Medical Publishing Potboilers

08/04/2010 03:59 PM |

According to wikipedia "Potboiler or pot-boiler is a term used to describe a poor quality novel, play, opera, or film, or other creative work that was created quickly to make money to pay for the creator's daily expenses (thus the imagery of "boil the pot"^[1], which means "to provide one's livelihood"^[2]). Authors who create potboiler novels or screenplays are sometimes called hack writers."

Medical journals are full of potboilers writen by hack writers who today throw together reports designed to fit the media's appetite for stories fitting the anti-Big Pharma narrative...

Case in point: 

Outcome Reporting Among Drug Trials Registered in ClinicalTrials.gov

1. Florence T. Bourgeois, MD, MPH;
2. Srinivas Murthy, MD; and
3. Kenneth D. Mandl, MD, MPH

www.annals.org/content/153/3/158.full

Can you guess what the conclusion of the study was from the following headline?

Review Suggests Bias in Drug Study Reporting

Industry-funded trials more likely to have positive findings than other studies, analysis shows

www.businessweek.com/lifestyle/content/healthday/641567.html

You can spend your own $15 to get this potboiler on line or you can read the juicy parts of the hatchet job here.. You  just have to suffer through my commentary.

"Results were considered favorable if they were statistically significant (based on P values or CIs) and supported the efficacy or safety of the test drug or not favorable if they were not statistically significant for the efficacy or safety of the test drug (25). For noninferiority trials, if the test drug was equal to the comparison drug, the results were also classified as favorable."

An industry sponsored study showing any benefit even if barely statistically signiifcant is considered positive.  An industry sponsored study showing no difference in outcome in treatment compared to another drug or a placebo... that's also called a positive study.

There is also these important findings:

"Trials funded by industry were more likely to be phase 3 or 4 trials (88.7%; P < 0.001 across groups), to use an active comparator in controlled trials (36.8%; P = 0.010 across groups), to be multicenter (89.0%; P < 0.001 across groups), and to enroll more participants (median sample size, 306 participants; P < 0.001 across groups). Government-funded trials were most likely to be placebo-controlled (56.2%), whereas trials funded by nonprofit or nonfederal sources were least likely to be multicenter (24.6%) and tended to have the smallest sample size (median, 50 participants). Industry-funded trials were also most successful at enrolling the anticipated number of participants, with 84.9% of trials enrolling at least 75% of the planned number of participants (P < 0.001 across groups)"

In otherwords,  drug companies did more post market studies (increasingly required) and confirmatory trials (always required) that were more diverse and larger.  That explains in part the higher percentage of trials showing statistically significant efficacy.   Smaller studies that are underfunded and underpowered -- and less likely to enroll the number of patients regarded to achieve a level of confidence that results are reliable:  More likely  early phase studies looking at other endpoints.  No wonder industry sponsored trials are more likely to be "positive."   And just to be sure, the researchers toss treatment toss-ups into the positive category.  Nothing like creating your own standards.   I wonder how many product managers would regard a no-difference result to be "positive." 

So the authors twist the obvious into a conspiracy about how industry funding deliberately puts a happy face on otherwise lousy results...   But in the world of medical publishing, skewing data to stick to pharma is, dare I say, a positive.

So do the headlines about the study, which I bet few reporters even read.  
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Shuren-up Devices

08/04/2010 09:05 AM |

From the Wall Street Journal:

The Food and Drug Administration proposed shoring up medical-device approval rules that have been criticized as lax and inconsistent by consumer advocates and the agency itself.

The FDA aims to better define what devices can use an approval pathway known as 510(k), under which companies can get an accelerated decision on whether they can market a new product if they can show it is similar to an already approved device. The proposals, which will be open for public comment, will be closely watched by the device industry because more-stringent rules would raise development costs.

The FDA's top device regulator, Jeffrey Shuren, rejected suggestions that the changes would result in fewer devices being eligible for 510(k) approval or raise the need in general for extra medical studies. He said clarity was the main point of the effort.

