CRO Choice

04/13/2010 06:53 AM |

Biogen Idec is developing a test that can tell patients their odds of getting a deadly brain illness from Tysabri.

 

The screening tool could be marketed as early as 2011 if clinical trials involving 9,000 people show a low rate of false findings. The test is designed to detect the JC virus that causes progressive multifocal leukoencephalopathy, or PML, a brain-cell destroyer that can lead to disability and death. (Tysabri has been linked to 42 PML cases.)

 

If the test works, it is “absolutely a game changer,” said Patricia O’Looney, vice president of biomedical research at the National Multiple Sclerosis Society. With a false-negative rate of 2 percent, patients who are free of the virus would lower their risk of getting the brain disorder PML to 1 in 25,000 for the first three years of their Tysabri therapy. That’s 21^st century risk management.

And speaking of risk management, I’m chairing a panel on REMS today at the 19th Annual Partnerships in Clinical Trials conference.

A common question I get about REMS is – how is it different from what we used to call RiskMAPS?  I see two main differences.  The first, obviously and importantly, is that REMS has actual legislative language.  And that’s an important detail – but it’s one-dimensional.

The second, more important and contentious difference is the environment into which REMS was birthed -- an environment in which there is growing realization that the 21^st century FDA must add a third leg to its mission of safety and efficacy – and that third leg is safe use.  The safe use of drugs.  And the formulation, implementation and communication of plans – REMS plans -- that will assist physicians and patients achieve better outcomes through the strategies and tactics devised therein.

That being said, there are those in industry and in the broader healthcare policy arena who look at REMS and don’t see GEMS.

Many have looked at the FDAAA language on REMS and see it as an ill-advised green light for the FDA to inject itself into the practice of medicine.

While I agree that REMS does indeed represent an expansion of the FDA's authority, I do not agree that it is either ill advised or an over-extension of the agency’s purview.

The concept of "safe use" as an integral part of the FDA's 21st century mission and REMS as one of many tactics to achieve better patient care are contentious and crucial.  And it is that debate which brings us together today.

REMS must be viewed as a “win/win” situation for the agency (which can now move forward to approve drugs with higher risk profiles and have a more direct path for post-market surveillance), for sponsors (who can have their drugs approved with greater alacrity), for physicians (who will – at least in theory) have a more complete view of risks and benefits, and patients (who will have additional therapeutic options and will now – at least in certain circumstances – become a more complete part of the compliance/adherence proposition).

There’s much debate and discussion over where in the drug development process REMS should surface.  Acknowledgement that this cannot be done in the absence of data – and confusion as to how to deal with early (even Phase II information) that might be REMS relevant.  And “confusion” meaning both scientific uncertainty and internal confusion and discomfort.

There’s evident frustration about validated tools (the absence thereof).  But this was at least somewhat assuaged by the timely release of the FDA’s draft guidance on “Format and Content of Proposed REMS Assessments, and Proposed REMS Modifications.”  And it was a cool and refreshing draft indeed.

And there’s continued discussion as to whether or not companies should wait until the agency asks – or if sponsors should preemptively (you should excuse the expression) provide an outline of a potential REMS plan.  This is important not just as an issue of timeliness (as opposed to having the agency introduce the topic in a complete response letter), but also of responsibility.  If, as we all want to believe, the FDA must be both regulator of and colleague to industry, then what are the responsibilities of a sponsor relative to (among many other things) surfacing the REMS issue – and at what point in the process.  Nobody said it was going to be easy.

CDER Director, Dr. Janet Woodcock said that, “Safety means doing the right things for patients. FDA must consider post-approval issues as part of a drug’s lifecycle.”

Janet understands that there’s a real difference between “headlines and help.”  In other words, REMS and other safety mechanisms can be viewed as either “headlines” about “unsafe” drugs or in a more appropriate context of “safe use.” Janet opts for “safe use,” while others (in the media and elsewhere) seem more predisposed to the other.

According to Woodcock, “FDA does not control the health care system, so our improving the use of marketed drugs, to a great extent, is going to involve influence rather than control.”

“Influence rather than control” is a savvy and sophisticated concept -- one that many of our elected members of Congress could learn from, and one in which REMS plays an important role.

The FDA’s "Safe Use" initiative is the patient-facing sibling of the agency’s “Safety First” pharmacovigilance program. But it's more than that -- it's the FDA reasserting ownership of safety from those who would use it only as a mallet of fear. I will not mention names.

It's important to note that when the FDA announced the warfarin label change the agency (and Larry Lesko in particular) came under attack from critics who asserted that this was the FDA, inappropriately, telling doctors how to practice medicine.

Jane Axelrad, the associate director for policy at CDER, had to say about REMS, “These safety plans allow patients to have continued access to certain medicines for which there are safety concerns that can be managed through appropriate use.”

Whether you say “appropriate” use or “safe” use – the principle is the same – making sure that the risk/benefit analysis of any given therapy is communicated in a lucid and (when required) strident manner. 

Sometimes that requires a label change.  Sometimes it requires a REMS plan, but it will always require the active participation and leadership of the FDA in partnership with the pharmaceutical industry, physicians, and yes – even patients. 

Because no safe use program will succeed without the secret ingredient of patient responsibility.

