Yes we can ... have NICE in the USA

• 01.16.2009

Presented for your edification, a summary of CER provisions in the House Economic Recovery Bill:

APPROPRIATION OF $1.1 BILLION FOR CER RESEARCH

Subtitle B-Health and Human Services, AHRQ (pg. 141)

• $700 million is appropriated to carry out titles III, IX of the Public Health Service Act( establishes NIH, and AHRQ), title XI of the Social Security Act (CERTs program, peer review), and section 1013 of MMA to conduct or support CER. $400 million will be transferred to NIH (leaving $300 million to AHRQ).

• In addition, $400 million will be allocated at the discretion of Secretary of HHS for efforts that:

    o Compares the clinical outcomes, effectiveness, and appropriateness of items, services, and procedures that are used to prevent, diagnose, or treat disease

    o Encourage development of networks that can generate outcomes data

    o $1.5 million will go to the IOM for a report recommending national priorities for CER

• Public Accountability:

    o Secretary shall publish information on grants and contracts awarded with the funds

    o Shall disseminate research findings from grants and contracts to clinicians, patients, and the general public

    o Recipients of funds shall ensure an opportunity for public comment on the research

• Secretary will provide congressional committees an annual report research being conducted/supported and an operating plan for FY 2009 and FY 2010

ESTABLISHMENT OF ‘FEDERAL COORDINATING COUNCIL FOR COMPARATIVE EFFECTIVENESS RESEARCH

• Council shall coordinate and assist government agencies with conducting CER

• Council will advise Congress and President on CER infrastructure, CER funding, and other opportunities

• Council is composed of 15 members all of whom are federal officials/employees with responsibility for health-related programs, appointed by the president. Includes CMS, AHRQ, FDA, VA, DOD

• At least half the members will be physicians (working in government)

• By June 2009, the council will submit a report to the President and Congress detailing recommendations.

What does all this mean?

1. It is, if not a clone of the UK National Institute for Clinical Excellence (NICE), a kissin' cousin.

2. Absolutely nothing in the current legislative language would stimulate the development of measures and studies to advance personalized medicine.

3. There will be inevitable bias towards large randomized trials a la CATIE and ALLHAT.

4. And who will ARHQ rely on for its research? Most likely entities funded by HMOs and other payers with a goal towards cost containment.

5. The underlying assumption is that comparative effectiveness research will deliver improved outcomes via better quality evidence concerning the best treatment, prevention, and management of any given health condition. It assumes that comparative effectiveness research helps patients, providers, and payers of health care to make more informed decisions. But is there any evidence that these assumptions are true?

How about a study to determine whether comparative effectiveness research, compared to other types of research, actually delivers on these lofty goals? How about a meta-analysis to examine how comparatively effective comparative effectiveness research is?

6. And what if such a body swiftly morphs into a New World version of NICE, dictating de facto guidelines for reimbursement and coverage. Doesn't it become an obstacle to access, just like in the UK -- denying patients coverage to innovative uses of new mediccal technologies?

Yes we can ... what? Embrace a healthcare system that is cost-based rather than patient-centric?

No thank you.

Onions on pizza or blood pressure control?

• 01.16.2009

Minefields Along the Innovation Highway

• 01.16.2009

Outgoing Dept HHS Secretary Tevi Troy leaves Washington today for a well-deserved rest (rumors about a Yankee spring training contract can neither be confirmed nor denied) but not without an important parting word about the future of biomedical innovation in America.

This past year Dr. Troy held a series of town hall meetings throughout the country on the future of biomedical innovation. The account of his meetings were published today in a report entitled: Healthcare Innovation in the 21st Century.

He found:

"New and exciting technologies provide hope that pioneering new diagnostics, devices, drugs, and therapeutic interventions will be developed and made available to the public. However, the need to assess standards, clinical utility, safety, and cost all provide significant challenges and delays in translating scientific discovery to a marketable product. Biomedical innovation is fraught with uncertainty, risk, and a high probability of failure. Many new technologies – genomics, nanotechnology, advanced imaging, bioinformatics – offer great possibilities for the development of biomedical innovations. Yet these new technologies have also amplified the risk and uncertainty in the regulatory and payment pathways. Each of these new technologies raises questions about the safety, efficacy, and clinical use of products derived from these technologies. In many cases, the new technologies also challenge existing notions of how a biomedical innovation should be treated if it does not fall into a traditional regulatory or payment pathway, or straddles two existing pathways. In many cases, there may be a long lag between the emergence of a new technology and the issuance of regulatory guidance clarifying the pathway for product approval. Attendees noted that uncertainty can contribute to delays in the development and diffusion of new innovations, and can diminish investors’ willingness to invest in new technologies."

