Legal and political
“Editors’ Overview: The existence of compounded bioidentical hormones and compounding pharmacies in the USA are at imminent risk of disappearing as never before. In 2002, prior to the WHI, 18 million American women–40% of those in menopause–were receiving hormonal treatment, the vast majority of which was with Premarin and Prempro. At that time, these were the most popular and profitable pharmaceutically manufactured drugs of all time. The false and terrifying scare mistakenly presented in the WHI, that there was an increased risk of breast cancer, heart attack, and stroke, exploded out into the public and healthcare professional worlds. Even the WHI study itself was falsely reported, Premarin was associated with a 0.76 relative risk (RR), thus a lower risk than non-treated women. Prempro had a 1.26 RR, declared statistically insignificant within the WHI–but the report was still published and over the objections of some of the study committee members. a HRT usage and sales plummeted to the low millions. By the time there was some recovery with the resumption of treatment, over half of the menopausal women receiving hormones were now being treated with compounded bioidentical hormones (cBHRT).6a, 6b, 6c This colossal loss of market share to the pharmaceutical manufacturers and the startling rise of popularity of cBHRT is opined by many to be the trigger to the pharmaceutical manufacturers to urge the FDA to put pressure on the healthcare professionals dispensing and prescribing cBHRT.4 The FDA receives the lion’s share of its funding from the pharmaceutical industry. There was a significant effort by the FDA in 2008 to undermine the compounding pharmacists. A massive show of support from American women led to protections–and losses–to the proponents of cBHRT. The protections seemed apparent…and, simultaneously, the laws enacted put substantial financial burdens on compounding pharmacists. Fast forward to 2018 where the FDA tasked and funded the National Academy of Science, Engineering and Medicine (NASEM) to do a study on the cBHRT (described below). This process, right out of the gate was assessed as a “stacked deck” by knowledgeable physicians, compounding pharmacists, attorneys, and lobbyists (see below). The 12 members of the NASEM committee, PhD’s and MD’s, had zero experience prescribing, dispensing or scientifically studying cBHRT. The FDA appeared to have an agenda and had a major influence throughout the process on the proceedings, conclusions, and reports of the Committee–contrary to US law. And, as predicted by proponents of cBHRT, the recommendations of the Report have the teeth to begin the demise of cBHRT for healthcare providers, American women, and men. The report basically comes down to recommending this final outcome! 2 Fortunately, there has been a very robust response by compounding pharmacists, (APC: a4pc.org, compounding.com), the Alliance for Natural Health (ANH: https://anh-usa.org), a coalition of healthcare professionals: physicians, compounding pharmacists, scientists, attorneys, lobbyists, and more (cbhrtcoalition.org), and lay public (wethewomen.org). We are together mounting multiple efforts with great commitment and intention, to protect these vital treatment measures that make such a monumental difference in millions of women and men’s lives, in the USA and all over the world. Please join us. Please see below for a sampling of the information, actions, and science related to cBHRT. Please join us. We do not want to lose these precious hormones, and, we so easily could. Please join us.
Here is a sampling of relevant information:
- Recommendation 1: Restrict the use of compounded bioidentical hormone therapy (cBHT) preparations….to documented allergy to an active pharmaceutical ingredient or excipient of U.S. Food and Drug Administration (FDA)-approved drug product, or a documented requirement for a different dosage form.
- Patient preference alone should not determine the use of cBHT preparations.
- documented allergy to an active pharmaceutical ingredient or excipient of U.S. Food and Drug Administration (FDA)-approved drug product, or a documented requirement for a different dosage form.
- Patient preference alone should not determine the use of cBHT preparations.
2. FDA Response to NASEM Report
- Quoting from the FDA Website, paragraph 2: “Based on its research and analysis, NASEM determined there was a lack of rigorous evidence of safety and effectiveness from well-designed or properly controlled clinical studies. NASEM found information about the safety and effectiveness of cBHT came mostly from low-quality data, such as anecdotal claims, patient reports, and prescriber testimonies. Further, there is limited federal and state-level oversight of the quality and use of cBHT preparations. Given the lack of high-quality clinical evidence and minimal oversight of cBHT, NASEM concluded that their widespread use poses a public health concern.”
