Caveat Emptor

• 01.20.2012

Christopher Viehbacher, chief executive of Sanofi and chairman of PhRMA on PDUFA reauthorization:

"To make sure we're not ignoring unmet needs in primary care, we need a lot more clarity around the risk-benefit so there's predictability when we invest in these products.”

Predictability is the philosophical core of PDUFA.  And risk/benefit is at the heart of the FDA process.

To make PDUFA V a public health victory, the most important thing is to remove (or at best minimize) the politics.

Easier said than done?  Perhaps. 

“PDUFA without the Politics” speaks to the issues inside PDUFA minus the slings and arrows of partisan politics.

But judge for yourself. Click here for the full paper.

Limp Statins

• 01.19.2012

Non-communicable diseases (NCDs) are the leading cause of death and disease worldwide, killing more than 36 million people in 2008, with nearly 80% of these deaths occurring in low- and middle-income countries. And they’re projected to increase by 15% globally between 2010 and 2020.

The good news is the world’s recognition of the problem (World Health Organization’s Action Plan on NCDs, the Moscow Ministerial Declaration, the United Nations Civil Society Hearings in New York).

The bad news is that this could easily become next great insidious opportunity for drug counterfeiters. The false profits of fake statins, beta-blockers, ace inhibitors, etc. could be huge – as would the public health consequences.

And these counterfeit medicines will flood the developing world unless public health officials, law enforcement, and manufacturers get a jump on the issue. The way to combat this frightening problem is to stop it before it starts.

Unfortunately (at least to date) this has not been the general approach to addressing counterfeit medicines.  Meetings and discussion must now morph into planning and action. As Peggy Hamburg said last year at a meeting at the Council on Foreign Relations, the new reality for food and drug regulation is that it’s global and should be a topic for conversation at the next meeting of the G20. She warned that 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.

Amen.

We mustn’t allow Lipitor to become the new Viagra. Counterfeiting doesn’t need a new posterchild. It needs to be fought – and defeated.

PCORI is all about rationing

• 01.18.2012

If you didn't think CER and PCORI were just interested in rationing new treatments to control costs, the honest statements of the cer industry's leaders should cause you to reconsider. No mention of personalized medicine, genomics, patient level data or tailoring treatments. And CER, because it is after the fact will add costs and discourage innovation. Ignoring patient differences and designing studies designed to show no benefit wil harm patients.. http://www.kaiserhealthnews.org/Stories/2012/January/16/comparative-effectiveness-health-care-pcori.aspx

The Swede and Sour of Biosimilars

• 01.17.2012

The Stockholm Network and Amgen are organising a workshop on Policy Choices and Challenges in the field of biosimilars. The event will take place in Stockholm (Radisson Blu Waterfront Hotel) on 20 February (10.30-15.30).

Today the field of biosimilars presents several important challenges – safety, regulatory, legal and financial – which are the topic of discussion across the globe. Most of these discussions stem from the idea that, unlike the relatively straightforward process of introducing a generic equivalent to an original drug based on a new chemical entity, the process of introducing a biosimilar to an original biological drug is more complex. Indeed, finding the right policy prescription for the creation of a “biosimilar framework” has become a daunting task.

In particular, this workshop will focus on the following aspects:

Moore's Law Meets Medical Innovation at Digital Health Summit

• 01.16.2012

I spent three days and two nights in Las Vegas tired, hot and hungry.   No,  I didn't lose all my money playing black jack.  I was walking from one part of the endless Las Vegas convention center to another and from one mammoth hotel/casino to the next at the Consumer Electronics Show.   There were 150,000 plus there for the event and what I know about Vegas is unlike anything you might have seen in The Hangover except that because of the crowds I might have gotten more sleep and more to east if I had been left on roof of the MGM Grand in a drugged stupor.    And the wait for a bathroom would not have been as long either.   Who goes to Vegas and loses 5 pounds?  You are reading his post right now.

In any event the main reason for being their was to participate in sessions of the excellent Digital Health Summit ( http://digitalhealthsummit.com/ ) some which were hosted by Scientific American (http://www.scientificamerican.com/ ), on the impact of the digitization of medical knowledge on health and medical innovation.   The key breakthrough announced there was the ability of Life Technologies to sequence a person's genome for under $1000 and in less than 24 hours.   And that's for starters.  If costs and processing time continue to drop by 50 percent a year it will be possible to do the whole job for under $250 and within hours in a couple of years.   It's the difference between taking filim for developing at CVS and using a digital camera.

