Friday, September 10, 2021

FDA SHILLS SNAKE OIL

Researchers: Majority of patients with Alzheimer’s disease would not have been eligible for clinical trials of new controversial Alzheimer’s drug

Findings suggest more research is needed before treating patients with Alzheimer’s disease who have advanced age or many chronic conditions with aducanumab

Peer-Reviewed Publication

BETH ISRAEL DEACONESS MEDICAL CENTER

BOSTON – In June 2021, the Food & Drug Administration (FDA) granted accelerated approval for aducanumab to treat patients with mild cognitive impairment or mild dementia due to Alzheimer’s disease. The two phase-3 clinical trials of aducanumab on which the drug’s approval was based showed increased risk of certain adverse vascular events. Though the clinical trials excluded participants based on advanced age, certain chronic diseases and use of anti-clotting medications, FDA approval was granted without contraindications or precautions for use of the drug in these patient populations.

In a research letter in JAMA, physician-researchers at Beth Israel Deaconess Medical Center (BIDMC) examined medical claims for Medicare enrollees with a diagnosis of either cognitive impairment, Alzheimer’s disease, or Alzheimer’s disease related disorders. The team found that the vast majority of these patients had one or more conditions that would have excluded them from the aducanumab clinical trials, including cardiovascular disease, prior stroke, use of blood thinners, and age over 85 years.

“Our findings are concerning given the broad FDA labelling for aducanumab,” said corresponding author Timothy S. Anderson, MD, MAS, a clinician investigator and assistant professor medicine in the Division of General Medicine at BIDMC. “The public conversation on aducanumab has focused on limited benefit and high costs, it is equally important to consider that the majority of patients with Alzheimer’s disease are likely to face higher risks of adverse events than the patients studied in the trials.”

Analyzing data from more than 27 million Medicare beneficiaries, Anderson and colleagues found that more than 92 percent of patients with Alzheimer’s disease related dementia, 91 percent of patients with Alzheimer’s disease and 85 percent of patients with cognitive impairment met at least one of the aducanumab trial exclusion criterion. More than 77 percent of patients with Alzheimer’s disease related dementia met multiple exclusion criteria, as did majorities of patients with the other diagnoses.

“Clinical trials of aducanumab studied relatively healthy participants who do not reflect the majority of older adults with dementia in the US,” Anderson said. As a result, Medicare should consider restricting coverage for aducanumab to patients who meet the trial eligibility criteria, and additional clinical trials of the high-risk groups excluded from the prior trials should be required, including rigorous study of adverse events, prior to broadening coverage.”.”

Co-authors included Bruce E. Landon, MD, MBA, of Harvard Medical School and the Division of General Internal Medicine at BIDMC; John Z. Ayanian, MD, MPP, of University of Michigan; and Jeffrey Souza, MA, of Harvard Medical School.

This work was supported by grants from the National Institute on Aging (P01AG032952; L30AG060493; and R03AG064373). Dr. Anderson reports receiving grants from the American College of Cardiology and Boston Claude D. Pepper Older Americans Independence Center outside of the submitted work, and honoraria from Alosa Health, a non-profit educational organization with no relationship to any drug or device manufacturers.

About Beth Israel Deaconess Medical Center
Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding.

BIDMC is the official hospital of the Boston Red Sox. For more information, visit www.bidmc.org.

Beth Israel Deaconess Medical Center is a part of Beth Israel Lahey Health, a health care system that brings together academic medical centers and teaching hospitals, community and specialty hospitals, more than 4,800 physicians and 36,000 employees in a shared mission to expand access to great care and advance the science and practice of medicine through groundbreaking research and education.

