Captain Harry Kane is unhappy with the number of players who have withdrawn from the latest England squad, insisting "England comes before club".

There’s been much talk about the Great Resignation and what’s driving it. The pandemic has exacerbated a long-term problem: many of us struggle to find any pleasure in our work. But quitting isn’t the only the solution. Often, it’s not feasible. In this special series from HBR, we look at a different path: figuring out what you really love and crafting your current role around that. In this episode, we dig into the data showing why people feel so disengaged and what they feel is missing from their work. IdeaCast co-host Alison Beard speaks with Marcus Buckingham, head of research on people and performance at the ADP Research Institute and author of the new book Love + Work.

Online retail sales have been growing steadily in recent years, reaching record highs in 2015.  Shoppers spent a combined $4.33 billion on Thanksgiving Day and Black Friday alone.  Customers are purchasing things like clothing and accessories more than anything else, despite the fact they can’t try it on before buying.  This is great for retailers […]

The post Why are your customers unhappy? first appeared on TECH Intelligence and is written by Brian Wallace.

Music companies appeal, demanding payment for each song instead of each album.

Edwards recalls crying because she thought she looked stupid wearing a man's clothes for her girl group's music video which came out recently to support new single 'Confetti'.

Edwards recalls crying because she thought she looked stupid wearing a man's clothes for her girl group's music video which came out recently to support new single 'Confetti'.

Complaints about denied claims often concern the treatment the scheme will cover for a prescribed minimum benefit.

Investors holding more than a quarter of Shoprite shares opposed its executive pay, requiring SA's largest retailer to address dissenting shareholders' concerns.

Title: Unhappy at Work in Your 20s, Unhealthy in Your 40s?
Category: Health News
Created: 8/22/2016 12:00:00 AM
Last Editorial Review: 8/23/2016 12:00:00 AM

Tech companies are force-feeding people AI on search engines and social media platforms and there's no way to opt out. Google search, considered the gateway to the internet, is especially frustrating.

A new survey of plan sponsors sheds light on their satisfaction with transparency at large and small pharmacy benefit managers (PBMs).

As you will see, clients remain slightly more satisfied with the perceived transparency of smaller PBMs compared with the Big Three PBMs—CVS Caremark, Express Scripts, and Optum Rx.

However, plan sponsors are dissatisfied with transparency about how both large and small PBMs make money. Smaller PBMs have an edge, but it’s narrower than you might think.

Perhaps PBMs’ clients are unable or unwilling to negotiate better deals, write more effective contracts, and switch to more satisfying relationships. Or maybe they don’t mind the current system, despite the challenges for patients. Some argue that transparency could swoop down to solve this problem. Riddle me this: Should we watch what plan sponsors say, or what they do?

Read on to see what you think of my arguments below. Then, click here to share your thoughts with the Drug Channels community.
Read more »

“Children are not small adults.” We invoke this saying, in a vague and hand-wavy manner, whenever we talk about the need to study drugs in pediatric populations. It’s an interesting idea, but it really cries out for further elaboration. If they’re not small adults, what are they? Are pediatric efficacy and safety totally uncorrelated with adult efficacy and safety? Or are children actually kind of like small adults in certain important ways?

Pediatric post-marketing studies have been completed for over 200 compounds in the years since BPCA (2002, offering a reward of 6 months extra market exclusivity/patent life to any drug conducting requested pediatric studies) and PREA (2007, giving FDA power to require pediatric studies) were enacted. I think it is fair to say that at this point, it would be nice to have some sort of comprehensive idea of how FDA views the risks associated with treating children with medications tested only on adults. Are they in general less efficacious? More? Is PK in children predictable from adult studies a reasonable percentage of the time, or does it need to be recharacterized with every drug?

Essentially, my point is that BPCA/PREA is a pretty crude tool: it is both too broad in setting what is basically a single standard for all new adult medications, and too vague as to what exactly that standard is.

