Appendix A
Study Approach
Responding to a request by the U.S. Food and Drug Administration (FDA), the National Academies of Sciences, Engineering, and Medicine’s Committee on the Clinical Utility of Treating Patients with Compounded Bioidentical Hormone Replacement Therapy was charged with reviewing use patterns of compounded bioidentical hormone therapy (cBHT), the physiochemical properties of cBHT, and the available evidence on the safety and effectiveness of cBHT preparations.
COMMITTEE EXPERTISE
The National Academies appointed a 12-member committee of experts to address objectives in the Statement of Task. The resulting committee included experts in a variety of disciplines and fields, including drug research and development, pharmacology, toxicology, endocrinology, epidemiology, health literacy, pharmaceutical compounding and manufacturing, health risk mitigation, and health policy.
MEETINGS AND INFORMATION-GATHERING ACTIVITIES
The committee deliberated from March 2019 to April 2020, during the course of which it held five in-person meetings (March, May, June, August, and November) and four virtual meetings (one in September, two in January, and one in April). The March, May, June, and November meetings included portions open to the public. One of the January virtual
meetings was open in its entirety. All other meetings were closed to support the committee’s private deliberations.
In the open session meetings, the committee heard presentations from invited content experts on a wide variety of topics related to the committee’s charge. These open-session meetings also included periods of public comment, to provide an additional opportunity to present the committee with relevant information. The agendas for the five open-session meetings are presented here.
First Committee Meeting
Open Session Agenda
Tuesday, March 5, 2019
National Academies Keck Center
500 Fifth Street, NW, Washington, DC 20001
Part I
Sponsor Briefing: Discussion of the Committee’s Charge
1:15 p.m. | Welcome and Introductions |
JEROME (JERRY) STRAUSS III, M.D. | |
Committee Chair | |
1:20 p.m. | Sponsor Perspective on Charge to the Committee |
RUEY JU, PHARM.D., J.D., Study Sponsor | |
U.S. Food and Drug Administration | |
LESLEY FURLONG, M.D., Study Sponsor | |
U.S. Food and Drug Administration | |
2:00 p.m. | Discussion with Committee |
2:45 p.m. | BREAK |
Part II
Additional Context for the Study
3:00 p.m. | Key Stakeholder Perspectives |
BARBARA EXUM, PHARM.D., Director | |
Center for Compounding Practice and Research Virginia Commonwealth University |
TIMOTHY MCPHERSON, PH.D., Professor [REMOTE] | |
Department of Pharmaceutical Sciences | |
Southern Illinois University, Edwardsville | |
NESE YUKSEL, PHARM.D., Professor | |
Faculty of Pharmacy and Pharmaceutical Sciences | |
University of Alberta | |
4:00 p.m. | Discussion with Committee |
4:45 p.m. | Public Comments |
5:00 p.m. | ADJOURN |
Second Committee Meeting
Open Session Workshop Agenda
Monday, May 6, 2019
National Academies Keck Center
500 Fifth Street, NW, Washington, DC 20001
9:00 a.m. | Introductions |
LEIGH MILES JACKSON, PH.D., Study Director | |
Board on Health Sciences Policy | |
Health and Medicine Division | |
DONALD MATTISON, M.D. | |
Committee Chair | |
RUTH PARKER, M.D. | |
Committee Vice Chair |
Session I
Context for the Current Study
9:10 a.m. | Overview Session |
CYNTHIA STUENKEL, M.D. | |
University of California, San Diego | |
BRANT HARRELL, J.D. | |
Office of Tennessee Attorney General |
SARA ROTHMAN, M.P.H. | |
U.S. Food and Drug Administration | |
9:55 a.m. | Discussion and Q&A |
Session II
Consumer Engagement, Education, and Medical Care
10:40 a.m. | Perspectives from Consumers, Educators, and Medical Care Providers |
Consumer Education Perspectives | |
PHYLLIS GREENBERGER, M.S.W. | |
Healthy Women | |
CINDY PEARSON, M.D. [REMOTE] | |
National Women’s Health Network | |
LYN HOGREFE, M.S. [REMOTE] | |
Happy Hormone Cottage | |
Provider Perspectives | |
NANETTE SANTORO, M.D. [REMOTE] | |
University of Colorado Denver | |
ADRIAN SANDRA DOBS, M.D., M.H.S. | |
Johns Hopkins University School of Medicine | |
WANDA DYSON, M.D. | |
Change for Life Wellness & Aesthetics | |
DAVED ROSENSWEET, M.D. | |
The Menopause Method | |
12:40 p.m. | LUNCH BREAK |
Session III
Pharmaceutical Sciences and Compounding Panel
1:45 p.m. | Perspectives from Compounding Pharmacists |
A. J. DAY, PHARM.D., R.PH. [REMOTE] | |
Professional Compounding Centers of America | |
GUS BASSANI, PHARM.D. | |
Professional Compounding Centers of America |
JIM HRNCIR, R.PH. | |
Las Colinas Pharmacy | |
LOYD ALLEN, JR., PH.D., R.PH. [REMOTE] | |
International Journal of Pharmaceutical Compounding | |