JOURNAL

JAMA

DOI

10.1001/jama.2021.15286

ARTICLE TITLE

Representativeness of Participants Eligible to Be Enrolled in Clinical Trials of Aducanumab for Alzheimer Disease Compared With Medicare Beneficiaries With Alzheimer Disease and Mild Cognitive Impairment

ARTICLE PUBLICATION DATE

9-Sep-2021

Disclaimer: AAAS an

AMERIKA ONLY CARES ABOUT WHITE JUNKIES

Disparities in opioid overdose deaths continue to worsen for Black people, study suggests

NIH-supported study underscores the need for racially inclusive approach to address the opioid crisis in hard-hit areas

Peer-Reviewed Publication

NIH/NATIONAL INSTITUTE ON DRUG ABUSE

Non-Hispanic Black individuals in four U.S. states experienced a 38% increase in the rate of opioid overdose deaths from 2018 to 2019, while the rates for other race and ethnicity groups held steady or decreased, according to a new study by the National Institutes of Health published in the American Journal of Public Health. These alarming data are in line with other research documenting a widening of disparities in overdose deaths in Black communities in recent years, largely driven by heroin and illicit fentanyl. The research emphasizes the need for equitable, data-driven, community-based interventions that address these disparities.

The research was conducted as part of the HEALing Communities Study, which aims to significantly reduce opioid-related overdose deaths by helping communities implement evidence-based practices to treat opioid use disorder and reduce other harms associated with opioid use in New York, Massachusetts, Kentucky, and Ohio. It is the largest addiction implementation study ever conducted and is administered in partnership by NIH’s National Institute on Drug Abuse (NIDA) and the Substance Abuse and Mental Health Services Administration through the Helping to End Addiction Long-term Initiative, or NIH HEAL Initiative.

“We must explicitly examine and address how structural racism affects health and leads to drug use and overdose deaths,” said NIDA Director Nora D. Volkow, M.D. “Systemic racism fuels the opioid crisis, just as it contributes mightily to other areas of health disparities and inequity, especially for Black people. We must ensure that evidence-based interventions, tailored to communities, are able to cut through the economic and social factors that drive disparities in substance use and addiction, to reach all people in need of services.”

For this study, data were collected from death certificates for 2018 and 2019 across 67 communities with a total population of more than 8.3 million people in the four states participating in the HEALing Communities Study. The researchers calculated rates and trends of opioid overdose deaths overall and for each state, and then further analyzed trends by race and ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, other). Overall, the investigators observed no change in the opioid overdose death rate in these states from 2018 (38.3 deaths per 100,000 people) to 2019 (39.5 deaths per 100,000 people).

However, the researchers observed a 38% overall increase in the opioid overdose death rate for non-Hispanic Black individuals from 2018 to 2019, across these four states. There were no changes overall among the other racial and ethnic groups. Trends varied at the state level and increases among non-Hispanic Black individuals were highest in Kentucky (a 46% increase) and Ohio (a 45% increase). The investigators did not observe a significant increase in Massachusetts among non-Hispanic Black individuals. While opioid overdose death rates were unchanged for non-Hispanic Black individuals in New York, there was an 18% decline among non-Hispanic white individuals, suggesting that non-Hispanic Black individuals have not benefitted equally from prevention and treatment efforts.

The study authors note that these data add to the evidence of increasing disparities in opioid overdose deaths by race and ethnicity, and highlight the importance of access to timely, local data to inform effective community-tailored strategies to reduce these deaths. Numerous evidence-based prevention and treatment interventions exist for addressing the opioid overdose crisis, overdose education and naloxone distribution, medications for opioid use disorder, behavioral therapies, and recovery support services. Unfortunately, these interventions have largely failed to gain widespread implementation in community settings including addiction treatment, general medical care, social support services, schools, and the justice system.

To address this challenge, the HEALing Communities Study is working with local, state, and federal partners to gain access to data on opioid-related overdose fatalities, treatment, and other related health concerns in a timelier fashion and include important demographic information including race and ethnicity. Early access to these data was instrumental in informing HEALing Communities Study intervention planning, including discussions ensuring evidence-based practices are equitably available to all racial and ethnic groups. For example, these data informed partnerships with Black community organizations to improve access to overdose education and naloxone distribution.

While the data presented here were critical in shaping public health response, the timeliness of data about drug use, addiction, and overdose is an ongoing challenge. National and state data are typically collected annually, access to the data is limited, and data may not be available for months. Health data related to race and ethnicity may be limited or completely unavailable, and mortality data are particularly lagged due to the time required for toxicology testing.

