opinions into evidence to establish a causal linkbetween Parlodel and acute myocardial infarction (AMI);i others have refused admission ofexpert medical evidence claiming a link between Parlodel and seizures or strokes.ii Analysis ofone of the Parlodel cases, Globetti v. Sandoz Pharmaceutical Corporation,
is helpful inevaluating a court’s determination of how it approached compliance with its Daubert
Mrs. Globetti suffered an AMI about six days after delivering her sixth child, having
taken Parlodel twice daily after the child’s birth to suppress lactation. Her overall health wasgood, she was not a smoker or overweight, and had “protective” (very low) cholesterol levels.
She had no history of high blood pressure and had never experienced hypertension duringpregnancy nor delivery. Angiography of her heart wall failed to reveal any thrombus, dissection,or occlusion of the coronary artery that could account for the AMI. Her initial treatingcardiologist concluded her heart event had been caused by a spasm of the coronary artery. Thiscardiologist knew of the possible association between Parlodel and AMI but opined Mrs.
Globetti’s heart spasm was spontaneous. Other treating cardiologists and retained expertsexpressed medical opinions the Parlodel contributed to the arterial spasm that caused the AMI.
The defendant pharmaceutical company (Sandoz) challenged these causation opinions bysummary judgment motion.
Sandoz contended the medical expert opinion of the plaintiff’s treating and retained
doctors was nothing more than unscientific speculation, excludable under Daubert
. According toSandoz, plaintiffs needed an epidemiological study showing an increased risk of AMI associatedwith Parlodel use for a sufficiently reliable scientific opinion to be admissible. Plaintiffsopposed the motion, arguing that epidemiological evidence was not needed since there wasplenty of scientifically reliable data from which a medical expert could conclude Parlodel cancause vasoconstriction sufficiently severe to cause AMI: animal studies, case reports, Food andDrug Administration Adverse Drug Reaction Reports (ADRs) and the generally acceptedopinion of the medical community that Parlodel is a risk factor for AMI since it causesvasoconstriction.
opinion began its analysis by noting the four Daubert
factorsiv were neither
exclusive nor exhaustive, that it remains for the trial court to determine what procedures arenecessary for it to analyze the admissibility of an expert’s opinionv and Daubert
supplementedthe old Frye
standard with a more “flexible” approach. Thus, the “gatekeeping” role of the trialcourt requires a practical recognition of what can be known and how it is known. Thegatekeeping role is to separate opinions supported by appropriate validation based on “goodgrounds” from simple subjective speculation masquerading as scientific knowledge. The courtwrote:
It is not part of the trial judge’s gatekeeping role to determine whether the
proffered opinion is scientifically correct
in the way one might think ofthe law of gravity. The gatekeeping role is addressed to mere evidentiaryadmissibility; it is the fact-finder’s role (usually a jury) to determine whether theopinion is correct or worthy of credence. For the trial court to overreach in thegatekeeping function and determine whether the opinion evidence is correct orworthy of credence is to usurp the jury’s right to decide the facts of the case. Allthe trial judge is asked to decide is whether the proffered evidence is based on“good grounds” tied to the scientific method.vii
Three of plaintiffs’ experts used the differential diagnostic technique, wherein the
physician lists the known possible causes of a condition or disease, usually from most likely toleast likely, then utilizes diagnostic tests eliminating causes from the list until left with the mostlikely cause. Diagnostic tests typically include physical examination, medical history, testing ofblood and other body fluids, MRIs, CAT scans, X-rays and other techniques for “falsifying” ahypothesis the disease came from a particular listed cause. The court recognized tests such asthese performed on Mrs. Globetti are scientifically accepted techniques for confirming oreliminating specific causes for her AMI. Thus, the court considered the doctors’ conclusion theAMI was caused by an arterial spasm to be well-supported.
The court then considered the quality of the next part in the causation opinion that the
spasm was caused by plaintiff’s ingestion of Parlodel. Experts for plaintiffs reasoned Parlodelhas vasoconstrictive characteristics and is capable of causing a coronary artery spasm and wasthe most likely cause of AMI in the absence of any other reasonable explanation. Sandozattacked this reasoning by claiming there was no reliable evidence Parlodel can causevasconstriction and plaintiffs’ experts were incorrect in concluding there were no other causes forMrs. Globetti’s AMI.
