(Postage) Stamp of Disapproval

09/17/2012 07:38 AM |

Since the end of 2011 the FDA has sent 11 warning letters to companies in seven different countries that were exporting drugs to the U.S. after having let their required registration and listing expire.

The warning letter recipients also failed to respond to letters FDA sent them last year notifying them that they were not registered or listed for imports into the U.S., according to nearly identical language in the warning letters.

“FDA has established an ongoing program to identify drug manufacturing firms that have not complied with registration and listing requirements and to notify such firms of their ostensible noncompliance,” the agency said. “FDA has issued warning letters to some of the firms that have not responded to this notification and are out of compliance with registration and listing requirements. These warning letters have targeted firms whose lack of compliance has the greatest potential impact on FDA's regulatory mission.”

 FDA’s focus on compliance at foreign drug manufacturing facilities has been sharper since the tainted heparin scandal in 2008, and new provisions in the recently passed user fee legislation is designed to reduce the number of unregistered facilities -- particularly for generic drugs.

But that was before sequestration.

We’ll see.

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Expanding the Scope of What's Possible

09/14/2012 07:54 AM |

“The convergence of two powerful forces is driving today’s medical innovation to the top of the national agenda:  The urgent need for medical breakthroughs and the unprecedented opportunities created by recent advances in science.”

So said El Lilly & Company’s Grand Poobah John Lechleiter at yesterday’s “Advancing Medical Innovation” summit in Washington, DC. (The event was co-sponsored by Lilly and the Washington Post.)  I was pleased to attend.

More Lechleiter:

“Our only hope of breaking our of the crisis is through innovation that changes the terms of the trade-offs we must make and expands the scope of what’s possible.”

The Hoosier Honcho then offered a very potent example of what he meant:

“In the early 1950s, the cost of polio care in the US was predicted to be $100 billion by the year 2000 but, thanks to the advent in 1954 of the polio vaccine, the cost of treating polio in the US in the year 2000 was $100 million.”

In other words – the prediction was off by 99.9% because of game changing innovation.  Can we do that again? We’d better try – and try hard.

But Lechleiter offered a crucial caveat, “Realizing the benefits of medical innovation requires an ecosystem where innovation can thrive.”

Are we there yet?

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Thursday news

09/13/2012 10:46 AM |

Betsy McCaughey on ObamaCare’s hospital cuts:

President Obama is wooing seniors with promises to protect Medicare as they've known it. On the defensive because of the $716 billion his health care law takes from Medicare, Obama assures seniors he's cutting payments to hospitals and other providers, not their benefits. 

Don't be bamboozled. It's illogical to think that reducing what a hospital is paid to treat seniors won't harm their care. A mountain of scientific evidence proves the cuts will worsen the chance that an elderly patient survives a hospital stay and goes home. It’s reasonable to conclude that tens of thousands of seniors will die needlessly each year.

Under ObamaaCare, hospitals, hospice care, dialysis centers, and nursing homes will be paid less to care for the same number of seniors than if the health law had not been  enacted. Payments to doctors will also be cut.

Read more here.
 
 
Politico on the Hatch Act violation by HHS Secretary Sebelius:

INDEPENDENT COUNSEL: SEBELIUS CROSSED THE LINE - Limits on political maneuvering by public officials working on the taxpayers' dime are nebulous, byzantine and often blurred. But the Office of Special Counsel - an independent prosecuting authority - has concluded that HHS Secretary Kathleen Sebelius broke the law when she exhorted a North Carolina crowd last February to reelect her boss, President Barack Obama, during what was supposed to be an official visit. The determination - which OSC said was an isolated incident - creates an immediate headache for the Obama administration on a day that Census data showed a dip in uninsured Americans, partly because of the Affordable Care Act.

--From the OSC report: "[Sebelius] noted that North Carolina is critical in the next election and emphasized that it is 'hugely important to make sure we reelect the president.' These statements were made in Secretary Sebelius's official capacity and therefore violated the Hatch Act's prohibition against using official authority or influence to affect the results of an election."

