Avorn Responds

• 06.21.2011

Dr. Goldberg –

Our JAMA piece was not even about comparative effectiveness research, or about paying for treatments.  We agreed in it that orphan drugs for cancer may sometimes need to be approved with less valid data than is usually required, and called for better understanding how well these drugs work by studying their outcomes once they are on the market. But cancer patients do not benefit – and may well suffer more -- if a drug that does not work is approved and then given to them. We undertook this  analysis to help understand how patients with rare diseases could be provided with drugs that actually are going to help them; we certainly did not publish it because of some secret agenda to delay or deny treatment to people.  Your making such a wild charge just makes you look silly.

I also do not recall ever having said that BiDil should not be approved because we don’t know its mechanism of action. In any case, since it was just a combination of two widely available generic drugs, the treatment would be readily available whatever FDA did with the application for its approval as a patentable combination.

Reasonable people can (and do) differ about the best way to evaluate new medications, but this statement is so wild that it just looks weird. A flaming, inaccurate diatribe like this reflects badly on its author. Most others on the right have reassessed the wisdom of depicting those with whom they disagree as “malignant presence[s]” who want sick children to “drop dead,” and calling  for someone to “pull the plug” on them. Such hate speech just makes those who use it look like they are flailing around in ill-founded rage.

                 

Targeting IPAB

• 06.21.2011

FDA's Coalition of the Willing

• 06.21.2011

Back in February, Peggy Hamburg made some interesting comments at the Council on Foreign Relations:

* The new reality of food and drug regulation is that it’s global. In fact, it should be a topic for conversation at the next meeting of the G20.

* The recent crises in both food and drug safety will only repeat themselves unless regulatory agencies from around the world work in closer and more regular partnership.

* There is a responsibility on the part of the FDA and other more developed regulatory agencies around the world. (MHRA certainly comes to mind.) to help build “regulatory capacity” for those nation’s that want and need assistance. (Nigeria comes to mind.

* Part of a closer working relationship means a more regular and robust sharing of global intelligence on issues of counterfeiting. (And, for that matter – many other things too.)

* And lastly, “We can’t inspect our way out of this problem."

All good things – progressive things -- but, short of a regulatory Marshall Plan, things that will have to rely (at least initially) on personal relationships between senior officials at various regulatory agencies and a focus on what’s best for global public health writ large is convergent with what’s best for any given nation.

It’s not as easy as it sounds.

Beyond the generally difficult nature of international regulatory harmonization (yes friends, it is a lot harder than it looks) is the profoundly difficult issue of domestic economic interests and trade.

For example, every nation (from the United States to Nigeria) is concerned about counterfeit drugs and unsafe food coming across its borders.  That’s obvious. But are all nations equally concerned about controlling the export of counterfeit, unsafe, and substandard products to other nations?  That’s trade.

Principles aren’t principles, as my father used to say, until they hurt.

Today the FDA released a new report designed to monitor the rising tide of goods from abroad. It includes planned partnerships with counterpart regulators in other countries and better data-sharing between those regulators.

 

According to the report, imports of FDA-regulated products are growing at an estimated 15% annual rate.

 

Peggy Hamburg said it will likely take many years to implement its new approach, which also includes building up its IT capabilities to try to identify risks in the food and drug supplies before they pose serious harm and using public and private third parties to conduct audits and inspections on the agency’s behalf.

 

Hamburg said that the new approach “will require some up-front investments in terms of dollar resources, human resources and time,” she expects better sharing of data and strategies between regulators in different countries will eventually mean using fewer resources to achieve the same end.

 

“All of us are confronting the same set of challenges,” said John Taylor, acting principal deputy commissioner of food and drugs.

The Audacity of AFSSAPS

• 06.20.2011

Not all business travel is arduous.  I’ve just returned from the 11^th annual France-USA Conference on pharmaceuticals and health policy.  The meeting was in Paris.  Sometimes being a policy wonk has its perks.

My role was to debate NYU professor, Dr. Victor Rodwin on “The Current State of Obama’s Health Reforms.” It was fun and feisty – especially the parts where we both spoke in French. (Shout out to my high school French teacher, Linda Diaz!)

Dr. Rodwin regularly cited Commonwealth Fund research,  ‘Nuff said. I focused on the legality of the individual mandate, the growing “idealism gap” of those who want to improve our healthcare system – but not via the approaches of the Affordable Care Act, the increasing (and increasingly contradictory) roles of comparative effectiveness and patient-centered outcomes research, IPAB (and the creeping fear of Uncle Sam, MD), the dangerous vagaries of academic detailing, and the war against medical innovation (personified by President Obama’s call for a roll-back of biologics patent life from 12 to 7) and the issue of data exclusivity.