The FDA began reviewing its medical-device regulations in September after issuing a self-critical report that said top regulators bowed to outside political pressure when approving a ReGen Biologics Inc. knee device in 2008. Articles in The Wall Street Journal had pointed to the political pressure and other irregularities in the ReGen case. ReGen said its device was safe and effective and defended its activities before the FDA.

"There is widespread recognition that there's significant room for improvement in the way we operate," said Dr. Shuren, who directs the FDA Center for Devices and Radiological Health.

The FDA said it wants to develop guidance clarifying when older devices shouldn't be used as a benchmark, or "predicate," for comparison to a new product. The agency is still working on the guidelines, but said there appears to be confusion about the rules.

The agency also proposed creating a subset of Class II devices for which clinical or manufacturing data would be needed to bolster the case that they are substantially equivalent to an already approved product. Class II devices are generally considered to carry moderate risk to patients. Dr. Shuren said drug-infusion pumps, ubiquitous hospital products which the FDA is seeking to improve amid a history of problems, fall into this new "Class IIb" category.

Pump maker Baxter International Inc. is in the process of pulling 200,000 pumps off the U.S. market after the FDA decided it was moving too slowly to fix the devices, whose flaws have included failure to deliver the right amount of medicine.

The device industry's trade group said the proposals included a number of steps that would increase the consistency and predictability of the approval process, but as a whole threatened "significant disruption." Among the industry's complaints are an agency plan to include detailed information about new products, such as design schematics, in a public database. That would give foreign competitors access to proprietary information, potentially hurting U.S. manufacturers, said Stephen J. Ubl, president and chief executive of the Advanced Medical Technology Association.

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Total Partial Recall

08/03/2010 09:20 AM |

According to a poll of 802 registered voters by the Pew Charitable Trust's Prescription Project, more than three out of four are confident that prescription drugs made in the USA are free from contamination. However, fewer than one in 10 feel confident about medications made in India or China.

But what “made” represents can be misleading.  On the one hand it means “manufactured.” On the other it means “with ingredients from.”  And the two aren’t the same thing.

This is an important distinction for a number of reasons – especially when you’re asking the question to a general audience.  When you ask someone about their feelings about where a drug is “made,” they are going to assume that “made” means “manufactured.” And while that’s important – it’s only part of the story.

An estimated 80% of the substances used to make or package drugs sold in the United States are made in other countries – and increasingly those “other countries” are India and China. Globally, in 2007, 68% of ingredients of drugs sold worldwide came from India or China, vs. 49% in 2004.

 

As far as products that are manufactured abroad, it’s important for the American public to understand that the exact same GMP’s are required as a plant in the Lower 48.  The Pew poll didn’t share that information. It’s a game changer. 

 

More important is the issue of ingredients sourced from foreign nations.  Heparin comes to mind. (In 2007 and 2008, more than 100 patients in the USA died after taking heparin made with a contaminated active ingredient from China.) Attention must be paid and enhanced oversight is essential. 

 

From the legislative standpoint is the Drug Safety and Accountability Act of 2010, to be introduced today by Senator Michael Bennet (D, CO). The bill would empower the FDA to order recalls of unsafe batches of drugs. This recognizes the reality that the concept of “total recall” of a drug is a  very 20^th century concept.

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Commonwealth Fund Study on Women Leaves Us Wanting More

08/02/2010 01:15 PM |

The "study" is really a restatement of who will get covered when under Obamacare.  It duly notes that certain preventive services will not require a copay or deductible and that all health plans will be required to cover pregnancy and maternal care.  

The Commonwealth Fund report fails to consider the added cost of buying coverage for such services and ignores the fact that there out of pocket costs associated with maternal care under every  health plan.   It also fails to note that obtaining ob-gyn coverage under Medicaid is increasingly difficult.  In fact, ob-gyn services are hard to find under any circumstances.  Just wait till twice as many patients whose care will be reimbursed as one third private insurance rates flood the system. 