In fact, a 2008 published review from FDA staffers and a 2012 Institute of Medicine report both show one clear trend: in a significant majority of cases, pediatric studies resulted in validating the adult medication in children, mostly with predictable dose and formulation adjustments (77 of 108 compounds (71%) in the FDA review, and 27 of 45 (60%) in the IOM review, had label changes that simply reflected that use of the drug was acceptable in younger patients).

So, it seems, most of the time, children are in fact not terribly unlike small adults.

But it’s also true that the percentages of studies that show lack of efficacy, or bring to light a new safety issue with the drug’s use in children, is well above zero. There is some extremely important information here.

To paraphrase John Wanamaker: we know that half our PREA studies are a waste of time; we just don’t know which half.

This would seem to me to be the highest regulatory priority – to be able to predict which new drugs will work as expected in children, and which may truly require further study. After a couple hundred compounds have gone through this process, we really ought to be better positioned to understand how certain pharmacological properties might increase or decrease the risks of drugs behaving differently than expected in children. Unfortunately, neither the FDA nor the IOM papers venture any hypotheses about this – both end up providing long lists of examples of certain points, but not providing any explanatory mechanisms that might enable us to engage in some predictive risk assessment.

While FDASIA did not advance PREA in terms of more rigorously defining the scope of pediatric requirements (or, better yet, requiring FDA to do so), it did address one lingering concern by requiring that FDA publish non-compliance letters for sponsors that do not meet their commitments. (PREA, like FDAAA, is a bit plagued by lingering suspicions that it’s widely ignored by industry.)

The first batch of letters and responses has been published, and it offers some early insights into the problems engendered by the nebulous nature of PREA and its implementation.

These examples, unfortunately, are still a bit opaque – we will need to wait on the FDA responses to the sponsors to see if some of the counter-claims are deemed credible. In addition, there are a few references to prior deferral requests, but the details of the request (and rationales for the subsequent FDA denials) do not appear to be publicly available. You can read FDA’s take on the new postings on their blog, or in the predictably excellent coverage from Alec Gaffney at RAPS.

Looking through the first 4 drugs publicly identified for noncompliance, the clear trend is that there is no trend. All these PREA requirements have been missed for dramatically different reasons.

Here’s a quick rundown of the drugs at issue – and, more interestingly, the sponsor responses:

1. Renvela - Genzyme (full response)

Genzyme appears to be laying responsibility for the delay firmly at FDA’s feet here, basically claiming that FDA continued to pile on new requirements over time:

Genzyme’s correspondence with the FDA regarding pediatric plans and design of this study began in 2006 and included a face to face meeting with FDA in May 2009. Genzyme submitted 8 revisions of the pediatric study design based on feedback from FDA including that received in 4 General Advice Letters. The Advice Letter dated February 17, 2011  contained further recommendations on the study design, yet still required the final clinical study report  by December 31, 2011.

This highlights one of PREA’s real problems: the requirements as specified in most drug approval letters are not specific enough to fully dictate the study protocol. Instead, there is a lot of back and forth between the sponsor and FDA, and it seems that FDA does not always fully account for their own contribution to delays in getting studies started.

2. Hectorol - Genzyme (full response)

In this one, Genzyme blames the FDA not for too much feedback, but for none at all:

On December 22, 2010, Genzyme submitted a revised pediatric development plan (Serial No. 212) which was intended to address FDA feedback and concerns that had been received to date. This submission included proposed protocol HECT05310. [...] At this time, Genzyme has not received feedback from the FDA on the protocol included in the December 22, 2010 submission.

If this is true, it appears extremely embarrassing for FDA. Have they really not provided feedback in over 2.5 years, and yet still sending noncompliance letters to the sponsor? It will be very interesting to see an FDA response to this.

3. Cleviprex – The Medicines Company (full response)

This is the only case where the pharma company appears to be clearly trying to game the system a bit. According to their response:

Recognizing that, due to circumstances beyond the company’s control, the pediatric assessment could not be completed by the due date, The Medicines Company notified FDA in September 2010, and sought an extension. At that time, it was FDA’s view that no extensions were available. Following the passage of FDASIA, which specifically authorizes deferral extensions, the company again sought a deferral extension in December 2012. 