But does it require additional agency authority. At a recent House Energy and Commerce Health Subcommittee hearing FDA’s Principal Deputy Commissioner Josh Sharfstein said that FDA could use more authority to bring negotiations over a drug's Risk Evaluation and Mitigation Strategy to a close. The agency can require a REMS, he commented, but not specify its contents.

Another area that needs to be addressed, Sharfstein suggested, is the different treatment of brand and generic drugs when it comes to imposing a REMS with a communication plan for alerting health care professionals and patients about a drug's risk.

 
Brand sponsors must implement such a plan, whereas FDA must pay for and operate a communication plan for generic drugs, he noted. Something to think about as we head into the PDUFA reauthorization debate.

While some see REMS as mission creep, others see it as the natural and logical extension of FDA responsibility in our new age of more precise diagnostics and personalized medicine.

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In Vivo In LapDog Wonderland

04/12/2010 04:33 PM |

The IN VIVO blog folks, who seem to find nothing bad about comparative effectiveness research -- without pointing to any clinical or scientific evidence that it improves health outcomes or economic studies that show it does not reduce investment in innovation -- have found yet another great thing about CER:  It can be used to diss alternative medicine.  

Comparative Effectiveness Research and Alternative Medicine: Bring it On

"..Isn’t it at least possible that CER will focus on determining whether other commonly used therapies meet even that baseline standard?

So rather than thinking of CER as a threat to big pharmaceutical brands, maybe there is an alternative vision for how it might work. Literally: as a tool to test the value of so-called “alternative” medicine."


Wow.   As if that is the primary purpose of the $600 million a year the Agency for Healthcare Research and Quality will be receiving.   

The In Vivo folks note:  "Sebelius diplomatically avoided taking a stand on the value of alternative medicine, and stressed that private plans—not the feds—will decide what to cover."

I have a suggestion for In Vivo:  Less sucking up to Sebelius and more reporting.   Here is what the legislation actually has the feds deciding and using CER in making these decisions on behalf of consumers, doctors and private plans:

1. Development of a national health quality strategic plan that will be used for improving Federal payment policy with an emphasis on " quality and efficiency" (as in payments to health exchanges)
2.  Establishment of annual benchmarks for each relevant agency to achieve national priorities.  (see number 1)
3.   Establishment of a " process for regular reporting by the agencies to the Secretary on the implementation of the strategic plan.
4.  Strategies to align public and private payers with regard to quality and patient safety efforts.
5.  Incorporating quality improvement and measurement (using CER)  in the strategic plan for health information technology required by the American Recovery and Reinvestment Act

Just to make it clear (and maybe the In Vivo folks might want to break away from their fawning to check this out), the legislation requires: ‘quality
measure’ means a standard for measuring the performance and  improvement of population health or of health plans, providers of services, and other clinicians in the delivery of health care services.

Then too,  the legislation requires" A group health plan and a health insurance issuer offering group or individual health insurance coverage shall, at a minimum provide coverage for and shall not impose any cost sharing requirements for— ‘‘(1) evidence-based items or services that have in effect a rating of ‘A’ or ‘B’ in the current recommendations of the  United States Preventive Services Task Force; ‘‘(2) immunizations that have in effect a recommendation from the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention with respect to the individual involved; and ‘‘(3) with respect to infants, children, and adolescents, evidence-informed preventive care and screenings provided for in the comprehensive guidelines supported by the Health Resources and Services Administration. "

How is this evidence developed?  Through the application of comparative effectiveness research within the context of development of the quality strategic plan.

But of course " private plans—not the feds—will decide what to cover."

Which is why CER is required to be used to determine the the effect of new technologies on " national expenditures associated with a health care treatment, strategy, or health conditions....priorities in the National Strategy for quality care established under section 399H of the Public Health Service Act that are consistent with this section. "

But of course " private plans—not the feds—will decide what to cover."

In Vivo makes fun of those who worry about CER being used for rationing when it is obvious to them that all the CER dough will be allocated comparing flu shots to massages from chiropractors or aromatherapy.   Of course it will.  So we should ignore the fact that the legislation gives AHRQ significant authority in setting CER and quality agenda, control over dissemination of CER findings and preference in conducting and controlling CER research, especially as it pertains to coverage decisions for health plans, Medicaid and the Independent Medicare Advisory Board.  And we should ignorestatutory language stating:

The Secretary may only use evidence and findings from research conducted under section 1181 to make a determination regarding coverage under title XVIII if such use is through an iterative and transparent process which includes public comment and considers the effect on subpopulations.

Paragraph (1) shall not be construed as preventing the Secretary from using evidence or findings from such comparative clinical effectiveness research in determining coverage, reimbursement, or incentive programs under title XVIII based upon a comparison of the difference in the effectiveness of alternative treatments in extending an individual’s life due to the individual’s age, disability, or terminal illness.

‘‘(d)(1) The Secretary shall not use evidence or findings from comparative clinical effectiveness research conducted under section 1181 in determining coverage, reimbursement, or incentive programs under title XVIII in a manner that precludes, or with the intent to discourage, an individual from choosing a health care treatment based on how the individual values the tradeoff between extending the length of their life and the risk of disability.

‘‘(2)(A) Paragraph (1) shall not be construed to— ‘‘(i) limit the application of differential copayments under title XVIII based on factors such as cost or type of service; or ‘‘(ii) prevent the Secretary from using evidence or findings from such comparative clinical effectiveness research in determining coverage, reimbursement, or incentive programs under such title based upon a comparison of the difference in the effectiveness of alternative health care treatments in extending an individual’s life due to that individual’s age, disability, or terminal illness.

