Compensation for Drug Injury

In 1957 Mr Greenman, an American, was working with a Shopsmith, a tool that could be used as a saw, a drill, and a lathe, when a piece of the wood he was working on flew out and injured him. About a year later he brought an action against the retailer, and the manufacturer, Yuba Products Inc. He claimed breach of both “implied” and “express” warranty and negligence. Express warranty is when a seller makes a specific promise about his products, such as “This drug has no known side effects.” Implied warranty is a warranty which the law reads into every sale whereby a seller represents that his products are of merchantable quality and reasonably fit for their purpose. Mr Greenman’s case against the retailer was not upheld, but the jury found against the manufacturer and awarded $65 000 damages. Both Mr Greenman and the manufacturer appealed. The Californian Supreme Court in 1963 upheld the lower court’s decision. Justice Traynor wrote in his judgment:

Compensation for Drug Injury, Product liability all dressed up American style, BRITISH MEDICAL JOURNAL VOLUME 282, NCBI PubMed, PMC1505432, 9 May 1981.

A manufacturer is strictly liable when an article he places on the market, knowing that it is to be used without inspection for defects, proves to have a defect that causes an injury to a human being…. The purpose (of imposing strict liability on manufacturers) is to insure that the costs of injuries resulting from defective products are borne by the manufacturers that put such products on the market rather than by the injured persons who are powerless to protect themselves…. To establish the manufacturer’s liability it was sufficient that the plaintiff proved that he was injured while using the Shopsmith in a way it was intended to be used as a result of a defect in design and manufacture of which the plaintiff was not aware that made the Shopsmith unsafe for its intended use.”

A plaintiff had to prove only that he was injured because of a defect in a product: he had no need to prove negligence on the part of the manufacturer. Thus strict liability in tort for product induced injury appeared in the United States.

Restatement of Torts

In 1965 the American Law Institute drafted the Restatement (Second) of the Law of Torts. Stimulated by the Greenman case it included the principle of strict liability for product induced injury in Section 402A, which states:

  1. One who sells any product in a defective condition unreasonably dangerous to the user or consumer or to his property is subject to liability for physical harm thereby caused to the ultimate user or consumer, or to his property, if:
    • (a) the seller is engaged in the business of selling such a product, and
    • (b) it is expected to and does reach the user or consumer without substantial change in the condition in which it is sold.
  2. The rule stated in Subsection (1) applies although:
    • (a) the seller has exercised all possible care in the preparation and sale of his product, and
    • (b) the user or consumer has not bought the product from or entered into any contractional relation with the seller.

Two comments on the section are particularly relevant to prescription drugs.

Where, however, the product contains an ingredient to which a substantial number of the population are allergic … the seller is required to give warning against it, if he has knowledge, or by the application of reasonable, developed human skill and foresight should have knowledge, of the presence of the ingredient and its danger… Where warning is given, the seller may reasonably assume that it will be read and heeded; and a product bearing such a warning, which is safe for use if it is followed, is not in defective condition, nor is it unreasonably dangerous.

There are some products which, in the present state of human knowledge, are quite incapable of being made safe for their intended and ordinary use. These are especially common in the field of drugs…. Such a product, properly prepared, and accompanied by proper directions and warning, is not defective, nor is it unreasonably dangerous.

Thus a manufacturer was liable for all injuries resulting from drugs not made to the design specifications even if he had taken as much care as possible. He was not, however, strictly liable in most cases when the drug was made exactly to design specifications yet still injured the patient. Only if he had failed to warn of a side effect that he should have known about was he liable, and this effectively was the same as negligence. Similarly, the manufacturer needed to warn only of side effects that were foreseeable in a “substantial number” of users. Some courts-particularly in California-have now begun, however, to move beyond the Restatement and find manufacturers liable in cases where the design of a drug was defective. The complexities of the law may be illustrated by considering a few cases.

Claims against manufacturers

If a drug is not manufactured to the design specification and it injures somebody the manufacturer will be liable under negligence, breach of implied warranty, and strict liability. Most manufacturers are willing to accept this kind of liability, and it presents few legal problems.

Design defect, when a drug is developed, then tested as fully as possible, manufactured to specification, yet injures people after being put on to the market, is the crucial issue in product liability. Drug manufacturers are usually willing to accept liability for production defects and failure to warn, but they balk at liability without fault for design defects. Lawyers and consumers also think that design defects are the most important, and after thalidomide, practolol, and now diethylstilboestrol (DES) this is where they have concentrated their reforming energy.

The Debendox case, which has received much publicity, is an example of a case over an alleged design fault. Debendox (sold as Bendectin in the United States) is an antinausea drug manufactured by Richardson-Merrell for use in pregnancy. It has been sold in the United States for 23 years, and an estimated 30 million pregnant women throughout the world have taken the drug. In the last two years, however, some people have suggested that the drug may cause congenital malformations. Many lawsuits have resulted, and although a panel of the Food and Drug Administration has agreed unanimously that there is no demonstrated association between Bendectin and birth defects, these suits continue.

The first case to come to court was that brought by Michael and Elizabeth Mekdeci in Florida in 1980. They alleged that their son David was injured by the drug, and they sued Richardson Merrell for $12m. The court’s decision was a peculiar one, and was interpreted by both sides as a victory. The jury decided that nothing should be awarded to the boy and no damages should go to the parents, but the parents should receive $20 000 for medical expenses. A Federal judge overturned this decision on the grounds that it was inconsistent: if the jury thought the drug caused the injuries they should have awarded damages, if they did not think it did they should not have awarded anything. The case was retried, and the jury agreed unanimously that the drug had not caused the injuries. Although the original decision was clearly illogical, it is easy to imagine the jury’s thinking: they were unconvinced by the evidence, but they thought that a rich drug company would not miss $20 000, which would help the boy and his parents enormously.

Diethylstilboestrol: America’s thalidomide?

The DES cases are the most recent and most interesting drug liability cases in the United States. They have excited some lawyers, who see the legal changes made by the cases as revolutionary, and they have worried the drug companies.

Stilboestrol was first synthesised in 1937 in Britain. It was the first synthetic, non-steroidal, oestrogen-like substance, could be taken orally, and cost about 1/300th of the cost of natural oestrogens. A patent was not applied for. A dozen drug companies in the United States tested the drug and applied to the Food and Drug Administration for a licence to market the drug for a variety of uses-none of which concerned pregnancy. Licences were granted in the autumn of 1941. At that time a drug application would usually contain reports on about 150-300 patients. Applications to market DES included reports on more than 5000 patients, none of whom were pregnant. Doctors knew, however, that high doses of any oestrogen could cause cancer in rats, and the warnings of some companies suggested that the drug should be avoided in patients with cancerous or precancerous lesions of the breast or cervix.

In 1947 the FDA began to give permission for the drug to be used in treating women with problem pregnancies, particularly those who had early miscarriages. In 1952 the FDA allowed any company to market DES without needing to make a further application. By 1953 148 companies were manufacturing the drug, and since then about 300 companies have marketed it; about a third of those companies no longer exist. DES gained its peak use in problem pregnancies in the early ’50s, but its use had fallen sharply by 1960, when progesterone became available. The drug is estimated to have been used in about 1 million pregnancies in America.

In 1971 Dr Arthur Herbst and others reported a statistical association between mothers being given DES in pregnancy and their daughters subsequently developing clear cell adenocarcinoma of the vagina and cervix.3 Dr Herbst set up a worldwide register of this cancer in young women. He reported in 1979 on the 284 cases he had collected. About two-thirds of these women gave a history of their mother taking DES during pregnancy. The cancer is linked with the drug, but as Herbst has said: “We have clearly stated that the occurrence of these cancers is not due to DES alone.” Also about 900) of the “DES daughters” had adenosis of the vagina and they were more likely to have had miscarriages. There may be an increased incidence of genitourinary abnormalities in male offspring, and it is anybody’s guess what the effects might be as the sons and daughters get older.

The first case against a manufacturer was brought in 1971, and there are now more than 500 lawyers concerned in DES suits. One typical case is that of Joyce Bichler. In 1953 Dorothy Bichler, Joyce’s mother, was given a prescription for DES for vaginal bleeding while pregnant. Nobody knows who made the drug she was prescribed. The doctor prescribed the drug because he had read about it in a medical journal and knew “gynaecologists all over the world” were using it.

Joyce Bichler was born normal and healthy in January 1954, but in 1971 she had cancer diagnosed and underwent hysterectomy and vaginectomy. In October 1974 she and her father brought an action against Eli Lilly and Company, the Bronx Lebanon Hospital Centre, and the doctor. In March 1975 they also sued the chemist who had sold Dorothy Bichler the drug, but this suit was dismissed in May 1978. The case against the hospital was dismissed in April 1977.

In 1979 the court set a date for the remaining trials, ordered that there should be a separate trial on whether Lilly made the drug that Dorothy Bichler took, and also allowed that the plaintiff could maintain her case against Lilly even if she could not prove that the company had made the drug. The doctor settled out of court for $30 000, and the trials started in May 1979. The first jury decided that Lilly did not make the drug. In a second trial the jury found Lilly liable and awarded $500 000 damages. The trial ended on 16 July 1979, and Lilly are now appealing.

The decision is remarkable in several ways. It seems to fly in the face of the law written down in the Restatement (Second) of Torts. Drugs are products which are regarded as “unavoidably unsafe” and a manufacturer is not liable for every injury. The manufacturer is required to give a warning, however, “if he has knowledge, or by the application of reasonable, developed human skill and foresight should have knowledge, of the presence of the ingredient and the danger.” Also, Eli Lilly were held liable even though it could not be proved that it had made the drug because it had acted “in concert with unidentified other drug companies” in the testing and marketing of DES.

In another DES case this year the Supreme Court of California decided that a woman, Judith Sindell, who claims to have been injured by DES (and does not know which company made the drug) can sue all the companies who have manufactured DES. The only precedent in tort law is a case in which a hunter was shot while out with two other hunters. The court then was sure that one of the two hunters was negligent but as it could not know which it found both liable. It does seem a big jump, however, from holding two people liable knowing that one was negligent to holding almost a whole industry liable. Indeed, there is an attempt in the Californian legislature to overturn the Supreme Court’s decision.

Many lawyers see the Californian decision as a legal breakthrough: several women have suffered awful injuries and they should be compensated; the drug companies make money out ofsuccessful drugs, and they should beprepared to compensate for damages; the question of fault is irrelevant-it is simply a case that the drug companies are best able to pay. The drug companies, however, see this as an awful decision. The costs will be enormous, they argue; drug prices will rise steeply; competition and innovation will be reduced; companies will go bankrupt; and also companies will stop producing unpatented drugs. That would mean an end to generic prescribing, something that the Federal government is trying to introduce.

Failure to warn

American case law seems to dictate that a drug manufacturer cannot be liable for a side effect that he has warned a doctor about. Nor could the manufacturer (at least before the DES cases) be liable for not warning about unforeseeable side effects. Variations in State law and individual court decisions have made for inconsistencies, however, as in other product liability cases.

Richardson-Merrell marketed MER/29, a drug for lowering blood cholesterol concentrations, in April 1960 without any warnings of serious side effects. In mid-1961 the company produced a warning about possible hair loss and in December 1961 they added warnings about the possibility of eye damage. The company had, however, known about blindness in rats receiving high dosages since October 1960. The first human cases were reported in October 1961.

Some 5000 people were injured, but only 1500 filed suits, and of the five reported cases the plaintiff won in only two. Mr Toole took the drug from July 1960 until December 1961 and developed cataracts in both eyes. A Californian court in 1969 found for Mr Toole and awarded him $250 000 on the grounds of negligence in failing to adequately test the drug, failure to provide adequate warnings, fraud, and breach of express and implied warranty.

Mr Cudmore in Texas, however, got nothing for the same injuries. The court ruled that the manufacturer had no duty to warn unless “foreseeable” harm would result to “an appreciable number of persons.” Mr Lewis in Oregon also got nothing and the court ruled that: “We held that upon such facts a drug, properly tested, labelled with appropriate warnings, approved by the Food and Drug Administration, and marketed under federal regulation, is as a matter of law, a reasonably safe product.”

This raises another fundamental issue: does a Government licence mean that a drug has by definition been adequately tested ? The drug manufacturers think that they are caught in a double bind: they must spend a great deal of time and money to fulfil the FDA licensing criteria but in most States this gives them no legal protection if a serious side effect is subsequently discovered.