Until now, the thought of people obtaining and storing clinical, genetic and imaging knowledge through their smartphone was just a idea.  But as Eric Topol told us, the convergence is months away, not years.  Eric's new book,  The Creative Destruction of Medicine  --  quite simply the best book on how medical technology will transform health -- used some of these  nextgen technologies during his talk.    He showed a hand-held, clip-on smartphone electrocardiogram (EKG) reader, made by Qualcomm-funded AliveCor. http://alivecor.com/    Eric used the device to diagnose that a fellow airline passenger was having a heart attack.  The airplane made an emergency landing, allowing the man's life to be saved.   He also showed off a device from Sotera called Visi Wireless, which monitors glucose levels in an non-intrusive way, continuously, as well as tracking other characteristics (blood oxygen, etc.).  Topol joked that as soon as he ate one of the donuts served before his talk (at least someone got to eat) Visi had already shown the spike in his sugar levels, which he now watches because a scan of his genome shows he is at risk for Type 2 Diabetes.  

Think of the tricorder from Star Trek and you have an idea of where medicine is really going..



Such advances are being integrated into the design of products that consumers and doctors would actually find easy and enjoyable to use.    Specifically, the digitization of health knowledge -- moving from hardware to software and from the masses to the individual -- will make predicting and treating disease much more personal and faster.   It will not be inconceivable to be able to diagnose and begin treatment of  certain cancers in the same day and allow continuous montioring of progress all on the same device.  

The barriers to this revolution are cost, regulation and reimbursement.   But as Jason Goldberg (no relation), CEO of Ideal Life Technologies said: if everyone comes into the doctor's office or hospital with the latest information about what treatment they need and how providers performed, it will be nearly impossible not to respond.    I think the effort to regulate health care choices is pretty much dead...the future belongs to these tools and the ability they give us to crowd source new information and force change.    And as the gap between the potential for better health and government regulation widens, the demand for policy changes that lead to the democratization of medicine will grow.   Much like Blockbuster, brick and mortar bookstores and even desktop computers, the existing structures and interests that prop up 20th century medicine -- along with the regulations devised to sustain them -- will wither away.   Moore's Law -- the theory that the growth in computing power of semiconductors is exponential -- is now begining to have the same impact on health care as it did on other industries.     Good for consumers, bad for those seeking to centralize control of health care, great for going where no man has gone before.

Isaiah 2:4 and Fear of Commitment

• 01.16.2012

According to PhRMA:

Biopharmaceutical research companies are working to continue this progress and to meet new health challenges specific to children. These include:

• 54 for cancer, which, despite significant progress, is still the leading cause of death by disease among American children.

• 49 for infectious diseases, resulting in more than 164 million missed school days annually in American public schools due to the spread of infectious diseases.

• 48 for genetic disorders, including medicines for cystic fibrosis, which affects 30,000 American children and adults.

• 25 for neurologic disorders, including medicines for epilepsy, which affects more than 300,000 school children under age 14 in the United States

In addition to creating new medicines specifically for children, biopharmaceutical research companies are testing many existing medicines to determine safe and effective dosage levels for children. In 2007, Congress reauthorized both the Pediatric Research Equity Act (PREA) and the Best Pharmaceuticals for Children Act (BPCA), highly successful programs that generate new knowledge about medicines for use in children. PREA and BPCA are set to expire on October 1, 2012 unless reauthorized or made permanent by Congress.

BPCA and PREA have led to hundreds of pediatric studies covering more than 16 broad categories of diseases that affect children.  The research conducted as a result of BPCA and PREA has led to nearly 425 pediatric labeling changes since 1998, according to the FDA.

Crucial information as Congress considers reauthorization.

As Tim Franson (former regulatory guru at Eli Lilly & Co. and currently President of the USP Convention) said at the Center for Medicine in the Public Interest’s Capitol Hill conference on PDUFA:

These companion pieces of legislation have done more for pediatric drug development than anything in the past. I recall being involved in this when I was doing clinical trials. Very difficult to get companies to do studies on young children. This has stimulated that. It’s been good for American children and it should be made permanent.

