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HACHETTE Employees Protest New Conservative Imprint...


HACHETTE Employees Protest New Conservative Imprint...


(First column, 10th story, link)






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What the Universe Wants You to Know When You See Angel Number 33

Angel number 33 symbolizes spiritual growth, compassion, and creativity. Discover its powerful meaning in love, career, and life purpose as a Master Number.




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Nintendo will show off 'Donkey Kong Country' theme park expansion at live event today

Nintendo is set to show off the Donkey Kong Country expansion of its Super Nintendo World theme park today (Monday, November 11) at 5PM ET, the company revealed in a post on X. That means the new Universal Studios Japan area might finally open soon, after being delayed from the previously announced launch window of Spring 2024. 

The new park attraction featuring Mario's barrel-throwing nemesis was first revealed in 2021. The centerpiece is a ride called Mine Cart Madness, named after the best level in the 1994 SNES game Donkey Kong Country. After being blasted out of a barrel cannon, you'll take a mine cart ride through the jungle that includes a "leap across a collapsed track" as Nintendo showed in a render earlier this year.  

The direct livestream appears to be focused on Donkey Kong world alone, and Nintendo specifically pointed out that "no game information will be featured" — so don't expect any news on the next-gen Switch 2 console either. 

Donkey Kong Country will expand the park size by up to 70 percent, Nintendo said when it was announced. Current attractions at the Japan park are the Mario Kart: Kuppa's Challenge rollercoaster and Yoshi Adventure. Nintendo recently announced that it would open a Super Nintendo World attraction at Universal Studios Orlando on May 22nd, 2025 with the same attractions as the park in Osaka. 

This article originally appeared on Engadget at https://www.engadget.com/gaming/nintendo/nintendo-will-show-off-donkey-kong-country-theme-park-expansion-at-live-event-today-130015655.html?src=rss




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Amazon reportedly wants drivers to wear AR glasses for improved efficiency until robots can take over

Amazon is reportedly developing smart glasses for its delivery drivers, according to sources who spoke to Reuters. These glasses are intended to cut “seconds” from each delivery because, well, productivity or whatever. Sources say that they are an extension of the pre-existing Echo Frames smart glasses and are known by the internal code Amelia.

These seconds will be shaved off in a couple of ways. First of all, the glasses reportedly include an embedded display to guide delivery drivers around and within buildings. They will allegedly also provide drivers with “turn-by-turn navigation” instructions while driving. Finally, wearing AR glasses means that drivers won’t have to carry a handheld GPS device. You know what that means. They’ll be able to carry more packages at once. It’s a real mitzvah.

I’m being snarky, and for good reason, but there could be some actual benefit here. I’ve been a delivery driver before and often the biggest time-sink is wandering around labyrinthine building complexes like a lost puppy. I wouldn’t have minded a device that told me where the elevator was. However, I would not have liked being forced to wear cumbersome AR glasses to make that happen.

To that end, the sources tell Reuters that this project is not an absolute certainty. The glasses could be shelved if they don’t live up to the initial promise or if they’re too expensive to manufacture. Even if things go smoothly, it’ll likely be years before Amazon drivers are mandated to wear the glasses. The company is reportedly having trouble integrating a battery that can last a full eight-hour shift and settling on a design that doesn’t cause fatigue during use. There’s also the matter of collecting all of that building and neighborhood data, which is no small feat.

Amazon told Reuters that it is “continuously innovating to create an even safer and better delivery experience for drivers” but refused to comment on the existence of these AR glasses. "We otherwise don’t comment on our product roadmap,” a spokesperson said.

The Echo Frames have turned out to be a pretty big misfire for Amazon. The same report indicates that the company has sold only 10,000 units since the third-gen glasses came out last year.

This article originally appeared on Engadget at https://www.engadget.com/big-tech/amazon-reportedly-wants-drivers-to-wear-ar-glasses-for-improved-efficiency-until-robots-can-take-over-174910167.html?src=rss




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Waymo's driverless cars in LA County are now available to everyone

Waymo has announced expanded availability of its driverless rideshare service throughout Los Angeles. That’s right. Waymo One is now available to all customers anywhere in LA county, which is 80 square miles. The company has dropped the waitlist for area residents. Now LA residents will get to experience sitting in endless traffic with a series of cameras and navigational algos leading the way instead of a person.