Claims against prescribing doctors

In the United States injured people who are seeking compensation will commonly sue everybody possible. If they think that they have a good case against a drug company they will concentrate their energies there. Doctors are not involved when there is a defect in the drug or in the manufacturer’s warnings.

But claims are upheld against doctors in an inconsistent way for the following reasons: failing to follow the manufacturer’s labelling; ignoring contraindications; ignoring warnings against method of use; ignoring recommended dosage; using the wrong drug; and failing to obtain informed consent.

Some of these forms of liability will not seem outrageous to British doctors, but I want to dwell a little on following the manufacturer’s instructions and informed consent. Some British doctors are worried that if new product liability legislation is introduced they will have to follow manufacturers’ instructions strictly to avoid litigation. But this is not the case in the litigious United States. The AMA has said: “Drug labelling may have evidentiary weight for or against a physician, but the evidence is subject to refutation; drug labelling, per se, does not set the standard for what is good medical practice.” Another worry of some British doctors is that they will be obliged to tell patients of every conceivable side effect to avoid litigation. Again, this is not the case in the United States. The Americans do have a law of informed consent, but as George J Annas has written in the New England Journal of Medicine:

Perhaps the legal profession has been derelict in its exposition of the doctrine of informed consent, but it strikes me as almost incomprehensible that any physician would believe he had to “persist with a potentially frightening dissertation for ‘legal reasons“‘ in the face of a patient who protests that he does not want to hear it. This situation, of course, would be easily understood without reference to legal authority by anyone who understood the primary purposes of the informed-consent doctrine; to protect the patient’s right of self-determination, and to promote rational decision making. The first means that a patient’s expressed desire not to be told about risks should be honoured and the second that if the physician can document that risk disclosure will make the patient too ill or emotionally distraught as to foreclose a rational decision, no such disclosure need be made.

Even in the United States a doctor is not legally required to tell his patient everything.

Richard Smith, 1981

Click to download the full study.

More DES DiEthylStilbestrol Resources

The DES Cases and the Problem of Proving Causation

In January and February of 1976, army personnel at Fort Dix, New Jersey, became ill with flu-like symptoms. When studies showed a viral infection similar to the one responsible for the 1918-1919 Swine Flu pandemic, President Ford (and others) urged the appropriation of emergency funds for a nationwide influenza immunization program. Congress hurriedly appropriated $135,064,000, but problems developed almost immediately. One of the four manufacturers of the vaccine produced the wrong strain, and distribution was delayed. All four manufacturers raised liability insurance concerns and were unwilling to provide any vaccine without adequate insurance coverage. Concern arose that the mass-immunization program would not begin before the influenza season.

Mass immunization under The Swine Flu Act

The Congressional Response

Liability in Mass Immunization Programs, BYU Law Review, Volume 1980 | Issue 1 Article 6, s, 1980 BYU L. Rev. 69 (1980).

President Ford’s active involvement as well as the publicity associated with the mysterious outbreak of Legionnaires Disease in Philadelphia in July 1976, may have provided the needed stimulus for congressional action. The Swine Flu Act-provided the necessary assurance to the drug manufacturers by making lawsuits against the government the exclusive remedy for all actions connected with the Swine Flu program. The Act was passed precipitously, but not without concern that it could create an undesirable precedent. The United States accepted liability “for personal injury or death arising out of the administration of swine flu vaccine under the swine flu program and based upon the act or omission of a program participant in the same manner and to the same extent as the United States would be liable in any other action brought against it under the Federal Tort Claims Act.

Although the government cannot be held strictly liable under the Federal Tort Claims Act: the flu statute contained an exception: the liability of the United States could “be based on any theory of liability that would govern an action against such program participant under the law of the place where the act or omission occurred, including negligence, strict liability in tort, and breach of warranty. “Program participant” was to mean the manufacturer or distributor of the vaccine, and the public or private agencies, organizations, and medical personnel who provided swine flu inoculations without charge and in compliance with the informed consent form and procedures. The government also agreed not to invoke the “discretionary” act exemption of the Federal Tort Claims Act. Furthermore, if the swine flu action was brought within two years of the date of inoculation and was dismissed for failure to file an administrative claim, a plaintiff was given the longer of thirty days after dismissal or two years from the date the claim arose to file an administrative claim. The remedy against the United States was exclusive, and the case was to be tried without a jury as under the Federal Tort Claims Ac. Notwithstanding any provision of state law, the United States was entitled to indemnity against any program participant whose failure to carry out a contract with the government or whose negligence caused the injury.

A key concern addressed in the Act was the development of “a written informed consent form” with accompanying procedures, to assure that the risks and benefits from the swine flu vaccine were fully explained to each individual to whom the vaccine was to be administered. The Secretary of Health, Education, and Welfare (HEW), in consultation with the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, was directed to draft and implement this form.18 Notably, the consent form that was developed did not specifically warn of the possibility of contracting Guillain-Barre disease, a neurological disorder. After describing the influenza and the vaccine, the form included a paragraph entitled “Special Precautions,” which stated: “as with any vaccine or drug, the possibility of a severe or potentially fatal reaction exists. However, the flu vaccine has rarely been associated with severe or fatal reactions.” The vaccinee, or his guardian, signed in two places to affirm that he had read the statement about swine flu and the special precaution. A second form indicating that legal remedies were available against the United States Government was also distributed.

The Act required the Attorney General to defend all claims arising out of the swine flu program against federal government employees or program participants and their insurers. Upon certification of the Attorney General, the United States was to be substituted as party defendant and the action removed to the appropriate federal district court. However, a program participant could lose its protected status if it failed to cooperate with the government in processing or defending a claim. If this occurred, the court was required to substitute that party as defendant in place of the United States, and upon motion, remand any such suit to the court in which it was instituted. Of course, status as a program participant required that the public or private agency or health personnel provide the inoculation without charge and in compliance with the informed consent procedures.

The Guillain-Barre Litigation

Public concern about the safety of the vaccine and skepticism of the need for the program plagued the mass immunization efforts. After reports of suspected association between the swine flu vaccine and Guillain-Barre syndrome, the program was halted in December 1976. Under the provisions of the Federal Tort Claims Act, as incorporated in the Swine Flu Act, a claim had to be filed within two years after accrual.26 For nearly all claimants the accrual date would be the date of inoculation or shortly thereafter; hence, the filing deadline for most claimants would have been within a short period after December 1978.

As of December 1979 a total of 912 suits had been filed against the United States for $1,150,000,000 in damages. Of these suits, 814 have been consolidated for pretrial procedure in the District of Colombia. Four hundred and ninety-four of the claimants allege Guillain-Barre syndrome, 121 allege other neurological disorders, and 252 claim non neurological disorders. Forty-five deaths are alleged to have occurred as a result of Guillain-Barre. As of December 1, 1979, 3,813 administrative claims had been filed for a total of $3,417,000,000 in damages. Of these claims, 118 have been paid (settlements totaled $3.7 million), 1,580 have been denied, and 102 have been closed (withdrawn or abandoned by the claimant).

On June 16, 1978, HEW Secretary Califano announced that claimants for federal compensation would not need to prove negligence by Federal workers or others in the Swine Flu program as required by Federal law and the law in many state. Most claimants could therefore recover by showing that they developed Guillain-Barre as a result of the vaccination and that they consequently suffered the alleged damages. The Secretary adopted the policy for two related reasons. The first was that the consent form had neither warned individuals that there was a “one in one hundred thousand” risk that a person would contract Guillain-Barre, nor that “one in every two million” would die from the condition. The second was that the federal government, in an unprecedented effort, had actively urged Americans to be vaccinated. The Secretary emphasized, however, that this policy did not apply to any non-Guillain-Barre cases arising under the swine flu program, or to claims arising under any other government sponsored or supported immunization program.

Scope of Government and Manufacturer Liability

To date, constitutional attacks on the Swine Flu Act have been made in four reported cases. The statute has been attacked as being violative of due process, equal protection of the laws, the seventh amendment right to trial by jury, and the tenth amendment reservation of power to the states. Nevertheless, the constitutionality of the Act has been upheld in all the cases.

Before enactment of the federal liability legislation, some states, led by California, had adopted legislation exempting participants (licensed health professionals or facilities) from liability unless their behavior involved willful misconduct. In a recent swine flu case, the California statute was upheld despite claims that it involved special legislation, fostered economic discrimination, and violated the supremacy clause.36 When the federal legislation assumed its present form, the federal government was to be liable only if a private person “would be liable to the claimant in accordance with the law of the place where the act or omission occurred.” Therefore, in states like California, those injured by negligence during the administration of the program may receive no compensation.

Claims brought directly against the vaccine’s manufacturers have been similarly unavailing. An argument made in such efforts to sue the manufacturers directly is that the signing of an informed consent form is a sine qua non of the Act’s operation. This, however, is troublesome in view of the fact that an estimated 13% of those vaccinated may never have signed any form. In a recent case, the plaintiff, a doctor who had inoculated herself without signing the form, argued that because she had not signed the form her case fell outside the scope of the Act. The court refused to hold that drug manufacturers were required to comply with the informed consent procedures before they could be considered program participants. In dictum, however, the court stated that it was “arguable” that program participant status might not be conferred on an inoculating agency or other health personnel absent such compliance.

The full range of injuries to be compensated under the provisions of the Act remains undetermined. The language used by Congress is very broad, referring as it does to personal injury or death arising out of the administration of swine flu vaccine under the swine flu program and based upon the act or omission of a program participant. The Act further provides that “liability” may be based on any theory that would govern an action against such program participant under the law of the place where the act or omission occurred, including negligence, strict liability in tort, and breach of warranty. Injuries resulting from negligently broken or unsterilized injectors, or from negligently administered inoculations, would certainly be covered in those jurisdictions where negligence is actionable, but other situations are less certain. For example, a pending case alleges that the plaintiff fainted while leaving the building in which she had received a swine flu vaccination. Her fall resulted in several chipped teeth. If she merely tripped over a step, or had fallen on her way into the building, her injury could arguably fit within the broad language of the Act. Another injury arguably within the scope of the Act is negligently inflicted emotional distress. Many jurisdictions recognize the tort, especially where the requisite “impact” has been alleged. The inoculation itself would surely be sufficient impact.

Liability of Drug Manufacturers

During the Senate debate on the proposed swine flu legislation, many were made uneasy by the fact that the insurance companies viewed the risks of the program as being too great to insure against. A brief review of recent cases involving the liability of drug manufacturers in regard to ethical drugs suggests that the concern was not unfounded.

Drug Liability and the Duty to Warn

A claimant in any product liability action usually has a choice of several legal theories. Depending on the law of the jurisdiction and on the facts of the case, a plaintiff may proceed on theories of negligence, breach of warranty (implied or express), strict liability in tort, or misrepresentation. Obviously, practical considerations regarding evidentiary matters, the relevant statute of limitations, available defenses, and the availability of punitive damages, may well make one theory preferable to another. But often, the pleadings are couched in the alternative. The claimant with a drug related injury is no different from other plaintiffs in that he must allege one of the above legal theories in order to be heard and must establish the elements of his case in order to prevail. To date, the concept of no-fault recovery for drug-induced injuries urged by several legal scholars, particularly in mass immunization cases:= has been resisted in this country. The courts have also been unwilling to hold manufacturers “absolutely liable,” rejecting the theory that the production of drugs is an ultrahazardous activity.

The ethical-drug manufacturer has a duty to test and develop the drug properly,47 to comply with all government regulation : to keep abreast of developments in regard to the drug and to warn of side effects-a troublesome responsibility in recent years.

In the case of prescription drugs, a warning to the doctor is ordinarily held to satisfy the manufacturer’s duty. For a breach of that duty, the manufacturer is directly liable to the patient. It has been said that the manufacturer’s compliance with this duty enables the prescribing physician, the learned intermediary between the purchaser and the manufacturer, to balance the risk of possible harm against the benefits to be gained by the patient’s use of the drug. The rationale is that if the doctor is properly warned there is an excellent chance that injury to the patient can be avoided. This is particularly true if the injury takes place slowly. The duty to warn the medical profession is not measured in all cases by quantitative standards. In some circumstances, the manufacturer may have a duty to warn those few persons it knows will be injured by the drug’s side effect. Furthermore, the warning has to be brought home to the doctor undiluted by overpromotion of the drug.

