I. INTRODUCTION
There is a growing recognition that disease processes, the manifestations of disease, and physiological responses to treatment sometimes may differ in men and women. Thus, information from clinical studies that either exclude women or include them in numbers too small to provide meaningful information may be insufficient to extrapolate to health conditions and disease treatment in women.
HIV, Women and Access to Clinical Trials: Tort Liability and Lessons from DES, DUKE JOURNAL OF GENDER LAW & POLICY, Volume 5:167, 1998.
Although many factors may have contributed to the under representation of women in clinical studies, the potential exposure of drug trial sponsors to tort liability frequently is cited as one of the primary reasons for excluding women from trials. The true source of legal anxiety in the recruitment of female research subjects arises, however, not from a concern for women’s safety, but from the fear of potential injuries to their offspring. Observations and reports of birth defects in children of women who had been treated with thalidomide or bendectin brought liability concerns to the forefront. When the courts held manufacturers liable for injuries caused to the offspring of women exposed to Diethylstilbestrol (DES), it became yet another reason for excluding pregnant women and women of childbearing age from clinical trials.
The failure to include adequate numbers of women in clinical studies of HIV and AIDS has had a significant impact on the health and welfare of women afflicted with the disease. In addition, proponents of the inclusion of women claim that women’s under representation endangers not only the health of each individual woman denied the opportunity to participate, but also jeopardizes the health of their potential offspring. In light of the growing number of AIDS cases in women between the ages of twenty-five and forty-four, it is critical that the health needs of this subgroup, which encompasses women of childbearing age and pregnant women, be addressed and that this population not be denied the benefits of research.
Recently, pregnant women have served as subjects in clinical trials of AZT. The federal government, stimulated by the AIDS crisis in women, has introduced guidelines and proposals to encourage the inclusion of women of childbearing age in clinical trials. Are sponsors of these trials exposing themselves to the possibility of tort liability similar to that associated with DES? Or, has the tort liability barrier to the inclusion of women of childbearing age in clinical trials been broken? The purpose of this Article is to examine the tort liability experience with DES, compare it to the recent and ongoing trials of AZT in pregnant women, and extract lessons that can be used to mitigate against the likelihood of tort liability and to encourage the inclusion of women of childbearing age in clinical trials.
Part II of this Article discusses potential theories of tort liability for research-related injury. Part III briefly explores two countervailing aspects of tort liability related to women’s participation in clinical trials: (A) liability exposure resulting from injury to the offspring born of women who participated in clinical trials (that is, liability for inclusion of pregnant women and women of childbearing age); and (B) liability exposure resulting from injuries to a population as a result of the failure to test the product in that population (that is, liability for exclusion of women, or a subset of women). The analysis focuses particularly on the liability exposure of the clinical trial’s sponsor because the sponsor wields considerable influence in the selection of the subject population and is likely to bear the substantial financial burden of liability. Part IV of the Article discusses the implications of the cases that arose out of the research and clinical use of DES on tort liability considerations for HIV and AIDS treatment research in women of childbearing age. Specific comparisons are made to current research and clinical use of AZT by pregnant women to prevent perinatal transmission of HIV to offspring. Part V details the lessons that should be learned from the liability experience with DES when examining the tort liability barrier to women’s inclusion in clinical trials. The Article concludes with recommendations for mitigating tort liability exposure for the inclusion of women of childbearing age and pregnant women in clinical trials, including a discussion of the need for early adverse event detection and improved informed consent processes.
II. RESEARCH-RELATED INJURIES AND TORT LIABILITY
Very little information exists regarding liability claims for research injuries. This paucity of available data is at least partly a product of a low incidence of such injuries. The lack of information also may reflect the reality of legal actions—that whether meritorious or not, actions often are settled or simply are not reported. Whatever the reasons, only a very small body of case law exists relating to research injuries.
Three theories of tort recovery potentially are applicable to a claim of research injury: battery, negligence, and strict liability. The first, battery, is an intentional and unlawful bodily contact upon another person without that person’s consent. In the research context, a battery action could arise if an individual were used as a research subject without her knowledge or consent. Both compensatory and punitive damages may be awarded for battery.