Which if you flip it around means you can use CER to steer people to what you think is best using copays and limit coverage of new technologies if you think treatment A raises fewer questions about "safety" (and risk of death) than treatment B which is newer.  

And in the final analysis, has anyone asked what the additional cost and time will mean to patients in terms of life expectancy, morbidity, cost of care?
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The UnCERtainty Principle

04/12/2010 08:11 AM |

The soundbite about AHRQ and CER is that it’s “non-political.” That remains to be seen. Previous examples of Uncle Sam as CRO (CATIE, ALLHAT) speak otherwise.

Consider this – NICE (the National Institute for Health and Clinical Excellence) is suspending publication of all decisions until after the U.K. general elections on May 6th.  According to the Pink Sheet, “The decision reflects just how controversial the organization is in the U.K., where it has become a lightening rod for political debate.”

Something to think about.

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No Mas

04/09/2010 11:35 AM |

According to a study in the May issue of Pediatrics, many Spanish-speaking people in the United States receive prescription instructions from the pharmacy so poorly translated that the medications are potentially hazardous to their health. (The errors occur largely because of deficiencies in computer programs that most pharmacies rely on to translate medication information from English to Spanish.)

This is an important issue that should be immediately addressed by the FDA as part of the agency’s Safe Use initiative.

This is a real health disparity that can and must be fixed inmediatamente.

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Creating Social Networks To Discuss Healthcare Reform

04/08/2010 05:01 PM |

I spent about 40 minutes on the Handsoffmyhealth.org  Facebook page answering questions about the impact of health care reform from about 500 people who signed in.   

People wanted to know how much control the government will or would have over medical decisions.  And many people with cancer wrote in, wanting to know how the health plan might affect them and their ability to get insurance. 

I said that the key issue going forward is to preserve individual choice and the ability to get medical treatment based on need, not cost.

That said, the first steps being taken to implement health care legislation are as follows:

1.   Allocate $10 billion to the IRS and 17000 more IRS agents to review value of health care, whether you have it and to determine if your source of healthcare exempts you from paying a fine. 

2.   Allocate $250 million and add FBI agents to increase the number of Strike Teams swooping into the offices of physicians who seem to be overbilling based on an audit of claims data and not based on material evidence.

3.   Give the Agency for Healthcare Research and Quality an additional $600 million a year to develop guidelines for determining what technologies, services and treatments should be covered in a "quality" health plan and for how doctors should practice medicine based on comparative effectiveness benchmarks that ignore individual differences.

4.   Medicare cuts to hospice and home health care services. 

People at the lower end of the income scale with cancer and serious disabilities will be forced in Medicaid.  By 2014 the current rush of primary care doctors retiring and opting out of Medicaid will create "hollow health care" access.  For speciality care and cancer treatment, Medicaid will have the right to restrict access to care and drugs based on comparative effectiveness.   If a medicine is not on the Medicaid formulary you are out of luck. 

I also predicted that at some point in time a health plan will go under, prompting the administration to take it over like it did GM and the banks.  A very cheap way of creating a public option.   Expect a lot of bailing out of the "too big to fail" health plan.  ERs will be the place of last resort for millions and millions of other people will pay the fine, get coverage when they are sick, drop it when they are well again.   This churning takes places in Medicaid all the time and it will spread to health care insurance in general because the incentive to game the system is built into the bill.

Finally,  I suggested that just as people pay taxes and send their kids to public schools, people who want decent health care will pay up and buy into private health associations or go off-shore, paying out of pocket when they need or with the help of new gap insurance products. 

It may all that we can do is create escape routes and underground railroads to let people secure the care they want and when they need it. 

In America that is called market opportunity. 



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Dosing Dilemma

04/07/2010 01:47 PM |

We often talk about the four rights – the right medicine for the right patient at the right time in the right dose.  But that fourth “right” – dosing – often gets forgotten.

Today’s news, from the May edition of the American Journal of Preventive Medicine, finds that U.S. hospitalizations for poisoning by prescription opioids, sedatives and tranquilizers have jumped 65 percent from 1999 to 2006. That number is almost twice the increase in hospitalizations for poisonings by all other drugs and medicinal substances. “People are seeing headlines...and thinking 'it's sad and tragic but maybe it's just Hollywood,’ said lead author Jeffrey H. Coben, M.D., a professor and director of the Injury Control Research Center at the West Virginia University School of Medicine. “It's widespread throughout the U.S. and involves serious hospitalizations and is escalating at a rapid pace."

For those who don’t think that proper dosing isn’t an issue – think again.

It’s a killer.

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Rounding Third

04/06/2010 09:01 AM |

Lilly CEO John Lechleiter: "I believe China will make a significant contribution to medical innovation in this century.”

Sales too (the Chinese market for pharmaceuticals is currently ranked the 7th largest in the world - and could jump to number three as soon as next year) – but that’s not the point.  Lechleiter is thinking outside the box and it’s not the marketing and sales box.