At a time when Congress is pouring buckets of money on failing and floundering sectors of our economy, considering legislation to force banks to issue risky loans (once again) and proposals to restrict access to new medicines while showering tax credits on green technologies some of Dr. Troy's recommendations to remedy these solutions should be adopted:

Requiring that certain funds be set aside for purely
basic research, and that other NIH grants go to basic
and translation research that has a demonstrated or
probable connection to an improved health care
outcome.
􀂾 Moving away from a binary model of safety versus
effectiveness, by having the FDA make sure
consumers have information available to them about
the spectrum of risks and benefit inherent in every
drug, biological, and device – and how these risks and
benefits may vary from person to person.
􀂾 Allowing FDA to approve applications on the basis of
inferences from known biomedical effects, rather than
always requiring clinical trial data on sizeable
populations.
􀂾 Implementing value-based purchasing across different
parts of Medicare, so that Medicare pays providers for
value or outcomes provided to a beneficiary rather
than for each service or good.

Sadly, Congress and the media marches in another direction. That's because they hate innovation...or the innovators to be more precise. And mining the innovation highway to make it riskier and more dangerous to innovate is part of the game plan. Tevi has highlighted the threats to innovation. To the extent that they are turned into policies, we will know who the enemies of progress really are.

Of Mice and Meds

• 01.16.2009

Talk about pharmaceutical direct-to-consumer advertising!

Pfizer has just launched a commercial in British movie theaters  warning about the dangers of counterfeit medicines illegally purchased online .

The commercial, slotted to be shown in 600 theaters across the UK, shows a middle-aged man spitting up a rat after swallowing a pill that arrived in the mail.  (This alludes to the fact that some of the counterfeit drugs seized in the UK contained not API – but rat poison.)

According to an article in the Financial Times,

“The campaign reflects growing safety concerns – and commercial losses for the drug industry – caused by a rise in unregulated internet sales of medicines. It also marks an intriguing extension of the limits on advertising by drug companies to raise their public profile, in spite of tight restrictions on the marketing of prescription medicines to consumers. The film contains no reference to Pfizer’s medicines but shows the corporate logo alongside that of the Medicines and Healthcare Products Regulatory Agency, the UK watchdog that co-ordinates an increasing number of investigations and prosecutions of counterfeiters. It agreed to a pioneering partnership with the company.”

Well jolly good all around.  Now let’s see if Pfizer will reach out to the FDA to pursue a similar program here at home. – and whether the FDA will have the courage to step up to the plate and accept the offer. That’s precisely the kind of pubic interest partnership the world’s biggest life sciences company needs in order to demonstrate that it’s heart – and pocketbook -- are in the right place.  That it's in the public health business first and the selling drugs business second.  And it’s just the kind of unambiguous, bold and innovative messaging the FDA needs to remind the American people – including some of our elected officials -- that drug importation is unsafe healthcare practice and unsound public policy.

To view the commercial, click here.

How big is the problem of counterfeit drugs?  According to CNN:

“Many of the world's bogus drugs originate in Asia, particularly China, according to the U.S. Center for Medicine in the Public Interest. The fakes oftentimes are exported and change hands many times before reaching their unwitting consumers."These are criminal organizations that are manufacturing, distributing and selling counterfeit medicines," says Thomas Kubic, a former FBI agent and president of the Pharmaceutical Security Institute, a group funded by drugmakers. The growing trade has been fueled by the growth of Internet drug sales and the lure of lucrative profits. The Center for Medicine in the Public Interest expects global sales of fake drugs to reach $75 billion by 2010.”

The complete CNN story can be found here.

Perhaps the weakest link in the European chain of custody is parallel trade. In Europe, parallel trade (what we call “importation”) is legal between all 25 EU member states. And last year 140 million individual drug packages were parallel imported throughout the European Union — and an independent wholesaler repackaged each and every one. This means that, literally, parallel traders open 140 million packets of drugs, remove their contents and repackage them. But these parallel profiteers are in the moneymaking business, not the safety business. And mistakes happen. For example, new labels incorrectly state the dosage strength; the new label says the box contains tablets, but inside are capsules; the expiration date and batch numbers on the medicine boxes don’t match the actual batch and dates of expiration of the medicines inside; and patient information materials are often in the wrong language or are out of date. Oops.