The court concluded plaintiffs’ experts based their opinion Parlodel can cause
vasoconstriction sufficiently severe to cause an AMI on sound scientific evidence andmethodologies. As foundation for their opinions plaintiffs’ experts cited animal studies of ergotalkaloids similar to Parlodel to have a vasoconstrictive effect; Sandoz acknowledged and reliedupon these studies in internal documents. Case reports and ADRs reported to the FDA wereconsistent with literature reviews that identified Parlodel as a risk factor for AMI in thepostpartum period. Also, several medical textbooks state that bromocriptine (the chemicalcompound from which comes Parlodel) is a risk factor for AMI in the postpartum period. Thesesources and others were more than adequate evidence from which a reliable conclusion could bedrawn about the association between Parlodel use, arterial spasm and AMI. Sandoz pointed outthere is no epidemiological study showing an increased risk of AMI associated withbromocriptine. This lack of study, according to defendant, was fatal to plaintiffs. The courtdisagreed. Plaintiffs argued and the court agreed that an epidemiological study of the associationbetween Parlodel and AMI is not practical because of the relative rarity of AMIs amongpostpartum women. The court wrote:
To gather a population of postpartum women with a sufficient sub-population ofthose who have suffered an AMI to be statistically significant would requirehundreds of thousands, if not millions, of women. The evidence suggests that
AMI occurs in postpartum women at the rare rate of 1 to 1.5 per 100,000 livebirths. Thus, even in a study of one million women, the sub-population of thosesuffering an AMI would be only ten to fifteen women, far from enough to allowdrawing any statistically significant conclusions. In short, the best scientificevidence available as a practical matter
is that presented by plaintiffs’ experts.viii
The court also commented on the ethical problems associated with experimenting on humanbeings just to satisfy an evidentiary standard. A control-group study would require administeringParlodel to women and exposing them to the possibility of strokes and heart attacks. Thus, forthe association between Parlodel and AMI or stroke to be scientifically established, a scientistmust expect a number of deaths to occur among the test subjects.
The court further noted although one can question the adequacy of the scientific evidence
relied upon by plaintiffs’ experts, the validity of the methodologies is adequate. Thus, the courtdenied the defendant’s motion for summary judgment on medical causation since there is reliablescientific information from which a reasonable scientific inference can be drawn that Parlodelcan cause vasoconstriction under circumstances of low vascular resistance and that suchvasoconstriction can cause arterial spasm to occlude a coronary artery leading to a myocardialinfarction.
iGlobetti v. Sandoz Pharmaceutical Corporation,
111 F.Supp. 2d 1174 (N.D. Alabama 2000);
Anderson v. Sandoz Pharmaceutical Corporation
, 77 F.Supp. 2d 804 (S.D. Texas 1999).
Hollander v. Sandoz Pharmaceutical Corporation
, 95 F.Supp. 2d 1230 (W.D. Okla. 2000);Glastetter v. Novartis Pharmaceutical Corporation
, 107 F.Supp. 2d 1015 (E.D. Mo. 2000); Brumbaugh v. Sandoz Pharmaceutical Corporation
, 77 F.Supp. 2d 1153 (D. Mont. 1999)
101 F.Supp. 2d 1174 (N.D. Alabama 2000).
These factors were testability, peer review and publication, assessing the known or potentialrate of error of the proposition, and whether it has found general acceptance in the scientificcommunity.
See Kumho Tire Company, Ltd. v. Carmichael,
526 U.S. 137, 119 S.Ct. 1167, 143 L.Ed. 2d 238(1999).
Frye v. United States
, 293 F. 1013 (1923).
101 F.Supp. 2d at 1177.
11th NAPRECA Symposium Book of Proceedings, Antananarivo, Madagascar Natural Products and Drug Discovery through a Network of Partnerships Philippe Rasoanaivo, David Ramanitrahasimbola, Dina Rakotondramanana, Voahangy Ramanandraibe, Suzanne Ratsimamanga Institut Malgache de Recherches Appliquées Abstract We present here relevant result obtained from a network of collaborations. Mala
Dr. Prasad S. Dalvi Designation: Associate Professor Email ID: [email protected] Phone No: +91 20 65101870 (Ext. 21) Qualification: MD, PhD Area of Specialization: Molecular Biology, Neurobiology, Physiology Academic Qualifications Ph.D. (Physiology) (2006 – 2012) Faculty of Medicine, University of Toronto, Canada Thesis title : Molecular Mechan