A further controversial and unresolved question is whether a drug manufacturer may be held liable for failure to warn of unforeseeable risks, or whether its liability for failure to warn is limited to those risks which it knows or has reason to know are inherent in the use of its drug. In a recent case, Hamilton u. Hardy, the two theories were distinguished by the Colorado Court of Appeals. Finding error in the trial court’s refusal to instruct the jury on strict liability for the defendant doctor’s failure to warn concerning the dangers of Ovulen, the court remarked that the evidence which proves a failure to warn is the same under both theories, but refused to find the theories identical.

Under strict liability, the test is whether the failure of Searle to adequately warn of the potentially dangerous propensities of its product rendered that product unreasonably dangerous. It is of no import whether the drug manufacturer’s warning comported with the warning a reasonably prudeht drug manufacturer would have given. Strict tort liability shifts the focus from the conduct of the manufacturer to the nature of the product.

The court proposed the following test to determine whether the evidence submitted warranted a finding for the plaintiff:

A way to determine the dangerousness of the article, as distinguished from the seller’s culpability, is to assume the seller knew of the product’s propensity to injure as it did, and then to ask whether, with such knowledge, he would have been [acting unreasonably] in selling it without a warning.

The opposing view was articulated clearly by the Michigan Supreme Court in the recent case of Smith v. E. R. Squibb & Sons, Inc. The plaintiffs deceased wife suffered a rare anaphylactic reaction when the defendant’s product, Renografin-60, was injected into her blood stream. Breach of implied warranty and negligence were pleaded, but the trial court refused to instruct the jury regarding the warranty theory. The supreme court affirmed, commenting:

When the factual issue is not whether the product itself is defective, but is whether the manufacturer has provided adequate warnings, the existence of a product defect and a breach of duty is determined by the same standard-reasonable care under the circumstances… …  Consequently, when liability turns on the adequacy of a warning, the issue is one of reasonable care, regardless of whether the theory pled is negligence, implied warranty or strict liability in tort.

It has been held that the manufacturer’s duty to warn the medical profession extends beyond the prescribing physician. In a case involving oral contraceptives, the Oregon Supreme Court stated:

It is especially important that the treating doctor receive the manufacturer’s warning where it is impossible to predict in advance whether a particular patient is apt to suffer adverse effects from a drug, since the treating doctor may be more likely to observe the actual symptoms of the drug’s untoward consequences… … The warning should be sufficient to apprise the general practitioner as well as the “unusually sophisticated medical man of the dangerous propensities of the drug.

The Polio Cases and the Duty to Warn

Several recent cases involving polio vaccines have further delineated the drug manufacturer’s duty to warn, and in so doing have greatly alarmed the drug industry. The original polio vaccine was the Salk vaccine (dead virus). Later the Sabin oral vaccine was developed, as types I, II, and III. The Sabin vaccine was licensed by the Division of Biologic Standards (DBS), which was then a part of HEW. In 1960 an advisory committee was established by the Surgeon General to review polio prevention. After a showing of some association between the type I11 Sabin polio vaccine and the development of polio in adults, the advisory committee recommended in 1962 that the vaccine’s use be limited to children in nonepidemic situations. The committee further recommended that the type I11 vaccine only be used for adults with the full recognition of its minuscule risk (estimated to be about 7.6 per million for persons over twenty years of age). The manufacturers sold their vaccines to mass immunization clinics that were often established with the assistance of drug salesmen. In most instances, no warnings were given, and doctors did not individually evaluate a person’s need for the drug.

In Davis v. Wyeth Laboratories, Inc, the plaintiff contracted polio thirty days after receiving a type III Sabin vaccine in a Montana clinic. A pharmacist had been delegated the task of administering the vaccine in the absence of a doctor. The court considered the manufacturer’s alleged failure to warn the plaintiff of the risk as sufficient to expose it to strict liability in tort. Since the vaccine presented a known risk that could not be narrowly defined, it could be properly marketed only by full disclosure of the existence and extent of the risk involved. The court observed that the risk of the plaintiff contracting polio from the wild virus was about the same as the risk of contracting polio from the vaccine. Even though Wyeth had technically warned the medical society, it failed in its responsibility since it knew that the drug was not dispensed as a “prescription drug” and that the warnings were not reaching the consumer. The court suggested means of communication the manufacturer could have undertaken, such as advertisements, posters, oral warnings, or releases to be read and signed by recipients of the vaccine.

In Reyes u. Wyeth Laboratorie , an eight month-old child given trivalent vaccine at a health clinic in a rural Texas community developed polio. The mother had been given no warnings by the registered nurse who administered the vaccine. Although the defendant contended that there was an epidemic of wild polio in the county at the time the child became ill, and that Samples of the virus taken from the child upon admission to the hospital were “probably wild, 70 the jury found that the vaccine caused the child’s polio. The court established two tests whereby a manufacturer would be liable: (1) whether the product was so unsafe that its marketing alone was “unreasonably dangerous per se,” or (2) whether the product was marketed without sufficient safeguards and was therefore “unreasonably dangerous as marketed. Because of the legitimate public interest in preventing polio, marketing the vaccine was held to be justified. However, under the circumstances of the vaccine’s administration, where no individualized medical judgment intervened between the manufacturer and the ultimate consumer, the manufacturer was “required to warn the ultimate consumer, or to see that he was warned. The court postulated a rebuttable presumption that the consumer would have read any warning provided by the manufacturer, and acted so as to minimize the risks.

The fifteen year old patient in Cunningham v. Charles Pfizer & Co. was given the type I Sabin vaccine in a Tulsa, Oklahoma clinic and subsequently developed polio. The defendant claimed there was no evidence that the plaintiff would have refused to take the vaccine had the warnings been given to him or to his parents. The court held that the plaintiff was not required to present any direct evidence on this point and was entitled to a rebuttable presumption. In view of the fact that there was considerable risk of contracting polio from natural sources at the time the vaccine was given (twelve cases of polio occurred in Tulsa during October and November 1962, two months before the plaintiffs inoculation), the court concluded that the issue of whether the plaintiff as a reasonably prudent person would have refused to take the vaccine had adequate warning been given was for the jury.

In Givens v. Lederle, the plaintiffs young daughter was given an oral vaccine by her pediatrician. The mother, who had never received a polio vaccination of any kind, developed polio within nine days of her daughter’s ingestion of the third dose of vaccine. On the insert packaged with the vaccine, the defendant Lederle had stated that:

Para1ytic disease … has been reported … in some instances, in persons who were in close contact with subjects who had been given live oral polio virus vaccine. Fortunately, such occurrences are rare, and it could not be definitely established that any such case was due to the vaccine strain and was not coincidental with infection due to naturally occurring poliomyelitis, or other entroviruses.

Mrs. Givens had received no warnings from her pediatrician. At the first trial, the judge had kept the jury from hearing evidence on the issue of whether oral vaccine can cause polio. After the Reyes decision, the court reversed itself and granted the plaintiffs motion for a new trial. In turn relying upon Reyes, the reviewing court upheld the lower court’s action, and stated that in Reyes it was not a significant factual distinction that the vaccine had actually been ingested by the plaintiff, because the defendant’s “warning” admitted that some persons in close contact with vaccinees had developed paralytic diseases. The only issue was whether polio could be transmitted to someone in close contact. Testimony showed that a mother changing her baby’s diapers would be particularly susceptible to contracting the disease. In addition, because administration of the vaccine by a private pediatrician rather than personnel in a county health clinic, was not “nearly so great” a difference as the defendant had argued it to be, the manufacturer’s duty to warn the patient extended to this situation. The doctor testified that the vaccine had been administered in a manner more similar to procedures followed at a small health clinic than to normal procedures used in prescribing drugs. If this was true, then the defendant was responsible for taking definite steps to warn the consumer directly. Even if the drug were considered a prescription drug, the court found that the enclosed warning did not adequately state the risk. The doctor testified that the manner of stating the one in three million risk was a “very nebulous way of putting it.

Thus, the drug manufacturers duty to warn has been extended beyond the prescribing physician to the entire medical community. How this warning is to be communicated to doctors specializing in different areas of medicine is not clear. Furthermore, in the absence of a learned intermediary, the warning must be given to the patient himself, and sometimes even to a third party. In Givens a close relative was allegedly harmed, but the court did not limit its holding to close relatives. Therefore, the scope of the duty owed third persons remains unclear. It is also unclear how a proper warning is to be drafted when a manufacturer possesses incomplete information, but has some suspicion, based on a statistically small sample of reported cases, that its drug may cause adverse side effects.

The fact that the drug package insert has been approved by the FDA does not relieve the drug manufacturer of its obligation to communicate an adequate warning to the users of the drug. An Oregon case indicating that a drug complying with FDA regulations was reasonably safe as a matter of law has been expressly overruled. The warnings required by such agencies may be only minimal,sl and therefore do not provide an adequate standard by which to measure a manufacturer’s duty.

The DES Cases and the Problem of Proving Causation

There are other uncertainties peculiar to drug litigation. Because of the lengthy time interval between ingestion of a drug and manifestation of the injury, and the even longer period between the injury and the identification of the drug as its probable cause, a plaintiff may have difficulty in identifying the drug’s manufacturer. Nowhere is this problem evidenced more clearly than in the current DES litigation.

In 1941 the FDA approved DES after twelve drug companies filed new drug applications. In support of their request the companies submitted a joint clinical file. The purpose for which the drug was approved in 1941 did not include its subsequent and popular use for the prevention of miscarriages. In 1947 new applications for that use were submitted by the twelve companies and others, and from 1947 to 1971 the drug was manufactured by hundreds of drug companies and prescribed for millions of women. In 1971 statistical evidence indicated a significant association between DES and the development of cancer in the users’ daughters who had been exposed in utero. The FDA banned the drug in 1971 as unsafe and ineffective in preventing miscarriage. Although there were several hundred manufacturers of DES and related drugs, it was estimated that Eli Lilly and five or six other manufacturers accounted for 90% of the market. Nevevertheless, it was extremely unlikely that any plaintiff would be able to trace back the particular DES taken by her mother to any one individual manufacturer.

Prior tort cases provided some guidelines for the DES plaintiffs. Hall v. E. I. Du Pont De Nemours & CO. consolidated two cases arising out of eighteen separate accidents in which children were injured by dynamite blasting caps. The explosions destroyed the evidence of manufacture in most cases. The plaintiffs joined the six major domestic manufacturers of blasting caps and their trade association, alleging that the defendants knew that the caps were dangerous and that they had agreed not to put warnings on them. The court held that the defendants were not entitled to a dismissal of the plaintiffs’ claims since the plaintiffs were claiming joint control of risk by explicit agreement-i.e., concert of action. The court went on to add that the plaintiffs could either submit evidence of defendants parallel behavior sufficient to support an inference of tacit agreement, or allege that, acting independently, the defendants had adhered to an industry-wide standard with regard to the safety of blasting caps. The court discussed enterprise liability and emphasized its special applicability to industries composed of a small number of units. The burden of proving causation was shifted to the defendant despite the possibility that the caps might have come from other unnamed sources.

Another approach for DES plaintiffs is the “alternative liability theory.” In Summers v. Tice, the plaintiffs two companions fired their guns simultaneously and carelessly in his direction. Only one bullet actually hit the plaintiff, but it was impossible to prove which defendant had caused the injury. The court justified its concept of joint and several liability on the grounds that when all the defendants are potential wrongdoers, fairness requires a finding of joint liability unless the defendants can individually exonerate themselves.

In the related case of Anderson v. Somberg, the plaintiff was injured when part of a surgical instrument broke off in his spinal canal during an operation. He sued the doctor and hospital for negligence, the distributor for breach of warranty, and the instrument’s manufacturer in strict liability. The court held that because it was apparent that at least one of the defendants was liable for the plaintiffs injury, all were jointly liable unless proven otherwise. No other theory of liability could reasonably be applied. “Since defendants had engaged in conduct which activated legal obligations by each of them to plaintiff, … the failure of any defendant to prove his nonculpability would trigger liability; and further, … at least one would be liable.