The report conveys the impression that all these services will be free and widely available.  And it does not account for any increase in insurance premiums or efforts to limits coverage of new services to control costs. 

tinyurl.com/26wo4br



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Trials -- and Error

08/02/2010 10:04 AM |

An FDA advisory committee’s 12-1 vote to remove Avastin’s breast cancer indication is unloved - -and misunderstood – by Senator David Vitter (R, LA) who called the decision “essentially government rationing.”

“I shudder at the thought of a government panel assigning a value to a day of a person’s life,” Vitter said in a statement. “It is sickening to think that care would be withheld from a patient simply because their life is not deemed valuable enough.” In a letter to the FDA cancer division leader, Richard Pazdur, Vitter said the committee’s vote appeared to be based on cost effectiveness, not safety issues.

Not so.

New studies presented to the panel showed more side effects among women being treated with Avastin and no overall survival benefit, though they did show women taking the drug had an extra month to 2.9 months of progression-free survival.

Whether or not you agree with the panel’s viewpoint on the clinical efficacy – they can’t be dinged by making a decision based on cost.  That’s just unfair.

While the fear of cost-based care trumping patient-centric medicine is real – the Avastin issue is one of data.

Senator Vitter’s clarion call is accurate – we need to be vigilant to call “comparative effectiveness” what it is – rationing.  But this is not the right instance to do so.

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Plan C?

08/02/2010 08:54 AM |

A women's health advocacy group that hopes to meet with FDA within the next year to explore potentially switching oral contraceptives to OTC may be hard-pressed to find a pharmaceutical company interested in sponsoring such a venture.

The Oral Contraceptives Over-the-Counter Working Group, coordinated by Ibis Reproductive Health, is "interested in moving oral contraceptives over the counter as a way to increase access to" the drugs, "especially for women who now face barriers to access," such as needing a prescription, said Daniel Grossman, leader of the working group and senior associate at Ibis.

"We are currently in the process of talking with a number of potential partners about what would be needed for a switch, and are hoping to meet with FDA in the next few months to discuss the regulatory pathway," said Grossman, an obstetrician-gynecologist.

One aspect the group needs to explore is finding a drug firm as a partner to sponsor a potential switch application.

Grossman said the working group is not interested in sponsoring a switch application or filing a citizen petition to switch the category.

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Med Guide Tide

07/30/2010 07:50 AM |

The Pink Sheet reports that pharmacist groups asked FDA to create a few common templates for risk evaluation and mitigation strategies so they can better anticipate and implement the programs into their practices.

 

FDA and industry groups spoke in favor of REMS templates July 27, the first day of a two-day agency workshop gathering comments on the program. FDA expects to use the comments to help formulate more guidance for REMS on drugs.

 

Janet Woodcock said an effort will begin in the fall to develop a standard REMS system.

 

"Each program is proposed by the drug sponsor and then it's negotiated between the sponsor and the FDA and is uniquely tailored to the risks of that particular drug," Woodcock said. "So we don't have the kind of standardization and consistency of the programs that would be ideal."

 

Additional REMS changes already have been proposed, including allowing medication guides to be developed outside the REMS process.

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The Kaiser Health News Conglomerate

07/29/2010 06:03 PM |

Poll shows opposition to health care overhaul declining

By David S. Hilzenrath

Washington Post Staff Writer
Thursday, July 29, 2010; 12:02 AM

 

Opposition to the landmark health care overhaul declined over the past month, to 35 percent from 41 percent, according to the latest results of a tracking poll, reported Thursday.