--Sebelius admitted she shouldn't have injected politics into an official event but pointed to her office's immediate decision to reclassify the event as a campaign stop and to reimburse the U.S. Treasury for her travel. More telling, though, was her explanation for the lapse: "As I have also explained, keeping the roles straight can be a difficult task, particularly on mixed trips that involve both campaign and official stops on the same day."

Read more here.



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OTC and DTC -- Whither Fair Balance?

09/13/2012 06:42 AM |

Much important discussion of late about possible new categories for Rx-to-OTC switching – namely erectile dysfunction medicines and statins.  But how does this impact consumer information? Consider the impact of the FDA-to-FTC switch.

The FDA requires prescription drug advertising to provide consumers with a "fair balance" of risks and benefits. The FTC, on the other hand, holds drug advertisements to the same standards as other consumer products, requiring a "reasonable" standard of truthfulness.

What’s the impact on how these products are presented to consumers?

According to a new study, when prescription drugs become available over-the-counter, advertisements for the medications are less likely to tell consumers about the potential harms and side effects. This according to Dr. Jeremy Greene, an associate professor in the history of medicine department and the department of medicine at Johns Hopkins University (study published in the September 12th issue of the Journal of the American Medical Association).

Greene and his colleagues analyzed print and broadcast advertisements for four commonly used drugs that were heavily marketed to consumers as prescription drugs and then approved for sale over-the-counter.

The drugs included loratadine (brand name: Claritin, sold over-the-counter since 2002), omeprazole (brand name: Prilosec, went over-the-counter in 2004), orlistat (brand name: Alli, Xenical, sold over-the-counter since 2007), and cetirizine (brand name: Zyrtec, sold over-the-counter since 2008).

When the drugs were available only by prescription, 70 percent of the ads mentioned potential harms. After the drugs were available over-the-counter, only 11 percent did, the investigators found.

After drugs became available over-the-counter, only about half of print and broadcast advertisements mentioned a drug's generic name, compared to 94 percent of ads when drugs were prescription-only. Knowing a drug's generic name can help consumers make sure they're not taking more than one medication that has it as a component, risking overdose, Greene explained.

Greene believes that the FDA should be given authority to regulate marketing of over-the-counter drugs, or perhaps the FTC should adopt guidelines similar to what the FDA requires.

Rather than asking either underfunded agency to take on more work (for which they are neither staffed nor suited), perhaps OTC advertisers should consider what they could do to better educate consumers. After all, a key FDA consideration in approving an Rx-to-OTC switch is whether consumers understand key communication objectives of the label, relating to directions for use, contraindications, in-use warnings and precautions.

Knowledge is power.

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Court to FDA: A picture won't be worth 1000 words

09/12/2012 07:38 AM |

A very interesting post from pointoflaw.com:

FDA's "graphic" cigarette warnings struck down

The FDA has suffered another setback in its relentless campaign to turn every cigarette pack into a "mini-billboard" for its anti-smoking agenda. The US Court of Appeals for the DC Circuit has upheld a lower court decision striking down the agency's rules that would require cigarette makers to include certain government-approved "graphic warnings" against smoking. Nothing too extreme, mind you, just a man blowing smoke out of a tracheotomy hole and similar pictures.

As reported last November, U.S. District Judge Richard Leon initially granted a preliminary injunction against the FDA rules. In February of this year, he issued a final ruling striking down the graphic warning requirement as unconstitutional "compelled speech." The DC Circuit affirmed on August 24.

The Supreme Court has long recognized that the First Amendment right to say what you want would be meaningless if the government could force you to say things you don't want. In Wooley v. Maynard, for example, the Court affirmed that Jehovah's Witnesses in New Hampshire could not be forced to use license plates with the State's motto: Live Free or Die.

Although commercial speech often merits less protection under existing precedents, there is clearly a liberty problem with forcing manufacturers to do everything possible to dissuade potential customers from buying their product. As the DC Circuit points out, manufacturers have been compelled to include certain information on labeling or other advertising if the information is (1) strictly factual, and (2) without the information, the company's advertising would be misleading. In this case, however, the FDA doesn't argue that current cigarette labels are misleading -- they include all the textual warnings. The FDA just thinks that the packages aren't scary enough; thus, they would require that 50 percent of the front and back panels of every cigarette pack contain pictures, e.g., of women crying, small children, and the guy with the tracheotomy. As the DC Circuit concluded, the images do not convey factual information, but are "unabashed attempts to evoke emotion (and perhaps embarrassment) and browbeat customers into quitting.