According to the Pink Sheet, “Lilly has also begun linking an expanding array of Chinese scientists into its globe-spanning virtual research network. Eli Lilly's Robert Armstrong, one of the earliest advocates of replacing the R&D silos of traditional pharmaceutical companies with research networks that stretch from West to East, said in an earlier interview that Lilly is racing to construct a "dynamic matrix of partnerships across the globe aimed at R&D."

Lechleiter: "China is uniquely situated to play a key role in global pharmaceutical research and development … A growing number of Chinese scientists educated in other countries are returning home, adding to the tremendous human capital of this country and setting the stage for further innovation-driven growth. The 'brain drain' has become the 'brain gain' here in China.”

And, “As China seeks to expand its R&D base, what can this nation do to build its great potential to participate in the global innovation economy of the future?"

His primary suggestion involves IP rights – and rightfully so.

Leichleiter: "Above all there must be strong protection of intellectual property. China has made significant progress in intellectual property protection, developing a patent regime aligned with international systems. This is an essential first step to help foster innovation, but it is indeed just the first step.”

And without question there’s work to be done.  In December 2009 China passed a new patent law that will allow domestic Chinese pharmaceutical manufacturers to manufacture knock-offs of on-patent medicines – and export them to third countries.  According to Yin Xintian, director the regulations department of China’s State Intellectual Property Office, the new law will “ensure patients can get the drugs they need when they need them.”

Intellectual property rights are the fertile soil that facilitates the tree of pharmaceutical innovation to grow in the first place. To borrow an over-used adjective from the world of global climate change -- we must protect "sustainable" innovation. Jamie Love and Company may very well say, "A world without patents, amen." And they're right, because minus pharmaceutical IPR we'd all better start saying our prayers -- because that's the only way we're going to battle disease and improve the health of our global fraternity. That's a Silent Spring we cannot afford.

Leichleiter then issued a more general call for “conditions.”

"Creating and maintaining the conditions for innovation to flourish is challenging and complicated work - work that is never finished.”

Indeed.

Might this call for more “flourishing” conditions also include a regulatory “third way” to counterbalance both the FDA and EMEA? (Oops, I meant EMA).

Stay tuned.

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NHS' Wilde Card

04/05/2010 08:12 AM |

According to a report in the Sunday Telegraph, David Cameron, the leader of the British Conservative Party, wants all patients with cancer to have broader access to all approved medicines – whether or not their use is backed by the National Institute for Health and Clinical Excellence (NICE), the NHS' rationing body.

Last month, research found that up to 20,000 lives may have been shortened by decisions taken by the NICE in the past year.

The Telegraph writes that, “Handing decisions back to patients and their doctors is a significant dismantling of the current system … In making yesterday's pledge Cameron chose local decision-making – and its inherent risks – over state control.”

Oscar Wilde quipped, “Experience is the name everyone gives to their mistakes.”

If that’s the case, then we should learn from the experience of our trans-Atlantic cousins.

The complete Telegraph article can be found here.

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Big Sky. Bad Idea.

04/02/2010 09:54 AM |

According to a report in the Helena Independent Record:

Gov. Brian Schweitzer, who last month asked the federal government to approve a “waiver” so Montana could import prescription drugs at lower cost for state-funded health plans, has not submitted any of the usual documentation that accompanies a waiver request, his administration acknowledges. Instead, the governor wrote only a letter to U.S. Health and Human Services Secretary Kathleen Sebelius, asking that her agency grant Montana a “Medicaid waiver” allowing importation of lower-cost drugs from Canada.

“We have to work through the secretary’s office,” says Anna Whiting Sorrell, director of the state Department of Public Health and Human Services. “There is not another state that has requested this. We think the governor is forging a new path.”

News must travel slowly in Montana.

There have been numerous requests for such waivers.  And they’ve all been denied – for good reason.

Let’s look at the record.

Minnesota

During pre-announced visits by Minnesota State officials, Canadian Internet pharmacies were observed engaging in dangerous practices. For example:

• One pharmacy had its pharmacists check 100 new prescriptions or 300 refill prescriptions per hour, a volume so high that here is no way to assure safety.
  
  

• One pharmacy failed to label its products and several others failed to send any patient drug information to patients receiving prescription drugs.
  
  

• Drugs requiring refrigeration were being shipped un-refrigerated with no evidence that the products would remain stable.
  
  

• One pharmacy had no policy in place for drug recalls.  Representatives of the pharmacy allegedly said that the patient could contact the pharmacy about a recall “if they wished."
  
  

• One of the Canadian internet pharmacy presidents said, “We won’t have any problems getting drugs.  We have creative ways to get them.” 
  

• The FDA launched an investigation confiscating thousands of drug shipments headed for the U.S. Some of them were headed for Minnesotans who ordered them over the state’s Web site. When opened, nearly half claimed to be of Canadian origin, but “85 percent of them were from 27 other countries including Iran, Ecuador and China. And 30 of them were counterfeit. One Minnesota resident discovered that one of his “Canadian” drugs came from Greece, and another came from Vanuatu, a small island in the South Pacific. "I never heard of the place,” he said.

According to its latest statistics, Minnesota RxConnect fills about 138 prescriptions a month. That's for the whole state -- population: 5,167,101.