Support For Health Law Remains Steady While Opposition Drops

By Lexie Verdon

Jul 29, 2010

The percentage of people who view the new health bill unfavorably dropped 6 points to 35 percent in the past month, but that has not translated into a significant increase of supporters, according to the July tracking poll from the Kaiser Family Foundation. Overall support remained stable since the June survey, with about half the public expressing a favorable view of the overhaul, the poll found.
www.kaiserhealthnews.org/Stories/2010/July/29/health-reform-tracking-poll.aspx


If you find the two ledes strikingly, uh, similar, don't worry.  It's not plagiarism or even laziness on the part of the WaPo.  It's merely a product of the Kaiser Health News effort to "provide new opportunities for health care journalists to produce in-depth work and a new vehicle to distribute it through collaborations with major news organizations and on this Web site."   You see, it's really a jobs program first and a pass through mechanism of pro-government run health care reform "news" and surveys second. 

Kaiser Health News, which partners with USA Today, NPR, the New Republic along with many fair-minded types who were on the JournoList before it was circumscribed down to the Cabalist, is a venture of the Kaiser Family Foundation.  The foundation provides " strategic guidance".   That direction consists largely of ignoring original research critical of  health care reform in its current iteration and a slavish devotion to recycling the less than balanced or nuanced coverage of the fight over the implementation of the law.   Some guidance. 

Case in point is the echo chamber KHN creates by paying for polls and writing articles about the polls that are then essentially reprinted by WaPo and then blogged on by the Journolistas like Ezra Klein, Jonathan Cohn,  Kate Steadman, etc.   It would be sinister if it weren't so banal and boring...

The KHN and it's effort to consolidate control coverage of health care reporting and the shaping of public opinion about health care should not be set aside lightly.  It should be thrown away with great force...

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The Conflict of Interest Charade

07/29/2010 03:40 PM |

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Generic Lovenox: The Plot Thickens

07/28/2010 03:33 PM |

Sanofi is seeking to block Novartis from selling the generic version of Lovenox.  A federal court refused to stop sales of the product, approved by the FDA July 23, pending the outcome of an August 17 hearing. 

Meanwhile, Sanofi is pursuing Genzyme, maybe, instead of or in addition to making an 'authorized' generic version of their product...

To underscore a point Peter made, analysts who think that the approval of generic Lovenox will unleash a flood of follow-on biologics had better readjust their sights and projections.  Or at least read the FDA's approvable letter to Novartis and Momenta: 


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Bernstein Bares

07/28/2010 08:18 AM |

"Many in the industry have felt that if FDA ultimately approves generic versions of Lovenox and it makes those generics fully 'substitutable' - which it just has - then this might signal what FDA may also ultimately do when it comes to 'true' biologics that generic companies are also pursuing," Tim Anderson, an analyst with Bernstein Research, wrote in a research note on the recent agency action.

Not necessarily.

Remember, the FDA has the authority to use its discretion in asking for new clinical trials for biosimilars and – here’s the sticky question – is Lovenox really a biologic? Sticky question?  Not really -- because the answer is, "no."

When it comes to bioequivalence and biosimilars, the FDA will do the right thing.

After all (and with apologies to Senator Kerry), you can’t be for enhanced safety and against it at the same time.

Do not trust all men, but trust men of worth; the former course is silly, the latter a mark of prudence.

-- Democritus

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Axe falls on NHS services

07/27/2010 02:34 PM |

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I'm okay. You're UK.

07/26/2010 07:14 AM |

That Britain’s NHS will undergo an historic change (“Britain Plans to Decentralize National Health Care”) is significant, sobering but not surprising. It’s an experience with valuable lessons for us over here on the other side of the pond. 

 

Lessons about the inefficiencies of centralized government healthcare. There’s no value in calling it “socialist” when you can just say, “see, it doesn’t work.”  As the man said, “attention must be paid.”

 

Lessons about what happens when your system is based on a cost-centric rather than a patient-focused philosophy of healthcare.  Yes – we really need to put the 800-pound gorilla on the operating room table.  Who needs “death panels” when you have “deny panels.”

 

And, finally, lessons about money.  It really isn’t all about the amount of money you spend – if you don’t spend it in the right places.  And that’s Lesson #1.

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Care to comment, Dr. Berwick?