“The more local and timely data communities have access to, the more tailored their approach can be for interventions,” said lead author Marc Larochelle, M.D., M.P.H., a general internal medicine physician at Boston Medical Center and assistant professor of medicine at Boston University School of Medicine. “We know there are disparities in implementation of effective strategies for reducing opioid overdose deaths, but early access to better data like these allows communities to address equity with improved intentionality.”

The Helping to End Addiction Long-term Initiative and NIH HEAL Initiative, are registered service marks of the U.S. Department of Health and Human Services.

Reference: MR Larochelle, et al. Disparities in opioid overdose death trends by race/ethnicity, 2018-2019, from the HEALing Communities Study. American Journal of Public Health. DOI: 10.2105/AJPH.2021.306431 (2021).

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About the National Institute on Drug Abuse (NIDA): NIDA is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports most of the world’s research on the health aspects of drug use and addiction. The Institute carries out a large variety of programs to inform policy, improve practice, and advance addiction science. For more information about NIDA and its programs, visit www.nida.nih.gov.

About the NIH HEAL Initiative: The Helping to End Addiction Long-term Initiative, or NIH HEAL Initiative, is an aggressive, trans-NIH effort to speed scientific solutions to stem the national opioid public health crisis. Launched in April 2018, the initiative is focused on improving prevention and treatment strategies for opioid misuse and addiction and enhancing pain management. For more information, visit: https://heal.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health®

JOURNAL

American Journal of Public Health

DOI

10.2105/AJPH.2021.306431

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Disparities in opioid overdose death trends by race/ethnicity, 2018-2019, from the HEALing Communities Study

ARTICLE PUBLICATION DATE

9-Sep-2021

Megaprojects and the ‘need for speed’: How political indecision affects the timelines of large infrastructure investments

An analysis of 26 projects from Toronto and London, U.K. points to ‘long informal gestational periods’ as major factors in extending project timelines

BECHTEL LET HD MACHINERY SINK INTO MUSKEG WHILE CONSTRUCTING TAR SANDS IN FORT MAC

Peer-Reviewed Publication

UNIVERSITY OF TORONTO FACULTY OF APPLIED SCIENCE & ENGINEERING

Building a new transit line or a highway almost always takes longer than initially planned. A new study suggests that the biggest contributor to such delays isn’t necessarily the design, planning or even construction phases. Instead, it’s the time required for local or provincial authorities to decide what exactly they want to build.

“Here in Toronto, there is a strong need for infrastructure, such as more housing and better public transit — and really, we needed it years ago,” says University of Toronto Engineering Professor Shoshanna Saxe, one of the lead authors of a new study recently published in the European Journal of Transport and Infrastructure Research.

“With this big a deficit, there is a sense of urgency and a need to move fast. On the other hand, large infrastructure is expensive, permanent and causes a lot of disruption. You don’t want to end up building the wrong infrastructure by not taking the time to listen to the people who will be affected by it.”

Back in 2017, a series of joint workshops hosted by the University of Toronto and University College London (UCL) brought Saxe together with a new team of collaborators, including her fellow U of T Professor Matti Siemiatycki and Dr. Daniel Durrant at UCL’s Bartlett School of Planning.

Given their shared interest in infrastructure, they decided to crunch the numbers on the megaprojects from both Toronto and London, U.K., for which they could gather data.

The goal was to look at how long it takes to go from idea to opening for transport infrastructure, as well as how that time is being spent and whether projects that spend years in deliberation actually benefit from that opportunity for sober second thought.

“We looked at whether the gestational period led to any change along two metrics: either a location change — for example, rail stations in a different location — or a technological change in the project,” says Saxe.

“If we can point to either of those, it suggests that the time spent considering and reconsidering the project at least resulted in some change, potentially for the better. But for a lot of projects we looked at, things didn’t change that much.”

The team analyzed 16 projects with a total cost of more than $500 million from Toronto, and a further 10 with a cost of more than £500 million from London. Of these, more than half did not change significantly by the time construction started.