So, after hearing that they had to move forward in 2010, the company promptly waited 2 years to ask for another extension. During that time, the letter seems to imply that they did not try to move the study forward at all, preferring to roll the dice and wait for changing laws to help them get out from under the obligation.

4. Twinject/Adrenaclick – Amedra (full response)

The details of this one are heavily redacted, but it may also be a bit of gamesmanship from the sponsor. After purchasing the injectors, Amedra asked for a deferral. When the deferral was denied, they simply asked for the requirements to be waived altogether. That seems backwards, but perhaps there's a good reason for that.

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Startup employees often go on to found interesting ventures, basing their new work on the experience gained from their time building a company from scratch. But not all of those experiences are positive, and sometimes, a less-than-satisfactory exit can do more to fuel a founder’s fervor than anything else. In the case of Forward Earth’s […]

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X, formerly Twitter, is no longer the “digital town square” it once promised to be. Following the results of the U.S. presidential election, floods of users unhappy with the app’s latest direction are moving over to a competing app, Bluesky. Bluesky’s decentralized social media platform has steadily grown from 9+ million users as of September […]

© 2024 TechCrunch. All rights reserved. For personal use only.

Farmers’ organisations say the MSP did not match the increase in input costs

UDF-led Oppn. boycotts event; senior citizens in 75 wards trained to use mobile phones, internet, says Mayor

Retirement age for pilots and other staff at Air India is 58 years, whereas at Vistara it is 60 years

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The University of Washington in Seattle is a big place. It includes the Institute for Health Metrics and Evaluation (IHME), which has produced a widely-circulated and widely-criticized coronavirus model. As we’ve discussed, the IHME model is essentially a curve-fitting exercise that makes projections using the second derivative of the time trend on the log scale. […]

Many parents across the country are helping their children learn from home for the first time ever, but one man who has been home educating for years warns some parents might not like what they see.

It was not the landing the Jamaicans who arrived at Kingston’s Norman Manley International Airport on Wednesday evening would want again. The 43 Jamaican ship workers of the Marella Discovery 2 were among the 115 people aboard the TUI charter flight that touched down amid the Kingston breeze and evening sunset.

FIFA's decision to temporarily allow up to five substitutions per match to help cope with potential fixture congestion was met coolly in South America on Friday.

Title: 2 in 3 Women Unhappy With Their Breast Size. Could That Harm Their Health?
Category: Health News
Created: 2/6/2020 12:00:00 AM
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Radamel Falcao has had plenty of criticism for his disastrous loan spell at Manchester United and now his own mother says he has gone backwards and could leave Old Trafford this summer.

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The results showed a 13 per cent drop in support for the president from when he took office in 2016. They were carried out by the Military Times and staff at Syracuse University, New York.

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Red Bull's No 1 driver Max Verstappen, who is expected to seriously test Lewis Hamilton's dominance going forward, starred heavily during the documentary that premiered last month.

EXCLUSIVE BY MATT HUGHES AND SAMI MOKBEL: Sacked Charlton board members have charged the cash-strapped club more than £575,000 in consultancy fees and expenses.

Raheem Sterling claimed he would prove his aggression against Everton after being shocked by his low rating on FIFA 20 before his ePremier League Invitational quarter-final.

Environmental clearances in India have always raised questions, as noted in many reports in India Together. For years now, NGOs have opposed the Ministry of Environment, sometimes bitterly. Last year, the Ministry proposed a 're-engineered' regulation, and found a new opposition - the state governments. Kanchi Kohli has more.

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Its festival season, and many e-commerce sites including Flipkart, Snapdeal and Amazon are making a big sale offers. Most popularly, Flipkart is making a huge buzz in the market with its Big Billion Sale festival. The e-commerce site is claiming to