In the EU there is no requirement to record the batch numbers of parallel imported medicines. So if a batch of medicines originally intended for sale in Greece is recalled, tracing where the entire batch has gone (for example, from Athens to London through Canada to Indianapolis) is impossible. And all the large "legitimate" Canadian internet pharmacies already admit to getting their supplies from Europe. (An interesting and important side note is that these EU-sourced drugs aren't even legal for sale in Canada. So those who say we'll be getting "the same drugs as Canadians" are just plain wrong.)

In fact, parallel traded medicines account for about 20% (one in five) of all prescriptions filled by the same British pharmacies that have had a record numbers of counterfeit recalls. In other words, drugs purchased from a British pharmacy by a Canadian internet pharmacy to fulfill an order from an American cutomer could come from European Union nations such as Greece, Latvia, Poland, Malta, Cyprus, or Estonia.

Caveat Emptor is bad health care practice and even worse health care policy. Safety cannot be compromised, even if the truth is inconvenient.

$1.4 Billion for a Misdemeanor?

• 01.16.2009

Eil Lilly is paying $1.4 billion to settle charges relating to it's off-label promotion of Zyprexa.  The company pled guilty to a misdemeanor... That's an expensive slap on the wrist. 

Meanwhile, I wonder how much of that settlement will go to group such as The Prescription Project, Public Citizen, The Prescription Access Litigation Project, Community Catalyst, etc and trial attorneys as opposed to state governments..  How much will actually go to Medicaid patients instead of bottom feeders and the interest groups that front for them? 

$1.4 billion can buy a lot of research activity for medicines that could save the lives of kids with cancer or seniors with Alzheimers...instead most of it will go to tort lawyers.

Got Guidance?

• 01.15.2009

FDA Issues Guidances for Industry to Improve the Safety of Food, Feed and Drugs

The U.S. Food and Drug Administration today issued three guidances designed to help ensure the safety of FDA-regulated products in the supply chain. The documents issued today include the following:

·       Final Guidance for Industry on Voluntary Third-Party Certification Programs for Foods and Feeds;

·       Draft Guidance for Industry on Submission of Laboratory Packages by Accredited Laboratories; and

·       Draft Guidance for Industry on Standards for Securing the Drug Supply Chain – Standardized Numerical Identification for Prescription Drug Packages.

“The guidance documents reflect the FDA’s continued vigorous efforts to minimize the chances of unsafe products reaching American consumers,” said Jeffrey Shuren, M.D., J.D., associate commissioner for policy and planning.

The Final Guidance for Industry on Voluntary Third-Party Certification Programs for Foods and Feeds discusses the attributes of a third-party certification program that would merit the FDA’s confidence in the quality of the program’s audit. The guidance, finalizing a draft published on July 10, 2008, is intended as one of the steps in the FDA’s future recognition of voluntary third-party certification programs for foods and animal feeds. The document makes clear that it applies to any third-party certification body, including a private entity or a non-FDA federal, state, local or foreign regulatory body. Third-party certification programs can augment the ability of the FDA and the importing community to verify product safety.

The Draft Guidance for Industry on Submission of Laboratory Packages by Accredited Laboratories is intended to enhance the quality and reliability of test results submitted by importers to demonstrate that their products meet the FDA’s requirements. The guidance advises importers how to use accredited -- rather than non-accredited -- laboratories and makes recommendations about the quality and type of test data and information that these laboratories should produce in support of test results submitted to the FDA. The draft guidance is also intended to reduce the likelihood that an importer will select only favorable test results to submit to the FDA.

The Draft Guidance for Industry on Standards for Securing the Drug Supply Chain – Standardized Numerical Identification for Prescription Drug Packages is the first of several guidances and regulations that the FDA may issue to implement Section 913 of the Food and Drug Administration Amendments Act of 2007. This guidance recommends the standards that industry should use for the identification of individual packages containing prescription drugs. These standards will facilitate the adoption of a uniform electronic track and trace system for prescription drugs to further improve their safety and security. Both draft guidances have a 90-day comment period.