This is despite the fact that, in many cases, the informal planning periods lasted much longer than the actual building phase.

“Consultation and consideration before we invest billions of dollars is important,” says Saxe. “But there is also an opportunity cost to not acting. There’s a lot of good tied up in these projects that we could have had much earlier, if we had moved faster.”

Saxe says that in her opinion, the negative consequences of this ‘analysis paralysis’ are evident in the current infrastructure landscape of the Greater Toronto Area.

“Not building something is a choice,” she says. “Here in Toronto, we allowed our population to outgrow the carrying capacity of our public transportation network, to the point where a huge number of people now have no choice but to drive cars, with all of the cost, pollution and congestion that come with that.”

“We didn’t consciously design that system — rather it was a consequence of not choosing to design a different one. What I would like to see is an honest discussion about priorities, and a commitment to following through with the funding necessary to make them a reality.”

DOI

10.18757/ejtir.2021.21.3.5515

Study: No serious COVID-19 Vaccine side effects in breastfeeding moms, infants

Researchers found after Pfizer and Moderna vaccine, breastfeeding mothers experienced similar side effects to what has previously been reported in non-breastfeeding women, and infants exhibited no serious side effects

Peer-Reviewed Publication

UNIVERSITY OF CALIFORNIA - SAN DIEGO

In December 2020, two novel messenger RNA (mRNA) vaccines for SARS-CoV-2 received emergency use authorization from the U.S. Food and Drug Administration; however, the early trials excluded lactating women, leading to questions about their safety in this specific population.

In a recent study, published in the online edition of Breastfeeding Medicine, researchers at University of California San Diego School of Medicine found that breastfeeding mothers who received either the Pfizer-BioNTech or Moderna vaccination reported the same local or systemic symptoms as what has been previously reported in non-breastfeeding women, with no serious side effects in the breastfed infants.

“A mother’s first concern is the safety of her child,” said Christina Chambers, PhD, MPH, professor of pediatrics at UC San Diego School of Medicine and professor in the Herbert Wertheim School of Public Health and Human Longevity Science. “Our study, along with previous research, suggests the Pfizer and Moderna vaccines are not red flags for breastfeeding mothers and their infants.”

The results found that more than 85 percent of the 180 breastfeeding women in the study who received an mRNA COVID-19 vaccine reported temporary localized symptoms, such as pain, redness, swelling or itching at the injection site, and systemic side effects, including chills, muscle/body aches, fever and vomiting, with higher frequency following the second dose.

Additionally, following the second dose of vaccine, women who received the Moderna brand were significantly more likely to report symptoms. A small proportion of women following the first dose of either vaccine brand reported a reduction in milk supply, and significantly more women reported a reduction in milk supply following the second dose of Moderna.

“We want to emphasize that the reduction in milk supply was in a small subset of women and came back fully within 72 hours after vaccination. We also cannot be certain that the supply reduction was a side effect of the vaccine or another unknown factor,” said Chambers. “What we do know is that the vaccine is incredibly effective in providing protection from COVID-19, which has proven to be a devastating and serious virus with possible long-term side effects.”

Irritability and poor sleep were reported in some breastfed children, but no serious adverse events.

“We know the many benefits of breastfeeding. Breast milk provides an abundance of nutritional components to infants that provide many health benefits, from stronger immune systems to lower rates of obesity and other conditions and illnesses,” said Chambers.

“Our results should encourage lactating women to get the COVID-19 vaccine and to continue to breastfeed their infants. They do not have to choose one over the other. Both are critical.”

The breastfeeding women recruited for the study enrolled into the Mommy’s Milk Human Milk Research Biorepository at UC San Diego, which strives to understand the numerous benefits human milk offers at a molecular level and uses these findings to improve the health and development of all children.

“This study would not be possible without the tremendous support of our staff and students, and the women across the nation who were willing to enroll and provide breast milk samples,” said Kerri Bertrand, first author of the study and research manager of the Mommy’s Milk Human Milk Research Biorepository. “Together, we are finding life-saving, evidence-based answers to crucial questions that arose when the pandemic first hit.”