The second theory, negligence, requires the plaintiff to prove that the defendant owed the plaintiff a legal duty of care, that the defendant breached that duty, that the plaintiff suffered an injury, and that the injury was caused by the breach of the defendant’s duty. The duties owed to a research subject include the duty to provide adequate information about the potential risks of a research project and the duty to conduct and to monitor research properly. Negligence actions in the research context likely would raise issues concerning the duty to provide the study subject with informed consent. The plaintiff is required to present evidence of the standard of care for informed consent (that is, what constitutes reasonable disclosure under the circumstances), that the defendant breached this standard, that the research subject would not have chosen to participate in the research project if she had known about an undisclosed risk, and that the risk caused her injury. Negligence awards are compensatory, although in the case of extreme, or “gross” negligence, plaintiffs also may recover punitive damages, and third parties sometimes recover damages for loss of consortium.
The third theory of tort recovery, strict liability, does not require the plaintiff to prove the defendant’s negligence. While the second Restatement of Torts suggests that a manufacturer may be strictly liable if a product is sold “in a defective condition unreasonably dangerous to the user or consumer,” it also provides that drug manufacturers will not be liable as long as the drug, including those that are “new or experimental,” is “properly prepared and marketed, and a proper warning is given.” The rationale for this caveat rests on an acknowledgment that the therapeutic benefits of drugs outweigh known and reasonable risks. The newly-adopted third Restatement of Torts: Products Liability clarifies the circumstances under which prescription drug and medical device manufacturers will be held strictly liable for harm caused by their products. Under section 6 of the third Restatement of Torts, a “manufacturer of a prescription drug or medical device who sells or otherwise distributes a defective drug or medical device is subject to liability for harm to persons caused by the defect.” A product may be deemed defective because of a “manufacturing defect,” or because the product is not reasonably safe due to design or inadequate instructions or warnings of foreseeable risks of harm. The product must be defective at the time of sale or distribution for strict liability principles to apply. Unlike the strict liability limitation in the second Restatement of Torts, the newly-revised section and its accompanying notes do not address expressly liability for drugs used in the research context. Case law prior to the adoption of the third Restatement, however, suggests that the inclusion of the term “distributes” as an alternative to “sells” covers the use of drugs in the research context.
III. COUNTERVAILING ASPECTS OF TORT LIABILITY RELATED TO WOMEN’S PARTICIPATION IN CLINICAL TRIALS
A. Tort Liability for Inclusion of Women of Childbearing Age in Clinical Trials
The informed consent process is a central feature in how research is conducted today. This concept requires the disclosure of all facts “necessary to form the basis of an intelligent consent by the patient to the proposed treatment.” From a clinical trial sponsor’s perspective, the informed consent process not only preserves the autonomous decisionmaking of potential subjects, but also minimizes the sponsor’s liability exposure for research injuries. Specifically, a research subject may state a claim for battery by establishing that she never consented or knew of her participation in the study. If her initial consent were secured without adequate disclosure of risks, she may raise a claim of negligence. If risks were known to, or were foreseeable by, the sponsor but not disclosed to the subject, the subject then could bring a strict liability action.
The success of claims brought by, or on behalf of, offspring who were injured as a result of a mother’s participation in research is less clear, because an unborn child does not have the capacity to consent to participation. This appears to be the basis of sponsors’ fear of liability for including pregnant women and women of childbearing age in clinical trials, raising the questions of whether a mother’s consent to participate in a clinical trial immunizes the sponsor against tort liability for harm to offspring and whether a woman can consent to research risks on behalf of her fetus.
Only three reported cases involve alleged research injuries to offspring as a result of a woman’s participation in a clinical study, and in all three cases the research subjects were pregnant women. Two of the cases concerned the experimental use of DES, and the third involved the ingestion of radioactive iron. As discussed below, none of the pregnant women in these cases were given the opportunity to consent to participate in the study, nor were they informed that they were being used as research subjects.