Wisconsin

Modeled on the Minnesota program, the Wisconsin site hawks its promise and hides its dangers. All of the legalese buries the fact that the state doesn’t except any responsibility for the safety or effectiveness of any medicines bought on the State’s website.  For example, the State won’t even guarantee that the drugs ordered are what the customer will receive. Not only that, but the State also says that they will not accept any legal responsibility or liability should any of the drugs cause a problem.  The Governor is hiding the fact that his website puts any user into a dangerous buyer beware situation.  Here’s the exact verbiage from the Wisconsin site:

“In no event shall the State Portal or its employees be liable for any direct, indirect, incidental, special, exemplary, or consequential damages (including, but not limited to, procurement of substitute goods or services; loss of use, data, or profits; or business interruption) however caused and on any theory of liability, whether in contract, strict liability, or tort (including negligence or otherwise) arising in any way out of the use of this system, even if advised of the possibility of such damage. This disclaimer of liability applies to any damages or injury, including but not limited to those caused by any failure of performance, error, omission, interruption, deletion, defect, delay in operation or transmission, computer virus, communication line failure, theft or destruction or unauthorized access to, alteration of, or use of record, whether for breach of contract, tortious behavior, negligence or under any other cause of action.”

Illinois

Remember Wrong-Way Rod Blagojevich’s swagger over his “I-Save-RX”program? Over 19 months of operation, a grand total of 3,689 Illinois residents used the program -- which equals approximately .02% of the population.

The City Experience

Remember Springfield, MA and “the New Boston Tea Party?” Well the city of Springfield has been out of “drugs from Canada business” since August 2006.

And speaking of Boston tea parties, according to a story in the Boston Globe, “Four years after Mayor Thomas M. Menino bucked federal regulators and made Boston the biggest city nationally to offer low-cost Canadian prescription drugs to employees and retirees, the program has fizzled, never having attracted more than a few dozen participants.”

And then, of course, there are those pesky safety issues.

Attention Governor Schweitzer -- The drugs being sent to U.S. customers from Canadian internet pharmacies are not “the same drugs Canadians get.” That bit of rhetoric is just plain wrong. Canadian internet pharmacies – by their own admission – are sourcing their drugs from the European Union. And while they may say their drugs come from the United Kingdom, let’s not conveniently forget that 20% of all the medicines sold in the UK are parallel imported from other nations in the EU – like Spain, Greece, Portugal, and Lithuania.

Last month Governor Schweitzer said that Montana could buy some of the drugs directly from wholesalers in Canada or place the orders and have them delivered to pharmacies around the state, for purchase by people covered by publicly funded health plans.

Someone should refer the Governor to Bartlett's Familiar Quotations:

“Those who cannot learn from history are doomed to repeat it”

And if that familiar quote from Santayana doesn’t get the point across, here’s a related one – “Remember the Alamo.”

The Montana state slogan is “the last best place.”  Maybe so.

But not for drug importation.

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Unleavened Thoughts About the Healthcare Regime

04/02/2010 07:28 AM |

I don't want to think in terms of repeal. Rather, I would prefer to use a medical or scientific analogy in describing how to respond to the effects of the legislation.The bill itself is a virus and we the people are the host if you will. Or consider it an experiment with every American forced into participation. Either way, we will be subject to new "solutions" that will have unknown consequences and side effects.  As with any social experiment or massive program of social engineering, we will experience the end product in ways much different than promised.  (If anyone has used on-line dating services, you know what I am talking about.) 

Strategically, demanding outright repeal or defunding of health care reform sounds great to a small group. To build support for fundamental changes in what is now law will require exactly what the supporters of the current bill engaged in, nothing less and probably more:

1.    Consistent and persistent evaluation of the performance of health care delivery systems. These standards should be easily grasped by most people and communicated easliy in visual form too.   Are doctors leaving the system? Are people paying more or less for insurance? Are people any healthier?  

2.    Warning signs. The other side is hell bent on using health care reform to reduce our long term debt. Debt will rise because of spending unrelated to health care reform.To turn health care reform and by extension, every doctor and hospital, into any agent of deficit reduction first and foremost is a rationale for rationing care. And it is an immoral one at that. 

3.    An increasing reliance on the use of comparative effectiveness research to shape policy and health care coverage decisions. Increasiningly, to justify the need to avoid financial Armageddon,  policymakers will rely upon CER to help make hard choices to slow health care spending in order to avoid “financial catastrophe.” If that sounds a lot like the narrative of the climate change crowd who used self-serving and secretive studies to support policies that also would lead to a decline in economic growth in order to save the planet, you are right. The “science” of CER demonstrating that a half to a third of health care spending is wasteful  has much in common with the that of the hockey stick project about the atmosphere evaporating. It is not empirical or biological, it is speculative and has never been evaluated for it’s real impact on public health or human well-being. Should we take prescriptions that are not tested or are not based on an accurate representation of human or biological mechanisms? Yet CER is precisely that and it may be used to determine what preventive services are covered and what new benefits will qualify for reimbursement.  It is possible to opt out of government run care because of conscientious objection to CER? I hope so..

4.    Impact on innovation. Largely unnoticed, drug companies are filling up pipelines with new products.More and more of them are based on  novel targets and rely on biomarkers linked to specific pathways and small populations. The number of molecular diagnostics to help predict,  diagnose and monitor the progression of diseases or response to medicines are growing as is the business capacity to provide doctors and hospitals the ability to use this information. The progress will be incremental but it will come. The question is will future policies add to the cost and pace of progress or not?  CER is only one such challenge.  And alone it’s proponents will be left looking foolish and backwards. However changes to the FDA regulatory process can easily increase the time and cost of bringing new products to market and reduce the effective patent life of niche medicines.  Demands to have a new center for drug safety review all NDAs before they go to market and for CER studies as a condition for approval would impose huge costs on innovation and the pubic health.   Similarly, CER requirements can add more delay and uncertainty to the R&D process.    