This expanded service starts today and it offers “fully autonomous rides” at any time of the day or night. Let’s hear it for some drunken late night bonding with an algorithm. Waymo also says it’ll further expand the service area in the future. After all, Los Angeles comprises five counties. 

It’s been offering driverless rides to LA customers for a while now, but with a mandatory waitlist. Waymo One also started small in San Francisco and Phoenix before announcing similar expansions. The service will be coming to Austin and Atlanta in the near future.

All told, the company says over 300,000 Los Angeles residents have joined the waitlist for the service and Waymo One has completed “hundreds of thousands of paid trips across the city.” Waymo says these driverless rides are also highly rated, with an average rating of 4.7 stars out of five. A recent survey indicated that 98 percent of customers are satisfied with the service.

This article originally appeared on Engadget at https://www.engadget.com/transportation/waymos-driverless-cars-in-la-county-are-now-available-to-everyone-173237519.html?src=rss




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PS5 exclusive Stellar Blade is coming to PC

This year's action RPG Stellar Blade has been a solid win for Sony as a PlayStation 5 exclusive. Developer Shift Up revealed in a recent quarterly earnings report that sales "have remained steady even as the initial surge has calmed" following its spring launch. But there may be a second boost coming for the game, because the studio is planning a PC port of Stellar Blade some time next year.

"Given recent trends like Steam’s growing presence in the AAA games market and the global success of Black Myth: Wukong, we are expecting the PC version to perform even better than the console version," the Korean company said when asked about their PC plans during the presentation.

The title referenced, Black Myth: Wukong, was able to set a new record for concurrent players in a single-player game on Steam when it launched on the platform in August. That's a lofty goal for any game to reach, so we'll have to see how successful Shift Up can be in reaching an international audience on PC.

This article originally appeared on Engadget at https://www.engadget.com/gaming/ps5-exclusive-stellar-blade-is-coming-to-pc-231625263.html?src=rss




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India's Hindus bathe in holy river defiled by pollution

New Delhi (AFP) Nov 7, 2024
Sweeping aside thick toxic scum, thousands of Hindu devotees ignored court warnings Thursday against bathing in the sacred but sewage-filled Yamuna river, a grim display of environmental degradation in India's capital. Thousands celebrated the festival of Chhath Puja for the Hindu sun god Surya, entering the stinking waters to pray as the evening rays set in the sky. A parliamentary repo




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Drowning mangroves in Maldives signal global coastal risk

London, UK (SPX) Nov 13, 2024
Mangrove forests in the Maldives are facing a severe threat as they succumb to rising sea levels and climate changes, according to a new study led by Northumbria University researchers and published in *Scientific Reports*. The study highlights that the Maldives, known for its low-lying islands, experienced significant mangrove dieback since 2020 due to rapid sea-level rise and the effects




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Artist José González is creating an underwater universe — with an iPad

José González is an illustrator, author and animator originally from Buenos Aires now living in English Harbour. González was selected to be one of the Artists in Residence at Business and Arts N.L. (Un)Common Threads Creativity and Innovation Summit happening on Nov. 7. In advance of the summit, González has been busy preparing for his installation, which will feature a large-scale fish tank with animated sea creatures brought to life through projections and augmented reality.




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Vivez l’expérience de l’Université de Sherbrooke sur la Rive-Sud

Depuis 35 ans, l’Université de Sherbrooke est présente à Longueuil.




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Canada, prepare for the big squeeze. Trump will press on several sensitive fronts

Donald Trump's second term as U.S. president carries implications at home and abroad. That includes potentially wreaking havoc on global economies through the aggressive use of tariffs.




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Canadian trade survived the first Trump presidency. Here's how it can survive the second

Donald Trump is returning to the White House with big plans to remake the global trade landscape. That could be a disaster for Canada's economy. But key players of the last trade war believe they can mitigate the damage.




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Alberta government fires AIMCo board, four top executives, in 'reset' for pension fund manager

The province says the move comes "after years of AIMCo consistently failing to meet its mandated benchmark returns." For now, Finance Minister Nate Horner has been appointed the AIMCo board's sole director and chair. Senior public servant Ray Gilmour has been appointed interim CEO.



  • News/Canada/Edmonton

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Canada Post workers give 72-hour notice to strike as company warns of financial impact

The union representing Canada Post workers said it will be in a legal strike position on Friday, exactly one year after talks on a new contract began. But the union is holding back on deciding whether a job action will take place immediately.