Plaintiffs have recently used analogous arguments-with varying degrees of success-jn attempting to trace liability back to the DES manufacturers. In McCreery v. Eli Lilly & CO. the court refused to accept the “sketchy and limited factual circumstances presented in the plaintiffs argument of concerted activity,” and held that the plaintiff must, “before benefiting from the shift of the evidentiary burden, identify the manufacturer.” Since knowledge of the manufacturer was more accessible to the plaintiff (whose mother had known of and possessed the prescription, and had chosen the doctor and druggist), the court affirmed the summary judgment for the defendant. A contrary result was reached in Sindell v. Abbott Laboratories, where the plaintiffs alleged concerted action and theories of alternative liability. And in the much publicized New York case of Bichler v. Eli Lilly & Co., a jury awarded $500,000 to a twenty five year old woman who developed vaginal and cervical cancer as a result of her mother’s ingestion of DES. There the plaintiff alleged joint enterprise liability. This approach, if successful on appeal, is sure to have a major impact on the more than 400 DES suits still pending.

Application of Statutes of Limitation

Since a plaintiff in a drug liability action may plead a variety of legal theories-e.g., negligence, warranty, strict liability in tort, it is necessary at the outset to determine which statute of limitations period applies to each cause of action pleaded. Typically, the tort or personal injury limitation is two or three years and accrues at the time of injury. The warranty limitation under the Uniform Commercial Code is four years and accrues from the date the sales contract is breached. It is, of course, entirely possible that the limitation period for one cause of action will have expired while that of another remains viable.

A second and far more complicated question is when the cause of action accrues. The Uniform Commercial Code provides that the action accrues when the breach occurs, regardless of the aggrieved party’s lack of knowledge of the breach. A breach of warranty occurs when tender of delivery is made…  Nonetheless, there are at least four points at which a tort cause of action may accrue: (1) when the defendant breaches his duty, (2) when the plaintiff suffers harm, (3) when the plaintiff is or should be aware of his injury, or (4) when the plaintiff is or should be aware of the causal relationship between his harm and the defendant’s misconduct. In most tort actions these events occur simultaneously and the time of accrual is clear. But this is seldom the case in drug induced injuries. It is impossible to generalize the law regarding statutory interpretation insofar as it affects drug litigation, except to point out that it is in a state of flux.

Some jurisdictions, led by New York, have adopted the strict position that the cause of action accrues when there is a wrongful invasion of personal or property rights, regardless of whether the plaintiff realizes he has been injured. Most lower courts in New York have persisted in this “first breath” rule, despite a more liberal approach to malpractice claims that involve the leaving of a foreign object in a patient’s body-for which the statute does not begin to run until the patient could reasonably have discovered the injury106-and despite the more liberal tolling of the statute by the continued treatment by the physician. Recently, exceptions to these rules have been made in products liability cases brought for occupational disease in strict tort liability. It has also been held that the continuous treatment of an attending physician may be imputed to the manufacturer of a medical device, thus tolling the statutory period applicable to claims against the manufaturer.

Other jurisdictions have adopted the liberal discovery of injury rule. Yet even with these jurisdictions generalizations are dangerous. Clearly, the plaintiff may learn of his injury many years before he is able to identify its cause. Some courts have held that the statute begins to run at the time the plaintiff knew or should have known of his injury. Knowledge of injury is only apparent if the injury is a “traumatic” one. However, if the plaintiff has not been made aware that his rights were violated, the modern trend and majority position in products liability actions is that the plaintiffs action accrues when he discovers, or in the exercise of reasonable diligence should discover, that his injury may have been caused by the defendant’s conduct, rather than when he simply discovers that he has been injured. On the issue of fairness to the drug companies, the New Hampshire Supreme Court has observed:

With respect to their expectations of repose, drug companies are unique among most potential tort feasors. The harmful propensities of drugs are often not fully known at the time the drugs are marketed. These companies know or at least should expect that some time may pass before the harmful effects of their products manifest themselves in drug users and that there may be another lapse of time before the injured person is able to discover the causal connection between his injury and the drug he consumed…. Given these unique circumstances and the fact that the scope of a drug manufacturer’s liability is substantial and seems to expand continually through the growth of substantive tort and warranty doctrines, … we do not think the drug company can reasonably expect to be immune to suit before its customer has a fair opportunity to discover the company’s tortious conduct.

The Recent DES Case of Mink v. University of Chicago

A recent case, Mink v. University of Chicago,l13 posed many of the issues discussed in this article. There the plaintiffs brought a diversity action on behalf of themselves and some 1,000 women who were given DES as part of an experimental study allegedly conducted by the named defendant and Eli Lilly & Co. They claimed that they and their children had suffered reproductive tract abnormalities and had incurred an increased risk of cancer. In their complaint they sought recovery on three causes of action. They first alleged battery, since the medical experiment was conducted without their knowledge or consent. The court distinguished this case from those in which the patients at least knew that they were being given some form of a drug. In those cases negligent failure to disclose risks had to be pleaded and proved, and injury had to be alleged. The gist of the battery claim was nonconsent-the tort being complete without hostile intent, and without personal injury. The issue of whether implied consent had been given was left to the jury. The second count was in strict liability and was dismissed because the named plaintiffs had alleged no injury to themselves. In their amended complaint they sought damages for alleged injury to other class members, but this was held to be an insufficient allegation of injury to the named plaintiffs. The third claim was that no effort had been made to notify the plaintiffs of their participation in the experiment until 1975 or 1976, even though the relationship between DES and cancer was known to the medical community as early as 1971. The court recognized a continuing duty to warn on the part of both the university and the drug manufacturer, but dismissed this count for failure to state a cause of action. In their amended complaint, plaintiffs sought to compel the defendants to notify all the women given DES as part of the experiment. Since the plaintiffs proposed class had never been certified, and since the named plaintiffs already were aware of the DES menace, the plaintiffs could not show that there was an ongoing controversy at the time the complaint was filed. The named plaintiffs knew of the dangers and thus had no need for further notice.

The concerns of the manufacturers and their insurers therefore appear more understandable in the context of recent developments in drug litigation. Despite the articulated concerns of Congress, it seems inevitable that future mass inoculation programs will involve an attempt to have the government underwrite the costs of liability. For this reason it is important to refer to the Federal Torts Claims Ad, and particularly to the “discretionary act” exception, which has so often been invoked by the government in avoiding liability.

Mass Immunization and The Federal Tort Claims Act

Two cases are particularly relevant in considering governmental liability for drug approval and distribution. In Griffin v. United States, the plaintiff allegedly contracted polio as a result of ingesting the type III Sabin vaccine. She brought an action against the government claiming that the vaccine had been negligently tested by the Division of Biologic Standards (DBS) and had been approved for release in violation of agency standards. Since the application and not the content of the agency rules was attacked, the court held that the discretionary function exception did not apply. The court commented:

The “discretion” protected by the section is not that of the judge-a power to decide within the limits of positive rules of law subject to judicial review. It is the discretion of the executive or the administrator to act according to one’s judgment of the best course, a concept of substantial historical ancestry in American law… Where there is room for policy judgment and decision, there is discretion.

While DBS had the right to weigh five criteria of neurovirulence , its judgment was that of a professional, not a policy maker. It was purely a scientific determination since DBS’ responsibility was limited to merely executing the policy judgments of the Surgeon General. Furthermore, in approving this lot of vaccine, DBS had exceeded its authority by disregarding the mandatory regulatory command and had diluted the results of the tests performed by considering “biological variation.” The violation of a nondiscretionary command takes what otherwise might be characterized as a ‘discretionary function‘ outside the scope of the statutory exception.

However, in Gray v. United States the plaintiff was unsuccessful in her suit. She alleged that she had been injured when her mother ingested DES and sued both Eli Lilly and the federal government, relying on Griffin as precedent. Summary judgment was granted both defendants. The court commented that the FDA was given a general statutory mandate to assure the public that a marketed drug was safe for use. There were no particular scientific tests or measuring sticks existing whereby the FDA had to qualify a new drug, but rather it was given the liberty to consider all factors it deemed relevant in the determination of a drug’s safety. Congress had chosen the FDA to be the decision maker, … and its judgments … must be beyond private scrutiny and litigation.

Conclusion

Thus, a clear message emerges: in any future mass inoculation program, agency action must be “nondiscretionary” if the federal government is to be held liable. To the extent possible, specific “measuring sticks” or tests should be specified. In view of the strict liability claim frequently made in drug litigation, it is likely that the government will be forced to concede liability on that ground despite the present limitation on liability. It is clear that the government must develop clear guidelines for protecting participants in the mass immunization programs it deems necessary. In the absence of such protection, we may expect continued resistance from drug manufacturers, health care providers, and their insurers to any participation in such programs.

Nina S. Appel, 1980

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Pharmaceutical Manufacturers Liability for Unforeseen Adverse Drug Reactions

INTRODUCTION

Illness is the common companion of life; medicine aids the body in responding to illness, but adverse reactions to drugs are as old as Medicine. Harm inflicted when healing was anticipated has always been an unwelcome surprise evoking a desire for redress. This feeling is reflected as far back as 2200 B.C. in the Code of Hammurabi, which declared that a physician who caused the death of a patient should suffer the loss of his hand. Illness or death resulting from a drug taken for its curative value still affronts the sensibilities. Injured parties increasingly look to the legal system to fix the responsibility and determine who will bear the cost of an adverse drug reaction.

An adverse drug reaction is a “noxious and unintended” response “which occurs at doses used in man for prophylaxis, diagnosis or therapy.”‘ The majority of these reactions are either mild physical effects that do not require treatment, or moderate reactions that necessitate discontinuation of the offending agent and may demand some countermeasures. These drug reactions may be classified medically as an insult to the body, but it is doubtful that the insult is of a sufficient magnitude to require a legal remedy. In contrast, the severe adverse drug reaction that brings a person close to death and results in extensive medical treatment or permanent injury, and the lethal drug reaction, may be conducive to tort litigation.

The scope of the problem of adverse drug reactions is not narrow, either in its cost to the affected individual or to society. The reported frequency in studies of these reactions ranges from less than one in one hundred to more than one in four drug administrations. The Boston Surveillance Group conducted an intensive in-hospital study to obviate the problems encountered with previous studies that were poorly controlled and designed. The survey lasted four years and involved eleven hospitals and 6,750 patients. Almost five percent of all drug exposures were associated with an adverse event. One of every 200 drug exposures was associated with a “life threatening” adverse reaction, and 0.4% of the monitored patients died of drug attributable causes. In addition to the physical effects on the human body, estimates of the monetary cost of adverse drug reactions range from one billion dollars per year, three billion dollars per year and one-seventh of all hospital days, to four and one half billion dollars per year.

The drugs that cause these adverse reactions are developed, produced, and marketed by pharmaceutical manufacturers. Drug-related injuries are increasingly the basis of causes of action brought in strict liability in tort. These cases define the outer limits of strict liability [and present the] most difficult questions of policy . This Note explores these outer limits and addresses these policy questions. It examines the problems encountered by imposing strict liability for unforeseen adverse drug reactions on pharmaceutical manufacturers, and compares this approach to their liability under the recently proposed Model Uniform Product Liability Act (Model Act).

STRICT LIABILITY IN TORT AND DRUG RELATED INJURIES

The Liability of Pharmaceutical Manufacturers for Unforeseen Adverse Drug Reactions, Fordham Law Review, Volume 49, Issue 5, Article 4, 1980.

Originally, negligence was the primary vehicle for recovering damages from manufacturers for physical injuries caused by their products. The success of the action turned on the plaintiff’s ability to isolate the defendant’s specific negligent act and prove by a preponderance of the evidence that the negligence was the proximate cause of the plaintiff’s injury , Courts, frequently faced with a severely injured plaintiff, strained to ease this burden, and they recognized a cause of action for personal injury under a contract-like theory of breach of implied warranty. The American Law Institute finalized the process by adopting a formulation for strict products liability. Section 402A of the Restatement (Second) of Torts delineates strict products liability for physical harm to the user or consumer:

  • One who sells any product in a defective condition unreasonably dangerous to the user or consumer or to his property is subject to liability for physical harm thereby caused to the ultimate user or consumer, or to his property, if
    • the seller is engaged in the business of selling such a product,
    • and it is expected to and does reach the user or consumer without substantial change in the condition in which it is sold.
  • The rule stated in Subsection (1) applies although
    • the seller has exercised all possible care in the preparation and sale of his product,
    • and the user or consumer has not bought the product from or entered into any contractual relation with the seller.