07/24/2010 02:41 PM |

From the pages of the New York Times.  Draw your own conclusions.

Britain Plans to Decentralize National Health Care

By SARAH LYALL

LONDON — Perhaps the only consistent thing about Britain’s socialized health care system is that it is in a perpetual state of flux, its structure constantly changing as governments search for the elusive formula that will deliver the best care for the cheapest price while costs and demand escalate.

Even as the new coalition government said it would make enormous cuts in the public sector, it initially promised to leave health care alone. But in one of its most surprising moves so far, it has done the opposite, proposing what would be the most radical reorganization of the National Health Service, as the system is called, since its inception in 1948.

Practical details of the plan are still sketchy. But its aim is clear: to shift control of England’s $160 billion annual health budget from a centralized bureaucracy to doctors at the local level. Under the plan, $100 billion to $125 billion a year would be meted out to general practitioners, who would use the money to buy services from hospitals and other health care providers.

The plan would also shrink the bureaucratic apparatus, in keeping with the government’s goal to effect $30 billion in “efficiency savings” in the health budget by 2014 and to reduce administrative costs by 45 percent. Tens of thousands of jobs would be lost because layers of bureaucracy would be abolished.

In a document, or white paper, outlining the plan, the government admitted that the changes would “cause significant disruption and loss of jobs.” But it said: “The current architecture of the health system has developed piecemeal, involves duplication and is unwieldy. Liberating the N.H.S., and putting power in the hands of patients and clinicians, means we will be able to effect a radical simplification, and remove layers of management.”

The health secretary, Andrew Lansley, also promised to put more power in the hands of patients. Currently, how and where patients are treated, and by whom, is largely determined by decisions made by 150 entities known as primary care trusts — all of which would be abolished under the plan, with some of those choices going to patients. It would also abolish many current government-set targets, like limits on how long patients have to wait for treatment.

The plan, with many elements that need legislative approval to be enacted, applies only to England; other parts of Britain have separate systems.

The government announced the proposals this month. Reactions to them range from pleased to highly skeptical.

Many critics say that the plans are far too ambitious, particularly in the short period of time allotted, and they doubt that general practitioners are the right people to decide how the health care budget should be spent. Currently, the 150 primary care trusts make most of those decisions. Under the proposals, general practitioners would band together in regional consortia to buy services from hospitals and other providers.

It is likely that many such groups would have to spend money to hire outside managers to manage their budgets and negotiate with the providers, thus canceling out some of the savings.

David Furness, head of strategic development at the Social Market Foundation, a study group, said that under the plan, every general practitioner in London would, in effect, be responsible for a $3.4 million budget.

“It’s like getting your waiter to manage a restaurant,” Mr. Furness said. “The government is saying that G.P.’s know what the patient wants, just the way a waiter knows what you want to eat. But a waiter isn’t necessarily any good at ordering stock, managing the premises, talking to the chef — why would they be? They’re waiters.”

But advocacy groups for general practitioners welcomed the proposals.

“One of the great attractions of this is that it will be able to focus on what local people need,” said Prof. Steve Field, chairman of the Royal College of General Practitioners, which represents about 40,000 of the 50,000 general practitioners in the country. “This is about clinicians taking responsibility for making these decisions.”

Dr. Richard Vautrey, deputy chairman of the general practitioner committee at the British Medical Association, said general practitioners had long felt there were “far too many bureaucratic hurdles to leap” in the system, impeding communication. “In many places, the communication between G.P.’s and consultants in hospitals has become fragmented and distant,” he said.

The plan would also require all National Health Service hospitals to become “foundation trusts,” enterprises that are independent of health service control and accountable to an independent regulator (some hospitals currently operate in this fashion). This would result in a further loss of jobs, health care unions say, and also open the door to further privatization of the service.