All three guidances support the FDA’s import strategy emphasizing prevention of harm, intervention when risks are identified, and rapid response after harm has occurred.

The FDA’s guidance documents do not establish legally enforceable responsibilities.  Instead, guidances describe the agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited.

High (Blood Pressure) Gene

• 01.14.2009

People with a common variant of the gene STK39 tend to have higher blood pressure levels and are more likely to develop full-blown high blood pressure, also called hypertension, University of Maryland School of Medicine researchers found.

They identified the gene's role in high blood pressure susceptibility by analyzing the genes of 542 people in the insular Old Order Amish community in Lancaster County, Pennsylvania.

The researchers confirmed the findings by looking at the genes of another group of Amish people as well as four other groups of white people in the United States and Europe.

About 20 percent of the people studied had either one or two copies of this particular variant, the researchers said.

The gene produces a protein involved in regulating the way the kidneys process salt in the body -- a key factor in determining blood pressure, the researchers said.

Yen-Pei Christy Chang, who led the study appearing in the journal Proceedings of the National Academy of Sciences, said the findings could lead to the development of new high blood pressure drugs targeting the activity of STK39.

"What we hope is that by understanding STK39 we can use that information for personalized medicine, so we can actually predict which hypertensive patients should be on what class of medication and know that they will respond well and have minimal risk for side effects," Chang said in a telephone interview.

People with high blood pressure are more likely to develop heart attacks, heart failure, strokes and kidney disease.

While STK39 may play a pivotal role in some people, Chang said numerous other genes also may be involved. Many factors are involved in high blood pressure such as being overweight, lack of exercise, smoking and too much salt in the diet.

Several different types of medications are used to treat high blood pressure, including diuretics, beta blockers, ACE inhibitors, calcium channel blockers and others. Their effectiveness varies depending on the person, and doctors have a hard time knowing which is best for a particular patient.

Chang said the researchers want to determine how people with different versions of this gene respond to the various drugs and to lifestyle interventions such as cutting the amount of salt in the diet.

The Lancaster Amish are seen as ideal for genetic research because they are a genetically homogenous people whose ancestry can be traced to a small group who arrived from Europe in the 1700s. In addition to genetic similarity, they also maintain similar lifestyles in their close-knit rural communities.

(Editing by Maggie Fox and Vicki Allen)

The Sinking SCHIP

• 01.14.2009

Adding 30 billion or so to expand SCHIP is a done deal.  Now the question is whether there will be any accountability to the families who enroll in the program.

I am not even talking about health outcomes.  I am talking about the care actually being there.

As Woody Allen once said: "80 percent of success is showing up."  So therefore:

How long will families have to wait to see a doctor for both a sick or well check up?

How long will they have to wait to get referred to a specialist or receive authorization for a procedure or medicine?

Studies show that over time increases in SCHIP enrollment have done nothing to reduce the use of emergency rooms as a routine source of care.  Has anyone ever care to ask or find out why?  We know that "high ED use in some communities also likely reflects generic preferences for EDs as a source of care for nonurgent problems..." but shouldn't SCHIP be organized in ways to reward less expensive but equally effective sources of care?   For further details. see here.

This is not a matter of public vs. private as much it is as trying to make sure the health coverage some how translates into better health.   Without a sustained effort the promotes competition based on price, quality and convenience, SCHIP will degenerate into Medicaid for the middle class.  

A Good Housekeeping Seal for ... Diagnostics?

• 01.14.2009

According to a story in today’s USA Today:  Genetic testing boosts efficacy in cancer care,

 “Tailoring cancer therapies to fit a person's genetic makeup could spare thousands of patients from harmful side effects and save millions of dollars a year, a study shows … Although the newest cancer drugs offer a number of improvements over older therapies, they often cost thousands of dollars more a month …Treating a colorectal cancer patient with a drug called Erbitux, for example, costs more than $61,000 for a typical treatment with 24 doses, according to a study presented Tuesday at the American Society of Clinical Oncology meeting in San Francisco … Even patients with good insurance could pay thousands of dollars out-of-pocket for Erbitux or a similar drug, Vectibix …Over the past year or so, several studies have shown neither Erbitux or Vectibix works in patients with a certain genetic mutation, which occurs in 36% to 46% of tumors, says Veena Shankaran, a fellow at the Veterans Administration Center for the Management of Complex Chronic Care in Chicago, whose study focused on Erbitux … Giving Erbitux only to patients without the mutations would save the country up to $604 million a year, Shankaran says …Skipping Erbitux also would spare patients from its side effects, including a severe, acne-like rash, she says …Testing tumor tissue for the mutations "saves tons of money, and makes medical care better at the same time," says Leonard Saltz, a colorectal cancer specialist at New York's Memorial Sloan-Kettering Cancer Center … But no matter how many patients are treated, Shankaran says, the $452 cost of genetic testing will always be a bargain compared with wasting tens of thousands of dollars giving drugs to people who have no chance of being helped …That would allow patients to get the best medications right away, instead of wasting time and money on drugs that won't work, Shankaran says.”