These are substantive concerns about the new health care bill that can be  addressed through the writing of regulation and new legislation.  We intend to track these issues as we have in the past.   I don’t care if someone wants to call this approach repeal or reform or a do-over.  I would like to think of restoring and improving the health of the system and all Americans.

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Sunshine Supermen (and women)

04/01/2010 02:13 PM |

From the Pink Sheet:

Pfizer is the fifth pharma company to post its payments to healthcare professionals but the first to include payments to principal investigators and institutions for conducting clinical trials.

The company posted the information on March 31, announcing that it paid a total of $35 million to 4,500 health care professionals for speaking, consulting and research services. The figure also includes meals and travel reimbursement. Of this sum, approximately $15.3 million went to research organizations for new clinical trials initiated after July 1, 2009, and for ongoing or new research between July 1 and December 31, 2009.

Pfizer said the clinical trial payments cover participant recruitment, coordinating and conducting the clinical trails and completing compliance activities to ensure regulatory requirements are met.

Pfizer was required to post all payments or transfers of value to physicians, including those relating to research, under a corporate integrity agreement with HHS' Office of Inspector General. The CIA accompanied Pfizer's $2.3 billion settlement with the Department of Justice to resolve allegations of off-label marketing of four drugs and kickbacks to healthcare providers involving nine other drugs.

The company's payment report also specifies non-cash payments, such as for meals or educations items worth $25 or more and totaling $500 or more during the six-month period. Pfizer is the first company to report these non-cash expenditures.

Lilly was the first to post payments to healthcare providers for consulting and speaking engagements, followed by Merck, GlaxoSmithKline and Cephalon. Cephalon was the first to do so under a CIA, which required it to report figures for a full year. The other three posted data for a single quarter.

Lilly's Top Speakers Earn $150,000 In Six Months

Cephalon has been the only company to clearly designate its highest-paid doctors, breaking out payments in $10,000 increments as required under its CIA. Pfizer's CIA gave it the option of listing the payments in $10,000 increments or in the actual amount paid and the company chose to report individual sums for 4,856 entities.

A Pfizer spokesperson said nine individuals received $50,000 to $150,000 and the remainder received less than $50,000. The company set a cap of $50,000 per year for individual speakers. But those with particular expertise can be cleared to receive a maximum of $150,000.

By comparison, Cephalon paid three doctors more than $140,000 in speaking fees during the year. And in a one quarter period GlaxoSmithKline's top speaker earned $99,375, Lilly's highest paid physician received $70,050 and Merck's top earner received $22,600.

Companies are now required to post payments to healthcare professionals under a provision included in the health care reform legislation signed into law last week. The law requires reporting of payments for consulting and speaking engagements, the value of certain meals and non-cash items like educational materials.

Pfizer said it will post its next report on March 31, 2011, which will include a full year of data for 2010 and include the value of all financial transactions, regardless of value. The company will post payment reports quarterly beginning in June 2011.

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Janet Woodcock and the King of Siam

03/31/2010 11:17 AM |

To repeat that quote from Theodore Roosevelt, “When you’re in a hole, stop digging.”

Note to Amphastar Pharmaceuticals – stop digging.

Back in August Amphastar was so unsatisfied with the way the FDA was dealing with their file for generic Lovenox, they decided to claim unfair treatment at the hands of CDER Director Dr. Janet Woodcock.

Amphastar claimed that its rival, Momenta, had a "leg up" and was getting "special access."  And yet both companies were in the same place in the regulatory process and both companies are being asked for the same data sets.  And this is unfair why?

According to Amphastar it's unfair because CDER Director, Dr. Janet Woodcock co-authored a paper with one of Momenta's founders, MIT biological engineering professor Ram Sasisekharan, on how the FDA taskforce (on which they both served) identified and contained the cause of contaminated Chinese heparin imports.

Well, to nobody’s surprise, the inspector general of the Department of Health and Human Services has cleared Janet of all allegations of conflict of interest.

Not satisfied to acknowledge a boner of monumental proportions, Amphastar's general counsel, Jason Shandell, said that the FDA narrowly tailored its review to legal issues. "We never asserted she got any money—that would be illegal. Our focus was on the appearance of impropriety and its impact on the approval system.”

Remove foot from mouth, right?

Um – not so fast.  According to Politico: “For more than two months in late 2008, private investigators working for a drug company gathered information on a high-ranking official at the Food and Drug Administration – unearthing details about her husband, two daughters, and in-laws, and re-tracing her steps on a business trip she took to Thailand.

The drug company, Amphastar Pharmaceuticals Inc., paid more than $100,000 to Kroll, the New York-based private investigative firm, to uncover the information about Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, who oversees the agency’s new-drug approvals.”

And it gets worse. At one point, the investigators hired a freelance reporter to file Freedom of Information Act requests, using her status as a journalist to request Woodcock’s emails, phone records, voicemails, calendar and expense reports, among other documents – without mentioning that she was being paid for her efforts by a private investigative firm. Oops.