The Model Act 23 varies from section 402A by distinguishing the product manufacturer from the product seller in determining duties and liabilities. The manufacturer is “subject to liability to a claimant who proves by a preponderance of the evidence that the claimant’s harm was proximately caused because the product was defective.” Other “product seller[s],” such as retailers and wholesalers, are liable only when the claimant proves that the proximate cause of his injury was “such product seller’s failure to use reasonable care with respect to the product.

Physical harm is a basic element in establishing a prima facie case of strict products liability under section 402A. The actual physical injury is usually apparent in drug products liability cases, ranging from blindness, to irreversible brain damage, to death. The Model Act does not limit the cause of action to physical harm. It includes “mental anguish or emotional harm caused by the claimant’s being placed in direct personal physical danger. The action, however, lies only with the injured person and not with third parties.

To recover under Section 402A, a plaintiff must prove that the proximate cause of his injury was a defect in the product that rendered it “unreasonably dangerous.” Under the Model Act, a defect is proved by showing that the product was “unreasonably unsafe” in construction, in design, or because adequate warnings or instructions were not provided.

The construction or manufacturing defect generally occurs on the production line. In these cases, the product fails to meet the standards set by the manufacturer and differs significantly from other units. Such cases are rare with pharmaceuticals because of intensive and effective quality control. Injury from a manufacturing defect, however, renders the producer strictly liable under both section 402A and the Model Act, despite the most elaborate and detailed control system.

Although drugs may be properly manufactured, it is not presently possible to design an effective but completely safe drug. Almost all drugs have the potential to inflict serious harm. A problem arises in determining when this potential renders these drugs defective within the meaning of the law. Comment k to section 402A specifically identifies certain drugs as “unavoidably unsafe products.” It states that such a product, properly prepared, and accompanied by proper directions and warning, is not defective, nor is it unreasonably dangerous. . . . The seller of such products . . . is not to be held to strict liability for unfortunate consequences attending their use, merely because he has undertaken to supply the public with an apparently useful and desirable product, attended with a known but apparently reasonable risk.

Comment k does not limit drug liability under all conditions. It employs a “risk benefit” analysis by comparing the reasonableness of the risk with the benefit to be derived from the product. A product will be considered unreasonably dangerous only if its utility does not outweigh the magnitude of the danger. A problem arises in determining when to balance the risk and the benefit. Dean Keeton suggested that the benefit of the product should be weighed by the “magnitude of the scientifically perceivable danger as it is proved to be at the time of trial. Courts have held, however, that the balance is to be struck with the knowledge available at the time of injury. This accords with the language in Comment k referring to a “known but apparently reasonable risk.” Similarly, section 106 of the Model Act holds a seller liable only if he knew of the drug’s dangerous aspect and acted unreasonably by marketing it. The protection afforded by Comment k and the Model Act may be lost, however, if a drug that offered no substantial benefit caused an injury, even if it was not foreseeable. Such a drug could be considered “unreasonably dangerous” as marketed.

The majority of drugs from which litigation has arisen over the past twenty years are still marketed. The risk benefit ratio of these drugs still favors marketing. The defect, if any, lies neither in the manufacturing process nor in the formulation, but in the adequacy of the warning accompanying such pharmaceuticals. Comment h to section 402A provides that where . . . [the seller] has reason to anticipate that danger may result from a particular use. . . he may be required to give adequate warning of the danger … and a product sold without such warning is in a defective condition. The Model Act is in accord, and generally defines a defective product as one that was “unreasonably unsafe because adequate warnings or instructions were not provided.” If the product, for example, a drug, is one with “unavoidably dangerous aspects,” the Model Act holds the product seller liable if he failed to warn of the known danger. Courts have uniformly expressed a willingness to impose strict liability for drug related injuries when the duty to warn existed and was breached. Furthermore, failure to warn when a warning is required has been held sufficient to establish a defect. The plaintiff need not establish that the product reached him without substantial change because the defect is predicated on the warning, which is under the direct control of the manufacturer. Although the failure to warn must be established as the proximate cause of the harm, there is a presumption that an adequate warning will be heeded.

The threshold question involves delineating the parameters of the duty to warn. The proper role of foreseeability in the duty to warn is an integral aspect when discussing strict liability for unsforeseen adverse drug reactions. Additionally, it must be determined when the duty arises, to whom it is owed, and what constitutes an adequate warning.

DRUGS AND THE DUTY TO WARN

Foreseeability and the Duty to Warn

The Requirement of Foreseeability For Adverse Drug Reactions

Between seventy and eighty percent of adverse drug reactions result from the known side effects of established drugs. The pharmaceutical manufacturer has a duty to warn of these side effects. A drug marketed without a warning of known dangers is clearly defective, and the manufacturer will be held strictly liable for any resultant injury. Problems may arise, however, when a consumer is injured by an unforeseen, totally aberrant side effect of the drug. These cases negate the manufacturer’s ability to insulate itself from strict liability through an adequate warning because the formulation of an effective warning of unknown dangers presents insuperable semantic difficulties. Moreover, the alternative to liability for aberrant effects – withholding the drug from the market and continuing testing until all possible effects are revealed – is equally impractical because of the inherent limitations of such testing. Therefore, to promote the availability of beneficial new drugs, the law provides protection from strict liability for the pharmaceutical manufacturer when it cannot protect itself. Because imposition of the duty to warn is justified by the actual and constructive knowledge of the manufacturer, strict liability is not imposed for the failure to warn of unknowable adverse effects. The drug is considered defective only if the manufacturer does not warn of a known hazard.

Basing the imposition of a duty to warn on the manufacturer’s knowledge of the danger introduces the element of foreseeability into strict liability. Strict liability normally represents a shift in focus from the reasonableness of the actions of the manufacturer based on its apprehension of a perceived risk, to the essential character of the product. This incorporation of the negligence concept of foreseeability into the duty to warn has been criticized as a step backward “denying strict liability an independent viability.”

The Appropriate Foreseeability Standard

Several courts have acknowledged this incorporation of negligence elements into strict drug products liability, particularly when liability is based on breach of the duty to warn. Other courts have noted the similarities, but differentiated negligent breach of the duty to warn from strict liability based on the duty to warn. In Phillips v. Kiinwood Machine Co., the Oregon Supreme Court made a further departure from negligence by purging the foreseeability concept from strict liability. The court’s proposed test “to determine the dangerousness of the article, as distinguished from the seller’s culpability, is to assume the seller knew of the product’s propensity to injure as it did, and then to ask whether, with such knowledge, he would have been negligent in selling it without a warning.” This standard has been approved by only one reported drug related injury case. In Hamilton v. Hardy, the plaintiff suffered a stroke after taking the defendant manufacturer’s oral contraceptives for eleven months. The Colorado Court of Appeals held that the appropriate test to determine if the evidence is sufficient for the plaintiff to recover in strict liability would “assume the seller knew of the product’s propensity to injure as it did.’

Recently, the Indiana Court of Appeals expressly rejected the Phillips test in discussing drug related injuries. Even the Phillips court has acknowledged that the duty to warn is partially based on constructive knowledge. Foreseeability of harm is disregarded, however, in certain aspects of drug products liability. In Crocker v. Winthrop Laboratories, the manufacturer’s representatives promoted Talwin, a pain killer, as being positively nonaddictive. There was no evidence at the time of marketing that the drug was addictive. Mr. Crocker took Tawin, became addicted, and subsequently died from his debilitating addiction. The manufacturer was held liable because it went beyond merely stating that there was no evidence of harmful effects by actually promoting the drug as being without such effects. The positive representation negated the absence of foreseeability. This type of “express warranty” of a “material fact” also renders a manufacturer liable under the Model Act. In this situation, the manufacturer is claiming knowledge it does not have. It provides a false assurance of safety and induces unjustified reliance by the drug user, thereby losing the defense of unforeseeability.

The Crocker court recognized that because some products are so dangerous, the manufacturer should be liable without reference to his actual or constructive knowledge. “In the case of a generally beneficial or good product,” when the manufacturer’s liability is predicated on the adequacy of the warning, however, even the Crocker court was not prepared to compare the warning given with the facts known at the time of trial. 89 A problem in strict liability is setting limits, and like the Crocker court, other courts have stopped short of imposing strict liability for failure to warn when the hazard was unknown. The duty to warn can arise only when there is knowledge of the hazard. This knowledge is not imputed to the manufacturer from the facts available at the time of trial, but is determined by what was known at the time of injury. The Model Act also adopts this approach by requiring actual or constructive knowledge when liability is based on a breach of the duty to warn.

This adherence to a foreseeability standard may wed strict tort liability to negligence when the action is based on the breach of a duty to warn. Dean Prosser’s 1960 statement that “there is not one case in a hundred in which strict liability would result in recovery where negligence does not” continues to be valid in these cases. Commentators have noted the concern that this adherence to the negligence standard will work a hardship on the plaintiff through the imposition of a heavy burden of proof.

When the severely injured victim of an adverse drug reaction is before the court, however, there is a reluctance to let the injury go unremedied. 98 An examination of the elements of the duty to warn illustrates the exercise of judicial flexibility, even within the bounds of foreseeability, in providing redress.

When Is There A Duty To Warn?

When the defect in a drug is the failure to warn, this failure “is by definition the manufacturer’s dereliction.” Therefore, the plaintiff need not prove either that “the defect existed at the time the drug left the hands of the defendant,” or that the defendant actually knew of the hazard that caused the injury. It is enough that knowledge of the hazard existed. The pharmaceutical manufacturer is accountable as an expert in the field and is attributed both actual and constructive knowledge of its product.

Actual knowledge is first acquired through extensive premarket testing. A manufacturer that does not test its product may be precluded from raising the defense that no available test could have revealed the adverse effect that caused the injury. Once the drug is marketed, the manufacturer is responsible for knowledge received from reports of adverse reactions. A single letter reporting one adverse event may be offered as evidence of the manufacturer’s actual knowledge. The manufacturer may be charged with the duty to warn even if the exact nature of the adverse reaction is unknown.

The duty to warn continues after marketing is commenced. New information concerning the drug’s composition and effects must be incorporated into the warning. Information contained in medical journals and other scientific literature will be imputed to the manufacturer because of the duty to keep abreast of these sources. If the adverse drug effect is reported in any of these sources prior to a particular plaintiff’s injury, the determination whether the defendant “was or should have been sufficiently certain” of this effect to be under a duty to warn may be left to the jury. Once the duty to warn arises, the manufacturer must effectively transmit the warning to the consumer

To Whom Must The Warning Be Given?

Initially, the pharmaceutical manufacturer was under no duty to warn persons who were allergic to the product or who experienced an idiosyncratic reaction. A warning was required only when an appreciable number of persons experienced a particular side effect. These limitations have been specifically rejected. Allergies and physical idiosyncracies are merely factors to consider in determining the parameters of the duty to warn. Although it may be harder to anticipate allergic reactions. these reactions are considered foreseeable and a duty to warn is imposed, regardless of the nonexistence of appreciable numbers. A duty to warn exists even if the people affected represent a small number of idiosyncratic or hypersensitive users. In reality, the actual chance of occurrence may be very small. For example, the manufacturer of Sabin polio vaccine was charged with the duty to warn even though the risk of vaccine-induced polio was, at maximum, one in three million administrations.

The duty to warn of dangers in prescription drugs is generally discharged when an adequate warning is transmitted to the consumer’s physician.  Although the consumer need not be directly apprised of any danger, both the prescribing and the treating physician must be warned. Because drug effects are so complex, only a medical expert is expected to be able to appreciate and balance the potential benefits of the drug with the hazards of administration. Therefore, the physician stands as the ” ‘learned intermediary’ between manufacturer [or seller] and consumer.” The Model Act adopts this reasoning and provides that “Iflor products that may be legally used only by or under the supervision of a class of experts, warnings or instructions may be provided to the using or supervisory expert.” The transmission of the warning to the consumer is dependent on the medical judgment of the physician.

Nevertheless, when a prescription drug is distributed in such a way that the role of the “learned intermediary” is eliminated, as with the mass polio immunization program, – no one stands between manufacturer and consumer. In such cases, the warning must run directly to the consumer. Even the administration of a vaccine by a doctor in his private office may be sufficiently clinic-like so that the duty to warn is not discharged by transmitting a warning only to the physician. In all cases, the duty to warn will be discharged only by the effective transmission of an adequate warning.

 What Is An Adequate Warning?