My summation – “L’audace, l’audace. Toujours l’audace.”

Another fascinating presentation was offered by Dominique Maraninchi, the relatively new (since the end of February 2011) General Manager of AFSSAPS. That means he’s the French equivalent of the Commissioner of the FDA.

France is going through it’s own “Vioxx Moment,” having recently rescinded the market license for Mediator (a diabetes drug that was widely used off label as a weight loss treatment). “L’Affaire Mediator” is a big deal and has created a public outcry for change and reform.  Sound familiar?  (FYI – for more detailed information on the Mediator issue, see here.)

Much of what Dr. Maraninchi had to say will sound very familiar to FDA watchers:

AFSSAPS must:

·      Reestablish trust

·      Enhance pharmacovigilance and do a better job analyzing data and drawing conclusions

·      Be more transparent (a truly radical concept for the French bureaucracy)

·      Be more accountable

·      Offer more information and explanations about its decisions via “bon usage” (safe use)

These might sound rather derivative to a US audience, they are not. While they certainly do share much of what the FDA is trying to accomplish, (1) the French system is very different and these initiatives will require different strategies and tactics, (2) as such, their efforts will deliver different results, and (3) there will be much for the Wizards of White Oak to learn from the AFSSAPS experience.

Another echo of FDA came from Yves Burr (a member of France's National Assembly and chair of that body’s working group on medicines and health products), who asked, “Do we have the courage to put the patient in a role where they can be heard?”

Dr. Maraninchi ended his presentation with a statement of principle that should be widely discussed inside the FDA:

“It is better to make a decision than to have no decision at all.”

Perhaps he should testify at the upcoming Congressional hearings on PDUFA?

What's Wrong With Paying KOLs?

• 06.17.2011

Ed Silverman at pharmalot ran a three part series of blogs on physician compensation for being key opinion leaders, consulting with pharma, etc that is very balanced and factual. 

Paying doctor as consultants or to speak about products/treatments is problematic when the physician in question is not an expert or not disclosing the payment.   And it's no more problematic than a doctor who is paid to write or speak against a product or even does so because of an ideological or cultural belief that any new drug is inherently useless or overhyped.  In fact, the latter case is even more troubling since it is shaped not by science or clinical practice but an agenda.

Second, having attended sessions where KOL have spoken (and disclosed support) it is obvious that doctors are not drinking kool-aid.  They are curious, skeptical, interested in getting additional information about the risks and benefits of drugs and devices.  

Finally, the ongoing effort to ban pharma payments to doctors is part of a larger effort to substitute information provided by or supported by industry by groups that want to impose their views and control all medical information. 

Diffusion of innovation is evil to the opponents of pharma supported KOL.  So is any research or clinical finding funded by drug companies.  This is a purist and paranoid view of science. 

Meanwhile, pharmalot is hosting a webinar on a subject every drug company and doctor should be  paying attention to.  I encourage everyone to tune in.

How Can Pharma Use Social Media for Real-Time Intelligence and Research?

Tuesday, June 21, 2011
2:00 p.m. ET | 11:00 a.m. PT
Webcast Duration: 1 hour
Registration: $59
Register Now - Click Here!

Over here first. Over there second.

• 06.17.2011

As reported from the kind folks over at lilypad ...

FDA Data on Cancer Drug Approvals

June 16th, 2011 | By: Greg Kueterman

Swiss (en)Guard

• 06.17.2011

Research-based pharmaceutical industry launches collaborative framework to tackle NCDs
 
Geneva, New York, 16 June 2011 – The research-based pharmaceutical industry launches today a Framework for Action to respond to concerns that cardiovascular disease, cancer, diabetes and chronic respiratory diseases are posing mounting threats to public health as well as public and private finances worldwide. The industry’s ten-point Framework scopes out specific areas of action to tackle non-communicable diseases (NCDs) including innovation, access and affordability, prevention and health education. It also underscores the essential role of partnerships and dialogue in implementing the Framework. The NCD Framework for Action brings together the global research-based pharmaceutical industry in support of the World Health Organization’s (WHO) Action Plan on NCDs and the Moscow Ministerial Declaration. It will be presented today at the United Nations (UN) Civil Society Hearings in New York, held to prepare for the UN High Level Meeting on NCDs to take place in September, which aims to secure an action- oriented UN response to the rise of NCDs. The aim is that the NCD Framework for Action will provide a sound basis for the research-based pharmaceutical industry to partner with the people on the ground, governments and the WHO to find ways to address prevention, care and treatment for NCDs in the developing world.