And worse.

According to Politico, “On behalf of the drug company Kroll also investigated a second FDA official – Moheb Nasr, director of the FDA’s Office of New Drug Quality Assessment, creating a file on him that included his birth date, the price he paid for his home, and details of his education and professional background.”

And here’s a lesson to all of you drugwonks out there – do NOT let your lawyer act as spokesperson.

 “I feel like as a citizen you have a right to question your government and a right to look at public information,” said Amphastar’s general counsel, Jason Shandell. “There was no impropriety here.”

So now the conversation has moved Amphastar’s boner.  Solid PR.

And to make things even worse for Amphastar, they’re now squarely in the crosshairs of Senator Max Baucus (D, MT), who said it was “an outrage,” and has demanded that Kroll tell him how often private detectives target public officials.

“Pharmaceutical companies should be focusing on getting their drugs approved based on health research and science rather than wasting their resources hiring private investigators to snoop around the lives of FDA regulators and their families,” said the Senator.

An apology is in order.  Read More & Comment...

Hear Henry Roar

03/30/2010 07:30 PM |

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Repeal and Replace?

03/30/2010 06:08 PM |

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Pryor To Voting

03/30/2010 05:51 PM |

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Take two aspirin and call me in November

03/30/2010 05:43 PM |

Starting in January, you will no longer be able to tap your HSA to cover aspirin, vitamins and other over-the-counter medications, unless they are prescribed by a doctor. 

Patient choice:  strike one.
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Berwick and the Angry Itch

03/29/2010 08:51 AM |

Donald Berwick as CMS Administrator? By all accounts a good choice. But what does it mean for the upcoming battle royale over comparative effectiveness and patient choice?

According to Robert Pear, “Dr. Berwick could help shield the White House from Republican charges that Mr. Obama’s policies would lead to the rationing of care or even a government takeover.”

This conditional shield comes courtesy of remarks Dr. Berwick made last December. Speaking at the annual conference of the Institute for Healthcare Improvement (which he heads), he challenged the audience thus, “Over the next three years, reduce the total resource consumption of your health care system, no matter where you start, by 10%. Do that without a single instance of harm, without rationing effective care, without excluding needed services for any population you serve.”

Okay – sounds good and we should give Dr. Berwick the benefit of the doubt that when he says he’s against the rationing of “effective care,” he means effective care that’s defined by an MD in the field – and not Uncle Sam, MD inside the Beltway.

But vigilance is required, especially now that it’s precisely Uncle Sam who is going to be paying more and more of the bills for this “effective care.” And vigilance is even more important considering that AHRQ (now the nation’s leading practitioner of comparative effectiveness studies) plans to hire a PR firm to help create a “publicity center” for comparative effectiveness reports and materials.

If you recall the debacle that followed the government’s “publicity center” efforts behind CATIE and ALLHAT – you know why vigilance is the order of the day.

The “angry itch” is the desire for payers (both public and private) to opt for the least expensive treatment rather than the one that’s best for the patient. An itch that’s often penny-wise and pound-foolish.  An itch that’s dangerous when scratched.

Let’s all wish Dr. Berwick great success.  He has big shoes to fill and a tough road ahead.

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Head 'em off at the (innovation) pass

03/26/2010 07:03 AM |

The UK has launched a pilot of its "Innovation Pass" process, which will provide £25 million in funding for medicines that treat very rare diseases but are not evaluated at launch by the National Institute for health and Clinical Excellence (NICE).

Innovation passes were first proposed in the UK's office for life sciences' Life Sciences Blueprint, issued last year. The government has run a public consultation on the proposals since then.

There’s a maximum spending cap of only £8 million per year for each individual product – and uncertainty over long-term funding. The pilot is to run for three years, but government funding of £25 million has only been arranged for the first year.

Products included in the pilot Innovation Pass scheme will automatically be appraised by NICE after the end of three years, raising the suspicions that they could be rejected for use in the UK national health service (NHS) at that stage.

NICE giveth and NICE taketh away since it will set up and run an advisory committee that will select products based on defined criteria. These criteria include the medicine being a significant medical innovation (acting at a new target receptor, for example), it should satisfy an unmet clinical need, and is expected to have a substantial impact. Additional studies to gain further clinical data should be planned.

The government will pay an amount to the pharmaceutical company for supplying the medicine based on a price-volume agreement (the number of patients multiplied by the price), rather than paying for each dose of drug dispensed. This is to ensure a financial return for the company. Products would normally be submitted for consideration at around the same time as they are filed for marketing approval.

BUT … the sum asked for by the company will be judged to be reasonable or not by a governmental/NHS panel that will look at the cost of therapeutically similar medicines, the actual cost of the medicine in other European countries, and the cost of its research and manufacture.

This judgment on whether the cost is reasonable or not will then be passed to NICE's advisory committee, which will produce a list of drugs for funding, which will be approved by government ministers.

Sounds familiar.

NICE work … if you can get it.

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A Goodman is hard to find

03/25/2010 08:54 AM |

FDA Chief Scientist Jesse Goodman to Representative Rosa DeLauro (D/CT and Chairwoman of the Agricultural Appropriations Subcommittee), "I think what FDA really needs is a 5- to 10-year building effort/re-building effort. And it's not just rebuilding to what was. I think it's being a part of building the science of the future."

