Opinion ID: 1387894
Heading Depth: 1
Heading Rank: 2

Heading: was there evidence of breach of defendants' duty?

Text: Having established that the manufacturer of a prescription drug is under a duty to give adequate and timely warnings to the medical profession of any dangerous side effects of that drug of which the manufacturer has actual or constructive knowledge, we turn to the instant record and consider the question of whether there was sufficient evidence to permit the jury to find that defendants herein failed to satisfy that duty.
Because the ethical drug manufacturer has only the duty to warn the medical profession of those adverse effects of which it knows, or has reason to know, the adequacy of the warnings given by each defendant depends upon the actual and constructive knowledge of that defendant before and during the period in which Mrs. McEwen used its drug. For Syntex, the relevant interval began on December 3, 1966, when plaintiff first took Norinyl, and ended on December 20, 1967, when she changed to Ortho-Novum oral contraceptives. [13] From that date, plaintiff used Ortho-Novum until approximately December 22, 1968, and this is the relevant time span with reference to Ortho's knowledge. Before discussing the specific items of evidence considered by the jury, we reiterate that the Norinyl and Ortho-Novum pills taken by plaintiff were chemically identical and that the defendants shared information concerning adverse reactions resulting from use of these drugs. Numerous studies, reports and other documents were admitted into evidence and discussed by the expert witnesses. Some of these materials support Mrs. McEwen's contention that defendants knew, or should have known, of the dangerous propensities of their oral contraceptives during the time plaintiff was using them. Dr. Wendel, plaintiff's expert witness, [14] testified that three studies were undertaken in Great Britain during 1965-66 to determine whether a cause-and-effect relationship existed between the use of oral contraceptives and thrombosis, thromboembolism and other related vascular diseases. On cross-examination, Dr. Wendel testified that a preliminary report stating the results of these studies was published in the British Medical Journal on May 6, 1967, [15] and that this preliminary report was the final conclusive convincing evidence of a cause-and-effect relationship between the ingestion of oral contraceptives and such disorders. [16] Each defendant is held to have constructive knowledge of this report. O'Hare v. Merck & Co., supra 381 F.2d at 291. Another important investigation was the cooperative two-year oral drug safety study conducted by Ortho and Syntex. The purpose of this study was to determine the effects on rats of norethindrone and mestranol (the components of defendants' oral contraceptives). An interim report received in evidence reported the findings with reference to rats treated from December 31, 1965, to March 31, 1966. Dr. Wendel testified that this interim report indicated that defendants' oral contraceptives injured the rats' eyes, and that some of the lesions resemble, to me, very much the lesions found in the retinas of Mrs. McEwen. One of the rats treated with norethindrone experienced a local retinal hemorrhage. Also received in evidence was a 1965 article [17] stating the results of an inquiry into the occurrence of ocular disorders in women using oral contraceptives. Upon cross-examination, Dr. Wendel testified with reference to this report: Q Do you know of any article by any doctor that implicates oral contraceptives prior to January 1, 1969 with retinal hemorrhages or retinal occlusions? A The Walsh article, ja. Q The Walsh article does? A As I studied it, among his sixty or some patients there are nine which had ocular lesions which, in my opinion, resembled changes found in Mrs. McEwen. In addition to these studies, there was further evidence tending to show that each manufacturer had some knowledge during the relevant time periods of a connection between the use of its oral contraceptive and injuries such as those suffered by plaintiff. For example, the Norinyl package inserts [18] in effect during the period in which plaintiff took that drug included the following warnings: [19] CONTRAINDICATIONS[ [20] ] 1.    At this time Norinyl is not recommended in patients with thrombophlebitis or with a history of thrombophlebitis or pulmonary embolism.      WARNING Discontinue medication pending examination if there is sudden partial or complete loss of vision, or if there is a sudden onset of proptosis, diplopia or migraine. If examination reveals papilledema or retinal vascular lesions, medication should be withdrawn. The above-quoted admonition concerning loss of vision was added as a precaution to the November 1967 Ortho-Novum package insert. An additional precaution was added to the Ortho-Novum package insert dated December 1967: 10. Because of the occasional occurrence of thrombophlebitis and pulmonary embolism in patients taking oral contraceptives, the physician should be alert to the earliest manifestations of the disease. The same Ortho-Novum insert noted thrombophlebitis, pulmonary embolism and neuro-ocular lesions among the side effects observed in patients receiving oral contraceptives. That insert also stated that the clinical laboratory results of coagulation tests indicated that Ortho-Novum affected various characteristics of blood clotting. Finally, the June 1968 package insert for Ortho-Novum revealed the conclusion of the studies conducted in Great Britain and reported in April 1968 that there is a seven to tenfold increase in mortality and morbidity due to thromboembolic diseases in women taking oral contraceptives. The insert further warned the physician to be alert to the earliest manifestation of thrombotic disorders, including retinal thrombosis, and to discontinue the drug immediately if such disorders occurred or were suspected. This insert also stated that available evidence is suggestive of an association between the use of Ortho-Novum and [n]euro-ocular lesions, e.g., retinal thrombosis   . Viewing all the testimonial and documentary evidence in its entirety, there was substantial evidence that each defendant knew, or should have known, that its oral contraceptive had a dangerous propensity to cause the kind of harm suffered by plaintiff. [21] This is not to say that defendants did not produce substantial evidence tending to prove that they did not have such knowledge during the relevant times. [22] Our sole function, however, has been completed by our determination that reasonable men might differ upon the point. It was for the trier of fact to resolve the conflict.