NCDs are the leading cause of death and disease worldwide, killing more than 36 million people in 2008, with nearly 80% of these deaths occuring in low- and middle-income countries. NCD deaths are projected to increase by 15% globally between 2010 and 2020. In part, this is due to progress made in combating infectious diseases through economic growth, development, and better treatment options; but it is also largely linked to lifestyle choices. For most infectious diseases, rapid access to diagnosis and treatment is an imperative for patient survival. But for NCDs the “lifecycle” is different, and there may be many actions that can take place, such as prevention, before medicines or other treatments need to be prescribed.

The Framework for Action on NCDs focuses on the areas where the research-based pharmaceutical industry can make the most significant difference, such as innovation, access and affordability, but also prevention and health education. Eduardo Pisani, IFPMA Director General explains: “The framework is just the beginning; our vision is to work with others to identify what can be done in practice to help poor people to access the care and treatment they need. Together we want to find ideas for concrete actions to put on the table in the aftermath of the UN NCD Summit in September. The Framework is our roadmap for this work.” The IFPMA also pledges to report regularly on industry’s progress and share updates with stakeholders, such as the WHO and other interested agencies.

The Framework confirms the industry’s crucial role in continued investment in R&D programmes dedicated to the development of innovative medicines for the prevention and treatment of NCDs to enhance the lives of patients. There are currently over 1,500 medicines in the pipeline for major NCDs. The industry will also endeavour to address its innovation towards the specific needs of developing world populations and settings. To this end, in addition to the Framework, the pharmaceutical industry will launch a programme of research that will improve its understanding of the specific needs of developing world populations.

Actions on access and affordability of NCD treatments include promoting the right policy, regulatory and supply chain environments that secure optimal quality of care for patients and enable companies individually to implement commercially sustainable access and pricing strategies for the supply of NCD vaccines and medicines to the developing world.

It is estimated that half of deaths caused each year by NCDs are preventable[1], and lifestyle choices that often accompany improvements in living standards, such as unhealthy diet and tobacco use, are part of the explanation. The Framework for Action highlights the importance of prevention so that individuals can make informed lifestyle choices. Industry is also working with the World Health Professions Alliance to develop an NCD scorecard that will be shared with over 26 million health care professionals in more than 130 countries to help encourage patients to identify and prevent risky behaviors. Reducing disability or deaths through increased investment in prevention programs will contribute to higher economic growth and allow limited resources to be focused efficiently on patients most in need.

Eduardo Pisani, IFPMA Director General explains: “This NCD Framework for Action represents a paradigm shift for the research-based pharmaceutical industry. It puts our industry’s collective global health responsibilities firmly at the forefront of how we see our role in the global health community. Let’s be clear: it is not about altruism, but rather about revolutionising our relationship to others. Times are tough for governments, business and patients. In order to tackle the rise of NCDs, and stay the course, we need to look at sustainable new approaches to global health which have prevention at its core.”

Jerry Avorn and Co: Harvard's Kevorkian Corp

• 06.16.2011

Jerry Avorn has been a long time malignant presence on the health policy scene.  Among his contributions has been a frontal assault on one of the most effective drugs developed to treat heart failure in African Americans (BiDil) by claiming it shouldn't be approved because we didn't know the mechanism of action.  That brought a swift response from the FDA's Bob Temple who noted that if the FDA only approved drugs where the mechanism of actio was known, a lot of people alive today would be dead.

Now Avorn and part of his crew, Aaron Kesselheim and Jan Myers are arguing that drugs for rare diseases are not studied long enough and don't have enough people in clinical trials AND should be studied in randomized controlled trials.

Avorn, Kesselheim and Myers to kids dying of rare disease:  Drop dead while we study you as long as we deem it appropriate. Note to Kesselheim and the rest of the Kevorkian Corp: orphan drug trials are designed to reflect the size and needs of patients, not the use of CER as a rationale for rationing.

Orphan drugs add more years to  life than any other class of treatments.  Two-thirds of the people who benefit are kids who can now live longer instead of dying painfully.   But CER advocates like Avorn and Kesslehim want   longer and more complicated trials because they know, as with Avastin , average results will reduce the number of treatments. CER will be a death sentence to many children.  People like Kesselheim and Avorn raise the bloody shirt of drug safety to justify their position.  Here's my view: let them say no to orphan drugs when it might save the life of their loved ones out of safety concerns and leave the rest of us alone.  Please.