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CSIS had concerns about Abdelrazik's motives ahead of trip to Sudan, investigator testifies

Canada's intelligence agency amassed a sizable file on Abousfian Abdelrazik's suspected terrorism ties in the early 2000s, although the validity of that intelligence was called into question during the Montreal man's Federal Court case.




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Mercedes steering health drive

You’ll start a daily workout when you get behind the wheel if you drive a Mercedes with the Fit & Healthy system.




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Bolt drivers win right to holiday and minimum wage

Thousands of drivers on ride-hailing and food delivery app Bolt have won a legal claim to be classed as workers.




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NCCE to add NCAHP representatives as part of Council meetings

The National Commission for Allied Health Professionals (NCAHP), constituted by the Union ministry of health and family welfare in the beginning of this year, will have its official representative in the National




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AIOCD urges DCGI to immediately stop partnership between Swiggy & PharmEasy for rapid drug delivery

Raising deep concern over the partnership between Swiggy Instamart and PharmEasy for a rapid drug delivery model, the All India Organization of Chemists and Druggists (AIOCD) has apprised the Drug Controller




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DGTR issues directive for sunset review anti─dumping investigation on Aniline imports from China

The Directorate General of Trade Remedies (DGTR), under the Ministry of Commerce and Industry, has issued a notice to all interested parties involved in the sunset review of the anti─dumping investigation




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Nvision Biomedical 3D-printed PEEK Interbody System receives FDA clearance

Nvision Biomedical Technologies and Invibio Biomaterial Solutions have announced that the FDA has granted clearance of the first 3D-Printed PEEK Interbody System made from PEEK-OPTIMA.




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Five steps to successful medical device development

Dr Euan McBrearty, head of commerical & innovation, Wideblue shares five steps to successful medical device development.




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The Universe in 100 Colors Provides a Stunning Tour through Science

A science photo book probes the colors we can see—and even “forbidden” colors we can’t




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The International Space Station Has Been Leaking for Five Years

Pesky leaks on the International Space Station aren’t the most serious issue facing U.S. human spaceflight




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Magnetoelectric Material Stimulates Neurons Minimally Invasively

Researchers at Rice University have developed a magnetoelectric material that converts a magnetic field into an electric field. The material can be formulated such that it can be injected into the body, near a neuron, and then an alternating magnetic field can be applied to the area from outside the body. Magnetic fields are very […]




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The Pivotal Role of Technology in Delivering Effective Patient Services

Today’s guest post comes from George Moore, Chief Information Technology Officer at CareMetx.

As George explains using novel survey data, manufacturers view new technologies  as crucial for patient services. He then explains how digital technology, artificial intelligence (AI), and machine learning (ML) can be used to improve patient adherence and increase hub efficiencies.

To learn more, download CareMetx’s new 2024 Patient Services ReportRevealing Manufacturer Priorities: Patients Naturally Take Center Stage.

Read on for George’s insights.
Read more »
       




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Innovative Models for Improving Access and Visibility for Specialty-Lite and Retail Therapies

Today’s guest post comes from Timothy Nielsen, Vice President of Customer Success at AssistRx.

Timothy discusses the affordability and patient journey challenges of specialty-lite products for patients, manufacturers, and health care providers. He explains how AssistRx's Advanced Access Anywhere (AAA) solution streamlines processes for specialty-lite products and facilitates enrollment via a digital hub.

To learn more, register for AssistRx's free webinar on October 8: Meet Your Patients Where They Are & Gain Visibility: Even at Retail.

Read on for Timothy’s insights.
Read more »
       




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Five Crucial Trends Facing U.S. Drug Wholesalers in 2024 and Beyond

As regular readers of Drug Channels know, U.S. distribution and dispensing channels for prescription drugs are undergoing significant evolution and consolidation as the changing economics of pharmaceuticals challenge conventional business models.

During this period of volatility, the core business model of the Big Three public pharmaceutical distribution companies—Cardinal Health, Cencora, and McKesson—remains intact. Put simply: Buy low, sell high, collect early, and pay late.

But as I explain below, wholesalers continue to position themselves as essential intermediaries by expanding their industry position and strengthening their economic fundamentals.

Read on for five key pricing, pharmacy, provider, and manufacturer trends that are driving the U.S. drug wholesaling industry.

