Latest Drugwonks' Blog
The PCORI projects are politically safe and scientifically unsensational. Chloform in print as Mark Twain would say. In it's effort to avoid political controversy PCORI has exposed itself to be financially wasteful and clinically irrelevant.
http://www.pcori.org/assets/PFA_Awards_Dec_2012_FINAL.pdf
Bob Temple is having nightmares – and it’s not because of too much coffee before bedtime.
Bob envisions a nightmare situation if the Caronia ruling enables companies to promote drugs for uses that are not supported by well-controlled clinical trials.
Temple, deputy director for clinical science in the Center for Drug Evaluation and Research, discussed the decision at the FDA/CMS Summit in Washington Dec. 11. The U.S. Court of Appeals for the Second Circuit ruled in United States v. Caronia that the government cannot prosecute pharmaceutical manufacturers or their representatives under the Food, Drug, and Cosmetic Act for speech promoting the lawful, off-label use of an approved drug.
“What is worth talking about is what the consequences would be if people could promote uses that they hadn’t established, hadn’t bothered to get through the system,” Temple stated. “I’m horrified by that.”
Temple expressed concern that the Caronia ruling could undermine the 1962 amendments to the FDCA, which require that drugs be proven to be effective as well as safe. He said that prior to 1962 people did not know whether drugs worked. “If this [ruling] were to change the situation so that yes, people had to get their first claim in with adequate and well-controlled studies, but after that they didn’t have to bother anymore, and if that made them not bother anymore, that would be a nightmare.”
“There are all kinds of things that if you didn’t know the answer [it] would be terrible, and having people promote those uses is frankly terrifying,” said Temple.
“First of all, things that are wonderful would never be approved,” he stated, noting that most of the known cardiovascular outcomes were secondary outcomes. “There are all kinds of things that if you didn’t know the answer [it] would be terrible, and having people promote those uses is frankly terrifying.”
The unintended (but entirely predictable) consequences of the dangerous idiots of vaccine denial continue to spread.
A group of prominent doctors and public health experts warns in articles to be published today in the journal Pediatrics that banning thimerosal, a mercury compound used as a preservative in vaccines, would devastate public health efforts in developing countries.
Banning it would require switching to single-dose vials for vaccines, which would cost far more and require new networks of cold storage facilities and additional capacity for waste disposal, the authors of the articles said.
“The result would be millions of people, predominantly in low- and middle-income countries, with significantly restricted access to lifesaving vaccines for many years,” they wrote.
Fears of autism? Entirely bogus. The Gray Lady reports that “the evidence is overwhelming that thimerosal is not harmful …” And according to Louis Z. Cooper, former president of the American Academy of Pediatrics, “Science clearly documented that we can’t find hazards from thimerosal in vaccines. The preservative plays a critical role in distribution of vaccine to the global community.”
According to Dr. Heidi Larson, senior lecturer at the London School of Hygiene and Tropical Medicine “You can’t just pull the plug on something without having a plan for an alternative.”
The full New York Times article can be found here.
According to Reuters, “Medical providers have begun to think more about cost, as well as safety and effectiveness, when they decide on cancer treatments.”
That’s a pretty common statement these days – but it’s important to consider and discuss that “cost” is as relative a concept as “safety and effectiveness.”
Doctors at New York's Memorial Sloan-Kettering Cancer Center decided in November not to use Zaltrap, (an $11,000 a month medicine for colon cancer) because it has only a "modest" impact on survival, works no better than Avastin, a similar but cheaper competitor, and has worse side effects.
"In cases where there are co-pays, they really do effect the consumer," says Mark Mynhier of PricewaterhouseCoopers. "Patients are saying 'I can't afford to pay 10 or 20 percent of a $100,000 therapy.”
That is true for many patients – and perhaps for most patients. But what about patients for whom Zaltrap works better than Avastin?
Reuters: “Linking value to patient outcomes … is particularly important in oncology, where treatment costs can total tens of thousands of dollars a year.
Certainly. But outcomes data must also be used to learn about specific patient responsiveness – and lead to the development of better companion diagnostics.
Reuters: “As scientists unravel the biological underpinnings of cancer cells, new targeted therapies are being developed, but the process is expensive.”
Alas, Dr. Leonard Saltz, chief of Memorial Sloan-Kettering's gastrointestinal oncology service said the solution might just be to walk away from drugs with small, incremental benefits.