And yet, the government would have the courts review its rules under the weakest form of scrutiny available. By the FDA's logic, the government could dictate that every stick of butter be wrapped in images of open-heart surgery, that every candy bar be emblazoned with pictures of rotting teeth, and every sugary drink carry images of obese children -- and these rules would be virtually unreviewable.

The FDA could not even produce evidence that the graphic images would be effective -- the agency estimated a mere 0.088 decrease in smoking rates as a result of the shock-and-awe campaign. Ultimately, the agency seems to want the graphic warnings because "everybody else is doing it." The FDA cited a "strong worldwide consensus" based on the actions of various countries, including Mongolia, Venezuela, Singapore, and Iran. " It is worth noting," the Court said, "that the constitutions of these countries do not necessarily protect individual liberties as stringently as does the United States Constitution." You can say that again.

The case is R.J. Reynolds Tobacco Co. v. FDA, No. 11-5332, slip op. (DC Cir. Aug. 24, 2012).

  Read More & Comment...

9/11

09/11/2012 03:10 PM |

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More to do. More to know. More to manage.

09/11/2012 07:46 AM |

From the pages of Medical Marketing & Media …

Amid misspent billions, the promise of personalized medicine

The Institute of Medicine has released a report putting the cost of unnecessary medical care at $750 billion a year and counting. What does it mean for pharmas? Depends on how you read it. 

The IOM determined that three quarters of a trillion dollars (yes, that's trillion, with a ‘t') in health spending was wasted in 2009 – around 30% of all US healthcare spending – due to unnecessary services rendered, excessive administrative costs, fraud and other causes. Unnecessary services accounts for the largest chunk of that number, at around $210 billion, followed by “excess administrative costs,” at $190 billion, and then “inefficiently delivered care,” including mistakes and the unnecessary use of pricey providers, at $130 billion. “Prices that are too high,” defined as “services and products beyond competitive benchmarks,” costs $105 billion, while fraud runs $75 billion and “Missed prevention opportunities” $55 million. 

Expressed through a different, and starker, metric, IOM noted estimates that around 75,000 deaths might have been averted in 2005 had all states delivered care as well as the best-performing ones. 

While the report, “Best Care at Lower Cost: The Path to Continuously Learning Health Care in America,” doesn't have much to say about costs associated with drugs and biologics, specifically, it could provide fodder for advocates of European-style cost curbing for federal programs, but it also adds urgency to the movement towards personalized medicine. 

“The slippery slope to comparative effectiveness is there,” says Peter Pitts of the Center for Medicine in the Public Interest. He worries that a price control scheme like the UK's NICE could be implemented in the name of efficiency, but also sees the report's findings dovetailing nicely with the drug industry's move towards more narrowly targeted drugs, biologics and diagnostics. 

“If the idea is to get the right treatment to the right patient at the right dose as early in the cycle as possible, even if that sometimes means a more expensive drug rather than a generic, that's going to save money over the “fail your way to success” route [of cycling through multiple treatments until one works],” said Pitts.

The IOM sees several big factors impeding efficiency in US care delivery – chief among them, the lack of price transparency and collaboration between across providers, institutions and other players. And then there's the sheer complexity of modern healthcare, made all the more daunting by Big Data and the rapidly multiplying number of available therapies and procedures.  

“The US healthcare system is characterized by more to do, more to know and more to manage than at any time in history,” says the report.

As medical technology has progressed, the volume of information available to practitioners has multiplied exponentially. The number of journals and other research publications has more than tripled over the past four decades, from 200,000 in 1970 to 750,000 in 2010, the report notes. 

The IOM is an influential body of the National Academy of Sciences whose pronouncements can have far-reaching effects on regulators and policymakers. In recent years, the group has taken on thorny topics like consumer advertising of prescription drugs, CME and industry influence on the practice of medicine.    Read More & Comment...