- As a reminder:
- This NASEM Committee was tasked and funded by the FDA
The FDA receives major funding from the pharmaceutical industry4
- The pharmaceutical industry had the most popular and profitable prescription drugs of all time
- Premarin and Prempro—18 million American women were being treated—until the Women’s Health Initiative (WHI) study in 2002 (falsely) reported increased risk. Hormone treatment of women cascaded, 80% of women stopping hormone treatment.. By a 2017 study, there was recovery to women being treated to approx. 5 million.
- Issue: more than half of these women are being treated with compounded bioidentical hormones.
- Many believe this loss of market share is the principal reason that the FDA has been on a multifaceted program to eliminate compound
- This NASEM Committee was tasked and funded by the FDA
3. Responses to the NASEM report and the FDA Followup:
- “This report is evidence of yet another public attempt by FDA to discredit critical and life-sustaining compounded hormone therapies in the eyes of the public in favor of FDA-approved hormone therapies”
- The Report is just the latest chapter in a long battle initiated by FDA against compounders that specialize in cBHRT and the physicians and patients they serve. From its inception, the Study was not independent and demonstrated extraordinary bias, including gender bias.
- FDA unfairly and inappropriately influenced the NASEM Committee’s conclusions and recommendations to discredit cBHRT because it is not FDA-approved. The Federal Food, Drug, And Cosmetic Act (“FDCA”) via the Drug Quality Security Act (“DQSA”) exempt compounds like cBHRT from the new drug approval process, meaning FDA cannot evaluate compounded medication for its perceived clinical utility (i.e., for safety and effectiveness). FDA cannot, therefore, circumvent its governing federal statute and effectively force cBHRT through new drug approval via this commissioned Study.
- The Study was predicated on multiple forms of bias. In a review of who comprised the NASEM Committee, the materials the NASEM Committee chose to consider, and the organizations that provided data for the Study, it is clear that the scales were tipped far in favor of Big Pharma. The NASEM Committee also heavily relied on studies that it claimed demonstrated “methodologic rigor,” which have traditionally used the male body as the default and excluded women, and are therefore rooted in striking gender bias. These multiple forms of bias seriously call into question the credibility of the Report and the NASEM Committee’s conclusions and recommendations.
- FDA’s adoption or use of the Report violates FACA. FACA requires the membership of an advisory committee to be fairly balanced, and it also prohibits a federal agency from managing or controlling an advisory committee. In this case, the FDA heavily influenced the NASEM Committee and its conclusions and recommendations that the FDA, in essence, managed and controlled NASEM Committee. Jane Axelrad’s involvement, as well as the active measures the FDA took to control the outcome of the study, demonstrate the FDA’s undue influence over the NASEM Committee and its results. Accordingly, FDA may not adopt the Report without violating FACA.
- …we strongly discourage FDA from engaging the Pharmacy Compounding Advisory Committee (“PCAC”) for any evaluation of whether a bioidentical hormone in any form, including pellet form, should be a candidate for FDA’s Difficult to Compound List. It appears that PCAC itself is in violation of FACA for failing to be fairly balanced in the points of view represented and the functions it performs and is therefore in no position to be evaluating whether hormone therapies or categories thereof should be included on FDA’s Difficult to Compound List. Further, should PCAC place certain bioidentical hormones and pellets on the Difficult to Compound List, this will have devastating effects on the health and wellbeing of the millions of patients treated with cBHRT.
