Bulletin Today
APhA Staff
The American Academy of Sleep Medicine has initiated an investigation into the safety of melatonin, which is increasingly used as a solution for chronic insomnia.
The body produces this potent hormone naturally from the pineal gland in large volumes at night to signal that it is time to sleep and at lower levels during the daylight hours.
The concern is not only whether high amounts of melatonin might be harmful, but also whether they might have an unfavorable effect on blood sugar, blood vessels, body temperature, and other physiological functions.
Melatonin is available OTC, often in the form of fruit-flavored gummy chews. In addition to having varied and unregulated levels of melatonin, OTC products often contain serotonin or unknown byproducts whose effect in this setting are uncertain. Melatonin may be safe over the short term, according to researchers, but is more questionable over the long term—particularly as it relates to potential disruption of puberty in pediatric users.
With so many unknowns, FDA will probably need to regulate melatonin as a medication, said Muhammad Adeel Rishi, MD, vice chair of the academy’s Public Safety Committee.
In the meantime, the academy recommends that both children and adults refrain from using melatonin as a sleep aid while the investigation is being conducted. ■
FDA increases racial and ethnic diversity in clinical trials
FDA issued a draft guidance document for developing plans to enroll more participants in clinical trials from underrepresented racial and ethnic populations. The draft guidance advises sponsors of medical products to develop and submit a race and ethnicity diversity plan to the agency based on a framework outlined in the guidance early in clinical development.
Obstacles to participation among racial and ethnic groups may include language and cultural differences, suspicions about the clinical research system, insufficient trial recruitment and retention efforts, and caregiver or family responsibilities, according to FDA.
To support FDA’s goal of advancing more diverse participation, the Office of Minority Health and Health Equity created the Diversity in Clinical Trials Initiative, which features ongoing public education and outreach efforts.
The initiative also uses several culturally and linguistically customized resources, tools, and strategies, including educational materials in multiple languages and a dedicated webpage with public service announcements and videos.
One of the targets of the Biden Administration’s Cancer Moonshot program is to curb disparities in access to cancer screenings, diagnostics, and treatment. The draft guidance was developed by the Oncology Center of Excellence’s Project Equity, which aims to ensure that the data submitted to FDA for approval of oncology medical products adequately reflect the demographic representation of participants for whom the medical products are intended. ■
USPSTF issues update to aspirin use and CVD
The U.S. Preventive Task Force (USPSTF) has updated its 2016 recommendation on the use of aspirin to protect against cardiovascular disease (CVD) and colorectal cancer (CRC).
The new recommendation advises against starting low-dose aspirin for primary prevention of CVD in anyone aged 60 years and older, who USPSTF said will garner no net benefit from the therapy.
Based on the evidence, USPSTF identified a small net benefit from aspirin therapy in adults aged 40 to 59 years, who have a 10% or higher risk of CVD over 10 years.
Patients with no elevated risk for bleeding and the ability to follow a daily regimen are most likely to benefit, according to the revised guideline, which previously recommended low-dose aspirin for Americans aged 60 to 69 years with a 10-year CVD risk of at least 10%.
The suggestions are made with moderate certainty in the evidence. New trial findings and other data, however, were insufficient to demonstrate a favorable effect on CRC incidence or mortality associated with aspirin therapy. ■
CMS eliminates retroactive DIR fees
CMS has issued a final rule that put an end to PBM’s retroactive application of direct and indirect remuneration (DIR) fees, requiring that they be reflected in the negotiated price the patient pays at the pharmacy counter. The rule included all price concessions beginning on January 1, 2024.
CMS’ final rule also put an end to a proposed loophole that would have given authority to the Medicare Advantage Part D plans and PBMs to determine how much, if any, of the pharmacy price concessions they would pass through to patients at the point of sale during the coverage gap in the Medicare Part D program.
APhA and many of their members recommended the change to CMS and expressed gratitude that the agency took its advice. “APhA appreciates CMS’ efforts to end the uncertainty and lack of drug cost transparency at the pharmacy caused by retroactive DIR fees,” the organization wrote in a statement.