A November Vote That Matters: Rare Disease Advocate of the Year

09/10/2012 02:12 PM |

The EveryLife Foundation for Rare Diseases is seeking nominations for it's Rare Voice Awards honoree.   You can go the website of this courageous coalition and vote until September 21st.    

There are many patient advocacy organizations.  Most are more interested in getting a "seat at the table" of the Washington policy community.    A few, like Everylife Foundation for Rare Diseases, are focused on removing the barriers to faster and broader access.  The group was the leading voice for reforms that accelerate the development of drugs for rare disease..  You can join it's movement for medical progress by voting for a Rare Voice Award honoree.   Here's a link to the nomination page: http://rarevoiceawards.org/nominate/

The number of deserving awardess are growing.   Just nominating someone can shine a light on their efforts.   


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Post marketing enhancements and clinical trial advancements

09/10/2012 07:45 AM |

OPQ, I see you

BioCentury reports that the FDA is considering the creation of a new office to oversee quality throughout the lifecycle of a drug.

According to CDER Director, Dr. Janet Woodcock, the new Office of Pharmaceutical Quality would take on some of the functions currently within the Office of Pharmaceutical Science, as well as some functions from the Office of Manufacturing and Product Quality in the Office of Compliance. Woodcock said it is imperative that CDER "have a drug quality program as robust as those programs we presently have for drug efficacy and drug safety."

Woodcock also proposed to elevate the Office of Generic Drugs to a "super" office as a result of the new user fee program for generics. OGD Director Greg Geba would continue to lead the office and would report to Woodcock.

And speaking of adaptive clinical trials

Exciting story in the New York Times about advances in treatment for squamous cell lung cancer and, “a new type of treatment in which drugs are tailored to match the genetic abnormality in each patient.”

The study is part of the Cancer Genome Atlas, a large project by the National Institutes of Health to examine genetic abnormalities in cancer. The study of squamous cell lung cancer is the second genetic analysis of a common cancer, coming on the heels of a study of colon cancer.

“As a result, the usual way of testing drugs by giving them to everyone with a particular type of cancer no longer makes sense. So researchers are planning a new type of testing program for squamous cell cancer that will match the major genetic abnormality in each patient with a drug designed to attack it, a harbinger of what many say will be the future of cancer research.”

“The old way of doing clinical trials where patients are only tied together by the organ where their cancer originated, those days are passing,” said Dr. Mace Rothenberg, senior vice president of Pfizer oncology.

  Read More & Comment...

Compounding the Problem

09/07/2012 08:28 AM |

A judge in the U.S. District Court for the District of Columbia has dismissed KV Pharmaceuticals suit against the FDA over the company's preterm birth drug Makena hydroxyprogesterone caproate.

After developing an FDA approved version of a drug that was in danger of becoming obsolete, KV promptly – and without warning – decided to charge $1500 per dose. The company was rightly criticized for the sudden jump in price and did the right thing by cutting the retail price of the drug to $680 and offering the drug at a reduced price to a wide range of organizations.

And yet the FDA decided to allow pharmacists to continue compounding even though KV developed the drug to put an end to the risk associated with compounding products.  (FYI -- The FDA is currently Investigating bacteria that sickened 19 people at Alabama hospitals and may have killed nine and has turned up at compounding pharmacy in Alabama. And there are many other examples.)

Is this a victory for the public health?

KV filed suit against the FDA, alleging that the agency's policy of non-enforcement for compounded hydroxyprogesterone caproate products violated KV's right to market exclusivity for Makena under the Orphan Drug Act.

No dice.

Judge Army Berman said KV's allegations relate to FDA's discretionary enforcement activities and are therefore "unreviewable claims." She said in her ruling that the "case is fundamentally an effort to get the court to direct and oversee the FDA's enforcement activities, and that it cannot do." We agree with Judge Berman -- but it's a dangerous precedent.

Last month, KV filed for Chapter 11 bankruptcy because it has been "unable to realize the full value" of Makena, citing FDA's lack of enforcement of the market exclusivity.