Bravo.  By all means. Rather than look backwards to “the good old days” (whatever that means) let’s improve and move forward. It’s not rocket science – but it’s good to hear the agency’s Chief Scientist say it. 

And change starts from within.  According to Goodman, "What I want to do is begin to use the resources we have and the leadership we have to encourage and identify and free-up some of the time of our promising junior and mid-level people to beef up their education. Because if we just do it as leaders of the center or agencies, that doesn't have all the transformational power."

Absolutely right.  When I served at the FDA (along with Jesse), one of the most valuable lessons I learned was that dictates from “on high” don’t get the job done.  Real change happens because all levels of the agency understand and embrace the philosophy of those changes. Change may begin at the top – but success or failure is determined by the agency’s 11,000+ career professionals.

Change is never easy but, as W. Edwards Deming commented, "Change is not required.  Survival is not mandatory."

Goodman: “"It's very challenging. It's almost like taking the current state of the agency from sort of always swimming to keep our heads just above the water to something that is a truly outstanding scientific partner and really has the power and relationships it needs. And by power I don't mean power over people, but the mental and scientific tools to have the ability to make decisions. So it's a process and it's going to take a while and we need to get the best and the brightest."

Now maybe Representative DeLauro will finally embrace the Reagan/Udall Foundation.

We’ll see.

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"Gee I Hope This Works"

03/24/2010 12:04 PM |

Excellent article by the Washington Post's Ruth Marcus on the need to humble in our predictions about the impact (negative and positive) of healthcare reform and to be a bit more precise in our analysis going forward.  Specifically, we should be asking: Will this improve health? Make care more affordable and convenient? Extend life? Reduce health disparities? Accelerate the seach for cures?  I think her article provides a template for anyone wishing to gauge the value of health care reform going forward. 

- 24 March 2010, The Washington Post  (By Ruth Marcus)

The conventions of political pontification do not allow for admissions of uncertainty or ambivalence. Thus, Sunday night's House debate on health care featured bombastic declarations from both sides about the impending disaster (Republicans) or nirvana (Democrats) being ushered in.
In fact, the occasion called for more humility than hyperbole, however unlikely that may have been given the setting. If I were a member of Congress, my floor speech before casting a yes vote would have boiled down to:

Gee, I hope this works.

One of the astonishing aspects of the health-care debate is how little is actually known about the implications of a change this far-reaching. Everyone has a theory, and a model to match, but even some of the most fundamental questions remain the subject of debate.

On the most basic of all -- does having health insurance lead to better health? -- the evidence is solid but not unanimous. The Institute of Medicine , reviewing the literature in 2009, found that "the body of evidence on the health consequences of health insurance is stronger than ever before. . . . Simply stated: Health insurance coverage matters ."

But a study that same year by Richard Kronick, a former health-care adviser to President Bill Clinton, found "little evidence to suggest that extending insurance coverage to all adults would have a large effect on the number of deaths in the United States ." Kronick's study has been criticized because it did not adjust for the fact that those in poor health are more likely to seek insurance. But the disagreement underscores the difficulty of knowing precisely what changes are in store.

To take another example, one common assertion has been that the uninsured end up getting health care -- just more expensive health care, in emergency rooms and when conditions have worsened, with the costs passed on to the rest of the population. The notion that the tab is being picked up one way or another makes intuitive sense.

A new National Bureau of Economic Research paper by Michael Anderson, Carlos Dobkin and Tal Gross questions this assumption. The researchers examined health-care consumption by 19-year-olds who had just been dropped from their parents' coverage. They found that not having insurance resulted in a 40 percent reduction in emergency room visits -- "contradicting the conventional wisdom that the uninsured are more likely to visit" the emergency room and a 61 percent drop in hospital admissions.

"Overall, these results suggest that an expansion in health insurance coverage would substantially increase the amount of care that currently uninsured individuals receive and require an increase in net expenditures," the authors write. Emergency room visits could increase by 13 million annually, and hospital admissions by 3.8 million, they project.

So prudence is in order when tinkering with such an interconnected system and when making confident predictions about the effects of reform, for good or ill. Will younger adults, who account for about half the population of uninsured non-elderly adults, sign up for coverage -- or will they pay the fine instead? How will that decision affect premium levels and the adequacy of federal subsidies?

Will the expansion of coverage create a shortage of health-care providers and result in higher prices, or will, for example, higher Medicaid payments for primary-care doctors stem an exodus of doctors from the program? Will employers add coverage because workers facing the mandate to obtain insurance will press for it, or will they drop it because it will be cheaper to pay the penalty and let employees fend for themselves?

Will increased coverage of preventive care save money because diseases will be caught earlier -- or will the added cost of widespread screening exceed the economic benefits? The Congressional Budget Office has concluded that, "for most preventive services, expanded utilization leads to higher, not lower, medical spending overall ."

The legislation is a risk worth taking. Millions of Americans are without insurance, a national scandal that should have been addressed long ago. Rising health-care costs threaten the nation's fiscal security, and the new law holds the promise of beginning to stem the increases.

The status quo is unsustainable. A new study by the Urban Institute shows how, without reform, the numbers of the uninsured will rise, employers will continue to drop coverage and premiums will climb.

Still, for those who express cocky certitude about how this is going to turn out, the best prescription is a generous dose of caution
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