The researchers noted that a limitation of the study was that symptoms post vaccination were self-reported and suggested additional studies will be needed to see if the findings can be generalized to a larger population.

Co-authors include: Gordon Honerkamp-Smith, UC San Diego.

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JOURNAL

Breastfeeding Medicine

DOI

10.1089/bfm.2021.0169

Impact of COVID-19 vaccination on breastfeeding

Peer-Reviewed Publication

MARY ANN LIEBERT, INC./GENETIC ENGINEERING NEWS

Impact of COVID-19 Vaccination on Breastfeeding — IMAGE: THE JOURNAL PUBLISHES ORIGINAL SCIENTIFIC PAPERS, REVIEWS, AND CASE STUDIES ON A BROAD SPECTRUM OF TOPICS IN LACTATION MEDICINE. IT PRESENTS EVIDENCE-BASED RESEARCH ADVANCES AND EXPLORES THE IMMEDIATE AND LONG-TERM OUTCOMES OF BREASTFEEDING, INCLUDING THE EPIDEMIOLOGIC, PHYSIOLOGIC, AND PSYCHOLOGICAL BENEFITS OF BREASTFEEDING. view more
CREDIT: MARY ANN LIEBERT, INC., PUBLISHERS

New Rochelle, NY, September 8, 2021—COVID-19 vaccination results in minimal disruption of lactation. Vaccination also has no adverse impact on the breastfed child, according to two studies published in the peer-reviewed journal Breastfeeding Medicine. Click here to read the first article now.

Skyler McLaurin-Jiang, MD, MPH, and coauthors from Texas Tech University Health Sciences Center, School of Medicine, surveyed 4,455 breastfeeding mothers who underwent COVIC-19 vaccination. They reported that 1.7% of respondents reported a negative impact on breastfeeding post-vaccination. Those mothers were more likely to have experienced symptoms associated with the vaccine. “Even among mothers who reported an adverse impact on breastfeeding, maternal opinion about vaccination and confidence in their decision to receive the COVID-19 vaccine were high,” said the authors.

Kerri Bertrand, MPH, and coauthors from the University of California San Diego, enrolled 180 women in the Mommy’s Milk Human Milk Research Biorepository. Few events were reported for children following maternal vaccination with either the first or second dose of vaccine. The most common child events following dose two were irritability, poor sleep, and drowsiness. “These data are reassuring regarding the safety of vaccination in breastfeeding women and their breastfed children with either of the mRNA COVID-19 vaccines,” said the authors in their article.

“These studies reinforce the conclusion that breastfeeding mothers should be vaccinated while continuing to nurse their infants without concern,” says Arthur I. Eidelman, MD, Editor-in-Chief of Breastfeeding Medicine.

Research reported in this publication was supported by the National Institutes of Health under Award Number 1R21HD104412-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

About the Journal
Breastfeeding Medicine, the official journal of the Academy of Breastfeeding Medicine, is an authoritative, peer-reviewed, multidisciplinary journal published 10 times per year in print and online. The Journal publishes original scientific papers, reviews, and case studies on a broad spectrum of topics in lactation medicine. It presents evidence-based research advances and explores the immediate and long-term outcomes of breastfeeding, including the epidemiologic, physiologic, and psychological benefits of breastfeeding. Tables of content and a sample issue may be viewed on the Breastfeeding Medicine website.

About the Academy of Breastfeeding Medicine
The Academy of Breastfeeding Medicine (ABM) is a worldwide organization of medical doctors dedicated to the promotion, protection, and support of breastfeeding. Our mission is to unite members of the various medical specialties with this common purpose. For more than 20 years, ABM has been bringing doctors together to provide evidence-based solutions to the challenges facing breastfeeding across the globe. A vast body of research has demonstrated significant nutritional, physiological, and psychological benefits for both mothers and children that last well beyond infancy. But while breastfeeding is the foundation of a lifetime of health and well-being, clinical practice lags behind scientific evidence. By building on our legacy of research into this field and sharing it with the broader medical community, we can overcome barriers, influence health policies, and change behaviors.