The government has promised that the new plan will not affect patient care and that the health care budget will not be cut. But some experts say those assertions are misleading. The previous government, controlled by the Labour Party, poured money into the health service — the budget is now about three times what it was when Labour took over, in 1997 — but the increases have stopped. The government has said the budget will continue to rise in real terms for the next five years, but it is unlikely that the increases will keep up with the rising costs of care and the demands of an aging population.

“The real mistake that is being made by the health secretary is to drive through an ideologically determined program of reorganization which is motivated by the principle of efficiency savings,” said Robin Durie, a senior lecturer in politics at the University of Exeter. “History shows clearly that quality will suffer as a consequence.”

Dr. Durie added, “The gulf between the rhetoric of the white paper and the technicalities of what is involved in the various elements of the overall reorganization being proposed is just extraordinary.”

For example, he asked, how will the government make good on its promise to give patients more choice — a promise that seems to require a degree of administrative oversight — while cutting so many managers from the system?

“How will the delivery of all this choice be funded?” Dr. Durie asked. “And how will the management of the delivery of choice be funded?”

Dr. Vautrey said the country needed to have a “mature debate about what the N.H.S. can and cannot afford.”

He said: “It is a sign of the mixed messages that government sends out. They talk about choice and competition and increased patient expectations at the same time as they tell the service they need to cut costs and refer less and prescribe less. People need to understand that while the needs of everyone may be met, their wants will be limited.”

As they prepare for the change, many doctors are wondering whether it will be permanent this time around.

“Many of our colleagues have seen this cycle of change repeatedly,” Dr. Vautrey said. “Many would look at previous reorganizations and compare it to this one and wonder how long the current change will last before the next one comes along.”

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Gutter Politics on DTC Genetic Testing

07/24/2010 04:38 AM |

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Thick Skin. Thin Blood.

07/23/2010 03:06 PM |

And you know who you are ...

WASHINGTON—The Food and Drug Administration approved the first generic version of the big-selling blood thinner Lovenox, in a victory for a unit of Novartis AG.

The Novartis unit, Sandoz, and partner Momenta Pharmaceuticals Inc. have been in a tug of war for years with a California-based company, Amphastar Pharmaceuticals Inc., to win FDA approval for generic versions of Lovenox.

Amphastar has accused the FDA and its drug-division leaders of favoritism in the past year, noting that Momenta worked closely with the FDA on safety issues and investigations in recent years. Momenta has said its relationship with the FDA is appropriate.

Sanofi has fought to protect Lovenox from generic competition, saying that the drug is too complex to be completely copied safely. Researchers with ties to Sanofi recently filed citizens' petitions to the FDA asking the agency not to approve any company's enoxaparin.

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News you can use -- maybe

07/23/2010 09:19 AM |

The good news:  FDA Social Media Guidance. The bad news:  FDA Social Media Guidance.

Here’s how my interview with emarketer begins:

eMarketer: The FDA is expected to issue guidance on the use of social media this year. What do you think it will look like?

Peter Pitts:

There are a lot of ifs. The first if is, is this really a good thing? A lot of times when you ask for regulation and you get it, you may not be happy with it. If marketers are waiting for FDA guidance with the assumption that it’s going to make their jobs easier, that’s very much open to question.

And here’s how it ends:

Peter Pitts:

The concept of being incomplaunce vs. doing the right thig for the public health cannot be contradictory to each other and right now they are. The issue is to step up to the plate and do what's right instead of what is legally conservative.

For everything in the middle, see here.

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Boozman targets Blanche

07/22/2010 01:16 PM |

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Health care law = Bad for business

07/21/2010 11:02 AM |

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Berwick's Final Solution for Healthcare Reform

07/20/2010 08:57 PM |

I urge you to read this document, produced by Berwick and funded by health plans on how to reduce healthcare spending... Berwick's model of what health system does the best of reducing costs by improving health outcomes.  Once again the NHS.   Particularly disturbing is Berwick's belief that improving the patient 'experience' somehow makes up for ceding control of payment decisions on access to technology, particularly those who suffer from chronic illness. 



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