3:15 p.m. | Discussion with Committee |
4:00 p.m. | Public Comments |
4:15 p.m. | ADJOURN |
Third Committee Meeting
Open Session Agenda
Thursday, June 27, 2019
National Academies Keck Center
500 Fifth Street, NW, Washington, DC 20001
12:45 p.m. | Welcome and Introductions |
DONALD MATTISON, M.D. | |
Committee Chair | |
RUTH PARKER, M.D. | |
Committee Vice Chair | |
12:50 p.m. | Presentations from Invited Speakers |
LOYD ALLEN, JR., PH.D., R.PH. | |
International Journal of Pharmaceutical Compounding | |
JANE AXELRAD, J.D. | |
Axelrad Solutions LLC | |
REBECCA GLASER, M.D. | |
Millennium Wellness Center | |
2:45 p.m. | Public Comments |
3:00 p.m. | ADJOURN |
Sixth Committee Meeting
Open Session Agenda
Tuesday, November 12, 2019
National Academies Keck Center
500 Fifth Street, NW, Washington, DC 20001
12:45 p.m. | Doors Open |
1:00 p.m. | Introductions |
LEIGH MILES JACKSON, PH.D., Study Director | |
Board on Health Sciences Policy | |
Health and Medicine Division | |
DONALD MATTISON, M.D. | |
Committee Chair | |
RUTH PARKER, M.D. | |
Committee Vice Chair | |
1:05 p.m. | Perspectives from Professional Associations and Organizations |
THOMAS MENIGHAN, B.S.PHARM., M.BA., SC.D. (HON), FAPHA | |
Executive Vice President and Chief Executive Officer | |
American Pharmacists Association | |
RONNA B. HAUSER, PHARM.D. | |
Vice President | |
Policy & Government Affairs Operations | |
National Community Pharmacist Association | |
1:30 p.m. | Q&A and Discussion (moderated by committee members) |
1:45 p.m. | Perspectives from Providers |
GARY S. DONOVITZ, M.D., FACOG | |
Founder | |
BioTE Medical, LLC | |
PAMELA SMITH, M.D., M.P.H., M.S. | |
Founder and Director | |
Center for Personalized Medicine | |
2:15 p.m. | Q&A and Discussion (moderated by committee members) |
2:45 p.m. | BREAK |
3:00 p.m. | Perspectives from Compounding Pharmacists |
PETER KOSHLAND, PHARM.D. | |
Chief Executive Officer | |
Koshland Pharmacy | |
GINA BESTEMAN, R.PH. | |
Director | |
Compounding and Dispensing | |
Women’s International Pharmacy | |
3:30 p.m. | Q&A and Discussion (moderated by committee members) |
4:00 p.m. | Public Comments |
4:30 p.m. | ADJOURN |
Seventh Committee Meeting
Open Session Agenda
Tuesday, January 14, 2019
National Academies Keck Center
500 Fifth Street, NW, Washington, DC 20001
12:00 p.m. | Introductions |
LEIGH MILES JACKSON, PH.D., Study Director | |
Board on Health Sciences Policy | |
Health and Medicine Division | |
DONALD MATTISON, M.D. | |
Committee Chair | |
RUTH PARKER, M.D. | |
Committee Vice Chair | |
12:05 p.m. | Perspectives from Invited Speakers |
RACHEL PONTIKES, J.D. | |
Partner | |
Reed Smith LLP |
ANGELA DEROSA, D.O., M.B.A. | |
Medical Director | |
Belmar Pharmacy & Belmar Select Outsourcing | |
DOUG CAMMANN, R.PH. | |
Vice President | |
Operations | |
AnazaoHealth Corporation | |
DONALD PRENTISS | |
President | |
Operations | |
Carie Boyd’s Prescription Shop | |
THOMAS C. KUPIEC, PH.D. | |
President and Chief Executive Officer | |
ARL BioPharma, Inc., DNA Solutions, Inc., The Kupiec Group, LLC | |
1:20 p.m. | Q&A and Discussion (moderated by committee members) |
1:40 p.m. | Public Comments |
2:00 p.m. | ADJOURN |
RESOURCES SUBMITTED BY STAKEHOLDERS
Recognizing the limited information available addressing the use, safety, effectiveness, and patient perspectives of cBHT, the committee also made concerted efforts to collect and review relevant anecdotal, survey, and (when possible) quantitative data from national stakeholders to supplement their research efforts. For example, relevant data were submitted by stakeholders, including FDA, Professional Compounding Centers of America, National Association of Boards of Pharmacy, Massachusetts Board of Registration in Pharmacy, Office of Tennessee Attorney General, National Women’s Health Network, representatives of 503A compounding pharmacies and 503B outsourcing facilities; an editor-in-chief of a leading compounding journal; nonprofit medical and pharmaceutical societies and organizations; compounding advocacy organizations; and nonprofit wellness organizations; women’s health advocacy groups; and medical prescribers and researchers of cBHT. Several testimonies, position statements, and letters were also submitted by Alliance for Natural Health, Alliance for Pharmacy Compounding, American Pharmacists Association,
American Society for Reproductive Medicine, Endocrine Society, International Academy of Compounding Pharmacists, National Community Pharmacists Association, Reed Smith LLP, Senator Lamar Alexander, Congressman Mark Pocan and Chris Stewart, and thousands of patients and professional advocates of cBHT.