Is this a victory for pregnant women?

Certainly the FDA has the authority to ensure the availability of products and indirectly considers affordability.  It did so when it kept generic asthma inhalers on the market for several years rather than forcing them off to comply with an EPA requirement to remove inhalers powered by CFCs. I was at the agency at the time and the issue of inner city access was hotly debated.

That was (IMHO) a considered and organized action based on much thought and many meetings with stakeholders. The KV action (IMHO) was a reaction to media hype and political pressure.  The FDA even got involved in a little demagoguery when it cited the fact that the NIH had provided KV with support to conduct clinical trials as the agency’s reason to allow the compounding. Given that logic, should every drug developed in cooperation with the NIH or based on NIH research be denied market exclusivity?

Remember Plan B and remember that politics and FDA decisions should never be compounded   Read More & Comment...

Sequestration = Castration

09/06/2012 08:10 AM |

If the White House mandates the sequestration of the FDA budget the hurt will be shouldered by the public health.

PDUFA dollars cover reviews – but what about all of the other non-user fee items the FDA has on its plate – like advancing regulatory science and combatting counterfeiting, and developing standards for biosimilars and enhancing the safety and security of our food supply – to name only a few?

Sequestration = Castration of the FDA's mission.

Less is not more.

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Biomarker For Depression And it's Treatment

09/05/2012 02:13 PM |

Image: Jiri Hodan The Best Science Writing Online 2012 Showcasing more than fifty of the most provocative, original, and significant online essays from 2011, The Best Science Writing Online 2012 will change the way... Read More » By Amy Maxmen of Nature magazine People who live with clinical depression must also suffer the ‘trial and error’ approach that psychiatrists take when prescribing antidepressants. Now, a study published this week signifies the beginning of the end of guesswork. In it, a blood test predicts who will respond well to a novel treatment for depression, and who might even fare worse.“We haven’t had a test like this in psychiatry before,” says Andy Miller, a professor of psychiatry at Emory University and an author on the study in Archives of General Psychiatry. “There is no brain scan, no physiological measure that tells you whether a patient will respond to one drug more than another.” The test identifies an inflammatory protein in blood, C-reactive protein or CRP, that indicates internal inflammation. Whereas 62% of depressed participants with high CRP levels responded well to the new treatment, only 33% of participants with low CRP levels did. The correlation was not entirely unexpected, because the drug suppresses inflammation, and Miller thinks that inflammation underlies depression in some people. To test whether a potent anti-inflammatory could soothe the malady, his team recruited 60 people who had lived with major depression for more than a decade and had received no relief from antidepressants. Half of the participants received monthly treatments of the rheumatoid arthritis drug, Janssen’s Infliximab, and half received a placebo. Overall, Infliximab did not seem to work. However, when Miller’s team analyzed how the subset of participants with high CRP faired, it turns out they responded well to the drug, with a relief from sadness, suicidal thoughts, anxiety and other symptoms. Since the late 1980s, researchers have sporadically hypothesized that inflammation can lead to depression. The theory is that depressed behavior might be beneficial in the short term because it reserves an injured animal’s energy for healing rather than romping around in the sunlight. Although the hypothesis has never received widespread support, researchers have found that some depressed patients indeed bear elevated levels of inflammatory proteins. On the basis of the results from this relatively small study, a biologic drug such as Infliximab might be a better option in the anti-inflammatory realm than Cox-2 inhibitors such as aspirin, which come with unwanted side effects, says Miller. Although he knows of no Infliximab-like drug in development for depression, he says that companies might be encouraged by his team’s results. What’s more, with a biomarker to predict a response, companies will have a better chance of success. Robert Dantzer, a neuroimmunologist at MD Anderson Cancer Center in Houston, Texas, notes that some of the participants in the low-CRP group fared worse on Infliximab than on placebo. Thus, the CRP test could be as important a tool for excluding depressed patients from taking anti-inflammatory therapies as for predicting responders. This article is reproduced with permission from the magazine Nature. The article was first published on September 5, 2012.   Read More & Comment...