DES is a synthetic hormone that was prescribed widely to pregnant women from the 1940s through 1971 to prevent miscarriage. Twenty years after its first use, researchers discovered that some of the daughters of the women who had taken the drug had developed a rare form of vaginal cancer. By that time, at least 1.5 million offspring had been exposed to DES, and hundreds of claims arose against the manufacturers who had produced the drug.
In the early 1950s, large controlled clinical trials of DES were conducted on pregnant women at the University of Chicago, which led to the cases of alleged research-related injury. Both cases were brought after the discovery of the carcinogenic potential of DES in offspring of women who had been given DES. In Mink v. University of Chicago, three women, on behalf of themselves and approximately one thousand women who had participated in the trials, alleged injury, as well as increased risk of injury, to their daughters. In Wetherill v. University of Chicago, the plaintiffs were two daughters who had contracted cancer that they attributed to the DES that was administered to their mothers while they were pregnant. In both Mink and Wetherill the plaintiffs claimed that the women taking DES never knew that they were participating in an experiment or that they were even taking DES.
In the hearing in Mink on whether the case brought by the mothers against the manufacturer and the institution conducting the research should be dismissed, the court held that the manufacturers had a duty to notify the women about the risks posed by DES at the time when the company became aware of them or should have become aware of them. The court permitted the battery allegations against the University of Chicago to stand, stating that nonemergency treatment performed without consent or knowledge raises a claim of battery. The case was settled with financial compensation to the plaintiffs and an agreement by the University of Chicago to provide medical services to women in the trials and to their offspring. In Wetherill, the court permitted the daughters to bring an action against the manufacturer and the University of Chicago. This case also settled, although the terms of the settlement were undisclosed.
Finally, a recent decision denied a motion to dismiss a claim of research injuries to offspring resulting from a clinical study of radioactive iron isotopes, referred to as Section B of the Tennessee Vanderbilt Nutrition Project. In Craft v. Vanderbilt University, the plaintiffs included both pregnant women and their offspring who brought an action against the organizations that sponsored the study, conducted by Vanderbilt University. While receiving prenatal care at Vanderbilt in the late 1940s, over 800 pregnant women were given radioactive iron as a part of a study to trace iron absorption in pregnant women. The plaintiffs maintained that they were never informed of the radioactive nature of the study or the risks of drinking the “vitamin drink” or “cocktail,” or given the opportunity to refuse to participate in the research study. The plaintiffs alleged that the risk of radiation was known at the time the iron was administered, and that the results of a follow-up study conducted in the 1960s that indicated a high risk of cancer from the radioactive iron were never revealed to the study participants. The court denied the defendants’ motions to dismiss and for summary judgment.
These cases are instructive because the courts permitted actions in battery where offspring were injured as a result of their mothers’ participation in research; these cases did not involve informed consent, however, because none of the women allegedly consented to participate in the research. Thus, these cases do not establish or identify the boundaries of liability for injuries to offspring when a woman properly has consented to participate in a clinical trial.
There is, however, some support in federal regulations and in non-researchrelated case law concerning risks of injury to offspring for the argument that the informed consent of the mother will be sufficient to shield the sponsor from liability. Analysis of those sources suggests that the purpose of the clinical trial may be important in determining whether the sponsor will be liable, that is, whether or not the trial drug is intended to benefit the health of the mother, the fetus, both, or neither. Roberts v. Patel explicitly recognized a mother’s ability to consent to medical treatment for an unborn fetus. Roberts appears to indicate that when the drug is intended to benefit the health of the fetus, when no negligence is involved, and when the informed consent of the woman is obtained (including a warning about the potential for risks to the fetus), the drug manufacturer will not be held liable for offspring injury.
