Advancing Clinical Research with Pregnant and Lactating Populations Overcoming Real and Perceived Liability Risks (2024) / Chapter Skim
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2 Legal Liability
2 Legal Liability
Pages 49-80
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From page 49... ...
. This chapter examines and analyzes the liability landscape related to the participation of pregnant and lactating women in the clinical research of medical products.
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From page 50... ...
In other words, the risks of harm from the prod uct have not been evaluated in the controlled and monitored setting of a clinical trial, and without the generation of high-quality data through controlled clinical trials, health care providers and pregnant and lactat ing women are left to experiment -- with respect to safety, dosage, and effectiveness -- in the clinical setting. Yet there is reason to believe that manufacturers of approved products that cause harm to pregnant and lactating women, or their fetus or child, might be shielded from liability.
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From page 51... ...
In that context, liability is not anticipated to be any greater than with the general population; the only drug exposure is to the lactating woman and yet lactating women are also frequently excluded from clinical study. The committee's examination of civil liability includes both a review of the potential liability for harm to pregnant and lactating women and their fetus and/or child in the clinical research setting as well as the clinical setting.
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From page 52... ...
This includes cases deciding in favor of the defendant, settlements, the formation of multidistrict litigation, and other litigation-related activity. A SURVEY OF REPORTED LEGAL LIABILITY RISK A search of the literature revealed no existing survey on the legal liability risk associated with medical products researched in, and dis pensed to, pregnant and lactating women.
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From page 53... ...
No injuries were alleged in that case, though an appeal is pending.3 Postmarketing Liability for Pregnant Women In contrast to the dearth of legal cases in the clinical research setting, there are over 1,000 filed cases associated with pregnant women's post marketing use of medical products, both on-label and off-label, involving products prescribed for pregnancy-related conditions (e.g., Zofran -- morning sickness) and for general conditions nonspecific to pregnancy (e.g., Zoloft -- antidepressant)
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From page 54... ...
Discussion of the Case Survey Data Several conclusions may be drawn with a reasonable degree of con fidence based on the available data and general knowledge regarding the regulatory context and litigation involving medical products. In the most conservative interpretation, there is limited liability risk relating to the use of medical products in lactating women either in clinical research or through the use of approved medical products on the market.
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From page 55... ...
Similarly, although there are rough estimates of percentages of pregnant women who use medi cal products during pregnancy, there is no comprehensive reporting on how many pregnant women use those products or in what combinations. Nonetheless, this effort has produced a general profile of the landscape of legal liability relating to pregnant and lactating women's use of medical products.
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From page 56... ...
There are also aspects of clinical research that make lawsuits less likely to be filed, and if filed, to succeed, than other medical liability cases. Those factors continue to hold true even though there was an uptick in the number of clinical research claims (that did not involve pregnant and lactating women)
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From page 57... ...
There have been no reported cases based on injuries to pregnant or lactating participants in clinical trials since the 1963 promulgation of FDA investigational drug regulations. This would indicate that evidence of legal liability risk is not the driver of reticence in including pregnant and lactating women in clinical research.
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From page 58... ...
Liability Associated with the Use of Postmarketed Products As the case law demonstrates, there are legal liability risks to the use of medical products by pregnant and lactating women in the postmarket ing setting. Interestingly, there is arguably a scenario in which conduct ing clinical research in pregnant and lactating women could generate additional liability for the use of medical products in the clinical setting.6 Considerations Specific to Pregnancy It is not surprising that most of the cases involving injuries alleged to have been caused by in utero exposure to marketed medical products involve birth anomalies.
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From page 59... ...
. The potential for liability could be increased to the extent that the manufacturer encouraged use of the drug by or marketed the drug to pregnant and lactating women, such as by promoting it to OB-GYNs.
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From 1940 to 1971, DES was given to pregnant women to prevent miscarriage, premature labor, and related complications of pregnancy. DES use declined in the 1950s, after a double-blind clinical trial assessing pregnancy outcomes of women who received DES showed no benefit of taking DES in pregnancy.
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From page 61... ...
There is evidence of claims that include those arguments; for example, plaintiffs in the Paxil and Zofran cases did allege a failure to conduct studies about pregnancy risks. PERCEIVED LIABILITY Because the examination of legal liability risks associated with the participation of pregnant and lactating women in clinical research revealed little evidence of such risks, the committee then considered the potential drivers for the perception of liability.
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From page 62... ...
human subjects regulations applicable to pregnant women, discussed in detail in Chapter 3, do not apply to lactating women.8 It is possible that people simply view lactat ing women as part of a continuum from potentially pregnant to lactating and fail to disaggregate the different risks that are present at each stage. Regardless of the reason, conflating pregnant and lactating women does harm to lactating women by associating them with liability risk that evi dence does not support.
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From page 63... ...