Precautionary Principle Pablum

09/05/2012 08:10 AM |

Here we go again. Thomas J. Moore and Curt D. Furberg (in a new JAMA article) accuse the FDA of compromising safety for speed.

As usual, Janet Woodcock places the matter in the appropriate perspective. "I'd like to stress that where there are unmet medical needs, the public has told us they are willing to accept greater risks," Dr. Woodcock said. "The cancer community in particular says we haven't used accelerated approvals enough."

Here’s the truth -- there is no such thing as a "safe" drug. It's the patient who must understand the risks required to achieve the benefit. That’s why the patient voice must be heard during all phases of the regulatory review process.

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Atop OMOP

09/05/2012 07:54 AM |

The Observational Medical Outcomes Partnership (OMOP), a public-private research project aimed at evaluating and validating methods of using observational health care databases for active drug safety surveillance, is considering closer collaboration with FDA’s Mini Sentinel and the Patient-Centered Outcomes Research Institute.

The OMOP executive board proposes working with Mini Sentinel and PCORI in a tentative three-year plan posted recently on the project’s website for public comment. 

The OMOP board proposes to “coordinate OMOP’s research with the research and practice of others in the fields of risk and effectiveness identification and interpretation.”

Mini Sentinel is a pilot project for FDA’s Sentinel Initiative, which is envisioned as a national post-market safety surveillance program drawing from a network of medical claims data and electronic health records.

 PCORI was established by the Affordable Care Act to sponsor outcomes research, including comparative effectiveness research, for drugs and other medical treatments.

OMOP’s other proposed activities include developing a framework for incorporating observational data and stakeholder perspectives into decision making, as well as methods to enable active surveillance and risk identification for newly marketed medical products.

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Chinese (Regulatory) Checkers

09/04/2012 09:17 AM |

The problem is that, after this important joint action, we're still hungry for more.

The China State Food and Drug Administration (SFDA) has joined forces with the FDA to shut down 18 Chinese-language web sites selling illegal drugs.

According to China Daily's report on Tuesday, the Sino-U.S. collaboration was launched in June this year and targeted Web sites in the U.S. advertising counterfeit drugs and health food. The 18 sites take down were run and hosted by Chinese speakers and aimed for Chinese consumers including Chinese Americans around the world, said Christopher Hickey, director of the U.S. FDA's China office.

"We welcome and appreciate the role played by the China State Food and Drug Administration to initiate the campaign and hope to continue combined efforts in the global fight against counterfeit drugs," he added.

The Sino-US collaborations was also part of a national clampdown on fake and illegal drugs within mainland China, said SFDA spokesperson Wang Lianglan in the report.

The operation saw police seizing 205 million tablets designed to look like branded drugs for treating male impotence, hypertension, diabetes and cancer, it noted. Wang added the SFDA will step up operations in the rest of the year with other law enforcement agencies and government departments to curb counterfeit medicince.

The next phase will see them enhance inspection of clinical trial for drugs made in China and meant for export to the United States, Hickey said.

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Authorized Biosimilars

08/31/2012 07:42 AM |

For all the talk about a predictable and appropriate FDA pathway for biosimilars, where’s the thinking about what happens after approval?

Since patient safety and product efficacy will be a justifiable cause of angst to wary physicians, how will biosimilars be detailed? And who will do the detailing? Will biosimilar manufacturers need to develop patient assistance programs? What about REMS issues (both IP and implementation)?

Can you say, “authorized biosimilars?”

(And what will Congress and the FTC have to say about that?)

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Making EMR work for physicians

08/29/2012 10:16 AM |

Rob Lamberts, M.D. offers some ideas on improving EMR use for physcians:
 
I am an EMR geek who isn’t so thrilled with the direction of EMR.  So what, I have been asked, would make EMR something that is really meaningful?  What would be the things that would truly help, and not just make more hoops for me to jump through?  A lot of this is not in the hands of the gods of meaningful use, but in the realm of the demons of reimbursement, but I will give it a try anyhow.
 
Read his list here.



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Solanezumab and Sustainable Innovataion

08/28/2012 08:34 AM |

The bad news is that solanezumab (Eli Lilly’s experimental Alzheimer's treatment) failed to meet its primary endpoints in two late-stage clinical trials in patients with mild to moderate levels of the disease. The good news is that investigators saw positive signs in some analyses of the studies.