For even more, check out DCI's new 2024-25 Economic Report on Pharmaceutical Wholesalers and Specialty Distributors, the fifteenth edition of our deep dive into wholesale distribution channels.Click here to download a free report overview (including key industry trends, the table of contents, and a list of exhibits)
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Transparency Shocker: Biosimilars Are Getting Cheaper—But Hospitals and Insurers Can Make Them Expensive

Here on Drug Channels, we have long highlighted the boom in provider-administered biosimilars. In contrast to the pharmacy market, adoption of these biosimilars is growing, prices are dropping, and formulary barriers continue to fall.

Novel transparency information reveals that this good news doesn’t always translate into savings. Below, we rely on a unique data set from Turquoise Health to examine how much four national commercial health plans—Aetna, Anthem, Cigna, and UnitedHealthcare—paid hospitals for Avastin and its two most significant biosimilar competitors.

As we demonstrate, health plans pay hospitals far above acquisition costs for biosimilars. What’s more, plans can pay hospitals more for a biosimilar than for the higher-cost reference product. The U.S. drug channel system is warping hospitals’ incentives to adopt biosimilars, while simultaneously raising costs for commercial plans.

The namesake of my alma mater once said: “Sunlight is said to be the best of disinfectants.” What would happen if we disinfected the entire channel?
Read more »
       




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Drug Channels Outlook 2025 (NEW Live Video Webinar)

Adam J. Fein, Ph.D., president of Drug Channels Institute (DCI) and the author of Drug Channels, invites you to join him for DCI’s new live video webinar:


This event will be broadcast live on
Friday, December 13, 2024,
from 12:00 p.m. to 1:30 p.m. ET

This post describes the event and explains how to purchase a registration. (Or, just click here to order.) The webinar will be broadcast from the Drug Channels studio in beautiful downtown Philadelphia.

This event is part of The Drug Channels 2024 Video Webinar Series. (Please note that our December 2024 webinar is *not* included with next year’s 2025 Video Webinar Series.)

WHAT YOU WILL LEARN

Join Dr. Fein as he helps you and your team get ready for 2025 by outlining key issues and uncertainties that will surely affect your planning. This event can be both a capstone of your annual learning and a touchpoint for the future. DCI’s Outlook webinars have proven to be reliable and informative guides to crucial aspects of the ever-evolving healthcare industry.

During the event, Dr. Fein will share his latest thinking and projections on a wide range of topics, including:
  • Latest predictions for the Inflation Reduction Act
  • Expectations for the Medicare Part D market in 2025 and beyond
  • Update on 340B Drug Pricing Program’s controversies
  • Impact of the new Trump administration and Congress on the drug channel
  • Vertical integration and consolidation trends—and prospects for dis-integration and de-consolidation
  • The state of biosimilar markets
  • What’s next for PBMs’ private label products and GPOs
  • Retail pharmacy’s future
  • Prospects for direct-to-patient channels
  • What’s ahead for discount cards and cash-pay pharmacies
  • The outlook for state and federal legislation on PBMs and the drug channel
  • Gross-to-net bubble developments
  • And much more!
PLUS: During the webinar, Dr. Fein will give participants an opportunity to unmute themselves and ask live questions. The webinar will last at least 90 minutes to accommodate audience questions.

As always, Dr. Fein will clearly distinguish his opinions and interpretations from the objective facts and data. He will draw from exclusive information found in DCI's economic reports .

Read on for full details on pricing and registration.
Read more »
       




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ACRO Announces Diversity and Inclusion Site Resource Grants Program

The ACRO D&I Site Resource Grants Program aims to help sites acquire the resources and skills that will get them selected for studies and improve the reach of clinical research into underrepresented communities.

The post ACRO Announces Diversity and Inclusion Site Resource Grants Program first appeared on ACRO.




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ACRO Announces Diversity and Inclusion Site Resource Grants Program

ACRO is pleased to announce the launch of the ACRO Diversity and Inclusion Site Resource Grants Program! The ACRO D&I Site Resource Grants Program aims to help sites acquire the resources and skills that will get them selected for studies and improve the reach of clinical research into underrepresented communities. “We are excited to invite […]

The post ACRO Announces Diversity and Inclusion Site Resource Grants Program first appeared on ACRO.




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Orphan Drugs at 30: Will Success Become Too Expensive?

The Orphan Drug Act (ODA) turned 30 this month, demonstrating that good laws really can have an enduring impact. Amidst the celebrations, a reporter asked me a provocative question: can we afford more orphan drugs costing hundreds of thousands of dollars per year? FDA Matters answered “yes.” However, I added a caveat that should worry everyone eager for orphan drugs to succeed. When genomics and personalized medicine become successful, this will multiply the number of rare diseases and the overall cost of orphan drugs, perhaps beyond what the system can bear.




