Benefit/Risk Management

• 01.24.2012

The need for better FDA risk/benefit methodologies isn’t just a concern for pharmaceutical companies – it’s a clinical issue for physicians.

According to a study in Medical Care (Dusetzina SB, et al "Impact of FDA drug risk communications on healthcare utilization and health behaviors: A systematic review" Med Care 2011), the attention that practicing physicians pay to FDA notices about drug risks appears is highly variable.

A literature review showed that serious adverse event warnings were the most heeded of all FDA communications, but, according co-author Caleb Alexander, MD, of the University of Chicago, responses varied.

And the cause wasn’t practice variation.

"We will need a better understanding of how to make [FDA risk communications] work, and where they can go wrong," Alexander said in a statement. "And we will need more and better studies of the successes and failures of this process."

Notices about use of drugs for certain populations tended to spill over into others, the authors reported. For instance, a warning about antidepressant use in children and adolescents led to declines in their use among adults as well.

"As with other public policies, FDA communications have the potential for unintended consequences.”

All the more reason to stop talking about "risk management" and start referring to "benefit/risk mangement."

The authors called for more research on factors associated with fast and sustained responses to risk communications, and continued work on characterizing the effects of advisories and warnings on a variety of behaviors "to enhance the science of risk communication regarding prescription drugs."

But it’s not just a problem for prescribers. A related issue is how well patients understand the risk/benefit equation of the medicines they are prescribed – and the answer is likely to be “very little.”

Why is this important? According to a Harris poll, more than one-third of Americans surveyed decided not to take a prescribed medicine because of safety concerns about risks and more than a quarter chose not to fill a prescription at all over safety concern.

Another reason to support benefit/risk management.

Per Gretchen S. Dieck, Ph.D., senior vice president, Safety and Risk Management for Pfizer, “… surveys of practicing physicians, health policy experts and the general public have revealed a lack of understanding of the fundamental safety science, processes and terminology.  This can contribute to misinformed decisions by patients about treatment options, which can lead to sub-optimal health outcomes.”

Also consider the report out of the University of Chicago (a national random sample mail survey of 599 primary care physicians and 600 psychiatrists from November 2007 to August 2008) indicates there is confusion among physicians about what is or is not “on-label.”

The responsibility of risk is shared.  It must be more than what the FDA expects from industry and more than what industry expects from the FDA.  It's what all parties to the public health conversation must expect from themselves.

The responsibility of risk means appreciating and actualizing the philosophy of the safe use of drugs. For example, the responsibility of risk means not just detailing—but detailing the label.

At a February 2009 meeting of the FDA’s Risk Communications Advisory Committee (February 26-27, 2009), there was open public comment on the issue of how to improve the written information currently provided to patients about the medicines they receive.

(Full disclosure, while I did not participate in this meeting I am a Special Government Employee consultant to this advisory committee.)

The remarks of Pam Budny, a regulatory affairs manager at Eli Lilly were of particular interest.

Patient labeling should be prepared by the sponsor just as is the case for physician labeling. Physician and patient labeling are inextricably linked in terms of the information they contain on benefits and risks.

Testing with patients and or caregivers prior to submission is a critical way to determine the usefulness of patient labeling prior to patient use.

These comments reinforce the concept of a sponsor-developed, FDA approved, “label detailing guide.” Assuming that either healthcare providers or patients read and understand the PI is, well – wrong.

The importance of clear and concise and usable patient and physician medical information is recognized but more needs to done to address it. In September 2011, the FDA reorganized the Patient Labeling Team (PLT), moving it from the Office of Surveillance and Epidemiology (OSE), Division of Risk Management (DRISK) to OMPI, Division of Medical Policy Programs. That was a good move. The goal of the Patient Labeling Team is to promote the safe and effective use of prescription medications by providing accurate and easily understood patient medication information. Both physician and patient education should begin with the drug label.

All the more reason for the FDA and the pharmaceutical industry to jointly develop (as part of the agency's Safe Use initiative) better ways to make the PI more user-friendly.

Janet Woodcock: “Only through coordinated interventions across all sectors of the health care system can we substantially reduce preventable injuries from using medications. All participants in the health care community have a role to play in reducing the risks and preventing injuries from medication use.”

The time for sponsor-created and FDA-approved label “detailing aids” is now.

Dark Shadows

• 01.23.2012

An important and informed opinion from CMPI Chairman, Dr. Michael Weber.

THE PHYSICIANS SUNSHINE ACT:  MORE DARKNESS THAN LIGHT

The New Year brings in its wake the Physicians Sunshine Act and its requirement that pharmaceutical and device companies document all their payments to doctors, medical practices and teaching hospitals so that, starting in 2013, these costs can be listed by the Center for Medicare and Medicaid Services on a public website.  This action will result in unintended (but not unforeseeable) consequences on 21^st century medical progress.

The Sunshine rules are unclear and complicated – a bad combination. Not only will direct compensation to doctors be reported, but also all other costs of industry-supported physician-related research, consulting and education. 

Why this drastic and invasive step?   Follow the money.  Sunshine supporters hope that physicians, seeing their compensation made public, will curtail their interactions with industry -- thus limiting the development and use of “expensive” new products.

Understandably, government and private health insurers want to keep costs stable.  And, with prescription co-pays being patients’ most visible expense, they might find this action appealing -- for a while – until they see how innovation and new treatments are seriously delayed.

Collaborations between physicians and industry are fundamental to advancing medicine.  Academic physicians have the experience to identify unmet clinical needs, advise on potential new treatments, design and conduct innovative research and, through publications and teaching, bring key information to colleagues and patients. Without in any way diminishing the governmental and non-profit agencies that support research, it is the partnership between physicians and industry that has created many, if not most, of the major medical breakthroughs that have reduced the rates of death and other serious outcomes in recent years – as any literature search of major medical journals will quickly confirm. 