While the committee has found very limited indications of legal liability risk in the context of clinical research with pregnant and lactating women, it is useful to understand the contours of that potential liability both to reduce uncertainty and to mitigate poten tial future liability, especially if clinical research involving pregnant and lactating women is to be expanded. Stakeholders Legal liability for research relating to the use of an investigational product by pregnant and lactating women involves medical product com panies and other research sponsors (e.g., contract research organizations)
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From page 64... ...
The legal bases for liability for injury resulting from research involving pregnant and lactating women are no different than the bases for any claim that arises in the context of clinical research generally. These claims arise under state law, mostly as torts, and include product liability, strict liability, breach of warranty, negligence, inadequate informed consent, failure to warn, and medical malpractice.
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From page 65... ...
, but rather to deliver generalizable scientific knowledge. Clinical research litigation is also a relatively new and rare phenomenon, and there are limited cases from which to glean informa tion about the relative duties of the various stakeholders and how legal principles applicable to medical product liability generally may apply.
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From page 66... ...
.15,16 In addition, if the information provided to the clinical investigator for the informed consent does not match information held by the sponsor, the learned intermediary doctrine may not apply.17 Finally, it is unclear how preemption doctrine may work to insulate a medical product sponsor from liability for failure to warn in a clinical research context. The theory of a preemption defense is that a manu facturer cannot be liable for injuries caused by a failure to warn if the applicable warnings were approved by FDA (Grossi and O'Connor, 2023)
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From page 67... ...
. IRBs were not originally a focus of drug-liability claims, even when clinical trials were involved, but creative claims by plaintiff's lawyers since the 1990s have greatly increased their exposure (Mello et al., 2003)
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From page 68... ...
The spe cifics of the laws vary from state to state, and not every state has a relevant statute that could apply to research involving pregnant and lactating women. A number of fetal personhood statutes went into effect after the U.S.
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From page 69... ...
. The table in Appendix C provides a "snapshot" of some of the state statutes that may affect research studies enrolling pregnant and lactating women.27 Unfortunately, it is impossible to provide a comprehensive table of all of the laws that might be relevant for conducting research in these populations.
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From page 70... ...
research that is done solely for the benefit of the fetus. Regarding research for the sole benefit of the pregnant woman or for the benefit of both the pregnant woman and the fetus, researchers must obtain the informed consent of the pregnant woman.
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From page 71... ...
It is therefore possible that a state may maintain that both parents should legally con sent to any research that may affect a fetus (Appendix E) .34 There is an argument that federal human subjects regulations preempt state laws in the context of clinical research, but that is an issue that has not yet been litigated in the courts.
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From page 72... ...
. Restrictive abortion laws should not affect clinical trials with lactating women, unless the lactating woman is also pregnant.
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From page 73... ...
, one of which is a case against a mother who took medication while pregnant that claims she failed to exercise "reasonable parental discretion."37 Participation in clinical research might insulate against such claims since the independent review may serve as additional evidence of "reasonableness," unless, of course, the research itself were subject to inquiry. In addition, in the general context of whether a mother can be held liable to her child for negligence while pregnant, courts tend not to recognize such a claim although they would likely recognize a claim against a third-party.38 As noted by the Massachusetts Supreme Court, "recognizing a pregnant woman's legal duty of care to her unborn child would present an unlimited number of circumstances that would likely give rise to litigation."39 This is also addressed in the Third Restatement of Torts, which reads "A number of courts have decided that mothers owe no duty of care to their unborn fetuses because of the infringement on autonomy and personal choice that such a duty would impose" (American Law Institute, 2010)
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From page 74... ...
A number of states have broad child abuse statutes that might be interpreted to expose a mother to liability because of medica tions taken while pregnant. Privacy concerns have long been a necessary consideration for research involving pregnant women, and there is evi dence that some states could attempt to expand their reporting require ments to clinical trial sponsors if they become aware of an induced or spontaneous abortion that might take place during clinical research.
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From page 75... ...
. No clinical studies on the COVID-19 vaccines for lactating women were reported in ClinicalTrials.
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From page 76... ...
Perceptions of liability are based on cultural narratives, which conflate clinical research with pregnant women with historical examples of drugs that were not subject to modern drug evaluation processes; ignore the potential benefits to pregnant and lactating women, their fetuses, and children resulting from research; and fail to account for the risk of harm and ensuing potential for liability resulting from failure to conduct clinical research in pregnant and lactating persons. REFERENCES Abraham, K
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From page 77... ...
2019. Guideline on the investigation of subgroups in confirmatory clinical trials.
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From page 78... ...
2022. The effects of COVID-19 vaccination on lactating women: A systematic review of the lit erature.
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From page 79... ...
2023. Inclusion of pregnant and lactating persons in clinical trials: Proceedings of a workshop.
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From page 80... ...
2021. Exclusion of pregnant and lactating women from COVID-19 vac cine trials: A missed opportunity.
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