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NY Passes Two Kids Privacy Bills to Restrict Access to Addictive Algorithmic Feeds

The New York legislature passed two bills on June 7, 2024 directed at children’s use of online technologies – the Stop Addictive Feeds Exploitation (SAFE) for Kids Act (S7694) that restricts access to addictive algorithmic feeds and the New York Child Data Protection Act (S7695) that bans sites from collecting, using, sharing or selling personal […]




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FTC Announces Final Rule to Prohibit Deceptive Online Reviews and Testimonials

Effective on October 21st of this year, the Federal Trade Commission (FTC) issued a new final rule that is intended to better combat ​“fake” reviews and testimonials by prohibiting the sale or purchase of “fake reviews” as well as granting the agency the opportunity to seek civil penalties against ​willful violators. The FTC made only […]




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Should the ACC Have a Live Meeting?

I was surprised to learn from a recent press release that the American College of Cardiology is planning to have some live participants at its annual scientific sessions meeting in May. The college said it is also partnering with a technology company to offer these participants a wearable monitoring device “as an added safety measure...

Click here to continue reading...




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Risk of mortality drops in COVID-19 patients given anticoagulation within a day of hospital admission, research finds

Starting COVID-19 patients on prophylactic anticoagulation within 24 hours of being admitted to hospital has been linked to a reduced risk of mortality.




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Semaglutide effective for weight loss in non-diabetic adults, research suggests

The type 2 diabetes mellitus drug semaglutide is effective for weight loss in non-diabetic overweight or obese adults, when taken alongside a reduced-calorie diet and exercise, researchers have found.




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MHRA to consult on making two progestogen-only contraceptives available without a prescription

Consultations on the reclassification of two progestogen-only contraceptive pills from prescription-only to pharmacy medicines have been launched.




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Pharmacies estimated to receive one referral per month through hospital-to-pharmacy referral service

Community pharmacies will receive an estimated 12 referrals from the Discharge Medicines Service per year.




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Neuro-Immunology: The Promise Of A Differentiated Approach To Neurodegenerative Disease

By Ivana Magovčević-Liebisch, CEO of Vigil Neuroscience, as part of the From The Trenches feature of LifeSciVC In the last decade, our industry has made great strides in combating cancer by harnessing the body’s own immune system. As it was

The post Neuro-Immunology: The Promise Of A Differentiated Approach To Neurodegenerative Disease appeared first on LifeSciVC.




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UK universities and NHS trusts that flout the rules on clinical trials identified in report to Parliament

An AllTrials report for the House of Commons Science and Technology Select Committee this week has found that 33 NHS trust sponsors and six UK universities are reporting none of their clinical trial results, while others have gone from 0% to 100% following an announcement from the Select Committee in January that universities and NHS […]




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Can FDA's New Transparency Survive Avandia?

PDUFA V commitments signal a strong commitment to tolerance of open debate in the face of uncertainty.

I can admit to a rather powerful lack of enthusiasm when reading about interpersonal squabbles. It’s even worse in the scientific world: when I read about debates getting mired in personal attacks I tend to simply stop reading and move on to something else.

However, the really interesting part of this week’s meeting of an FDA joint Advisory Committee to discuss the controversial diabetes drug Avandia – at least in the sense of likely long-term impact – is not the scientific question under discussion, but the surfacing and handling of the raging interpersonal battle going on right now inside the Division of Cardiovascular and Renal Products. So I'll have to swallow my distaste and follow along with the drama.

Two words that make us mistrust Duke:
 Anil Potti Christian Laettner

Not that the scientific question at hand – does Avandia pose significant heart risks? – isn't interesting. It is. But if there’s one thing that everyone seems to agree on, it’s that we don’t have good data on the topic. Despite the re-adjudication of RECORD, no one trusts its design (and, ironically, the one trial with a design to rigorously answer the question was halted after intense pressure, despite an AdComm recommendation that it continue).  And no one seems particularly enthused about changing the current status of Avandia: in all likelihood it will continue to be permitted to be marketed under heavy restrictions. Rather than changing the future of diabetes, I suspect the committee will be content to let us slog along the same mucky trail.