Amen.

Personalized medicine is not about denying care. It’s about providing “the four rights” (the right medicine in the right dose to the right patient at the right time). Personalized medicine can (indeed must!) be both cost-effective and patient-centric. 

Yet, on the reimbursement front, many payers aren’t ready to accept the up front expense – even though the longer-term savings can be substantial. For more on this issue see "Diagnostical Materialism.” 

Diagnostics reimbursement should be based on value rather than activity. 

On the regulatory front greater clarity and predictability are required.  At present, FDA guidance on diagnostic approvals are vague.  To reinforce the agency’s commitment to personalized medicine, the FDA should embrace ever-greater clarity and commitment to diagnostic tool review.  This should be a top priority of the agency’s Critical Path program.

The Critical Path Institute (created in 2005 by the University of Arizona and the U.S. Food and Drug Administration to standardize an approach to validating medical products) is working on a solution, a “GoodHousekeeping Seal of Approval” for diagnostics. C-PATH plans to launch its United States Diagnostic Standards in the coming months.

According to a recent article in the Journal of Life Sciences,

“The United States Diagnostic Standards will offer a voluntary certification for laboratory and pathology diagnostics, much like the Underwriters Laboratories certification for many tools and equipment. Companies already submit their tests to data test sites for evaluation prior to FDA submission, says Jeffrey Cossman, chief scientific officer of C-Path. This would take the place of a data test site.”

This speaks directly to the contentious issue of partnership between the FDA, industry and academia.  No one entity can do it alone.  This is a core philosophy that will, no doubt be vigorously debated in Congress – and by the next FDA commissioner. We need a stated policy of pragmatic partnerships.

Nobody said it going to be easy.

Want more oversight? Show me the money!

• 01.13.2009

Relative to FDA oversight of clinical trial investigator conflict of interest, the New York Time opines: 

"The inspector general of the Department of Health and Human Services reviewed all 118 applications for marketing drugs and medical devices that were approved by the F.D.A. in fiscal year 2007. It found appalling failures to collect information and act on it ...The inspector general made several suggestions, including stressing that the due diligence exemption should be used rarely. The agency accepted most, but it strongly opposed a recommendation that it require companies to submit financial conflict information before a clinical trial is started, not after it is completed. The F.D.A. complained that that would increase its workload for no clear gain, especially since many drugs or devices that enter clinical trials never reach the market ... Such bureaucratic excuses seem lame. Surely it would be better for the F.D.A. to eliminate potential conflicts before they can bias a trial than try to mitigate them after the results are in."

Absolutely.  Transparency.  Transparency.  Transparency.  The agency's lack of funding (and ensuing lack of manpower to accomplish the task in a thorough and timely manner) must be remedied.  Editorializing about the problem is important -- doing so about the solution, even more so.  Want the problem fixed?  Show me the money! Otherwise it's just rhetoric.

The Times continues:

"The agency’s lax performance underscores the need for Congress to pass legislation requiring all drug and device makers to report their financial arrangements with doctors in a public databank. That would make it harder for clinical investigators or sponsoring companies to hide potential conflicts, including those that might bias clinical trials for the F.D.A."

Not so fast.  Beyond the obvious fact that such a database would help nobody other than trial lawyers, a more dire unintended consequence would be the unfair stigmatization of doctors and scientists who participate in clinical trials sponsored by pharmaceutical companies. Fearful of jeopardizing their reputations, this could motivate many to leave clinical trial research altogether -- making trials more difficult tand more expensive to field in the first place.  And this outcome is most definitely not in the best interests of the public health.

Let's do the right thing -- but not get carried away.

The full Times editorial can be found here.