Sooner is Better

02/02/2009 12:31 PM |

"The president hopes in the next few days to announce a pick for commissioner at FDA," White House spokesman Robert Gibbs told a press briefing.  Read More & Comment...

Non-Interference: Daschle was for it before he was ...

02/02/2009 12:23 PM |

The attempts to revoke the Non-Interference Clause have begun. Representatives Marion Berry (D-Ark.) and Jan Schakowsky (D-Ill.) have introduced The Medicare Prescription Drug Savings and Choice Act (HR. 684), with companion legislation in the Senate soon to come from Senator Richard Durbin (D-Ill.) as S. 330.

The same members introduced similar bills in 2005 and 2007. Bad idea then.  Bad idea today.  At least they didn’t try to bury it in the stimulus package.

In addition to gutting the Non-Interference Clause (originally authored, it should be remembered – by Senators Kennedy and … Daschle) HR. 684 would create a federal drug plan option to compete with privately offered Part D plans.

"We have many reasons to be optimistic about the passage of this legislation," Schakowsky said. "It is very much in line with [President Barack Obama's] overall plan in that it gives people an option of a public plan or sticking with a private plan."

When combined with the "Federal Coordinating Council for Comparative Effectiveness Research" (a $1.1 billion earmark in the stimulus package that won’t create a single job on “Main Street”), there's the real potential for Uncle Sam to dictate that Part D prices be tied to prices in other countries -- a kind of Medicare reference price and a big step towards overall price controls.

And price controls = choice controls.

This new “Federal Council” (under the Agency for Healthcare Research and Quality and with zero patient group, industry or academic representation – it’s 100% government) would be responsible for "assessing the clinical benefit of covered Part D drugs and making recommendations to the secretary on which drugs should be included in the formulary."

In addition, an advisory committee can request AHRQ conduct clinical effectiveness and comparative effectiveness studies on drugs.

That means bureaucrats in Washington will be able to tell doctors how to practice medicine by dictating formulary options.

Wither competition? The Bill sponsors expect that if the bill becomes law, it would ultimately limit the number of plans participating in Part D, as private plans would drop out from competing with a publicly run plan.

And to that point, a few things worthy of consideration:

"It is not obvious that allowing the government to negotiate with pharmaceutical companies will lead to lower prices than those achieved by private drug plans. Private plans like Kaiser or United are able to negotiate deep discounts with pharmaceutical companies precisely because of the plans' ability to say no – the ability to include some drugs and to exclude others, allowing the market to judge the resulting formulary. On the other hand, when the government negotiates, its hands are tied because there are few drugs it can exclude without facing political backlash from doctors and the Medicare population, a very influential group of voters. Neither economic theory nor historical experience suggests government price negotiation will achieve lower drug prices. Congressional Democrats need to be careful in making the logical leap from market share to bargaining power. Empowering the government to negotiate with pharmaceutical companies is not necessarily equivalent to achieving lower drug prices. In fact, neither economic theory nor historical experience suggests that will be the outcome. Members should think carefully before jumping on the bandwagon – this promise may bring just the opposite of what was ordered."

Stanford Business School's Alain Enthoven and Kyna Fong

"Both the non-partisan Congressional Budget Office and Medicare actuaries have said they doubt the government could negotiate lower costs than the private sector. The theory behind Part D is that market forces and competition among drug plans, overseen by government, can achieve better results than a government-run program. The multitude of plans allows seniors to pick one that best meets their needs. Government price negotiation could leave people without drugs that manufacturers decide aren't sufficiently profitable under the plan. Medicare recipients account for half of all drug prescriptions. With that kind of clout, government might try to dictate prices, not just negotiate them. This could leave people without drugs that manufacturers decide aren't sufficiently profitable under the plan. The VA plan illustrates the point. It offers 1,300 drugs, compared with 4,300 available under Part D, prompting more than one-third of retired veterans to enroll in Medicare drug plans."

"Our View On Medicare Part D: Put Brakes On Drug Plan 'Fix,'" USA Today, 11/13/06

The bottom line here is that Part D is a tremendous success – due in no small part to the Non-Interference Clause.  Consider:

* The projected cost for Medicare Part D is $117 billion lower over the next decade than experts estimated just last summer. This means that over the 10-year period from 2008 to 2017, the estimated $915 billion cost of Part D fell to $798 billion.