About the Publisher
Mary Ann Liebert, Inc., publishers is known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research. A complete list of the firm's 90 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publisher’s website.

JOURNAL

Breastfeeding Medicine

METHOD OF RESEARCH

Case study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Impact of COVID-19 Vaccination on Breastfeeding

ARTICLE PUBLICATION DATE

8-Sep-2021

COMPARE AND CONTRAST

Experts make weak recommendation for medical cannabis for chronic pain

New guidance aims to address confusion around the role of medical cannabis in the management of chronic pain
Peer-Reviewed Publication
BMJ
In The BMJ today, a panel of international experts make a weak recommendation for a trial of non-inhaled medical cannabis or cannabinoids (chemicals found in cannabis) for people living with chronic pain, if standard care is not sufficient.
The recommendation applies to adults and children living with all types of moderate to severe chronic pain. It does not apply to smoked or vaporised forms of cannabis, recreational cannabis, or patients receiving end-of-life care.
Their advice is part of The BMJ’s Rapid Recommendations initiative - to produce rapid and trustworthy guidelines for clinical practice based on new evidence to help doctors make better decisions with their patients.
Medical cannabis is increasingly used to manage chronic pain, particularly in jurisdictions that have enacted policies to reduce use of opioids. However, existing guideline recommendations are inconsistent, and cannabis remains illegal for therapeutic use in many countries.
Today’s recommendation is based on systematic reviews of 32 randomised trials exploring the benefits and harms of medical cannabis or cannabinoids for chronic pain, 39 observational studies exploring long-term harms, 17 studies of cannabis substitution for opioids, and 15 studies of patient values and preferences.
After thoroughly reviewing this evidence, the panel was confident that non-inhaled medical cannabis or cannabinoids result in small to very small improvements in self reported pain intensity, physical functioning, and sleep quality, and no improvement in emotional, role, or social functioning.
The panel found no evidence linking psychosis to the use of medical cannabis or cannabinoids, but say they do carry a small to modest risk of mostly self limited and transient harms, such as loss of concentration, vomiting, drowsiness, and dizziness.
The panel was less confident about whether use of medical cannabis or cannabinoids resulted in reduced use of opioids, and found that potential serious harms including cannabis dependence, falls, suicidal ideation or suicide were uncommon, but this evidence was only very low certainty.
The recommendation is weak because of the close balance between benefits and harms of medical cannabis for chronic pain. However, the panel issued strong support for shared decision making to ensure patients make choices that reflect their values and personal context.
And they suggest further research should explore uncertainties such as optimal dose and formulation of therapy, and benefits and harms of inhaled medical cannabis, which may alter this recommendation.
In a linked editorial, researchers welcome this new patient centred guidance, but say clinicians should emphasise the harms associated with vaping or smoking cannabis, discourage self medication, and pay particular attention to vulnerable populations.
“Increased pharmacovigilance of all cannabis use remains a priority, along with an ambitious programme of rigorous research on the short and long term effectiveness and safety of individual cannabis products for specific types of chronic pain,” they conclude.

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Rapid Recommendation: Medical cannabis or cannabinoids for chronic pain: a clinical practice guideline

ARTICLE PUBLICATION DATE

8-Sep-2021

Can medical marijuana effectively treat childhood epilepsy?

Peer-Reviewed Publication
WILEY
Following media reports of children with epilepsies reportedly deriving benefits from medical marijuana (or cannabis-based medicinal products) accessed abroad, the UK government allowed clinicians to prescribe these products. A review published in Developmental Medicine & Child Neurology explores the science behind cannabis-based medicinal products in pediatric epilepsies and highlights areas that warrant additional research.
The authors also examined the prescribing environment surrounding these products. They found that a lack of quality evidence for efficacy and safety is the major obstacle to prescribing.
They stress that unlicensed cannabis-based medicinal products should not circumvent usual regulatory requirements before being prescribed. And they worry that children with epilepsy are at risk of being used as a “Trojan horse” for the cannabis industry, with widespread acceptance of medicinal cannabis accelerating the wider legalization of marijuana and opening up a highly lucrative commercial market.

