As part of my Human Biology major program, I used to attend weekly group discussions. Most weeks, I would leave the student-led class and feel satisfied with the way that discussions went; I felt that the time we took to share our opinions and/ or data left me with closure on a certain bioethical and/ or public health topic. However, there was one discussion that, until recently, I had not been able to decide on completely.
When presented with the idea that pregnant women should no longer be categorized as part of a “vulnerable population” within research studies, my gut reaction was to disagree. As a society, we view pregnant women as very delicate people and thus believe that they must be “vulnerable.” I recently came to realize that my initial opinion was guided by stubbornness and planting myself in a belief without deliberately thinking it through. While this topic deserves a much deeper analysis, I believe that this brief outline sums up the major points.
Pregnant women (according to UVA’s Institutional Review Board) may currently participate in clinical research under these conditions: “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 or the risk to the fetus is minimal.” This makes complete sense, however, this is already true for all other research. As researchers, we are always trying to place the individuals in the least amount of risk possible [1].
I’d like to stress the definition of the word vulnerable within the clinical research realm. The term “vulnerable population” is generally saved for those that are not viewed as “autonomous agents and/ or their voluntariness is compromised” [2]. The members of this group include children, prisoners, and those that are cognitively impaired. These groups may either be easily coerced due to their situation or they may not be capable of making autonomous decisions. In my mind, however, a pregnant woman does not meet either of these standards. It is in fact insulting to insinuate that a woman, just because she is pregnant, cannot make a decision for herself.
Some may take this chance to argue that a child is at stake in this situation and that a woman cannot make a decision on the behalf of this child. (Worth mentioning is that both a mother and father must currently give consent for a pregnant woman to become a human research subject. There are some exceptions. [1].) There is this idea that the maternal-fetal interests may be at a crossroads with each other. Instead, for the most part, maternal-fetal interests are well-aligned [3]. If the maternal health is at risk, so is the child’s. If we do not have enough evidence to know what medications or treatments are beneficial for a pregnant woman, and her fetus, we cannot accurately treat them. Physicians are currently taking guesses with medications without being able to consult any research on the effects they may have on pregnancy. They are making assumptions based on little data, which is potentially more damaging than the alternative.
In the mid-1950s to early 1960s, many pregnant women in countries outside of the United States began taking thalidomide for nausea during pregnancy. Physicians soon discovered a connection between the drug and severe birth defects in babies. Fortunately for many pregnant American women, FDA inspector Frances Kelsey prevented approval of thalidomide in the United States because she felt there was insufficient data on the effectiveness and safety of the drug. After this incident, pharmaceutical companies were required to prove that drugs were both safe and effective [4]. According to a 2011 CDC research study, about 90% of pregnant woman take a medication at some point in their pregnancy and 70% take at least one prescription drug. These numbers have steadily increased since the 70’s as the stigma around pregnant women taking prescription drugs has started to slowly disappear [5]. Women feel safer taking medications even though there is not necessarily data supporting whether medications are safe or unsafe for pregnant women to take.
In a recent review, researchers found that only 1% of pharmaceutical-sponsored drug research is designed specifically for pregnant women. This study also found that, for studies of conditions that potentially affect pregnant women, 95% specifically excluded pregnant women from participating. If a condition does not solely apply to pregnant women, the FDA does not require that efficacy and safety of a medication be proved in pregnant women. This is clearly an issue because most conditions that pregnant women take medications for are not exclusive to just pregnant women. This leads to physicians making uneducated or undereducated guesses about medications they can prescribe to their pregnant patients [6].
Women in general have been discriminated against in the scientific realm for years now. Until the past five years or so, there was not much oversight for requiring animal trials to include both male and female animals. The male-focused studies have been used in order to reduce the “confounding contributions from the oestrous cycle.” In other words, the reproductive system of a female animal added more hormones, and therefore more variables to a study. It is extremely problematic to view the male body set as the “normal” body. Male and female systems do work differently and should be scientifically analyzed differently. However, I am unsure how this became equivalent to the female body being less important to examine or the female body being viewed as a male body with additional components [7]. The reason I bring this up is to show that we cannot treat all bodies in different categories, for lack of a better term, as equivalent because it can be detrimental. The National Institute of Health is increasing their oversight on equal male and female animal participation because there were sex differences in multiple medications, such as multiple sclerosis medications and aspirin.