Federal regulations promulgated by the U.S. Department of Health and Human Services over twenty years ago, and supported by an ethical analysis by a national bioethics commission, suggest that under certain circumstances it may be acceptable to perform research with pregnant women where the trial drug is intended solely to benefit the mother’s health. The regulations provide that research on pregnant women can be approved “where the purpose of the activity is to meet the health needs of the mother and the fetus will be placed at risk only to the minimum extent necessary to meet such needs.” The regulations also require that informed consent include the possible impact of the research on the fetus. In the same way compliance with FDA regulations is evidence of a manufacturer’s reasonableness in marketing a drug; these regulations and the work of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research might be used to provide evidence for the standard of conduct of a reasonable researcher. Following this reasoning, the best case for mitigating liability would be if the research subject were a pregnant woman with a life-threatening illness, if the woman is appropriately advised of the foreseeable risks to her and to her fetus (based on existing scientific information, including animal studies), and if the woman has no other known alternatives. This argument therefore would not support a protocol that poses very serious risks to the unborn child and offers little prospect of medical benefit to the woman.
Dicta in a 1991 Supreme Court employment discrimination case may provide additional support for asserting that the informed consent of the woman will preclude the imposition of liability. In UAW v. Johnson Controls, Inc., the company’s argument for excluding women (whether pregnant or not) from jobs with potentially high levels of lead exposure was based on a fear of injury to potential children. The Court rejected this justification for exclusion, supporting instead the autonomous decisionmaking authority of the pregnant or potentially-pregnant woman. The Court commented that “if, under general tort principles, Title VII bans sex-specific fetal-protection policies, the employer fully informs the woman of the risk, and the employer has not acted negligently, the basis for holding an employer liable seems remote at best.”
Following the foregoing reasoning, liability appears to be minimized when there is adequate informed consent by the woman, which includes disclosure of possible risks to the fetus (provided, of course, that there are no other negligent actions by those in the research enterprise). In addition, the low incidence of research injury and the difficulties in proving causation for research injury minimize the likelihood of liability imposition. Any assessment of liability exposure, however, must be balanced against considerations of possible liability for excluding women of childbearing age from clinical trials.
B. Tort Liability and Exclusion of Women of Childbearing Age from Clinical Trials
Liability for excluding women from clinical trials has not been addressed directly by the courts, but there is some tangential support in case law. The potential for liability for excluding women from clinical trials reflects a conceptual shift among members of the research community and the public towards participation in research. Historically, serving as a research subject was viewed as benefiting others, sometimes at significant personal risk; federal policies therefore focused on protecting subjects’ rights and interests, and preventing abuse. Today, participation often offers a high likelihood of direct medical benefit, and participants now assert their “right” to enter a study. In addition, heightened public awareness and concern about the potential impact of exclusion likely will act to increase the probability of legal action. The specter of liability falls predominantly on the manufacturers of the experimental drugs.
Liability for exclusion may arise when a woman takes a drug or treatment that was not tested on women but proves to be more dangerous or less effective in women once the drug is on the market. The case law makes it clear that inadequate testing is a basis for imposition of liability on both negligence and strict liability principles and courts have not hesitated to evaluate research design critically and to scrutinize the activities of sponsors. For example, in West v. Johnson & Johnson Products, Inc., damages were awarded to a woman allegedly injured as a result of using a tampon where the manufacturer failed to test the product adequately. Similarly, in Taylor v. Wyeth Laboratories, Inc., the court found that an oral contraceptive manufacturer’s potential negligence was a jury question where the manufacturer failed to examine the causal relationship suggested by studies showing that women with a particular blood type experienced a disproportionate number of adverse reactions to the drug.
Manufacturers are at risk under strict liability principles for defective product design, and inadequate testing may be considered a design defect. In addition, manufacturers have a duty to warn about foreseeable risks that should have been known, a requirement that can be met only with state-of-the-art product testing. With the current state of knowledge and sensitivity to potential physiological gender differences, an argument could be made that male-only studies do not qualify as “state-of-the-art.” The protection afforded by the third Restatement of Torts and by the second Restatement’s limitation may not be available: a manufacturer’s claim that a drug is unavoidably unsafe may be undermined if it is not tested on women but nonetheless causes harm. A similar argument could be made concerning testing on women of childbearing age. Women in clinical trials who are counseled personally about the known risks and possibility of unknown risks of the drug to them and to their potential offspring probably are less likely to become pregnant while using the drug than women in the general population who rely on warnings found in package inserts proclaiming the unknown dangers in the event of pregnancy. In terms of medical outcome, and, therefore, potential liability, it would be more effective to monitor an unintended pregnancy and its outcome under controlled circumstances in a clinical trial setting than to allow a drug to be used by large numbers of women in the general population. The women who do not receive medical monitoring and who suffer injury to themselves or to their offspring may be more motivated to bring a legal action. These actions likely will prove costly to defend even if causation is not proven and no damages are awarded.
