Ethical Barriers to Perinatal Mental Health Research and Evidence-Based Treatment: An Empirical Study

Abstract

Although more than 500,000 women annually experience a psychiatric illness during pregnancy, and approximately 30% will be prescribed medication, no psychotropic medications are approved by the Food and Drug Administration (FDA) for use during pregnancy. In the absence of an evidence base, investigators, clinicians, and patients are concerned that we are “operating in a vast sea of ignorance.” International pregnancy registries and observational studies exist, but there are few randomized controlled trials (RCTs), the gold standard of evidence-based medicine, due to the fear of fetal harm, even in non-pharmacological research. Current research guidelines reflect the ambivalence of regulatory agencies regarding pregnant research participants and use ambiguous language unhelpful to institutional review boards (IRBs), leaving perinatal women the last “therapeutic orphans.” This is a review of the issues as identified by perinatal investigators and a proposal to draft new collaborative guidelines to facilitate perinatal mental health research necessary for empirically-based treatment.

Keywords:

• perinatal ethics
• perinatal mental health
• perinatal research
• pregnancy
• research

Acknowledgments

Dr. Brandon acknowledges support from the National Institute of Mental Health Mentored Patient-Oriented Research Award “Partner-Assisted Therapy for the Treatment of Depression during Pregnancy” (1K23MH085007-02) and the National Institutes of Health Clinical and Translational Science Award for the pilot project “Survey of Investigator Ethics Practices in Perinatal Mental Health Treatment Research” (1 UL1RR024982-01). Dr. Brandon also expresses gratitude to the March of Dimes, which identified her as the “Young Scholar of the Year in Perinatal Bioethics” for the work represented in this article, presented at the American Society of Bioethics and Humanities 2010 Annual Meeting in San Diego, CA. Scott Stuart, MD (University of Iowa), Adrienne Einarson, RN (Motherisk), Diane Shepherd, RN (Director of the University of Texas Southwestern Medical Center at Dallas Institutional Review Board), and Anne Clark, BA, CIP (UT Southwestern Institutional Review Board), assisted in designing the semistructured interview instrument. Also acknowledged from UT Southwestern are John Z. Sadler, MD, and Robin B. Jarrett, PhD, for mentoring; colleagues Geetha Shivakumar, MD, Simon Craddock Lee, PhD, MPH, and Stephen Inrig, PhD, for significant contributions to both the research and the ensuing article; and graduate student Nadia Ceccotti, MEd,for providing support with audio transcriptions.

Notes

1. The World Health Organization in 1993 defined perinatal as the period of time between 22 weeks of gestation and 7 days after childbirth. To economize verbiage, in this document perinatal refers to pregnancy and the early postpartum. (WHO 2001).

2. Phase 1: First experiment with human participants; pharmacokinetics, pharmacodynamics, and efficacy evaluated in small samples of 20–80 individuals. Phase 2: At dosages established in Phase 1, researchers collect additional information about disease treatment with close monitoring and the use of control groups, in usually not more than several hundred participants. Phase 3: Several hundred to several thousand participants enrolled for evidence of effectiveness and additional information regarding side effects. Phase 4: Postmarketing surveillance studies investigate risks, benefits, dosages, costs, quality of life, and/or use of the drug over a longer period of time in population samples under “real-life conditions” (FDA 2009.)

3. “A”—adequate and well-controlled studies in pregnant women and/or animal reproduction studies have failed to demonstrate a risk to the fetus; “B”—animal reproductive studies have failed to demonstrate a risk to the fetus but there are no adequate and well-controlled studies in pregnant women or animal studies have shown an adverse effect but studies in pregnant women have failed to demonstrate a risk; “C”—if there are no animal studies or animal studies have shown an adverse effect on the fetus and there are no adequate studies in humans, but the benefits from the use of the drug in pregnant women may be acceptable despite the risks; “D”—positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or human studies, but the potential benefits from the use of the drug may be acceptable despite the risks; and “X”—studies in animals or humans have demonstrated fetal abnormalities, or there is positive evidence of fetal risk from adverse reaction reports from investigational and/or marketing experience, and the risk of the use of the drug during pregnancy outweighs any potential benefits.

*N exceeds 14 because some investigators endorsed multiple items.

4. “The harms that result from unforeseeable risks—for example, in the human body's reaction to a new drug, medical device, or chemical—are not a basis of liability” (The Restatement (Third) of Torts, Products Liability § 2, cmt. N (1997)).