The really interesting question, that will potentially impact CDER for years to come, is how it can function with frothing, open dissent among its staffers. As has been widely reported, FDA reviewer Tom Marciniak has written a rather wild and vitriolic assessment of the RECORD trial, excoriating most everyone involved. In a particularly stunning passage, Marciniak appears to claim that the entire output of anyone working at Duke University cannot be trusted because of the fraud committed by Duke cancer researcher Anil Potti:
I would have thought that the two words “Anil Potti” are sufficient for convincing anyone that Duke University is a poor choice for a contractor whose task it is to confirm the integrity of scientific research. 
(One wonders how far Marciniak is willing to take his guilt-by-association theme. Are the words “Cheng Yi Liang” sufficient to convince us that all FDA employees, including Marciniak, are poor choices for deciding matter relating to publicly-traded companies? Should I not comment on government activities because I’m a resident of Illinois (my two words: “Rod Blagojevich”)?)

Rather than censoring or reprimanding Marciniak, his supervisors have taken the extraordinary step of letting him publicly air his criticisms, and then they have in turn publicly criticized his methods and approach.

I have been unable to think of a similar situation at any regulatory agency. The tolerance for dissent being displayed by FDA is, I believe, completely unprecedented.

And that’s the cliffhanger for me: can the FDA’s commitment to transparency extend so far as to accommodate public disagreements about its own approval decisions? Can it do so even when the disagreements take an extremely nasty and inappropriate tone?

  • Rather than considering that open debate is a good thing, will journalists jump on the drama and portray agency leadership as weak and indecisive?
  • Will the usual suspects in Congress be able to exploit this disagreement for their own political gain? How many House subcommittees will be summoning Janet Woodcock in the coming weeks?

I think what Bob Temple and Norman Stockbridge are doing is a tremendous experiment in open government. If they can pull it off, it could force other agencies to radically rethink how they go about crafting and implementing regulations. However, I also worry that it is politically simply not a viable approach, and that the agency will ultimately be seriously hurt by attacks from the media and legislators.

Where is this coming from?

As part of its recent PDUFA V commitment, the FDA put out a fascinating draft document, Structured Approach to Benefit-Risk Assessment in Drug Regulatory Decision-Making. It didn't get a lot of attention when first published back in February (few FDA documents do). However, it lays out a rather bold vision for how the FDA can acknowledge the existence of uncertainty in its evaluation of new drugs. Its proposed structure even envisions an open and honest accounting of divergent interpretations of data:
When they're frothing at the mouth, even Atticus
doesn't let them publish a review
A framework for benefit-risk decision-making that summarizes the relevant facts, uncertainties, and key areas of judgment, and clearly explains how these factors influence a regulatory decision, can greatly inform and clarify the regulatory discussion. Such a framework can provide transparency regarding the basis of conflicting recommendations made by different parties using the same information.
(Emphasis mine.)

Of course, the structured framework here is designed to reflect rational disagreement. Marciniak’s scattershot insults are in many ways a terrible first case for trying out a new level of transparency.

The draft framework notes that safety issues, like Avandia, are some of the major areas of uncertainty in the regulatory process. Contrast this vision of coolly and systematically addressing uncertainties with the sad reality of Marciniak’s attack:
In contrast to the prospective and highly planned studies of effectiveness, safety findings emerge from a wide range of sources, including spontaneous adverse event reports, epidemiology studies, meta-analyses of controlled trials, or in some cases from randomized, controlled trials. However, even controlled trials, where the evidence of an effect is generally most persuasive, can sometimes provide contradictory and inconsistent findings on safety as the analyses are in many cases not planned and often reflect multiple testing. A systematic approach that specifies the sources of evidence, the strength of each piece of evidence, and draws conclusions that explain how the uncertainty weighed on the decision, can lead to more explicit communication of regulatory decisions. We anticipate that this work will continue beyond FY 2013.
I hope that work will continue beyond 2013. Thoughtful, open discussions of real uncertainties are one of the most worthwhile goals FDA can aspire to, even if it means having to learn how to do so without letting the Marciniaks of the world scuttle the whole endeavor.

[Update June 6: Further bolstering the idea that the AdCom is just as much about FDA's ability to transparently manage differences of expert opinion in the face of uncertain data, CDER Director Janet Woodcock posted this note on the FDA's blog. She's pretty explicit about the bigger picture:
There have been, and continue to be, differences of opinion and scientific disputes, which is not uncommon within the agency, stemming from varied conclusions about the existing data, not only with Avandia, but with other FDA-regulated products. 
At FDA, we actively encourage and welcome robust scientific debate on the complex matters we deal with — as such a transparent approach ensures the scientific input we need, enriches the discussions, and enhances our decision-making.
I agree, and hope she can pull it off.]