IV. COMPARATIVE ISSUES OF TORT LIABILITY: AZT AND DES
Are we destined to repeat the DES experience with AZT use by pregnant women? What risk of liability might there be in the use of AZT in research involving pregnant women? An examination and comparison of issues arising in the use of DES and AZT follows.
A. Transplacental Carcinogenicity and AZT
Studies indicate that AZT use by an HIV-infected woman during pregnancy and by her infant after birth can reduce maternal-fetal transmission of HIV by up to two-thirds. On the basis of such studies, the U.S. Public Health Service and professional organizations have recommended that HIV-infected pregnant women take AZT. Because scientists suspect that AZT might have carcinogenic potential, there have been animal studies and follow-up studies in pregnant women and their offspring. No tumors have yet been observed in human studies of approximately 1000 children who had been exposed to AZT in utero and followed for an average of three years after birth. Preliminary results from one animal study conducted by the National Cancer Institute (NCI) indicated that very high doses of AZT during the third trimester of pregnancy increased the risk of tumors in the liver, lungs, and reproductive organs in mouse offspring. Another mouse study utilized a different protocol and was conducted by AZT’s manufacturer, Glaxo Wellcome. The results of this study indicated that AZT used during the course of pregnancy at somewhat higher doses than would be used in current clinical practice in humans, but at significantly lower levels than that of the NCI study, caused vaginal tumors in the offspring of mice exposed to AZT throughout their lifetime and resulted in no increased risk of cancer in the offspring of those mice exposed to AZT while pregnant.
In January 1997, the National Institutes of Health (NIH) convened an independent expert panel to review the data from these studies. The panel concluded that the two animal studies were of “uncertain relevance” to humans. Nonetheless, the panel
- identified the need for further research in this area, and specified research priorities;
- specified the need for counseling pregnant women about the possible cancer risk in offspring in clinical trials and clinical practice;
- emphasized the need for long-term follow-up of all exposed offspring, including those who were not infected with HIV;
- and recommended reassessment of the Public Health Service’s clinical practice guidelines.
Overall, the panel concluded that the “known benefits of AZT in preventing perinatal transmission appear to far outweigh the hypothetical concerns of transplacental carcinogenesis raised by the NCI mouse study.”
B. AZT versus DES
As AZT becomes accepted as the commonly-prescribed therapy for reducing the risk of perinatal HIV transmission, the potential for cancer in offspring raises the specter of DES liability. The key factors that distinguish research experience with AZT in pregnant women from that of DES are (1) the drug’s purpose, the woman’s health status, and the intended beneficiaries of the drug; (2) in the clinical trial, the woman’s consent, warnings of potential known and unknown fetal risks, and monitoring and follow-up of the study population; and (3) in clinical practice, the provision of warnings of potential risks to the woman and/or fetus and notification of results of new research studies. The way in which these factors are addressed likely will impact the potential liability for offspring injury. Table 1 below briefly compares these factors with respect to the use of AZT and DES by pregnant women in clinical trials and clinical practice. When considered side-by-side, the contrast in the experience with DES and AZT is stark.
In light of the NIH panel’s recommendations, it is unclear how and whether information about risks is being conveyed to pregnant women who formerly received, or currently are receiving, AZT. If information is not communicated properly, it raises the potential for liability in negligence and strict liability. If the recommendations concerning communication of risk and reevaluation of clinical practice guidelines are in fact implemented, however, risks of liability likely would be minimized in the case of AZT; the elements of consent, monitoring, additional research, and dissemination of information clearly distinguish research experience with AZT in pregnant women from that of DES.