"We simply can't afford to pay these very, very large amounts for drugs that offer most people very small benefit," Dr. Saltz said. "We haven't figured out how to rein it in."
Dr. Saltz’s comment, alas, reinforces the fact that physicians rarely understand the drug development process. There are few discontinuous “eureka!” moments in drug development. Progress comes step by step, one incremental innovation at a time. But physicians (and particularly oncologists such as Dr. Saltz) should appreciate the importance of incremental innovation.
Rather than a wholesale denial of a product such as Zaltrap (and minus robust outcomes data or a companion diagnostic tool) an interim strategy might be to adopt a risk-sharing scheme wherein pharmas and federal programs establish a measure of success for a therapy and companies reimburse the government when their products fail to meet that standard.
In other words, let’s measure and reward for clinical effectiveness and ensure that medicine remains patient-centric rather than cost-obsessed.
Day Two of the Social Media, Mobile & Gaming for Pharma Conference brought new insights and raised some important questions.
The question most on the minds of the audience was just what do practicing medical professionals know about the regulated environment of healthcare speech? The answer, it seems, is very little – and that which doctors and nurses do know … is wrong.
That is not an asset in the forward march of pharmaceutical companies towards a more regular and robust use of social media. In fact – it’s a deterrent. Perhaps its time for HCPs to learn not only “where drugs come from” (they generally do not understand the roles of pharmaceutical companies and the FDA), but also what the rules are for pharmaceutical industry communications.
As my grandmother used to say, “It couldn’t hurt.”
John Mack (aka, “Pharmaguy”) bemoaned the lack of more regular pharma participation in social media. When confronted with the issues of internal review and control he opined, “How can you use social media if your company doesn’t trust you?
Good question.
And then there was the inevitable debate over the value of “Big Data.” Is more information better?
As Francis Collins recently said, “We are living in an awkward interval where our ability to capture information often exceeds our ability to know what to do with it.”
Collins’ comment was directed at the complete human genome sequence – but is equally germane to an equally complex human proposition – social media.
Some interesting take-aways from Day One of the Social Media, Mobile & Gaming for Pharma Conference:
The significant investment (in both FTE and dollars) required to run social media programs led Eileen O’Brien (Siren Interactive) to comment that, “Social media is free like having a puppy is free.” As Elvis Costello says, “Accidents will happen.”
Katie White (Lundbeck) shared that part of her job is to “hold the line against marketing” relative to what social media should and should not be doing. Respect is earned. Katie, bar the door.
Laying claim to “the largest social media site on gout,” Gretchen Goller (PRA International) discussed the need for CROS to do more on social media to advance patient recruitment for both orphan products as well as for adaptive clinical trials for more common conditions. One question raised was how to make clinicaltrials.gov more of a social media proposition. Hm.
Crohn’s Disease activist Michael Weiss suggested that pharma companies send MSLs to participate on disease-specific social media sites. If these medical professionals are available to speak with physicians – why not with patients as well? Perhaps this is the first-ever composition for the Caronia Philharmonia.
After all, according to Claude Debussy, music is between the notes.
Brain Cells Made from Urine
Human excreta could be a powerful source of cells to study disease, bypassing some of the problems of using stem cells, such as the risk of developing tumors and difficulties in obtaining blood samples from children
By Monya Baker and Nature magazine | Monday, December 10, 2012 | 1
Getting neurons from cells discarded in urine, may one day help develop therapies for neurodegenerative diseases like Parkinson's disease.
Image: Lihui Wang
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Some of the waste that humans flush away every day could become a powerful source of brain cells to study disease, and may even one day be used in therapies for neurodegenerative diseases. Scientists have found a relatively straightforward way to persuade the cells discarded in human urine to turn into valuable neurons.
The technique, described online in a study in Nature Methods this week, does not involve embryonic stem cells. These come with serious drawbacks when transplanted, such as the risk of developing tumors. Instead, the method uses ordinary cells present in urine, and transforms them into neural progenitor cells — the precursors of brain cells. These precursor cells could help researchers to produce cells tailored to individuals more quickly and from more patients than current methods.
Researchers routinely reprogram cultured skin and blood cells into induced pluripotent stem (iPS) cells, which can go on to form any cell in the body. But urine is a much more accessible source.
Stem-cell biologist Duanqing Pei and his colleagues at China's Guangzhou Institutes of Biomedicine and Health, part of the Chinese Academy of Sciences, had previously shown that kidney epithelial cells in urine could be reprogrammed into iPS cells.
