Overcoming Liability Concerns in Vaccine Trials Involving Pregnant Women

Abstract

Without the protection of vaccines, the health of pregnant women may be compromised. But assessing the safety and efficacy of vaccines in pregnancy requires research in pregnancy. Furthermore, vaccinating women while they are pregnant may convey immunity to the fetus in utero, but assessing this possible benefit of maternal immunization also requires research. This article argues that one factor inhibiting vaccine research involving pregnant women is that vaccine manufacturers fear incurring liability if they fund such research. We argue that vaccine research in pregnancy can be ethical, and we explore some methods for overcoming vaccine manufacturers' fear of liability.

Keywords:

• inclusion
• liability
• pregnancy
• research ethics
• vaccines

Notes

1. Health Canada is the department of the Canadian federal government responsible for the regulation of health products.

2. In Canada, such boards are known as research ethics boards. Since these bodies have different names in different countries, we here adopt a generic descriptor.

3. The United States now has legislated a no-fault compensation system for vaccine injuries (U.S. Department of Health and Human Services, 2006b). The province of Quebec is the only Canadian jurisdiction with a legislated no-fault compensation scheme for vaccine injuries (Santé et Services Sociaux Québec, 2012).

4. Infants under 6 months of age have varied immune responses to different vaccine antigens, making immunization strategies at that age ineffective for many vaccines (Healy and Baker, 2006 p. 271).

5. For many of these infections—GBS and RSV in particular—the goal of vaccination would be the protection of infants after birth, rather than the protection of pregnant women. Influenza vaccination differs in this respect from vaccination against these infections: influenza vaccination is meant to benefit both the pregnant woman and the infant after birth. We assume that any research involving pregnant women as a conduit for an intervention meant to benefit infants would minimize risk to the pregnant research participants by proceeding only after safety trials have first been performed on nonpregnant subjects. See Subsection B.3. below, which outlines some measures for maintaining the safety of maternal immunization trials.

6. Inactivated vaccines are made up of dead microorganisms. Bacterial vaccines contain dead bacteria, or bacteria attenuated to disable their virulence, or bacteria similar to, but less dangerous than, the bacteria targeted by the vaccine. Toxoids are vaccines against toxic compounds that cause illness when it is these compounds that cause illness rather than the microorganism itself. In the case of toxoids, the toxicity of the compounds is inactivated. Live and live-attenuated virus vaccines are created by altering a live virus so that it is no longer pathogenic, but can still cause an immune response against the target virus in the recipient.

7. GBS can be transmitted from mother to the baby at the time of birth. In order to prevent transmission, pregnant women are routinely tested for the bacteria, and are offered antibiotic prophylaxis during labor and delivery if they test positive. RSV is common in the physical environment and is contracted through contact with a carrier. Serious lung infections caused by RSV are common in infants. Infants who are at risk can be given monthly injections of RSV immune globulin. Visitors to neonatal intensive care units can also put on gowns and regularly wash hands to avoid transmitting the virus.

8. The two examples presented here deal with methods of protecting vaccine manufacturers. Other incentives are possible. For example, as recently as the 1990s, insufficient pharmaceutical research involving children was conducted (Grieve et al., 2005). In order to rectify this problem, the U.S. Federal Government passed the Food and Drug Administration Modernization Act (1997), which contained a “pediatric exclusivity provision” granting pharmaceutical companies an additional six months of patent exclusivity if they conducted approved research on their products involving children (Grieve et al., 2005). Similar kinds of incentives may or may not increase vaccine research involving pregnant women. Though there are similarities between children and pregnant women as neglected research participants, there are noteworthy differences. For instance, vaccine manufacturers may judge that the market for children's vaccines is larger than that for vaccines used in pregnancy, or they may judge that research involving pregnant women is more complex and costlier. Such differences may affect the effectiveness of an incentive promoting research involving pregnant women.

9. Personal communication with S. Halperin, principal investigator, June 21 2011.

10. The IWK Health Centre is a public institution. Under the laws of the Canadian province of Nova Scotia, the health centre could not provide an indemnity to the vaccine manufacturer without approval of the cabinet of the provincial government. So Dalhousie University provided the indemnity alone.