According to Lilly, after combining the results from the total of 2,050 participants in both trials, it found statistically significant signs that the drug slowed memory loss in some patients, many with mild cases.

"We're encouraged by the signals we see here," said David Ricks, president of Lilly Bio-Medicines. He said the solanezumab findings validated the company's heavy investment in Alzheimer's treatments. Lilly plans to discuss the findings with regulators before determining how to proceed with the drug.

Happy talk or hopeful hypothesis?  Generally, combining the data from the two trials—aren't considered conclusive but are used to generate hypotheses that require further study and validation.

Importantly, the results from the pooled solanezumab data are to the first from any late-stage Alzheimer’s studies to suggest a benefit from an anti-beta amyloid compound.

Full data from the studies, based on an independent analysis by an academic national research consortium called the Alzheimer's Disease Cooperative Study, will be presented in October at scientific conferences in Boston and Monte Carlo, the company said.

As the Wall Street journal reports, “Much will depend on how regulators interpret the data. Usually the U.S. Food and Drug Administration makes decisions based on how experimental therapies perform in meeting the primary goals of pivotal trials.”

The Journal continues, “In the case of solanezumab, the FDA will have to weigh the potentially limited cognitive benefits against the lack of effective treatments, experts said. The agency could ask Lilly to do additional studies exploring further whether solanezumab does indeed slow down Alzheimer's progression in certain patients.”

True – but an even more important issue is understanding – and rewarding – incremental innovation. “Limited cognitive benefits” is in the eyes of the beholder, but the impact is anything but limited when it comes to our nation’s healthcare wallet.

As the prevalence impact of Alzheimer’s grows, so does the cost to the nation.

One in eight people age 65 and older (13 percent) has Alzheimer’s disease. Nearly half of people age 85 and older (45 percent) have Alzheimer’s disease. Of those with Alzheimer’s disease, an estimated four percent are under age 65, six percent are 65 to 74, 44 percent are 75 to 84, and 46 percent are 85 or older.

If Alzheimer’s Disease was a tradable stock, the demographics of the Baby Boom generation would make it a “must buy.”

The direct and indirect costs of Alzheimer’s and other dementias amount to more than $148 billion annually, which is more than the annual sales of any retailer in the world excluding Wal-Mart.

Is there value in slowing the progression of Alzheimer’s Disease? Certainly.

According to a study in Health Affairs (“Alzheimer's disease care: costs and potential savings”), monthly savings of $2,029 in formal services are possible if disease progression can be slowed. Annual institutional cost savings of $9,132 also are achievable if alternative residential settings are used.

Sometimes the biggest success stories rest on the foundations of failure. The solanezumab trials may have missed their primary endpoints – but they have succeeded in advancing our knowledge of Alzheimer’s Disease and provided a possible new and innovative option for patient’s (and family members) of this draconian disease.

Alas, solanezumab will not be the magic bullet that eradicates Alzheimer’s Disease from our lexicon of suffering – but it may yet be an important addition to our pharmacological armamentarium.

As FDA and then CMS decide on the value of solanezumab, it’s important to remember that innovation is slow. As any medical scientist will tell you, there are few "Eureka!" moments in health research. Progress comes step-by-step, one incremental innovation at a time.

Harvard University health economist (and Obama healthcare advisor) David Cutler has noted: "Virtually every study of medical innovation suggests that changes in the nature of medical care over time are clearly worth the cost."

The battle for the heart and soul of 21st century health care is the battle over innovation. And nothing short of victory is acceptable.

To borrow an over-used adjective from the world of global climate change -- we must protect "sustainable" innovation.

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WSJ Serves Up Sensational Editorial On Obamacare and 'Cheesecake Factory Medicine'

08/27/2012 03:58 PM |

Cheesecake Factory Medicine http://online.wsj.com/article/SB10000872396390444358404577605233123916096.html   Read More & Comment...