However, in that study the team used retroviruses to insert pluripotency genes into cells — a common technique in cell reprogramming. This alters the genetic make-up of cells and can make them less predictable, so in this study, Pei and his colleagues introduced the genes using vectors which did not integrate in the cellular genome.
One of their experiments produced round colonies of reprogrammed cells from urine that resembled pluripotent stem cells after only 12 days — about half the time usually required to produce iPS cells. When cultured further, the colonies took on the rosette shape common to neural stem cells.
Tumor-free
Pei and his colleagues transferred the cells to a growth medium used for neurons, and found that these reprogrammed cells went on to form functional neurons in the lab.
When the team repeated the experiment and transplanted the cells into newborn rat brains, the cells did not form tumors. Instead, when the brains were examined four weeks later, the cells had taken on the shape and molecular markers of neurons.
Neural progenitors proliferate in culture, so researchers can produce plenty of cells for their experiments. Getting enough cells has previously been a problem for such 'direct reprogramming' techniques, which produce neurons more quickly than producing and differentiating iPS cells.
“This could definitely speed things up,” says James Ellis, a medical geneticist at Toronto's Hospital for Sick Children in Ontario, Canada, who makes patient-specific iPS cells to study autism spectrum disorders.
The benefit of sourcing cells in this way is that urine can be collected from nearly any patient, says geneticist Marc Lalande, who creates iPS cells to study neurogenetic diseases at the University of Connecticut Health Center in Farmington, and is particularly intrigued by the possibility of making iPS cells and neural progenitors from the same patient.
“We work on childhood disorders,” he says. “And it's easier to get a child to give a urine sample than to prick them for blood.”
This article is reproduced with permission from the magazine Nature. The article was first published on December 9, 2012.
I am not one of those who in expressing opinions confine themselves to facts.
-- Mark Twain
What? Off-label communication is protected free speech?
Cry havoc and let slip the dogs of war!
Not so fast.
As Steve Usdin of BioCentury so aptly opines, the ruling is “far less consequential than media coverage suggests.”
According to Usdin:
… companies and individuals who take the decision as a signal that the rules of the road have changed and they are now free to promote off-label indications put themselves in great legal and economic peril, attorneys who helped persuade the court to overturn Caronia's conviction told BioCentury.
At the same time, the decision by one of the country's most influential and respected courts to overturn a criminal conviction on First Amendment grounds is persuasive evidence that, in the long term, FDA will have to change some of the assumptions underpinning its regulation of medical products.
FDA, which now has lost a string of First Amendment cases, cannot forever hold on to the notion that it is empowered to prohibit drug companies and their employees from saying things that anyone else is free to say. Sooner or later, according to legal experts, the agency will have to reconcile itself with the idea that industry has the right to truthful, non-misleading speech.
While change is inevitable, the pace of change is uncertain. It is also not clear who will shape that change - FDA employees, judges, or members of Congress.
In short the Caronia ruling didn’t really answer any questions so much as it opened up the conversation. And that alone is worth the price of admission.
What will it mean on the ground? In the short term, not much. But it’s not about instant gratification for aggressive marketers.
This ruling isn’t the beginning of the end of FDA warning letters on off-label communication -- but it very well may be the end of the beginning of such speech being off-limits to prudent corporate compliance officers.
Equally important, what will it mean for off-label conversations with patients and caregivers? What will it mean for regulated speech on social media?
As William Safire once said, “Is sloppiness in speech caused by ignorance or apathy? I don’t know and I don’t care.”
Usdin’s complete story, Free speech, in theory, can be found here.
TransCelerate Appoints Dalvir Gill as CEO
TransCelerate has named Dalvir Gill, PhD, as its Chief Executive Officer, effective January 1, 2013. Dr. Gill will lead the independent non-profit entity, which was formed by ten healthcare and pharmaceutical companies in September to improve the quality of clinical studies and bring new medicines to patients faster by facilitating the collaboration required to solve common challenges encountered during the clinical trial process. Dr. Gill will succeed Garry Neil, MD, who has served as interim CEO. Dr. Neil will remain as Chairman of the Board of Directors.
Dr. Gill has more than 25 years of drug development experience. Prior to his appointment as CEO of TransCelerate, he was the President of Phase II-IV Drug Development at PharmaNet-i3, an organization specializing in drug development services. In this role, Dr. Gill was responsible for a global business spanning nearly 40 countries.
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
