Collaboration in Regulatory Science to Facilitate Therapeutic Development for Pregnant Women

Author(s): Catherine Roca*, Leyla Sahin, Lynne Yao

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 5 , 2019


Become EABM
Become Reviewer
Call for Editor

Abstract:

Background: Therapeutic tragedies of the past, ethical concerns, and legal risks, among other factors have led to a conservative approach to clinical research during pregnancy, resulting in a de facto exclusion of pregnant women from most clinical therapeutics trials. As a result, there is a deficit of knowledge regarding the safety and proper dosing of medications during pregnancy, leaving prescribers with limited information available to support clinical decision-making. Additionally, there is little development of treatments for pregnancy-specific conditions.

Methods: This review describes the current need for therapeutic development in pregnant women, summarizes the history of regulations impacting this research area, and describes current efforts to increase the information used to help make decisions regarding the use of drugs during pregnancy and lactation. This is a brief review of the literature, federal regulations, and policies on research in pregnant women.

Results: While therapeutic development in pregnant women has been limited in the past, recent efforts by academic researchers, bioethicists, industry, advocacy groups, and federal agencies have sought to enhance strategies to increase the participation of pregnant women in clinical research that may benefit them and/or their fetus.

Conclusion: Collaborative efforts from all stakeholders, including industry, academia, advocacy groups, regulators, and other governmental agencies, if successful will increase the information needed to help make decisions regarding the use of drugs during pregnancy and lactation.

Keywords: Regulation, pregnancy, pregnant women, research, drug development, Food and Drug Administration.