It is presumed that an adequate warning will be heeded, but the essence of an adequate warning is not easily adduced. Federal law requires that drugs be labeled with appropriate instructions for use, as well as information on contraindications, side effects, and effectiveness. 130 Although compliance with these regulations does not make the warning adequate as a matter of law for purposes of civil liability, it may establish a minimum standard. Conversely, noncompliance may constitute negligence per se. Under the Model Act, compliance is evidence that the product is not defective, while noncompliance is accorded similar evidentiary weight in showing a defect.

A proper warning must adequately state the risk. In determining when the risk is adequately stated, a balance must be achieved. A warning may be adequate when experts say that a stronger warning would be incorrect. The warning must be strong enough, however, for if it remains unchanged when the manufacturer knows it is being widely disregarded, it will be considered inadequate. Finally, even the clearest, most complete, and most comprehensive warning will be inadequate if it can be shown that the manufacturer dissipated or eroded the effectiveness of the warning through overpromotion of the drug.

Specific guidelines for an adequate warning do not exist. The warning must be “reasonable under the circumstances.” Circumstances vary, however, and jurisdictions define “reasonable” differently. Although these differences may lead to inconsistent results, the consistency provided by absolute strict liability that removes foreseeability from the duty to warn would lead to even greater injustice.

THE EFFECT OF IMPOSING STRICT LIABILITY FOR UNFORESEEABLE ADVERSE DRUG EFFECTS

Foreseeability of harm could be eliminated as a necessary element in establishing liability for a breach of the duty to warn. The pharmaceutical manufacturer would simply be liable for any adverse drug reaction unless an adequate warning was previously transmitted. The complexity of drug products litigation might be reduced, and it would no longer be necessary to prove what information was known, when it was known, and if it was sufficiently known. This simplistic approach, however, is not one chosen by the courts or proposed in the Model Uniform Product Liability Act. Foreseeability is retained because its removal would clash with the two policies that justify the imposition of strict liability-providing incentives to more careful conduct, and risk allocation to the one in the best position to insure against failures.

The incentive theory is premised on the belief that strict products liability results in safer products. Of all products, however, this justification seems especially inappropriate as applied to ethical drugs. Drugs are properly characterized as unavoidably unsafe products, or products with “unavoidably dangerous aspects.” They are by nature toxic, although administration of the drug seeks to maximize the toxic effect in those parts of the body afflicted with the disease and to minimize it in other parts of the body.  For these reasons, it is irrational to suppose that a legal obligation imposed on a pharmaceutical manufacturer can alter the essential nature of a drug. Moreover, it is unlikely that the threat of strict liability would spur the manufacturer toward more intensive and extensive premarketing tests to reveal latent dangers.

The pharmaceutical industry is heavily regulated by statute and by the Food and Drug Administration (FDA). The Federal Food, Drug, and Cosmetic Act prohibits the marketing of a new drug until the FDA approves a New Drug Application submitted by the manufacturer that demonstrates the drug’s “safety” for its intended use. The thalidomide disaster, which caused the birth of severely deformed children, facilitated the adoption of the 1962 Harris-Kefauver Amendments. They require “safety and efficacy” for new drug approval, and provide for the withdrawal of approval of older drugs if new evidence reveals a serious challenge to their safety or efficacy. The FDA requires exhaustive premarket testing before it will approve a new drug. If the premarket testing plan is approved, the clinical investigation proceeds in three phases. Phase I examines the pharmacologic effects of the drug on human beings-what the drug does to humans and in what doses. In Phase II, the drug is administered to persons as therapy for a specific medical condition. The physiologic changes produced by the drug are intensively monitored. Such changes may be beneficial, in the form of treatment, or harmful, in the form of side effects. Phase III clinical studies involve larger numbers of patients. The studies continue to be carefully monitored and are used to define the most appropriate drug dosage and treatment techniques. The FDA must be informed of results and progress throughout the entire testing process. Many drugs may pass the first three phases but receive only limited FDA approval that requires postmarketing surveillance and initially, controlled distribution. This has been termed Phase IV, and eventually may represent an additional step for all drugs prior to full approval.

Strict liability is justified on the purely economic ground that the manufacturer is in the best position to absorb and distribute the cost of minimizing the risks associated with the product. Nevertheless, the incentive theory, with its resultant extensive testing, is an inadequate justification for imposing strict liability on pharmaceutical manufacturers because of the costs involved. Under present regulations, the cost of developing a new pharmaceutical is estimated at twelve million dollars. – The pharmaceutical industry is the major source for the development of new drugs, and, because it is a profit motivated industry, 1 66 the cost of more extensive testing for safer drugs would be reflected in higher drug prices. This result, however, may be equitable, because drug consumers directly benefit from increased safety and would directly bear the cost of minimizing the risk. Nevertheless, despite this one equitable argument, other costs of more extensive testing cannot be so fairly distributed and mitigate against imposing strict liability.

 

Data supplied by laboratory tests on animal models are, by nature, of limited application to human beings because of species difference. 167 Ultimately, the effects of a drug on a human can only be determined by testing it on human subjects. The costs of this type of more extensive safety testing would be less equally apportioned among consumers. Phase I clinical trials, the first administration of the drug to a human being, require healthy volunteers, who are usually male and often inmates in penal institutions. When a test drug is administered to any healthy subject, the attendant risk is very real, and the presence of a counterbalancing benefit to this individual is questionable. 169 The participants in Phase II and III clinical trials are seldom private patients. They have some chance to benefit from the drug because it was developed specifically to relieve their ailment. The preferred clinical trial, however, is a double-blind procedure in which the effects of a new drug are tested against either a placebo or an established therapeutic agent. Neither the administering physician nor the volunteer patient know the identity of the drug administered. The subject of such a trial assumes the risk of receiving no curative therapy if a placebo or a less effective treatment is assigned. Testing must actually be continued until one drug is proved significantly more effective to establish valid trial results. If drug safety could be achieved through more extensive testing, the price could not be judged by monetary cost alone. There is a human cost that falls primarily on the incarcerated, the indigent, and the ill.

Furthermore, society pays for the imposition of strict liability by being denied the benefit of new therapeutic agents.

There are two risks involved in the development of new drugs:

  1. the risk that unforeseen, perhaps catastrophic, injuries will result because a new drug is used in man too soon;
  2. and the risk that needless human suffering and death will occur because a beneficial drug is withheld from mankind too long.

Absolute liability for the adverse effects of new drugs would enlarge the latter risk to unacceptable proportions, while giving a remedy only to those injured by the former risk.

Prolonged premarket testing by pharmaceutical manufacturers to limit liability would result in an increase in “drug lag“–the phenomenon of new drugs being approved for use consistently later in the United States than in other medically advanced countries. Drug lag results in drugs being withheld from the public, as the manufacturer attempts, through testing, to uncover potentially serious side effects. – A drug manufacturer will never be sued by the multitudes who suffer because a drug was not released. Moreover, the deterrent effect of strict liability can be awesome. For example, if a drug with the potential therapeutic impact of penicillin is not released because of overly stringent testing procedures, more people will be harmed by the deprivation of that single agent than by all the toxicity that has occurred in the history of modern drug development.

More extensive premarket testing can therefore increase the cost of a drug and delay or even prevent its release, yet still fail to reveal some aberrent effect. The market is the ultimate laboratory, and the consumer is the ultimate test subject. The desire for “effective drugs developed without attendant risk or toxicity” has been termed a desire for “something for nothing,” wish for “progress without price“. No theory of strict liability can fulfill that desire or grant that wish.

Although the imposition of strict liability for failure to warn of unforeseen hazards cannot prevent injury by producing significantly safer pharmaceuticals, it can provide that the manufacturer will bear the cost of any injury that ensues. If drugs cannot be made completely safe, any loss suffered by the producer in compensating for consumer injury is a cost of engaging in such a business. The risk allocation theory envisions that this loss can be “treated as a cost of production against which liability insurance can be obtained.” If the hazard is unforeseeable, however, the resulting damages are equally unforeseeable and impossible to reflect accurately in the “product price schedule.” The ability of the manufacturer to anticipate and absorb the cost of product related injuries is significantly impaired by an unknowable danger. Furthermore, it is impossible to insure accurately against unforeseeable adverse drug reactions. The sufficiency and cost of any insurance may be severely disproportionate to the actual risk or loss. High premiums may force manufacturers to go uninsured, and manufacturers of high risk products, such as drugs, may become reluctant to develop new products.

It is not suggested that pharmaceutical manufacturers will completely terminate research and development of new drugs if held strictly liable for all adverse reactions. The pharmaceutical industry is highly competitive; new drugs must be produced to insure a company’s continued existence, and the potential benefits of a successful new drug are enormous. Nevertheless, the introduction of new drugs would be delayed, and certain agents might never be marketed, because the marketing of a new drug involves multiple riskbenefit analyses. The risk of adverse drug reactions must be balanced against the drug’s therapeutic effect. Furthermore, the risk of liability from adverse drug reactions must be weighed against the potential market for the drug. A drug with enormous therapeutic potential may have a limited market and be associated with a high degree of liability. This type of drug would be most adversely affected by the imposition of strict liability because the pharmaceutical manufacturers would probably shelve such a drug to limit the potential losses. For example, premature delivery is the major cause of infant death during the period immediately following birth, as well as a major cause of mental retardation. The search for a drug to control premature labor is a primary clinical objective, but the possible liability associated with marketing such a drug is substantial. The drug would be given during pregnancy, a high risk period for adverse effects. It would affect a high risk group, infants, particularly premature infants. Furthermore, the statute of limitations would be extended by the infancy of the potential plaintiff. Finally, the drug would have a limited market because it would be administered in acute, rather than chronic situations.

In these cases, the manufacturer only apparently bears the loss; the true cost is borne by society. Strict liability cannot effectively help prevent the injury; neither the incentive nor the risk allocation theories justify its imposition on pharmaceutical manufacturers. Other methods of injury prevention and compensation for unforeseeable adverse drug reactions should be considered.

SUGGESTIONS IN LIEU OF STRICT LIABILITY

Presently, the law has determined that the cost to society of strict liability for failure to warn of unforeseeable adverse drug effects is too high and, therefore, it exempts the manufacturer from liability in this limited situation. The injured consumer left without remedy. however, may not appreciate the justification for this decision. Courts have endeavored, within the limits of foreseeability, to provide a remedy, and these efforts are frequently successful. Further protection for the consumer, however, should be provided by the legislature.

The most effective drug attacks the etiology of a disease rather than the symptoms. The etiology is often obscure or unknown, and, therefore, therapy can only be palliative. Often, ignorance is the cause of problems stemming from unforeseeable adverse drug reactions, and knowledge can alleviate these problems. In the risk benefit calculus, it is essential to determine whether the marketing of the product, even with warnings, was justified either legally or medically. The key to such actual or constructive knowledge is a national reporting system for adverse drug effects.

Currently, the FDA’s Division of Drug Experience collects and evaluates information on drug usage, adverse reactions and other drug experience data. Presently available surveillance sources have helped substantiate the causal relationship of certain drugs with rare adverse reactions, such as DES and adenocarcinoma, and potassium chloride and gastrointestinal ulcerations. The recognized need to expand these information gathering sources has resulted in a joint project by the National Bureau of Standards, the FDA, and the Joint Commission on Prescription Drug Use to investigate practical techniques of postmarketing surveillance. The results of this project will soon be available. It already appears that the Phase IV period of monitored release prior to full FDA approval of new drugs will officially be required. The United Kingdom has adopted a similar system, under which the physician is informed of the limited nature of the drug approval and commits himself “to supply specific information on the response of each patient” to the manufacturer. Such a system performs a dual function. Information concerning the risks associated with the new drug is transmitted from the manufacturer to provide the basis for an informed choice. Second, information concerning the consumer’s reaction to the drug is transmitted back to the manufacturer to provide the basis for knowledgeable drug warnings and rational marketing policies.

A surveillance system that efficiently furnishes information on the effectiveness and the effects of new drugs restricts the defense of unforeseeability by making the unknown known. Someone must be injured before the danger is known, however, and the unforeseeability defense should remain against this initial injury. Any costs of unavoidable harms that would be shifted from the individual should be borne by society at large. An insurance program “that will … compensate the occasional victims of serious unwanted effects” would not only serve as a remedy by spreading the cost to society, but would also facilitate the operation of a surveillance system.