Although I bring the point of animal research up, I do want to note that including pregnant female animals in research is not enough to validate data. An analysis of a 2014 medical reference book showed that of the 93 drugs that are known to cause human developmental toxicity, nearly 20% of these drugs were miscategorized as low-risk based off of animal data. Researchers need to go a step further to include pregnant women in human trials to more accurately know effects and thus should remove their designation as a “vulnerable population.”
Going back to the current conditions of research in pregnant women, I want to reemphasize that women do not fit into the general definition of a “vulnerable population.” Yes, we should take measures to make sure there is minimal risk, but this applies to ALL research participants. I hope that by this point you agree that there is a high need for data on the effects of medication on pregnant women. I would like to present a solution that would minimize the risks to pregnant women and their fetuses: include pregnant women in Phase IV clinical trials.
It takes between eight and twelve years to approve a medication. The phases of clinical trials include: Phase I – assessing the safety of a drug or device, Phase II – testing the efficacy of a drug or device, Phase III – randomizing and blind testing in patients, and Phase IV – “Post Marketing Surveillance Trials” [8]. By Phase IV, a drug has been approved for consumer sale but acts to compare to drugs already on the market and discover their long-term effectiveness [9]. Because the drug is already approved at this point, deliberate inclusion of pregnant women in this part of clinical trials allows for what is currently happening to continue happening with a more thoughtful driving force. Physicians can continue to prescribe prescription drugs to pregnant women as they would before, but there is a record of the impacts for future patients and future research. A patient is still allowed to keep their autonomy and decide whether or not to continue with this treatment. The patient is informed, autonomous, and actions are being taken to minimize all risks. A policy to include pregnant women in Phase IV studies is affordable and should help to streamline/ consolidate physician knowledge on the impact of drugs on their patients.
Six months after starting this conversation with my Human Biology class, I have come to the realization that this research is necessary for the health of our future generations. If we remove pregnant women as “vulnerable populations” and increase their presence in Phase IV clinical trials, we are likely to accomplish the goal of adding valuable data to the medical field for the betterment of society. Pregnant women should not be categorized as vulnerable populations because they are quite the opposite; they are, instead, exceptionally valuable.
References:
"Institutional Review Board for Health Sciences Research (IRB-HSR)." Vulnerable Subjects - Pregnant Women, IRB-HSR. Accessed September 21, 2017. http://www.virginia.edu/vpr/irb/hsr/vulnerable_pregnancy.html.
Protection of Vulnerable Populations in Research In addition to vulnerable subject populations such as children, prisoners, and. Accessed September 23, 2017. http://research-compliance.umich.edu/sites/default/files/resource-download/protection_of_vulnerable_populations_in_research.pdf.
Lyerly, Anne Drapkin, Lisa M. Mitchell, Elizabeth Mitchell Armstrong, Lisa H. Harris, Rebecca Kukla, Miriam Kuppermann, and Margaret Olivia Little. "Risk and the Pregnant Body." The Hastings Center Report 39, no. 6 (2009): 34.
Fintel, Bara, Athena T. Samaras, and Edson Carias. "Helix Magazine." The Thalidomide Tragedy: Lessons for Drug Safety and Regulation | Helix Magazine. Accessed September 23, 2017. https://helix.northwestern.edu/article/thalidomide-tragedy-lessons-drug-safety-and-regulation.
"Treating for Two." Centers for Disease Control and Prevention. August 18, 2016. Accessed September 23, 2017. https://www.cdc.gov/pregnancy/meds/treatingfortwo/data.html.
Briggs, Gerald G., Janine E. Polifka, Katherine L. Wisner, Eric Gervais, Richard K. Miller, Anick Berard, Gideon Koren, Alicia Forinash, and Craig V. Towers. "Should pregnant women be included in phase IV clinical drug trials?." American journal of obstetrics and gynecology 213, no. 6 (2015): 810-815.
Clayton, Janine A., and Francis S. Collins. "Policy: NIH to balance sex in cell and animal studies." Nature News. Accessed September 23, 2017. http://www.nature.com/news/policy-nih-to-balance-sex-in-cell-and-animal-studies-1.15195.
"Overview of Clinical Trials." CenterWatch. Accessed September 23, 2017. https://www.centerwatch.com/clinical-trials/overview.aspx.
Briggs, Gerald G., Roger K. Freeman, and Sumner J. Yaffe. Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. Lippincott Williams & Wilkins, 2012.