COMMITTEE REQUEST FOR INFORMATION ON CBHT PREFERENCE AND USE
A “Dear Stakeholder” letter was emailed to a diverse group of study stakeholders in the summer of 2019.1 The letter invited the stakeholders to disseminate questionnaire links to their membership networks and/or followers in order to gather public input on the use of cBHT from three relevant populations: consumers, providers, and pharmacists and compounders.
A total of 3,370 respondents who self-identified as consumers initiated the questionnaire, and 2,068 completed it; 327 respondents who self-identified as prescribers started the questionnaire, and 180 finished it; and 386 respondents who self-identified as pharmacists or compounders began the questionnaire with 166 completing it. Although the majority of responses came from the United States, a portion of the overall input was received from the international community.
The questionnaire was not designed to capture a nationally representative sample of consumers, prescribers, or compounders, and therefore, likely has a high risk of selection bias. As a result of this confound, the questionnaire cannot be used to provide quantitative data to inform the conclusions on the use of cBHT. Instead, the committee used the qualitative responses as testimonial evidence to better understand overall perspectives on cBHT use and preference, evidence that is difficult to derive from the current evidence base.
Summary of Responses
Respondents Who Identified as Consumers
Respondents to the consumer questionnaire reported first learning about options for cBHT use from sources that included their physician and through word of mouth from other sources. Similarly, respondents reported relying on their physicians, as well as Internet sources, books,
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1 Stakeholders included medical societies, wellness centers and organizations, women’s health organizations, pharmacy associations, compounding organizations, government agencies, and education and research institutions.
and scientific literature, for information related to the potential safety and effectiveness of both cBHT and FDA-approved hormone therapy. Certain respondents expressed a lack of concern for the quality, safety, or effectiveness of cBHT preparations, while at the same time, also expressing concern for the quality, safety, and effectiveness of FDA-approved hormone therapy. Respondents who were satisfied with their use of cBHT tended to describe their satisfaction in terms of a preference for natural medications, overall improved well-being, and little to no adverse reactions.
Respondents Who Identified as Prescribers
Respondents who responded to the prescriber questionnaire specialized in fields including family medicine, obstetrics and gynecology, and wellness. Similarly, respondents represented various medical professions, including doctors of medicine (M.D.), doctors of osteopathy (D.O.), and nurse practitioners. Certain respondents expressed a lack of concern for the safety, product labeling, or quality of cBHT preparations, and reported a reliance on clinical trial data, professional experience, and patient response for evaluations on the safety and effectiveness of cBHT. Respondents varied widely in the types of circumstances they believed were appropriate to prescribe cBHT, in lieu of FDA-approved hormone therapy products. Certain respondents reported that they would prescribe only cBHT to their patients, while others described a narrow set of circumstances that would lead them to prescribe cBHT, in lieu of FDA-approved hormone therapies.
Respondents Who Identified as Pharmacists or Compounders
The respondents to the pharmacist and compounder questionnaire described a reliance on both published literature and professional experience for evidence on the potential safety and effectiveness of cBHT preparations. Resources for patients who describe the safety of cBHT formations varied—some respondents only provided oral instructions for use, others shared resources from compounding trade organizations, and still others distributed written information and instructions that were developed in house. Some respondents expressed having minimal concerns with the safety, labeling, or quality of cBHT preparations, while others stated that all hormones have risks.