Between 2010 and 2020, CMS reported that retroactive DIR fees increased by a staggering 107,400%.
These price concessions negotiated between PBMs and pharmacies participating in Medicare Part D networks are assessed weeks, or even months, after Part D beneficiaries’ prescriptions are filled. Retroactive DIR fees resulted in pharmacies realizing only long after the prescription was filled that they did not recoup their costs. These retroactive fees also resulted in patients paying more at the pharmacy counter for their prescription drugs.
CMS’ final rule does not remove DIR fees, but instead moves them to the point-of-sale negotiated price. This change in policy hopes to benefit patients by lowering out-of-pocket costs and helps pharmacists increase predictability, consistency, and transparency.
“Eliminating the retroactive use of DIR fees is a step in the right direction, but it’s only the tip of the iceberg to end PBMs’ business practices that are harmful to patients and hurt our nation’s pharmacies,” said Scott J. Knoer, MS, PharmD, FASHP, APhA executive vice president and CEO.
Though CMS’ rule acknowledged the impact of retroactive DIR fees, it failed to address the transition period for pharmacies from calendar year 2023 to 2024. Medicare Part D beneficiaries will start seeing lower out-of-pocket costs and pharmacies will receive the “lowest possible reimbursement” in 2024. However, PBMs will continue to collect retroactive DIR fees from 2023, which will create significant cash flow issues for pharmacies during the transition.
CMS also did not tackle other PBM policies such as negative reimbursements (through which the PBM reimburses the pharmacy less than it costs to acquire the drug) and “patient steering” for brand, generic, and specialty drugs to PBM-affiliated pharmacies.
“Although it provides some predictability for pharmacies, more action is needed to address PBMs’ anticompetitive practices that are impacting the viability of neighborhood pharmacies,” said Theresa Tolle, BSPharm, FAPhA, APhA president. ■
How effective are antidepressants?
Antidepressants, including serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors, are widely used in the United States despite a number of unknowns related to their clinical performance. One of the biggest unknowns stems from the dearth of evidence on the efficacy of the drugs over the long term, as most studies have followed up with participants for only 8 to 12 weeks. Researchers also do not know much about how antidepressants affect mental and physical quality of life over time.
A new study in PLOS One examined the effects of antidepressant use from 2005 to 2016 on patient-reported health-related quality of life for individuals with depression. The study, based on data from more than 17 million Americans participating in the U.S. Medical Expenditures Panel Survey, found no substantial differences in the changes in quality of life among patients who used antidepressants and those who did not. However, there are potential limitations to the study findings: the study compared groups of people who may have been experiencing different levels of depression, and the people who were taking antidepressants may have been taking them for a while and may have already experienced quality of life improvements before the study began.
The literature to date suggests that individuals do register modest improvement in symptoms in the initial months of antidepressant use, but the jury is still out on whether these small changes have a noticeable effect on mood or overall function. It is also up for debate whether the small improvements are worth the possible adverse effects, which may include nausea, agitation, weight gain, reduced libido, and indigestion. Additionally, the benefits of antidepressants appear to be much less pronounced in people with mild versus severe depression. That raises a red flag, too, because by one estimate nearly three-quarters of Americans who take the drugs have not even been diagnosed with depression. ■
More than 50% of people worldwide have headache disorders
More than 50% of people all over the world experienced a headache disorder in the past year, according to new research published in the Journal of Headache and Pain. The disorders—which include migraines, tension headaches, cluster headaches, and headaches related to things like exercise or sinusitis—affect 52% of people, the study found. Each day, an estimated 15.8% of the world’s population has a headache, the researchers said.
The study, which was based on a search of more than 350 scientific publications, noted differences in headache disorders by criteria such as gender and geographic area. Women reported more headache and migraine than men, with rates of 57.8% versus 44.4% and 17% versus 8.6%, respectively. More headaches were also reported in high-income countries than in low-income countries. According to the researchers, many published studies on headache disorders “were deficient in their reporting” despite continuing efforts to standardize methodologies. ■