[1]
Martin JA, Hamilton BE, Osterman MJ, Driscoll AK, Drake P. Births: Final data for 2017. National Vital Statistics Reports 2018; 67(8)
[2]
Mitchell AA, Gilboa SM, Werler MM, Kelley KE, Louik C, Hernandez-Diaz S. National Birth Defects Prevention Study. medication use during pregnancy with particular focus on prescription drugs. Am J Obstet Gynecol 2011; 205: 51.e1-8.
[3]
Scaffidi J, Mol BW, Keelan JA. The pregnant women as a drug orphan: a global survey of registered clinical trials of pharmacological interventions in pregnancy. BJOG 2017; 124(1): 132-40.
[4]
Task Force on Research Specific to Pregnant Women and Lactating Women, Report to Secretary, Health and Human Services, Congress,. 2018 Sep; Avaible from: https://www.nichd.nih.gov/ sites/default/files/2018-09/PRGLAC_Report.pdf
[5]
Penkov D, Tomasi P, Eichler I, Murphy D, Yao LP, Temeck J. Pediatric medicine development: an overview and comparison of regulatory processed in the European Union and United States. Ther Innov Regul Sci 2017; 51(3): 360-71.
[7]
U.S. Code of Federal Regulations, Title 21 Section 314.40.
[8]
Guidance for Industry M3(R2) Nonclinical safety studies for the conduct of human clinical trial and marketing authorization for pharmaceuticals.
[9]
Briggs GG, Polifka JE, Wisner KL, et al. Should pregnant women be included in phase IV clinical drug trials? Am J Obstet Gynecol 2015; 213(6): 810-5.
[10]
Schardein JL. Chemically-induced birth defects. 3rd ed. New York: Marcel Dekkar 2000.http://dx.doi.org/10.3109/9780203909904
[11]
Lo WY, Friedman JM. Teratogenicity of recently introduced medications in human pregnancy. Obstet Gynecol 2002; 100(3): 465-73.
[12]
Mazer-Amirshahi M, Samiee-Zarfarghandy S, Gray G, van den Anker JN. Trends in pregnancy labeling and data quality for USapproved pharmaceuticals. Am J Obstet Gynecol 2014; 211 690. e 1-11.
[13]
Pariente G, Leibson T, Carls A, Adams-Webber T, Ito S, Koren G. Pregnancy-associated changes in pharmacokinetics: a systematic review. PLoS Med 2016; 13(11): e1002160.
[14]
Mitchell J, Goodman J. Comparative effects of antidepressant medications and untreated major depression on pregnancy outcomes: a systematic review. Arch Women Ment Health 2018; 21(5): 505-16.
[15]
Cohen LS, Altshuler LL, Harlow BL, et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA 2006; 295(5): 499-507.
[16]
Pariente G, Leibson T, Carls A, Adams-Webber T, Ito S, Koren G. Pregnancy-associated changes in pharmacokinetics: a systematic review. PLoS Med 2016; 13(11): e1002160.
[17]
Constantine MM. Physiologic and pharmacokinetic changes in pregnancy. Front Pharmacol 2014; 5: 65.
[18]
Andrew MA, Easterling TR, Carr DB, et al. Amoxicillin pharmacokinetics in pregnant women: modeling and simulations of dosage strategies. Clin Pharmacol Ther 2007; 81(4): 547-56.
[19]
Leck IM, Millar ELM. Incidence of malformations since the introduction of thalidomide. BMJ Med 1962; 2(5296): 16-20.
[20]
Greene JA, Podolsky SH. Reform, regulation, and pharmaceuticals--the Kefauver-Harris Amendments at 50. N Engl J Med 2012; 367(16): 1481-3.
[21]
New York Times January 21, 1964, page 31 New York Edition “Hospital Accused on Cancer Study: Live Cells Given to Patients Without Their Consent, Director Tells Court. Allegations is Denied; Chronic Disease Institution Defends Action – Value of Tests is Praised Available from: https://www.nytimes.com/1964/01/21/ archives/hospital-accused-on-cancer-study-live-cells-given-to-patients.html
[22]
Ward R, Krugman S, Giles JP, Jacobs AM, Bodansky O. Infectious hepatitis; studies of its natural history and prevention. N Engl J Med 1958; 258(9): 407-16.
[24]
H.R. 7724 An Act to amend the Public Health Service Act.
[25]
Guidance for Industry General Considerations for the Clinical Evaluation of Drugs, Center for Drug Evaluation and Research Available from: . https://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/Guidances/ UCM071682.pdf
[26]
Parekh A, Fadiran EO, Uhl K, Throckmorton DC. Adverse effects in women: implications for drug development and regulatory policies. Expert Rev Clin Pharmacol 2011; 4(4): 453-66.
[27]
Food and Drug Administration.Guideline for the Study and Evaluation of Gender Differences in the Critical Evaluation of Drugs. Fed Regist 1993; 58(139): 39406-16.
[28]
Pinn VW. The role of NIH Office of Research on Women’s Health. Acad Med 1994; 69(9): 698-702.
[29]
IOM Institute of Medicine. Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies 1994; Vol. 1, Ed. Mastroianni A, Faden R, and Federman D. Washington, DC National Academy Press.
[30]
National Institutes of Health Revitalization Act of 1993. Public Law. Congress of the United States of America 1993; 1: 103-43.
[31]
Lyerly AD, Little MO, Faden R. The second wave: Toward responsible inclusion of pregnant women in research. Int J Fem Approaches Bioeth 2008; 1(2): 5-22.
[32]
Blehar MC, Spong C, Grady C, Goldkind SF, Sahin L, Clayton JA. Enrolling pregnant women: Issues in clinical research. Women’s Health Issues 2013. 23-1: E39-45.
[33]
Guidance for Industry: Establishing Pregnancy Exposure Registries. Food and Drug Administration Center for Drug Evaluation and Research August 2002 Available from: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM071639.pdf
[34]
Guidance for Industry: Pregnancy, Lactation, and Reproductive Potential: Labeling for Human Prescription Drug and Biologic Products- Content and Format Food and Drug Administration Center for Drug Evaluation and Research 2014 Dec..
[35]
Draft Guidance for Industry: Pharmacokinetics in Pregnancy: Study Design, Data Analysis, and Impact on Dosing and Labeling 2004 Oct; Available from: https://www.fda.gov/ downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM072133.pdf
[36]
U.S. Code of Federal Regulations, Title 21 Section 50.3(k)
[37]
Public Law 114-255, 114th Congress, 2016 Dec 13;.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 25
ISSUE: 5
Year: 2019
Published on: 02 June, 2019
Page: [609 - 614]
Pages: 6
DOI: 10.2174/1381612825666190328112202
Price: $65

Article Metrics

PDF: 30
HTML: 6
EPUB: 1
PRC: 1