V. LESSONS FROM DES FOR REDUCING POTENTIAL LIABILITY
Adverse reactions to experimental drugs and devices will occur despite the best preclinical testing. Imposition of tort liability is just one approach to compensate for these research-related injuries. Nationally recognized expert bodies have recommended mandatory no-fault compensation systems and inclusion of medical care reimbursement for research-related injuries in health care reform efforts. Private approaches include contractual models and voluntary adoption of compensation plans. These public policy alternatives, however, are unlikely to be adopted in the near future, and private approaches are employed infrequently. Without alternatives, tort liability, or the threat thereof, is left as the only realistic action for those seeking compensation for research injuries.
There are at least three lessons to be learned from the liability experience with DES that should be considered in addressing the tort liability barrier that women of childbearing age face in accessing research and experimental therapies.
First, the risk of liability for including women of childbearing age in clinical trials is quite small when compared to the potential for substantial liability when a drug is released into the general population and used by women of childbearing age without first being tested on this group. Clinical trial sponsors cannot escape the reach of tort liability by excluding women of childbearing age from research; sponsors will have to counterbalance liability exposure associated with offspring injury resulting from inclusion of women of childbearing age in clinical trials with liability exposure that arises when a drug is prescribed in clinical practice in a population of women of childbearing age in whom the drug has not been tested adequately. Excluding these women and ignoring the possibility that they may be, or may become, pregnant while taking a marketed drug is naive. The numerous legal actions, the number of women affected, and the magnitude of recovery for the clinical use of DES far exceeded that which arose from the research use of DES or that which could have arisen had there been adequate informed consent in the research studies.
Second, early adverse event detection reduces the number of children who will be exposed to the drug in the future, which will result in a corresponding reduction in the magnitude of liability exposure. An argument could be made to support claims of negligence and strict liability on grounds of failure to warn or failure to test adequately and that risks to offspring based on a mother’s exposure to a particular drug are reasonably foreseeable in the general population. This is especially true where a drug is intended to preserve pregnancy and the health of the fetus (DES) or to protect the health of the mother and the fetus (AZT), as one can argue that the “fetus can be seen as an intended beneficiary of the drug and a foreseeable victim of injury.” With strict liability claims, the sponsor will not be responsible for such harms unless they were known at the time of distribution. If such adverse events are discovered quickly and are made public, fewer injuries will occur in the future, and it is less likely that the sponsor will face a claim that a reasonable drug company would have discovered the effects in offspring earlier. The difficulty is that the potential for mutagenic or teratogenic effects may be low or may manifested only after a long latent period. At least three steps could be taken to reduce liability exposure for offspring injury in both the research and clinical use populations: (1) conduct animal reproductive studies and continue these studies following drug distribution in the general population; (2) initiate long-term medical follow-up in offspring of clinical trial participants who became pregnant during research participation; and (3) continue post-marketing surveillance in the general population of users. If such efforts are undertaken, it would be difficult to argue that a reasonable drug company could have discovered the effects in offspring earlier.
These approaches raise practical issues in need of resolution. Mechanisms need to be developed to locate and to maintain long-term contact with study participants and their offspring. Pregnant women and women of childbearing age should be notified of the potential for ongoing evaluation of their offspring as part of the informed consent process when they are advised that long-term and short-term risks to offspring are not yet known. Steps need to be taken to improve awareness of post-marketing surveillance efforts, including establishing registries among HIV-infected pregnant women, their offspring, and their health care providers. Locating offspring for post-trial and post-marketing surveillance raises particularly vexing issues in the HIV-infected population: if a mother succumbs to the disease, her children may be orphaned and difficult to locate. In addition, the demographics of HIV-infected women indicate that they and their children may be less likely to have access to regular medical care that would facilitate such follow-up.