A federally sponsored program might provide the means for the establishment and operation of a viable system. The federal government already plays an integral regulatory role in the passage of a new drug into the market place. No new drug can move in interstate commerce without government approval. Furthermore, the government sets the standards of “efficacy and safety” required for approval prior to marketing and is in the best position to distribute the costs of unforeseen adverse drug effects that result from marketing. The National Swine Flu Immunization Program, established pursuant to the Swine Flu Act of 1976, is a direct precedent for this type of government action. This legislation provided an exclusive remedy against the United States for injuries resulting from the administration of the swine flu vaccine. The government retained the right to sue the vaccine manufacturer for negligence or breach of contract in connection with the program. The constitutionality of the Swine Flu Act has been upheld. A similar program may provide an equitable way to compensate the victims of unforeseeable adverse drug reactions. Admittedly, the conception and implementation of such a program would not be without problems. A program directly patterned on the Swine Flu Act, incorporating the limitation of an exclusive remedy against the government, would not be desirable. The legislative goal should be to offer a government remedy when the plaintiff establishes the causal relation of injury and unforeseeable drug side effect, yet fails to demonstrate a breach of the duty to warn. Such legislation would compensate the injured plaintiff without inhibiting the development of beneficial new drugs. It would not result in lowering pharmaceutical industry safety standards because the manufacturer would still be directly liable for any breach of duty of care now imposed by the courts. The legislation required to deal with this sensitive area would necessarily be complex, but the problems raised by drug products liability are intricate. Complex questions are not well served by simplistic answers.

Kathleen H. Wilson, 1980

Click to download the full study.

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Diethylstilbestrol Contraindicated in Pregnancy

image of the FDA-building
Considering the risks and the numerous studies showing DiEthylStilbestrol inefficiency and harm, it is unbelievable that the FDA never banned the use of DES during pregnancy.

Abstract

Diethylstilbestrol Contraindicated in Pregnancy: Drug’s Use Linked to Adenocarcinoma in the Offspring

Selected Item from the FDA Drug Bulletin, November 1971, National Institutes of Health, PMCID: PMC1518220.

” WE WISH TO BRING to the attention of all physicians, hospitals, and medical personnel an important possible toxic effect of diethylstilbestrol (DES) reported for the first time in April 1971 by Herbst et al. From their studies the authors concluded that maternal ingestion of diethylstilbestrol during pregnancy appears to increase the risk of vaginal adenocarcinoma developing years later in the offspring exposed. The authors studied eight cases of adenocarcinoma of the vagina in patients born between 1946 and 1951. The malignancies were identified and treated between 1966 and 1969. In seven of the eight cases, there was a history -of maternal use of diethylstilbestrol. Because this type of malignancy in young girls had rarely been reported previously, the authors conducted a retrospective investigation in an attempt to find factors that may be associated with such malignancy in this age group. Four matched controls were established for each patient and the data obtained were subjected to statistical analysis. A statistically significant relationship was observed for three variables: diethylstilbestrol given during pregnancy (p=.00001), bleeding in that pregnancy (p=less than .05) and prior pregnancy loss (p=less than .01). It is obvious that the most significant of the variables is the administration of diethylstilbestrol during pregnancy. Since publication of this study, five additional cases of this malignancy associated with the maternal use of diethylstilbestrol have been reported by Greenwald et al. Dr. Herbst, in a recent communication to FDA, has reported an additional 15 cases associated with use of this drug, bringing the total number of known cases to 27. It must be emphasized that this type of epidemiologic study defines only an association and not necessarily a cause-and-effect relationship. Further studies are underway to clarify the significance of these findings.

In the meantime, the FDA is initiating the following precautionary actions:

  1. All manufacturers of DES or closely related congeners (dienestrol, hexestrol, benzestrol, promethestrol) are being notified that appropriate changes will be required in the labeling for such drugs. This change will consist in the listing of pregnancy as a contraindication to the use of diethylstilbestrol and the other above-mentioned compounds.
  2. All other estrogens will be required to have the following WARNING in their labeling: “A statistically significant association has been reported between maternal ingestion during pregnancy of diethylstilbestrol and the occurrence of vaginal carcinoma developing years later in the offspring. Whether such an association is applicable to all estrogens is not known at this time. In any event, estrogens are not indicated for use during pregnancy.
  3. Epidemiological studies are being initiated to determine the true incidence of this disease in young women, the number at risk, the characteristics of patient populations with this malignancy, and the probability of a cause-and-effect relationship.

Both FDA and the medical profession face a responsibility to help determine whether this reported association constitutes a cause-and-effect relationship. We ask that all physicians consider appropriate steps to assist FDA casefinding and to protect any patients who might be at risk.

It may be possible to trace the offspring of those mothers who received DES during pregnancy. All physicians should be especially’ alert for young women whose mothers may have received hormonal therapy during pregnancy, particularly those young women who may be experiencing irregular vaginal bleeding. The association should be a routine consideration for physicians whose practice includes young women.

This is a previously unsuspected health problem. Further information is essential to the FDA and to the medical profession. We ask your help in reporting any cases you encounter for entry in a case registry.

FDA will take every possible step to insure that you are kept abreast of new information as soon as it can be gathered and analyzed.

For your convenience, an adverse reaction reporting form is printed below. FDA will forward a supply of forms to each practicing physician as soon as they are printed. Facsimile forms are acceptable. ”

Remarks

Many articles about DiEthylStilbestrol (DES) mention that the Food and Drug Administration (FDA) banned DES for pregnant women in 1971.
The FDA did NOT ban DES, but issued a warning and urged doctors to stop prescribing it for their pregnant patients. Most doctors did, but not all, and the information regarding the contraindication took many years to reach France and other European countries where the drug continued to be prescribed to pregnant women. Since 1971,  many studies have shown a variety of health effects associated with DES exposure, adenocarcinoma but also breast cancer and infertility to name just a few.  In 2011, 40 years after the DES cancer link was made, the FDA acknowledged the DES tragedy but refused to apologize to the many victims of this drug scandal. To this day, not one drug company has ever apologized or accepted responsibility for the DES tragedy.

More DES DiEthylStilbestrol Resources

DES Adverts from Farming and Pharma Industries

image of DES adverts
DES Stilbosol patenting turned the cattle feed industry upside down in the mid 1950s with its phenomenal use by farmers.

Few years ago we started looking for DES images and videos, as mentioned on this gallery page.

With the years, the images have been arranged accordingly onto several Flickr albums.

Awesome Flickr Gallery:
fast, efficient and super easy plugin to create customisable photo galleries

Recently we found a WordPress plugin – demo version here – allowing to create multiple galleries with different parameters.

You’ll now be able to watch archived DES adverts, DES books,  manufactured DES drugs and DES research guides directly on this website.

Here is an example – on this post – from farming and pharma industries advertising DES.

[AFG_gallery id=’2′]

My DES Daughter Journey – Interview with June Stoyer

 

Recorded radio interview by The Organic View, with host, June Stoyer joined by DES Daughter DES Daughter Google+ icon Domino talking about her journey.

Part 1

Part 2

Part 3

Alternatively, click here to listen to the show, and/or download the iTunes podcast.

The Organic View Radio Show logo Host June Stoyer interviews the top CEO’s, experts, movers and shakers that affect the organic industry as well as our environment. The Organic View show explores all of the issues impacting the organic industry, proposed regulations, the environment, politics, living green and sustainability.

Read more about my DES Daughter journey : Introduction and Doctors.

Five Scary and Shocking Facts about Diethylstilbestrol

1. As early as 1939, researchers had shown that DES Diethylstilbestrol could cause cancer and changes in the reproductive tracts of mice and rats, but drug companies ignored these results ; they also tested DES on pregnant women without consent.

Image from A Healthy Baby Girl, a 1996 documentary in which filmmaker Judith Helfand chronicles the health consequences of her in utero exposure to diethylstilbestrol
DES did not lead to healthier babies, nor did it prevent miscarriages, according to research that began appearing in 1953

2. In 1953, a study of 2000 women at the University of Chicago showed that DES did not prevent miscarriage; on the contrary, it was associated with increases in premature labor and a higher rate of abortions.

3. Despite this study, the drug continued to be used.  It wasn’t until 1971 that American drug companies were legally obliged to label DES “unsuitable for pregnant women”.  The FDA did not ban the drug but issued a contraindication which means that the drug DES continued to be prescribed to pregnant women even after the link between a rare form of vaginal cancer in young women and prenatal exposure to DES was established.

4. A whole generation of new medical students and doctors don’t know about Diethylstilbestrol, yet a study published in 2011 confirmed lifetime risk of adverse health effect in DES daughters (the youngest are in their mid 30’s early 40’s).  DES is one of those cases where the patients often know more about its effects than the doctors.

5. DES is a multi-generational tragedy.  Research by the Netherlands Cancer Institute in 2002 suggests that hypospadias a misplaced opening of the penis occurred 20 times more frequently among third-generation sons.  In laboratory studies of elderly third-generation DES-exposed mice born to DES daughter mice, an increased risk of uterine cancers, benign ovarian tumors and lymphomas were found.  Third-generation male mice were shown to be at risk for certain reproductive tract tumors.

Are we going to ignore these results like we did in 1939?

Third-generation children, the offspring of DES daughters and DES sons, are just beginning to reach the age when relevant health problems can be studied.  Funding for more research is critically needed to continue to look for evidence of reproductive abnormalities and cancers among third-generation DES women and men to ensure they receive appropriate follow-up care.

Distilbène®: 20 Years of Legal Battle

Distilbène® is the trade name for a synthetic hormone (also known internationally as DES or diethylstilbestrol) prescribed in France between 1950 and 1977 to pregnant women to prevent miscarriages. In 1977, 6 years after the U.S. Food and Drug Administration (FDA) advised physicians to discontinue prescribing diethylstilbestrol to pregnant women because of its link to a rare vaginal cancer, UCB Pharma (the manufacturer of Distilbène® in France) decided to make public that the use of this drug was contra-indicated in pregnant women.  It is estimated that 200,000 French mothers have been prescribed DES and have given birth to 160,000 DES exposed daughters and sons. The number of children whose grandmother were given DES during pregnancy (DES 3rd generation) is yet to be assessed.

DES lawsuit lawyer imageEven though many French women have suffered from the devastating side effects of Distilbène®, very few have understandably taken their case to court. DES trials are long, complicated, expensive and painful for the DES victims and their families. Battling in court against giant and powerful pharmaceutical companies is not an easy thing to do when you also have to deal with health issues such as cancer and infertility linked to your DES exposure.  According to Mrs. Martine Verdier, French lawyer who specializes in DES court cases, only 150 to 170 lawsuits have been initiated by Distilbène®’s victims over the past fifteen years. Until 2009, many DES daughters who had filed lawsuits against UCB Pharma and Novartis who respectively distributed Distilbène® and Stilbestrol-Borne® in France were unsuccessful because they were unable to produce the documents proving that their mum had been prescribed the toxic and carcinogenic drug diethylstilboestrol.

A few landmarks in the French DES legal battle history

1991:

  • First lawsuits against UCB Pharma from French women with genital cancers whose mothers had been prescribed Distilbène® during pregnancy (14 years after Distilbène® stopped being prescribed in France and 20 years after DES stopped being prescribed in the USA).

2002:

  • May 24th – Victory for two DES daughters. After eleven years of court battle, the Tribunal of Nanterre recognizes UCB Pharma’s responsibility in the cancer developed by two DES victims. They are granted 15,244 euros in damages. UCB Pharma makes an appeal against the court decision.

2004:

  • April 30th: The Court of Appeal of Versailles confirms the responsibility of UCB Pharma in the 2002 above cases.
  • The number of lawsuits increases. However the court decisions remain inconsistent because of the difficulties for victims to prove the link between their cancer and Distilbène®.
  • December 17th: The Tribunal of Nanterre condemns UCB Pharma to pay 310,000 Euros in damages to the family of a deceased DES victim before the end of the procedure.
  • December 21st: A women who has developed cancer is unsuccessful in Marseille. The court says she can not prove that her mother was prescribed Distilbène® so no link can be established. Yet her body affected by this rare vaginal cancer called adenocarcinoma, so typical of DES exposure, is the ultimate proof. She appeals.

2006:

  • March 08th – The Court of Cassation confirms the responsibility of UCB Pharma in the Marseille court case.
  • March 19th – Three women won their cases against UCB Pharma and Novartis, who had requested the cancellation of the court decision during an appeal in a view to request an expertise, arguing that the victims should have provided the original DES prescriptions.
  • October 13th – The Court of Nanterre condemns UCB Pharma to pay 344,000 euros to the family of a young woman who died of cancer before the end of her trial.