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Waiver of Informed Consent - proposed changes in the 21st Century Cures Act

Adam Feuerstein points out - and expresses considerable alarm over - an overlooked clause in the 21st Century Cures Act:


In another tweet, he suggests that the act will "decimate" informed consent in drug trials. Subsequent responses and retweets  did nothing to clarify the situation, and if anything tended to spread, rather than address, Feuerstein's confusion.

Below is a quick recap of the current regulatory context and a real-life example of where the new wording may be helpful. In short, though, I think it's safe to say:


  1. Waiving informed consent is not new; it's already permitted under current regs
  2. The standards for obtaining a waiver of consent are stringent
  3. They may, in fact, be too stringent in a small number of situations
  4. The act may, in fact, be helpful in those situations
  5. Feuerstein may, in fact, need to chill out a little bit


(For the purposes of this discussion, I’m talking about drug trials, but I believe the device trial situation is parallel.)

Section 505(i) - the section this act proposes to amend - instructs the Secretary of Health and Human Services to propagate rules regarding clinical research. Subsection 4 addresses informed consent:

…the manufacturer, or the sponsor of the investigation, require[e] that experts using such drugs for investigational purposes certify to such manufacturer or sponsor that they will inform any human beings to whom such drugs, or any controls used in connection therewith, are being administered, or their representatives, that such drugs are being used for investigational purposes and will obtain the consent of such human beings or their representatives, except where it is not feasible or it is contrary to the best interests of such human beings.

[emphasis  mine]

Note that this section already recognizes situations where informed consent may be waived for practical or ethical reasons.

These rules were in fact promulgated under 45 CFR part 46, section 116. The relevant bit – as far as this conversation goes – regards circumstances under which informed consent might be fully or partially waived. Specifically, there are 4 criteria, all of which need to be met:

 (1) The research involves no more than minimal risk to the subjects;
 (2) The waiver or alteration will not adversely affect the rights and welfare of the subjects;
 (3) The research could not practicably be carried out without the waiver or alteration; and
 (4) Whenever appropriate, the subjects will be provided with additional pertinent information after participation.

In practice, this is an especially difficult set of criteria to meet for most studies. Criterion (1) rules out most “conventional” clinical trials, because the hallmarks of those trials (use of an investigational medicine, randomization of treatment, blinding of treatment allocation) are all deemed to be more than “minimal risk”. That leaves observational studies – but even many of these cannot clear the bar of criterion (3).

That word “practicably” is a doozy.

Here’s an all-too-real example from recent personal experience. A drug manufacturer wants to understand physicians’ rationales for performing a certain procedure. It seems – but there is little hard data – that a lot of physicians do not strictly follow guidelines on when to perform the procedure. So we devise a study: whenever the procedure is performed, we ask the physician to complete a quick form categorizing why they made their decision. We also ask him or her to transcribe a few pieces of data from the patient chart.

Even though the patients aren’t personally identifiable, the collection of medical data qualifies this as a clinical trial.

It’s a minimal risk trial, definitely: the trial doesn’t dictate at all what the doctor should do, it just asks him or her to record what they did and why, and supply a bit of medical context for the decision. All told, we estimated 15 minutes of physician time to complete the form.

The IRB monitoring the trial, however, denied our request for a waiver of informed consent, since it was “practicable” (not easy, but possible) to obtain informed consent from the patient.  Informed consent – even with a slimmed-down form – was going to take a minimum of 30 minutes, so the length of the physician’s involvement tripled. In addition, many physicians opted out of the trial because they felt that the informed consent process added unnecessary anxiety and alarm for their patients, and provided no corresponding benefit.

The end result was not surprising: the budget for the trial more than doubled, and enrollment was far below expectations.

Which leads to two questions:

1.       Did the informed consent appreciably help a single patient in the trial? Very arguably, no. Consenting to being “in” the trial made zero difference in the patients’ care, added time to their stay in the clinic, and possibly added to their anxiety.
2.       Was less knowledge collected as a result? Absolutely, yes. The sponsor could have run two studies for the same cost. Instead, they ultimately reduced the power of the trial in order to cut losses.