- FDA unfairly influenced the NASEM Committee to achieve its goals of discrediting cBHRT. FDA steered the NASEM Committee to conclude that cBHRT has no clinical utility and may be too difficult to compound. FDA did so in the following key ways: (1) by influencing the NASEM Committee’s definition of “clinical utility” in such a way that it effectively forces compounds through the new drug approval process, a process from which compounds are statutorily exempt; (2) by furthering its public campaign designed to discredit cBHRT; and (3) by indirectly encouraging the dominance of presenter and Report reviewer Jane Axelrad—who, as the former FDA lead on compounding for 21 years, is FDA on compounding issues
- Additionally, the NASEM Committee’s definition of “clinical utility” allows FDA to practice medicine—which the Agency is well aware it cannot do. As set out above, at FDA’s influence, the NASEM Committee defined “clinical utility” as a construct that reflects evidence about, among others, “therapeutic need.”12 The NASEM Committee clarified that “[i]n the context of this report, therapeutic need relates to the treatment of menopausal and male hypogonadism symptoms.”13 In other words, at the request and sponsorship of FDA, the NASEM Committee is evaluating whether a certain medication (i.e., cBHRT) treats two specific disease states—this is the practice of medicine, and the practice of medicine lies wholly outside the scope of FDA’s purview. Physicians—not FDA—are to determine which medication is appropriate to prescribe to best treat their patients. In commissioning NASEM to examine the “clinical utility” of treating patients with cBHRT, FDA effectively inserted itself into the decision-making process between a physician and his or her patient and called into question physicians’ judgment as to the use of cBHRT for treatment. Numerous courts have held that FDA does not have the legal authority to regulate the practice of medicine and even FDA has, in the past, acknowledged that it has no such authority.
- Rachael Pontikes 2nd submission to the FDA
- Before the Study even began, FDA provided one-sided information to NASEM on compounded medications, particularly hormone medications, that profoundly shaped the NASEM Committee’s position on cBHRT;
- As the Study began to materialize, FDA played a role in determining who should serve on the NASEM Committee and who NASEM should rely on as cBHRT subject-matter “experts”;
- [None of these professionals on the NASEM Committee treated women in menopause with cBHRT as part of their professional endeavors]
- [there are specific conflicts of interest in those advising the Board]
- During the course of the Study, FDA and the NASEM Committee consistently collaborated over substantive aspects of the Study; and
- Finally, FDA was given the opportunity to review and comment on the Report before it was published—a Report that was supposed to be advice independent from FDA.
- APC Alliance for Pharmacy Compounding: The APC has been putting forth a prodigious effort to address the NASEM/FDA pressure.Intheir immediate response9 to the NASEM report they had several key points:
- The NASEM study committee was populated by esteemed healthcare professionals, but there was not a pharmacist with patient-facing experience, much less a pharmacy compounder, in their number. Neither was there a physician with substantive experience in bioidentical hormone therapy. Likewise, the peer reviewers for the study included few compounders – but did include one former FDA employee (and current FDA contractor) who is a long-time, well-known opponent of pharmacy compounding.
- Although compounded drugs are exempt from the new drug approval process because they are prepared to meet individual patient needs, the foundation of NASEM’s analysis seems to focus on the absence of new-drug-caliber studies of compounded meds. The report makes an illogical leap by effectively deeming cBHT unsafe unless it can mirror drug manufacturing in terms of safety and effectiveness data, labeling, AE reporting, pharmacokinetic data, and scale of clinical trials.
- NASEM said it based its recommendations in large part on a review of literature, but identifies only 13 studies as having, in the judgment of the committee, suitable “rigor and relevance” – these, out of literally hundreds of studies out there, not to mention abundant patient outcomes data that could and should have been considered and weighed.
- The report calls for restricting the use of cBHT to patients with allergies to FDA-approved drugs, despite the fact that many FDA-approved therapies may not meet the dosing needs of patients – a point not addressed by the report’s recommendations.
- The recommendations seem to suggest that a prescriber’s medical judgment and a patient’s preferences should play no role in determining a proper course of treatment – a stunning assertion that is applied to no other aspect of medicine or pharmacy care. Women’s needs are much more complex than the cookie-cutter approach offered by current FDA-approved drugs. Individualized therapy is the result of a balanced approach between prescriber, patient, and pharmacist assessing each patient’s unique needs.
- The NASEM study seems to suggest that states that do not adopt USP <795> and <797> chapters in whole, without question or amendment, are somehow under-regulating compounders, yet it provides no evidence of patient harm that has resulted in states that adhere to different standards.
- The report cites concerns over bioavailability. However, many compounders or prescribers perform saliva or serum testing to confirm cBHT is appropriate therapy. Yet how many prescribers routinely check levels of FDA-approved products?
- The report sends mixed messages. Individualized therapy is a part of the FDA’s newly established goal of creating personalized therapies to target each patient. Factors such as age, weight, genetics, past medical history all contribute to appropriate treatment and dosage selection. Yet these NASEM recommendations seem to assert that FDA-approved drugs are always superior to compounded therapies.