How does a sponsor determine the point at which scientific conclusions from ongoing research and monitoring become foreseeable risks that would require a duty to warn clinical and research populations? This question is no different for harm that potentially may affect offspring than for any other affected population, as experience with AZT points out. As discussed earlier, an independent panel of the National Institutes of Health was convened to review the data from two animal studies. The panel stressed the need for counseling all HIV-infected pregnant women in clinical practice or in clinical trials about the risk of AZT treatment interventions, advocated a thorough reassessment of the Public Health Service guidelines on the use of AZT to reduce the risk of perinatally-acquired HIV infection, and identified additional research priorities. Sponsors may not only want to conduct their own studies, but also may want to convene independent panels to review data as it emerges to ensure that they are meeting a reasonableness standard that will not be judged harshly in court.
Once a foreseeable risk is established, whether through post-trial or postmarketing surveillance, the study and clinical population must be reached through medical alerts and directives, which must be tailored to the population that they are intended to benefit. For example, sponsors should consider whether the standard approaches through the “learned intermediary” are acceptable in light of the population using the drug. HIV-infected women and their offspring may not have access to regular medical care. Perhaps more important to minimizing liability exposure, strategies need to be developed to identify and to notify the population of offspring exposed to AZT who may have been orphaned at an early age and who were fortunate not to have contracted the disease through perinatal transmission. This population is likely to be lost easily in follow-up.
Third, adequate warnings provided during the informed consent process should greatly reduce the likelihood of recovery in a tort action. General legal theories of liability and case law in both the research and the clinical contexts indicate that adequate informed consent is paramount to minimizing the risk of a successful legal action for research injury. The Institute of Medicine’s Committee on the Ethical and Legal Issues Relating to the Inclusion of Women in Clinical Studies provided comprehensive guidance on information that should be incorporated into the informed consent process when women (and men) of reproductive age, lactating women, and pregnant women participate in clinical trials. For women and men of reproductive age, such information includes risks to reproduction and potential offspring, and, where appropriate, discussions of birth control and pregnancy termination options. For lactating women, the consent process includes the notification and identification, if possible, of risks to offspring. Finally, for pregnant women, adequate information includes evaluating risks and benefits to themselves, their pregnancies, and their potential offspring. Pregnant women also should be urged to consult their obstetrical care providers before they participate. As with all research, an interactive consent process with the potential research subject, rather than sole reliance on a signed consent form, improves the meaningfulness and quality of the informed consent process. These additional actions are important especially when the perception of liability exposure is considered to be high.
It is disturbing that some informed consent processes lack even the minimum of information described above. One review of informed consent documents in thirty-six AIDS clinical trials indicated that only seventeen percent provided information about known teratogenic risk and that specific directions were not provided should a pregnancy occur during the clinical trial. Because institutions, institutional review boards, and researchers could be held accountable for missteps in the informed consent process, clinical trial sponsors have a strong incentive to develop effective strategies to communicate this important information to the research subjects through these other parties.
The potentially-significant benefit of these actions should not be underestimated. Studies outside the clinical trial context underscore the impact of good communication between providers and patients in reducing the likelihood of malpractice claims. Although no studies have evaluated liability exposure reduction for research injury and the role of the relationship between the research subject and the investigators, institutions, or sponsors, studies have indicated the importance of the trust relationship between the subject and those conducting studies in motivating people to participate in clinical studies. Building on and solidifying this relationship may be valuable in reducing liability exposure for research injury.
VI. CONCLUSION
Tort liability for inclusion of women in clinical trials is just one of the potential barriers hindering advances in women’s health, as well as the health of society as a whole. Earlier inclusion of women of childbearing age in HIV and AIDS research would have prevented serious harm to women’s health and reduced the burden on the health care system of treating HIV-infected women, their partners, and their children. In addition to balancing the risk of liability for inclusion against liability for exclusion, steps can be taken to minimize liability exposure. It is imperative that follow-up studies in offspring and ongoing monitoring be conducted and that information on risk be communicated immediately to all those affected by participation in clinical trials. While trials must be constructed and monitored carefully in order to address the tort liability barrier, the search for a cure simply cannot exclude women.
Anna C. Mastroianni, 06/10/98.
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