Why not make them permanent? Here’s Vince Ventimiglia (former HHS Assistant Secretary) on that topic (also from the same CMPI event):

The argument I heard when we first set the five-year term, and that I heard again when we tried to make it permanent in subsequent years, was that we want to hold these guys accountable. It’s more to use it as a tool against industry -- and hold out the prospect that it could be removed.

To which Tim Franson added:

If I’m looking for a return on an investment, I need certainty well in advance of five years on types of studies I should be conducting and I need to know the benefit I’m getting at the end. I think five years is far too short a period of time. There’s an accumulated body of evidence, of companies fulfilling their commitments. Maybe its time we make it permanent. I think this point of holding up renewal like the Sword Damocles isn’t very persuasive even to sponsors.

Considering the success of these two programs, perhaps it’s time to take that political sword and beat it into a public health ploughshare.

Drugwonks Hits the Highbeam Top10

• 01.14.2012

HighBeam Research chooses top 10 blogs for medical research

When looking for understanding and information, most people turn first to the Internet, and in return, those with information are sharing it via online sites and blogs. This may be the most true within the medical community. Blogs and online libraries have grown to be valuable resources for students, professors, working professionals and the general public who have not traditionally had such easy access. As an organization involved with medical research and providing medical resources, HighBeam Research would like to acknowledge our favorite medical blogs.

These top 10 blogs for medical research were handpicked by the HighBeam Research staff as our favorites and included based on their level of insightful and original content as well as the authority and trust that the authors enjoy in the Medical space. Here are our picks:

• Science Based Medicine: Dedicated to evaluating medical treatments and products of interest to the public in a scientific light
• Corante: In the Pipeline: Weblog about developments in pharmacology and chemistry
• Life in the Fast Lane: Dedicated to providing online emergency medicine and critical care insights
• Clinical Correlations: The NYU Langone Internal Medicine Blog – A Daily Dose of Medicine
• Science Roll: A doctor’s journey in genetics PhD and medicine through Web 2.0
• Dr. Shock: Focusing on psychology and the treatment of depression
• Cases Blog: Health news updated daily by an Assistant Professor at University of Chicago
• DrugWonks: The web log of the Center for Medicine in the Public Interest (CMPI), a forum offering rigorous and compelling research on the most critical issues affecting current drug policy
• Academic Life in Emergency Medicine: Collaborating, meeting, and sharing with inspiring people in the academic world of Emergency Medicine
• BMA Blog: Views from BMA Cymru Wales on health, politics and just about anything

Occam Sock'em

• 01.13.2012

Why did Willy Sutton rob banks? “That’s where the money is.” This apocryphal aphorism led to what is called “Sutton's Law,” that when diagnosing, one should first consider the obvious.

President Obama and Medicare directors nationwide should pay heed.  If we want to lower health care costs (or, more honestly, health care spending), we need to look at where the spending takes place. It’s a classic case of Occam’s razor.

According to the Agency for Healthcare Research and Quality (AHRQ), the top 1 percent of health care spenders is responsible for more than 20 percent of all health care spending. And the bottom 50 percent represent only 2.9 percent of the nation's health care bill.

And while this is not news, it seldom seems news fit to print.  After all, it just doesn’t justify a lot of political agendas and editorial opinions that prefer a simplistic, one-size-fits-all single payer national healthcare “solution.”

The National Journal opines, “The data suggest that health care policies designed to reduce spending of healthy populations may be of limited value in reducing overall costs. The big savings can be achieved by reducing the costs of the biggest health care users.”

Entia non sunt multiplicanda praeter necessitatem.

This raises an important question, why didn’t Florida maintain its  “Healthy State” program where high-cost Medicaid recipient care was being managed and overall costs were going down? And why aren’t more states aggressively pursuing solutions like the Hoosier State’s “Healthy Indiana” program, where Governor Daniels made personal responsibility central? Instead public and private payers continue to rely on population-based approaches when science and data – and best practice -- suggest that what we require are more personalized and preventative approaches.

To address the 800-pound gorilla in the room, it also demands a thoughtful national dialogue on end of life care. (77% of Medicare decedents’ expenditures occur in the last year of life – 52% in the last two months of life and 40% in the last month.)