Thankfully, Congress is putting it’s foot down in support of innovation and personalized medicine.  Sen. Robert Casey, D-Penn., has introduced legislation last March to support this research. The Creating Hope Act of 2011, will provide incentives “to develop treatments for rare diseases that are often less profitable than treatments for more common medical conditions."  Meanwhile, Senators Jon Kyl R-TX and Mitch McConnell R-KY are sponsoring  The Preserving Access to Targeted, Individualized, and Effective New Treatments and Services (PATIENTS) Act of 2011.  The PATIENTS Act would bar the federal government from using “comparative effectiveness research” to deny or delay coverage of a health-care treatment….”

Today medical innovatons can use the understanding of how we get sick to prevent disease or death.  Such advances lead to longer, better lives, enriching us all.  CER, by design, censors these biological insights.  It deliberately delays progress by demanding studies that, by ignoring individual differences,  conclude no one benefits from medical progress.   It is used to justify rationing, not make individuals more sustainable. To save ourselves and children dying of rare diseases we have to pull the plug on CER and it’s adherents.   Starting with Kessleheim, Myers and Avorn -- Harvard's Kevorkian Krew -- is a great place to start.

The Last Mile Towards First-to-File

• 06.15.2011

From today's edition of The Washington Times:

Protect inventors with strong patent reform:

Shift to ‘first-to-file’ would make system more efficient, less costly

By Peter J. Pitts

 

While there are many problems with the U.S. health care system, it's undeniable that our country leads the world in producing the most advanced medical techniques, drugs and lifesaving technology.

 

Today, our leadership in this field is being threatened - not just by taxes, regulations or the new health care reform law - but also by a patent system that is increasingly ill-equipped to do its job of rewarding inventors and innovation.

Now that we are tantalizingly close to reforms that will modernize and strengthen the U.S. patent system, a small group of misguided ideologues is threatening to derail the effort.

 

There's no question that innovation is the lifeblood of our economy and strong patents are innovation's backbone. But over the years, the U.S. patent system has failed to keep pace with changes in the economy that demand stronger patents, faster approvals and patents that are recognized by our key trading partners.

 

There are numerous problems. For starters, the Patent and Trademark Office (PTO) faces an astonishingly large backlog of 700,000 patent applications, and inventors typically wait three years before getting a patent. Inventors then face the prospect of lawsuits challenging their patents, which cost an average $400,000 to defend.

 

Because the U.S. patent system is different from those of most other industrialized countries, inventors can find themselves with patent rights in the United States, but not abroad, cutting the value of their patents.

 

As Rep. Lamar Smith, Texas Republican, put it: "The current patent system is outdated and bogged down by frivolous lawsuits and uncertainty regarding patent ownership."

 

Legislation pending in the House would go far to fix these problems. It would, for example, let the PTO set its own fees so it has the funds needed to do its job, ending congressional raids on the PTO's budget while protecting small, independent inventors with heavily discounted fees.

 

It would more effectively weed out wrongful patents and settle disputes through a vastly improved "supplemental examination" process.

 

But most important, the legislation would shift the United States from a "first-to-invent" system to a "first-to-file" system.

As things stand, if an inventor is the first to file a patent, he still can be challenged by someone who claims to have invented the same thing earlier but failed to file it with the PTO. That results in too much uncertainty and far too much litigation over patent rights, which is why so many other countries moved to a first-to-file system. Under that system, the first to file with the Patent Office is the rightful patent holder, making patents easier and less costly to defend.

Most lawmakers in the United States realize the need to make these changes, and earlier this year, the Senate voted 95-5 to pass the America Invents Act. A similar bill passed the House Judiciary Committee by an equally strong 32-3 vote.

 

But with the finish line in sight, a small group of conservative lawmakers want to derail the bill, claiming it is an unconstitutional attempt to subvert our patent system in deference to European and Asian governments. Phyllis Schlafly has called it an "un-American" effort by liberals to "put us on the road to a borderless patent system." Those arguments are misguided at best.

 

First, the fact that the reforms so far have received overwhelming support from GOP lawmakers shows that it's not some liberal conspiracy. The House bill's sponsor, Texas' Mr. Smith, has a lifetime American Conservative Union rating of 92 out of 100.

 

Second, the measure is clearly constitutional. In fact, Michael Mukasey, who was President George W. Bush's attorney general from 2007 to 2009, reviewed the bill and concluded that it was "both constitutional and wise."