2009:

  • September 24th – Turning point – The Supreme Court reverses the burden of proof, forcing UCB Pharma and Novartis to prove that their product is not responsible for the health issues of the DES victims who are taking their case to court. It is a massive step forward in the history of French DES legal battles since it allows women not to be dismissed when they can’t show proof that diethylstilbestrol have been prescribed to their mum. The Court however, gives victims who can’t show the original drug prescription the opportunity to pursue either Novartis or UCB Pharma and claim for compensation. The pursued laboratory now has to prove that the victims did not take their drug, but the competitor’s. UCB Pharma distributed Distilbène® which was by far the main drug used in France whilst Novartis distributed Stilbestrol-Borne®. So it is expected that the battle between UCB Pharma and Novartis is going to be fierce. Novartis won’t want to share responsibilities and compensations costs when their drug’s sales represented only 2% of the market share compared to 98% for UCB Pharma.
  • The same year, the Court also condemns UCB Pharma to pay “compensation provisions” of 70,000 Euros to a young disabled girl of 12 and 60,000 Euros to her parents.

2011:

  • June 09th – First victory for DES third generation – The Versailles Court of Appeal confirms the decision of the Court of Nanterre made in April 2009 and recognizes a link between taking Distilbène® and disability in the third generation, giving the grandson of a woman who was prescribed Distilbène® 1.7 million Euros in damages.

I wish the decision of the Court of Appeal of Versailles will encourage other victims to engage in this legal battle but it takes more than courage to file a lawsuit for such a complex and difficult journey against what seems to be a lost battle. I really admire the victims and their families who took their DES cases to court and thank them, as well as their lawyers, for allowing justice to make progress not only for them but for many other victims who may consider going to court in the future.

Distilbène®: 20 Years of Legal Battle is just a quick overview of the main dates in the history of DES French lawsuits. These lawsuits won’t bring back the DES daughters who died from cancer to the families affected by di-ethyl stilbestrol. They won’t repair the long term damages of this toxic drug but if nothing else they show that DES is not something invented by the media, or something that DES exposed individuals, like myself, should feel guilty about. We are victims and we deserve that justice is made.

I am missing important information and this blog post doesn’t highlight enough the pain and suffering the victims and their families had to go through to seek justice and get compensation. If you are considering filing a DES lawsuit make sure you seek expert advice and professional support from your local DES Action group.

Sources: Réseau DES France, Le Point.fr

More DES DiEthylStilbestrol Resources

DES National Public Education Campaigns

Listen to the short radio interview featuring Carol Devine, founder and coordinator of DES Action Australia (NSW), and Dr Jules Black, Queensland Gyneocologist and sexuality expert, about the silence around the DES issue and the difficulties to push for a much needed Australian DES National Public Education Campaign 10 years after the USA first DES national campaign launched in 2001. In Australia it is estimated that 740,000 people have been exposed to DES diethylstilbestrol, yet no such campaign has been held. These people are not receiving proper medical treatment, or making truly informed decisions about their healthcare, as a result.

Culture of Silence on sex hormone link to cancerRadio Interview about DES featuring Carol Devine and Dr Jules Black, produced by Annamarie Reyes April 05th, 2011.

Below is a short summary and a few quotes from this interesting radio interview from down under:

DES National Public Education Campaigns or the Wall of Silence

The USA has moved to legislate to make it compulsory that a DES National Public Education Campaign is held for DES affected communities. Dr Black explains that the USA acting first on public campaigns came out of increased pressure amongst affected women in the number of millions. In Australia he says “I found constantly with my patients a wall of silence”.

“Since the Food and Drug Administration approved this drug it was important for them to make sure this drug was ok (…). It wasn’t (…). There was a certain degree of cover up fear at first but then when the story came out and due to pressure by female organisations, support groups and so on, they admitted”, comments Dr Black. The FDA acknowledged the DES tragedy 40 years after they issued a warning about the DES cancer link.

The equivalent support group in Australia pushing for change is DES Action Australia (NSW). Carol Devine, the coordinator, explains the strugle to put the issue on the public agenda since the 1970’s when the issue came to light. The USA could not keep it quiet anymore. Too many people were affected by Diethylstilbestrol exposure. The USA went as far as holding a DES National Public Education Campaign in 2001 which led to legislate that research should happen and DES and potential DES affected people should be informed. “Over there”, comments Carol Devine, there is a fantastic body of women called DES Action USA. They are all right behind making sure these things happen in the USA”. In Australia, Carol Devine sent all the documentation papers about the USA DES National Public Education Campaign to the Australian Federal Health Minister. A few days later she received the package back in her doorstep saying “We do not require these”. “It has been a total shut down on this issue in Australia and quite frankly this is a national disgrace” comments Carol. Advocates in Australia have no choice but take the matters to the Human Rights Commission.

What’s the situation in France and Europe?

Reseau DES France educational brochure front cover image

In France and in other parts of Europe, the FDA warning issued in 1971 about the health concerns related to Di-ethyl Stilbestrol didn’t get heard and the drug continued to be prescribed to pregnant women until the late 1970’s early 1980’s. The support group Réseau DES France was established in 1994. Their first DES public education campaign was launched in 1997 with the brochure “DES Distilbène® Exposure, the questions you ask yourself” aimed at raising DES awareness amongst the general public. Since 1994 Réseau DES France has engaged in many areas (information, cooperation, advocacy and lobbying, and DES lawsuits to name just a few). They’ve achieved many results and successes such a the right to longer maternity leave for DES pregnancies.

In the United Kingdom, Ireland and the Netherlands support groups have also been created. DES Action UK launched a petition in 2009 to demand a Public Enquiry aimed at investigating the effects of the drug diethylstilboestrol (DES) on women. They collected 130 signatures. “The government statistics are hopelessly out of date and information is not freely or widely made available by the government” write the petition creators Nick de Bois and Barbara Killick.

I can’t stress enough the importance and crucial need for efficient DES National Public Education Campaigns to ensure all people affected by DES exposure are aware of its side effects for them and their children. Collaboration between DES Action groups is also very important. The silence around the DES issue poses health risks in itself as many people including doctors don’t even know what DES is, what the health risks are, and how to prevent them. With so many people affected by it, and so few aware that they have been exposed, it is the responsibility of our governments to raise public awareness of this global health catastrophe.

I wish DES Action Australia (NSW) the very best of luck with their battle for an Australian DES National Public Education Campaign and hope more DES daughters and sons will make their voice heard. We are not alone in this; Millions of people around the world have been exposed to DES so surely if we shout loud enough we will be heard not only by governments but also by fellow DES victims unaware of their DES exposure and its health risks.

Sources: Réseau DES France, DES Action Australia (NSW), DES Action UK

DES Cancer Link 40th Anniversary

The DES (Diethylstilbestrol) Drug Disaster, 40 Years Later

Below is a guest post from DES Daughter and WONDER DRUG screenwriter Caitlin McCarthy.

The DES Tragedy Is Far From Over

By Caitlin McCarthy

Caitlin McCarthy cover page Boston Globe image
In the April 18, 2011 issue of The Boston Globe, WONDER DRUG screenwriter Caitlin McCarthy appeared on the cover and in the feature story about DES

April 22, 2011 marks the 40th anniversary of the DES cancer link being made at Boston’s Massachusetts General Hospital.  DES (diethylstilbestrol), a toxic and carcinogenic synthetic estrogen, is considered the world’s first drug disaster. It was prescribed to millions of pregnant women for decades: from 1938 until 1971 (and in a small number of cases for several years thereafter) in the United States; and until the mid-1980s in parts of Latin America, Europe, Australia, and the Third World. The currently proven effects of exposure include a rare vaginal cancer in DES Daughters; greater risk for breast cancer in DES Mothers; possible risk for testicular cancer in DES Sons; abnormal reproductive organs; infertility; high-risk pregnancies; and an increased risk for breast cancer in DES Daughters after age 40. There are a number of other suspected effects, including auto-immune disorders, but many of these effects are still awaiting further research.

I’m a DES Daughter who was born at the tail end of the tragedy in the U.S. My mother was unknowingly prescribed a prenatal vitamin which contained DES. I didn’t discover my DES exposure until 2005, when a doctor made the connection during a colposcopy. How scary is that?

What’s even scarier is that I’m not alone. Around the world, there are thousands – maybe even millions – of people walking around today, totally unaware that they, too, were exposed to DES. All of these people are not receiving proper medical treatment, or making truly informed decisions about their healthcare, as a result.

In an effort to raise awareness about DES, I wrote a feature film screenplay entitled WONDER DRUG. Set in Boston, Massachusetts, WONDER DRUG interweaves the lives of a Big Pharma executive, feminist doctor, and thirtysomething newlywed across different decades. The script has won awards or received nominations in over 20 international film festival screenplay competitions and labs, including selection as an Alfred P. Sloan Foundation script for the prestigious Hamptons Screenwriters Lab, and a live staged reading of select scenes at the 15th Annual Hamptons International Film Festival, sponsored by the Sloan Foundation and starring Steve Guttenberg (THREE MEN AND A BABY) and Alysia Reiner (SIDEWAYS). Acclaimed independent director Tom Gilroy (SPRING FORWARD) has expressed an interest in directing WONDER DRUG. All we need now is financing. (Producers can contact me via my official website: www.caitlinmccarthy.com.)

I also worked jointly with the offices of US Senators John Kerry (D-MA) and Scott Brown (R-MA) on obtaining an apology from the FDA for the DES drug disaster. That effort was first publicized on acclaimed author Elizabeth Searle’s website, and later picked up by renowned media outlets such as The Huffington Post.. (Thank you, Diana Bianchini, for writing the HuffPo piece!).

The FDA declined to apologize, but did send a three-page letter to Senators Kerry and Brown acknowledging DES as a “tragedy” on February 22, 2011. Upon reading the FDA acknowledgement, I immediately emailed Jeanne Ireland (who signed the FDA’s letter), asking the FDA to remove DES from its webpage touting DES as one of its milestones in “100 Years of Promoting and Protecting Women’s Health.” Jeanne Ireland didn’t respond to me. Instead, she palmed me off on Marsha B. Henderson, Associate Commissioner for Women’s Health (Acting) for the FDA. (Check out the communication between Caitlin and Ms. Henderson by reading the post: The FDA is lying by omission).

To this day, the offensive item about DES remains on the FDA’s website. And to this day, not one drug company has ever apologized or accepted responsibility for the DES tragedy. Nevertheless, they have paid millions in verdicts and out-of-court settlements to DES Daughters and Sons who suffered injuries from their exposure.

I am grateful that the 40th anniversary of the DES cancer link has triggered a flurry of press coverage.  The Boston Globe recently ran a feature story about concerns for third generation effects; WCVB-TV Boston’s “Chronicle” newsmagazine aired a DES segment; Reuters published an item about DES Grandsons; New England Journal of Medicine ran an article about living with DES exposure; and Psychology Today features a story about remembering DES’s “tragic chapter in American childbirth.” Even the old “Lou Grant” TV episode about DES is making the rounds on Hulu.

On April 25, 1985, Ronald Reagan was the only US President to proclaim a National DES Awareness Week. No other president has ever done that. Why? DES is far from a dead issue.

I will continue my fight to raise awareness about the DES drug disaster. DES victims are the canaries in the coalmine when it comes to synthetic estrogen. The reproductive abnormalities, cancers, and infertility we deal with daily show what could happen to the human race if we don’t employ the precautionary principle. It suggests we act to protect public health when there is credible evidence of harm, rather than wait for absolute proof. What we do now clearly has an impact on future generations. Please join this fight with me.

Caitlin McCarthy ImageABOUT CAITLIN MCCARTHY:

Caitlin McCarthy received her Master of Fine Arts in Creative Writing from Emerson College, which is ranked by U.S. News & World Report as one of the best graduate programs in the country.  An award-winning screenwriter at international film festivals and labs, Caitlin has a screenplay project in development: RESISTANCE with Populus Pictures and director Si Wall (SPEED DATE; THE DINNER PARTY).  In addition to screenwriting, Caitlin serves as an English teacher at an inner-city public high school. Prior to education, Caitlin worked in public relations, where she fostered relationships with the press and crafted messages for companies that were delivered worldwide.