And what better time to raise this issue than during a Presidential election cycle.

A Day That Will Live in Regulatory Infamy

• 01.12.2012

Will December 7th, 2011, be a day that will live in regulatory infamy?

That’s when Secretary of Health and Human Services Kathleen Sebelius overruled a decision of the Food and Drug Administration (FDA) on the over-the-counter (OTC) status of emergency contraception.

By reversing an FDA decision, the Secretary set a dangerous precedent for all-comers to lobby Congress, the Department of Health and Human Services and the White House on any and all FDA decisions—directly inserting politics into what must be a scientifically driven process.

"Should the HHS Decision to Overrule FDA on Plan B be Reversed?" is addressed head on in the latest issue of the Food and Drug Law Institute’s Policy Forum (Volume 2, Issue 1, January 11, 2012).

I think it’s a timely and provocative read.  (After all, I wrote it.)

FDA in the Pink?

• 01.11.2012

Statistics are like a bikini.  What they show you is interesting, but what they conceal is essential.

Nevertheless, someone at the FDA owes the Pink Sheet a thank-you note.

The Pink Sheet reports that:

The agency has been trumpeting the 30 new molecular entity and new biologic entity approvals from CDER in 2011 – the most since 2004 and a welcome sign of recovery after the approvals doldrums in between – but it also deserves recognition for achieving an unprecedented, near-perfect rate of PDUFA review goal compliance (96.7%) while maintaining healthy rates of first-cycle approvals (63.3%), and time to approval (an average of 15 months)

CDER Review Performance In The PDUFA IV Era
Year	Approvals (average time to approval)	User fee compliance	First-cycle review share	First-cycle share, Standard	First-cycle share, Priority
2011	30 (15 mo.)	96.7%	63.3%	43.8%	85.7%
2010	21 (15.1 mo.)	86%	76.2%	75%	77.8%
2009	25 (17.3 mo)	72%	58%	47%	66.7%
2008	24 (17.9 mo.)	70%	67%	53.3%	88.9%

Consistency is becoming a hallmark of FDA’s review activity, with nearly identical average times to approval in the two years following the adjustment period for implementation of the FDA Amendments Act. The striking difference between 2010 and 2011 is the number of approvals, not the parameters of the reviews – showing FDA can deliver the same performance with a higher volume.

Innovative drugs drove the positive review trends, with 12 first-in-class agents among the CDER NMEs and NBEs, representing 40% of calendar year 2011 approvals.

First-in-class status correlates closely but imperfectly with priority review status, another marker of innovation that incorporates not only pioneer mechanisms but also unmet medical needs. By the metrics, the 2011 class did not vary significantly from the level of innovation in recent years, though the significance of some of the innovative products cleared in 2011 certainly makes the class notable.

The difference in time to approval between the first-cycle and second-cycle approvals is stark. On average, the penalty for going to the second review cycle was 19.6 months, the difference between the 7.8 month average time to approval for all NMEs and novel BLAs (CDER and CBER) approved in one review cycle and the 27.5 month average for products requiring two review cycles.

FDA could not have posted a good year for new drug approvals without plentiful applications based on well-constructed clinical programs – an aspect in the hands of industry. But the agency can also make its own luck. The case studies of drug approvals published each month by Pharmaceutical Approvals Monthly suggest that the agency will show great creativity and flexibility in analyzing and acquiring data for new products that address unmet medical needs.

The Pink Sheet ends it’s analysis with the comment, “As the agency heads into PDUFA reauthorization, FDA’s review success will be a powerful argument that the agency knows what it is doing. Just look at the numbers.”

Just so, but as Vince Ventimiglia, Former Assistant Secretary for Legislation at the US Department of Health and Human Services, commented at a recent Center for Medicine in the Public Interest conference on PDUFA, numbers are very much determined by who provides them.  He called one myth about PDUFA, “Lie to Me." When it comes to numbers, he asks, “Are they always true? And the answer is no. It behooves you to look very carefully at FDA numbers, Department of HHS numbers, and OMB numbers as a package. They’re not always in sync with each other."

As Mark Twain said, “Facts are stubborn things, but statistics are more pliable.”