 

Third, the change from first-to-invent to first-to-file isn't as revolutionary as critics make it seem. PTO Director David Kappos notes that of the 3 million patents filed in the past seven years, just 25 were granted to inventors who weren't the first to invent, with just one granted to an independent inventor.

 

"In the last seven years," he told a congressional panel in March, "only one independent inventor's filing would have received a different outcome under the first-inventor-to-file system. That's one in 3 million."

 

What these reforms would do is make the patent system stronger, more transparent, fairer, faster, less costly and more in line with our major trading partners. Does that seem un-American?

 

In the past, our patent system served our inventors and our country as well. Now we have the opportunity to renew our patent system so it can effectively encourage, protect and reward inventors and keep the United States on the cutting edge of health care well into the next century.

 

Let's not blow it.

The Death of Hope

• 06.14.2011

Add people suffering from mental illness to the body count from the war of fear waged against drug companies:
tinyurl.com/3rkxvkp

Psychopharmacology in crisis

Researchers warn of 'withdrawal of hope' as funding shrivels.

Daniel Cressey

Many people affected by mental illness are facing a bleak future as drug companies abandon research into the area and other funding providers fail to take up the slack, according to a new report.

Produced for the European College of Neuropsychopharmacology (ECNP), the report warns that "research in new treatments for brain disorders is under threat". With current treatments inadequate for many patients, it says, "withdrawal of research resources is a withdrawal of hope for patients and their families"¹.

A number of formerly big players in neuroscience have all but abandoned the area recently as the pharmaceutical industry has undergone massive restructuring. AstraZeneca and GlaxoSmithKline have both cut research funding and closed down entire teams dedicated to developing drugs for psychiatric disorders.

Although some of the problems faced by the field also apply to other sections of the pharmaceutical industry, many are specific to researchers trying to hit targets in the brain.

David Nutt and Guy Goodwin, who authored the report following a recent ECNP meeting on the topic, note that it can take much longer to develop medicines for psychiatric disorders than for better-understood conditions such as cancer, and that potential drugs for psychiatric conditions have higher failure rates. These failures sometimes become apparent only late in the development process, making neuroscience an expensive and risky prospect for industry.

The coming crisis

Nutt, a neuropsychopharmacologist at Imperial College London, told reporters at a press conference in London on 13 June that "these are dark days for brain science".

Both authors add that, in addition to the dearth of pharmaceutical funding, there is still a stigma surrounding conditions such as depression. This feeds through into the money donated to advocacy groups. "Almost nothing" comes from charity groups for mental-health research, compared with huge charity funding in areas such as cancer, notes Goodwin, head of psychiatry at the University of Oxford, UK.

He warns of a "generational crisis" in terms of both training and capacity to develop new drugs for conditions such as depression and dementia, unless the withdrawal of pharmaceutical funding is addressed.

This warning is echoed by an editorial published last week in the British Journal of Clinical Pharmacology (BJCP). 'Vanishing clinical psychopharmacology', written by Joop van Gerven and Adam Cohen of the Leiden University Medical Centre in the Netherlands, outlines the perilous state of the field². Over the past year, the authors write, the BJCP has published only five papers in this area, none of which involved novel drugs.

At the 2011 meeting of the American Society for Clinical Pharmacology and Therapeutics, only 13 of 300 abstracts related to psychopharmacology and, again, none related to novel drugs. This situation mirrored that at the 2010 Collegium Internationale Neuro-Psychopharmacologicum, where 8 of 870 abstracts were on human psychopharmacology and four were on "new or relatively new mechanisms of action", they report.

The road ahead

Cohen says that much of the problem derives from a failure to develop the underlying science. Depression is a complex disease, yet to assess whether drugs work, researchers have to rely on crude tools such as questionnaires.

"People have not paid enough attention to how to measure depression, how to measure psychosis," he says. "When we develop new drugs, we still measure on these basic scales."

Developing new ways of assessing brain function and disease will reduce the risks in developing new drugs, van Gerven and Cohen argue in their editorial.

Nutt and Goodwin also suggest a number of ways forward. Patents could be longer-lived for drugs that take longer to develop, such as those for brain disorders, to encourage companies to work in the area. And researchers should lobby for European funding — such as that available from the Framework programme initiative — to set brain research as a priority.

Academia could also develop more creative relationships with industry in order to fill the gap in drug development, they argue. The ECNP is pushing the idea of a 'medicines chest', to which companies can assign compounds they are no longer actively developing to be taken forward by researchers in academia or elsewhere. Nutt says that several companies have already expressed an interest in this idea.

If the current research base is allowed to evaporate, Nutt warns, it will be decades before it can be built up to start again.