JOURNAL

Developmental Medicine & Child Neurology

DOI

10.1111/dmcn.15032

Third of cancer drugs without proven clinical benefit continue to be recommended for patients

Reforms needed to promote clarity about the basis on which the FDA approves or withdraws cancer drugs and to change positive recommendations when post-approval studies are negative

Peer-Reviewed Publication

BMJ

One third of cancer drugs that received accelerated approval from the US Food and Drug Administration (FDA) continue to be recommended in clinical guidelines after their confirmatory clinical trials fail to show improvement on their primary endpoints, finds a study published by The BMJ today.

A primary endpoint is the main result that is measured at the end of a study to see if a given treatment has worked (eg. the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins.

The researchers say clinical guidelines “should better align with the results of post-approval trials of cancer drugs that received accelerated approval.”

The FDA’s accelerated approval pathway allows drugs onto the market before their effectiveness has been proven to hasten patients’ access to promising new drugs. But as part of this approval, the manufacturer must conduct post-approval trials to confirm clinical benefit (improved survival or quality of life in the case of cancer drugs). If these trials show no benefit, the drug’s approval can be withdrawn.

However, post-approval trials can be delayed for several years, and the FDA has until very recently been slow in taking steps to withdraw the drug or indication when these trials are conducted and fail to demonstrate clinical benefit.

So a team of researchers in Canada and the US set out to investigate how the FDA handles cancer drugs that received accelerated approval but had negative post-approval trials, and whether these negative trials change treatment guidelines.

They searched the FDA database for all cancer drugs granted accelerated approval from the start of the programme in 1992 until December 2020 and identified 18 indications for 10 cancer drugs that failed to show clinical benefit in post-approval trials.

Of these, the approvals for 11 (61%) were voluntarily withdrawn, one was revoked, and six (33%) remained on the drug’s label, over an average of four years.

The researchers then reviewed the latest FDA and National Comprehensive Cancer Network (NCCN) guidelines and found that most of these drugs continued to receive high level endorsement, sometimes even after approval for the given indication had been withdrawn or revoked.

These are observational findings and the researchers point to some limitations, such as relying on publicly available information and pending decisions from the FDA on certain approvals, which may have affected the accuracy of their results.

Nevertheless, they say this is the most comprehensive study of its kind so far and the findings “reflect the lack of fulfilment of the compromise between speed and evidence that underpins the accelerated approval pathway.”

They acknowledge that a recent flurry of regulatory action “suggests that the FDA has paid greater attention to these situations in the past two years,” but call for additional guidance and reforms of the accelerated approval pathway “to assure that all FDA approved drugs are shown to be safe and effective for patients.”

[Ends]

DOI

https://www.bmj.com/content/374/bmj.n1959

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Research: Regulatory and clinical consequences of negative confirmatory trials of accelerated approval cancer drugs: retrospective observational study

Administrative tasks related to healthcare create burdens for U.S. patients

Peer-Reviewed Publication

WILEY

A new study published in Health Services Research found that many U.S. patients are burdened by administrative tasks related to their medical care. Such administrative tasks include appointment scheduling, obtaining information from an insurer or provider, obtaining prior authorizations, resolving insurance or provider billing issues, and resolving insurance premium problems.

In the survey-based study of 4,155 non-elderly adults, nearly three-quarters of respondents reported doing at least one healthcare-related administrative task in the past year, and nearly one-quarter of respondents reported delaying or foregoing needed care due to administrative tasks. Previous research has found that a similar proportion of patients have postponed or avoided needed care due to costs.

Administrative burdens fell disproportionately on people with high medical needs, such as those with disabilities. Also, existing racial and socioeconomic inequities were associated with greater administrative burdens.

“Financial costs are rightly a big focus in health policy, but our findings suggest patients’ administrative burdens are consequential and deserve attention from researchers, practitioners, and policymakers,” said corresponding author Michael Anne Kyle, PhD, of Harvard University.

JOURNAL

Health Services Research

DOI

10.1111/1475-6773.13861