Harmonizing BRAT

08/27/2012 10:12 AM |

The Pink Sheet reports that “An international group of regulators and drug companies have agreed in principle to a framework that sets out eight steps for assessing a drug’s benefits and risks and could set the stage for a global approach to evaluating drugs.”

The framework will not result in uniform decisions across countries, but rather will provide a structure for the benefit-risk assessment process as a number of efforts are underway to make the exercise more methodical and to develop systematic ways for regulators and sponsors to present, communicate and discuss drug data.

Methodologies to reach decisions may vary, but “if everybody follows those same basic eight steps, … any new method that you come up with to develop or to assess benefit-risk should be internationally acceptable because they follow these general eight-step principles,” Lawrence Liberti, executive director of the Centre for Innovation in Regulatory Science, explained in an interview.

The Eight-Step Benefit-Risk Assessment Framework can be found here.

A task force of representatives from eight regulatory agencies and six international pharmaceutical companies, organized by CIRS through its Unified Methodologies for Benefit-Risk Assessment initiative, endorsed the framework following a June 21-22 workshop held in Washington, D.C., to discuss global harmonization of the benefit-risk assessment process. FDA Senior Advisor Murray Lumpkin and GlaxoSmithKline Inc. Senior VP-Global Clinical Safety and Pharmacovigilance Frank Rockhold co-chaired the workshop of regulators, academics and industry representatives.

The CIRS-mediated effort is separate from the International Conference on Harmonization, a long-standing initiative to coordinate regulatory standards between the U.S., Europe and Japan. FDA recently put ICH periodic benefit-risk evaluation standards into draft guidance for post-market safety reporting

While the eight steps coming out of the CIRS effort create structure, the methodology for benefit-risk decision-making will not be uniform soon, if ever. A common lexicon should be developed, according to a synopsis of the meeting, which was not open to the public. But agencies vary in their weighting of benefit-risk parameters and there are regional differences in regulatory and cultural viewpoints, making uniformity difficult.

With general agreement on the framework, stakeholders now can focus their attention on developing those methodologies. “Time should be allowed for pragmatic methodological approaches to be developed, including adequate timing for feedback on best practices to emerge,” the synopsis says.

Four agencies that make up the Consortium on Benefit-Risk Assessment – Swissmedic, Health Canada, Singapore’s Health Sciences Authority and Australia’s Therapeutic Goods Administration – pilot-tested the methodology using information from applications for a drug they previously approved.

The BRAT process was pilot-tested by 13 companies during various stages of drug development. A case study of its application to evaluate Johnson & Johnson/Bayer HealthCare AG’s rivaroxaban found that such methodology can add rigor and transparency to decision-making and is easily used in regulatory settings, such as advisory committee meetings, according to the workshop synopsis.

FDA is field testing its benefit-risk framework with six products. With the FDA approach, reviewers list evidence/uncertainties and conclusions/reasons for five decision factors in a grid format and then analyze the implications. The factors are severity of condition, unmet medical need, clinical benefit, risk and risk management.

(FDA committed to a structured benefit-risk assessment framework for the drug review process as part of PFUFA V.)

Among FDA initiatives in this area is a basic roadmap to be used by patient groups interested in development of patient-reported outcome measures in a specific disease area.

The European Medicines Agency has a benefit-risk assessment methodology that it considers a simple qualitative tool. PrOACT-URL identifies the problem, determines the objective, considers the alternatives and their consequences (presented in tabular form) and makes tradeoffs through swing-weighting of the events. Sensitivity analysis determines the level of uncertainty.

On the developer’s side of the table, Diana Hughes, a vice president in Pfizer Inc.’s primary care business unit, suggested industry form a consortium with the mission of gaining a perspective on unmet medical need and patient experience. Companies should continue collaborating with advocacy groups and develop patient educational programs to elicit information on the most relevant aspects of a disease and advance a common approach to valuing and weighting benefit and risk, she said.

Workshop participants concluded that rules of engagement must be set to avoid any misperceptions of conflict-of-interest during interactions with patients, and that such interactions are consistent, scheduled and balanced. Patients would benefit from education on the inherent nature of uncertainty in benefit-risk decisions, according to the workshop.

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