Conducting clinical research has become so rigorous and sophisticated that those of us who serve as consultants and investigators to industry recognize it as a major commitment or even a primary career path.  In addition, as studies are completed, physician researchers add to their professional commitment by becoming the teachers of this new information.

Critics of these collaborations see compensation of physicians as evidence of undue influence on medical practice.  But doctors, like all professionals, should be paid fairly for their time and work.  In reality, industry is now so conscious of not appearing to overpay doctors that they employ stringent “fair value” scales to set fees for research, consulting and teaching activities.  The truth is that physicians who are busy with these activities are not as well rewarded as their fellow specialists in full-time clinical practice.  Adding to this remunerative divergence is that a key part of research, writing articles for publication, takes weeks of work -- often unpaid so as to avoid any suggestion of bias.

The Sunshine Act will create troubling misconceptions for and about physicians.  Payments reported for physicians by industry will likely include funding they didn’t personally receive nor will they take into account costs incurred by these physicians in paying their own staff and covering overhead expenses.  Doctors involved in industry-supported research and education may easily get discouraged and frustrated explaining these complexities to an audience already biased and sated by sensationalistic media reports of physicians “on the take.”   

And yet the Sunshine Act, paradoxically, could have a positive effect.  Despite the near impossibility of reliably interpreting all the reported data, this information might well serve as a yardstick of cooperative achievement --identifying those physicians at the forefront of medical innovation.

Weber, a former president of the American Society of Hypertension is Editor-In-Chief of the Journal of Clinical Hypertension, professor of medicine at SUNY Downstate College of Medicine, Chairman of the Center for Medicine in the Public Interest, and a member of the Association of Clinical Researchers and Educators. 

Patient Centered Outcomes Research Institute: So Yesterday, So Useless

• 01.22.2012

Last week life technologies announced it was launching the Benchtop Ion Proton Sequencer that will sequence an individual’s entire genome in less than 24 hours and for $99 a chip.   

This week the Patient Centered Outcomes Research Institute announced national priorities for comparative effectiveness research (CER).  Those ‘priorities’ included: spending money on comparative effectiveness research, spending money on communicating CER and spending money on learning how to carry out CER.  Note that no money is spent on comparing whether CER research produces better outcomes than what doctors usually do or genome informed medicine.   

Last week Life Technologies announced it was developing open-source software that doctors and patients can use to diagnose and select treatments. 

This week PCORI was discussing the idea of using a graphic comic book to explain the value of CER to consumers.  Really. 

Last week life Technologies and Eric Topol discussed how smartphones that combine genomic information with real time monitoring of illnesses (in 3-D) would be used to diagnose disease and monitor individualized response in real time in 1-2 years.

This week PCORI said that its national priority list is not final and it will take 1-2 years to come up with something final.    Carol Clancy, director of the Agency of Healthcare Research and Quality (AHRQ), said,  “We’re on a journey… (And) the process is at least as important as the final output or outcome, and it’s going to be an ongoing iterative process.”    Since AHRQ gets a 20 percent cut of what PCORI – a non-profit organization – raises through a surcharge on everyone’s health premiums (nearly a billion over ten years) no questions asked, I am sure Clancy hopes the journey is…iterative.

In five years Life Technologies will be able to sequence my genome in a couple of hours and for less than $100.    In five years, PCORI will have produced no original comparative studies but will have spent an average of $3 million on such research and nearly a billion dollars

It is already cheaper to sequence the genome of 1 million Americans than it is to for either AHRQ or PCORI to conduct reviews of old research.  And in five years Life Technologies will be able to sequence 100 million people for what PCORI will spend on studies that will be outdated by the time they are published and will still not be useful to guide individual treatment decisions. 

So why aren’t groups that are supposed to care about the disconnect between what entrepreneurs are producing to personalize medicine and what PCORI is babbling about at it’s endless series of meetings?  For instance, The National Pharmaceutical Council (NPC) is holding a conference on something called “Asymmetry in the Ability to Communicate CER Findings: Ethics and Issues for Informed Decision Making.”

http://www.npcnow.org/Public/Education___Events/Events/2012_events/Asymmetry_2012/asym12.aspx

I have no clue what asymmetrical abilities are.   The NPC brochure for the conference states:  “With billions of dollars being invested in comparative effectiveness research (CER), the good news is that the public will have increased access to health information in coming years. Yet as more and more information is communicated to patients, practitioners and payers, current regulatory policy may create asymmetries, or inequalities, in the ability of different stakeholders to convey information.” 

Now does everybody know what an asymmetry among stakeholders is?  Here’s a translation: how can stakeholders – apart from the usual suspects and the sales reps AHRQ is paying to peddle CER to doctors -- get a cut of PCORI dough?

NPC’s medical chief Robert Dubois claims: "CER has great potential to improve medical decision-making and as a result our overall health. However, the detail of how we implement and use CER is critical to achieving this goal."   http://www.sacbee.com/2012/01/20/4202757/national-pharmaceutical-council.html

It is clear that NPC doesn’t care whether PCORI and CER will impede the use and adoption of individualized genomic and clinical information.  It will not challenge PCORI raking in and spending $3 billion on the policy equivalent of shipping milk that is already past it’s expiration date. FDA or equal access to personalized medicine or not spent at all?  Why hasn’t one stakeholder (that’s Beltwayspeak for not criticizing dumb ideas for fear of not having a seat at “the table”) had the guts to ask if the money shouldn’t be spent on the FDA or making sure there is equal access to individualized medical information?

The Life Technologies breakthrough demonstrates the future is already here.   Too bad ‘stakeholders’ are propping up PCORI and pursuing 'asymmetries' instead of promoting personalized medicine.

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