With reference to the adequacy of defendants' warnings, the precise issue before us may be stated thus: Was there sufficient evidence for the trial court to permit the jury to decide whether reasonable warnings were given to the medical profession by each defendant concerning the pertinent dangers which that defendant knew, or should have known, were inherent in the use of its drug? We conclude that there was substantial evidence that the warnings of each defendant were inadequate and that the court properly allowed the jury to resolve the negligence question. We reach this conclusion by superimposing the warnings actually given over the dangers which were foreseeable by defendants. Although there are numerous methods available to the ethical drug manufacturer to communicate with the medical profession, [23] plaintiff and both defendants have focused primarily on the warnings in the relevant package inserts. Since neither defendant contends that it gave more complete information to doctors through any other means, we, too, will emphasize the cautionary instructions found in the inserts. However, before examining these warnings, we shall discuss defendants' contention that, as a matter of law, an ethical drug manufacturer discharges its duty to warn the medical profession merely by obtaining approval of its labeling from the Food and Drug Administration. Under this theory, the drug manufacturer could not be held liable if its warnings were commensurate with those required by the FDA, regardless of the scope of the manufacturer's knowledge of the adverse effects of its drug. Defendants rely chiefly upon the following language in Lewis v. Baker, 243 Or. 317, 324, 413 P.2d 400, 404 (1966), to support this theory:    We hold that    a drug, properly tested, labeled with appropriate warnings, approved by the Food and Drug Administration, and marketed properly under federal regulation, is, as a matter of law, a reasonably safe product.    (Emphasis ours.) Viewed in the context of the entire Lewis opinion, it is not clear that satisfaction of the requirement of appropriate warnings was to be achieved by mere compliance with the demands of the FDA. In any event, upon closer examination of the question, [24] we agree with the Supreme Court of California that [t]he warnings required by such agencies may be only minimal in nature and when the manufacturer or supplier knows of, or has reason to know of, greater dangers not included in the warning, its duty to warn may not be fulfilled. Stevens v. Parke, Davis & Co., supra 9 Cal.3d at 65, 107 Cal. Rptr. at 53, 507 P.2d at 661. We hold that the warnings given by an ethical drug manufacturer may be found inadequate, [a]lthough all of the government regulations and requirements have been satisfactorily met in the production and marketing of [the drug], and in the changes made in the literature   . Yarrow v. Sterling Drug, Inc., 263 F. Supp. 159, 162 (D.S.D. 1967), aff'd, 408 F.2d 978 (8th Cir.1969); accord Stromsodt v. Parke-Davis & Co., 257 F. Supp. 991 (D.N.D. 1966), aff'd, 411 F.2d 1390 (8th Cir.1969). See also Alman Brothers Farm & Feed Mill, Inc. v. Diamond Laboratories, Inc., 437 F.2d 1295 (5th Cir.1971). Lewis v. Baker, supra, insofar as it conflicts with this principle, is expressly overruled. Defendants, however, imply that the adequacy and timeliness of their package insert warnings were beyond their control, since the warnings were written by the FDA and required by federal law to be included in the inserts. Defendants overlook that portion of the Code of Federal Regulations specifically related to changes in drug labeling and advertising which notify the medical profession of a drug's untoward effects:   . (d) Changes of the following kinds    should be placed into effect at the earliest possible time: (1) The addition to package labeling, promotional labeling, and prescription drug advertising of additional warning, contraindication, side-effect, and precaution information. (2) The deletion from package labeling, promotional labeling, and drug advertising of false, misleading, or unsupported indications for use or claims for effectiveness.   . (e) It will be the policy of the Food and Drug Administration to take no action against a drug or applicant solely because changes of the kinds described in paragraph (d) of this section are placed in effect by the applicant prior to his receipt of a written notice of approval   . 21 C.F.R. § 130.9(d), (e) (effective Jan. 30, 1965). With reference to this amended version of 21 C.F.R. § 130.9, the following conclusion has been drawn: Prior to [the January 30, 1965] amendment [of § 130.9], the drug manufacturer could argue that the timeliness and the adequacy of the warning in a `Dear Doctor' letter was beyond its control  the FDA dictated when the letter would be sent and the final form that the warning would take   . In light of the above regulatory amendment [§ 130.9(d), (e)], the drug company should not be permitted to shift responsibility for the timeliness and the adequacy of warning letters to the FDA. 3 L. Frumer & M. Friedman, Products Liability 263-64, § 33.01(3)(c) (1960). Compliance with federal law did not prevent defendants from giving timely written warnings to the medical profession, either by means of Dear Doctor letters or through changes in their package inserts. [25] Moving to the adequacy of the warnings made by the respective defendants in their package inserts, the only inserts relevant to the liability of each defendant are those which were operative when that defendant's oral contraceptive was prescribed for and used by Mrs. McEwen. The warnings given by each defendant will be considered separately.