Bottom line, it appears that the modifications proposed in the 21st Century Cures Act really only targets trials like the one in the example. The language clearly retains criteria 1 and 2 of the current HHS regs, which are the most important from a patient safety perspective, but cuts down the “practicability” requirement, potentially permitting high quality studies to be run with less time and cost.

Ultimately, it looks like a very small, but positive, change to the current rules.

The rest of the act appears to be a mash-up of some very good and some very bad (or at least not fully thought out) ideas. However, this clause should not be cause for alarm.




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Noninvasive Spinal Stimulation Gets a (Current) Boost



In 2010, Melanie Reid fell off a horse and was paralyzed below the shoulders.

“You think, ‘I am where I am; nothing’s going to change,’ ” she said, but many years after her accident, she participated in a medical trial of a new, noninvasive rehabilitative device that can deliver more electrical stimulation than similar devices without harming the user. For Reid, use of the device has led to small improvements in her ability to use her hands, and meaningful changes to her daily life.

“Everyone thinks with spinal injury all you want to do is be able to walk again, but if you’re a tetraplegic or quadriplegic, what matters most is working hands,” said Reid, a columnist for The Times, as part of a press briefing. “There’s no miracles in spinal injury, but tiny gains can be life-changing.”

For the study, Reid used a new noninvasive therapeutic device produced by Onward Medical. The device, ARC-EX (“EX” indicating “external”), uses electrodes placed along the spine near the site of injury—in the case of quadriplegia, the neck—to promote nerve activity and growth during physical-therapy exercises. The goal is to not only increase motor function while the device is attached and operating, but the long-term effectiveness of rehabilitation drills. A study focused on arm and hand abilities in patients with quadriplegia was published 20 May in Nature Medicine.

Researchers have been investigating electrical stimulation as a treatment for spinal cord injury for roughly 40 years, but “one of the innovations in this system is using a very high-frequency waveform,” said coauthor Chet Moritz, a neurotechnologist at the University of Washington. The ARC-EX uses a 10-kilohertz carrier frequency overlay, which researchers think may numb the skin beneath the electrode, allowing patients to tolerate five times as much amperage as from similar exploratory devices. For Reid, this manifested as a noticeable “buzz,” which felt strange, but not painful.

The study included 60 participants across 14 sites around the world. Each participant undertook two months of standard physical therapy, followed by two months of therapy combined with the ARC-EX. Although aspects of treatment such as electrode placement were fairly standardized, the current amplitude was personalized to each patient, and sometimes individual exercises, said Moritz.

The ARC-EX uses a 10-kilohertz current to provider stronger stimulation for people with spinal cord injuries.

Over 70 percent of patients showed an increase in at least one measurement of both strength and function between standard therapy and ARC-EX therapy. These changes also meant that 87 percent of study participants noted some improvement in quality of life in a followup questionnaire. No major safety concerns tied to the device or rehabilitation process were reported.

Onward will seek approval from the U.S. Food and Drug Administration for the device by the end of 2024, said study coauthor Grégoire Courtine, a neuroscientist and cofounder of Onward Medical. Onward is also working on an implantable spinal stimulator called ARC-IM; other prosthetic approaches, such as robotic exoskeletons, are being investigated elsewhere. ARC-EX was presented as a potentially important cost-accessible, noninvasive treatment option, especially in the critical window for recovery a year or so after a spinal cord injury. However, the price to insurers or patients of a commercial version is still subject to negotiation.

The World Health Organization says there are over 15 million people with spinal cord injuries. Moritz estimates that around 90 percent of patients, even many with no movement in their hands, could benefit from the new therapy.

Dimitry Sayenko, who studies spinal cord injury recovery at Houston Methodist and was not involved in the study, praised the relatively large sample size and clear concern for patient safety. But he stresses that the mechanisms underlying spinal stimulation are not well understood. “So far it’s literally plug and play,” said Sayenko. “We don’t understand what’s happening under the electrodes for sure—we can only indirectly assume or speculate.”

The new study supports the idea that noninvasive spinal cord stimulation can provide some benefit to some people but was not designed to help predict who will benefit, precisely how people will benefit, or how to optimize care. The study authors acknowledged the limited scope and need for further research, which might help turn currently “tiny gains” into what Sayenko calls “larger, more dramatic, robust effects.”




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4 Areas Within Mental Health Care that Give Executives Hope

Mental health experts are hopeful about the de-stigmatization of behavioral health, the promise of AI and other areas, they shared at a recent conference.

The post 4 Areas Within Mental Health Care that Give Executives Hope appeared first on MedCity News.