Why?  Marketplace competition.

* And, according to a study published in the Annals of Internal Medicine, the Medicare drug benefit led to a 17 percent decrease in out-of-pocket expenses, or $9 a month, for seniors who enrolled in the new Medicare Part D benefit in 2006, the first full year prescription coverage became available in the federal health insurance program for the elderly and disabled.

* And the savings amounted to an extra 14 days of medicine for those who signed up, or a 19 percent increase in prescription usage.

Can Part D be made even better? Absolutely. But this is good news worth sharing -- and not because it helps any particular partisan political agenda but because it means that more Americans -- tens of millions of more Americans -- are getting access to the medicines (largely chronic medicines) that will help them live healthier lives. And this, in no small measure, significantly reduces more drastic medical interventions -- which in turn reduces our overall national health care spending.

We shouldn’t interfere with success.

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The Pluck Starts Here

01/30/2009 06:04 PM |

According to Senator Ben Nelson (D-NE), it's unclear whether President Obama's $819 billion economic stimulus bill will win enough support to pass in the Senate. "I don't even know how many Democrats will vote for it, as it stands today," he told FOX News.

Seems like the upper house is unhappy that the bill, passed by the other house on Wednesday, contains billions of dollars for programs that arguably won't spark much job growth. Senator Nelson wants to pluck out what he says are extraneous projects in the stimulus bill to pay for the amendment.

How about plucking out the “sneaking socialism of healthcare.” Specifically  the $1.1 billion for a "Federal Coordinating Council for Comparative Effectiveness Research."  Not only is this expense a slippery slope towards a NICE-like body for the U.S. – it wouldn’t create a single job for "Main Street."

Here’s a suggestion – give that money to the FDA to hire more scientists, reviewers, and inspectors, update their woeful IT infrastructure, and fund the agency’s Critical Path program.

That’s what I’d call a real stimulus package!

  Read More & Comment...

Economic Stimulus Package to Promote CER … Or Mandate it?

01/30/2009 04:07 PM |

  Read More & Comment...

Peanuts for Counterfeit Actions

01/30/2009 03:33 PM |

Well that’s what “consensus” gets you.

The World Health Organization has caved in to pressure by the developing countries (specifically India and Brazil), and dropped their resolution on counterfeit drugs. This non-decision is being portrayed as a victory for the developing world’s generic drug industry -- which has long opposed the WHO attempt.  Their objection is that, under the proposed new definition, their products could be defined as counterfeits.

The current definition of WHO says counterfeit drugs are 'medicines which are deliberately and fraudulently mislabeled with respect to identity or source.

The proposed definition proposed removes the clause “deliberately and fraudulently” and replaces it with “a medical product is counterfeit when there is a false representation in relation to its identity, history, or source.”  It also says that ‘this applies to the product, its container, packaging or other labeling information.”

What are really at play here are the issues of semantics and transparency. What’s the difference between a product that is knowingly “substandard” versus one that is “counterfeit?”  If a company deliberately fails to comply with manufacturing quality standards – what do you call the product?

For starters, you call it dangerous.

Another issue recently brought to public attention via an Associated Press story (see link here) is the manufacture of medicines in India destined for First World markets that result in the poisoning of the local population because of a lack of environmentally safe manufacturing processes.

If it’s wrong for Americans to buy products produced by slave labor, isn’t it just as wrong to purchase medicines from companies who have total disregard for the health and well-being of local citizenry?

As America focuses on peanuts as a metaphor for regulatory reform, perhaps it’s time for the global community to tie counterfeiting to corporate responsibility.

  Read More & Comment...

FDA Commish Rumor du Jour: Peggy Hamburg

01/30/2009 01:45 AM |

Whispers are that there is "a woman" in the mix and that it's Peggy Hamburg.

Here's her bio:

Margaret A. Hamburg, MD, Senior Scientist, Global Health and Security Initiative, NTI

One of the youngest people ever elected to the Institute of Medicine of the National Academy of Sciences, Dr. Margaret “Peggy” Hamburg is a highly regarded expert in community health and bio-defense, including preparedness for nuclear, biological, and chemical threats.  She currently serves as Senior Scientist for the Global Health and Security Initiative of the Nuclear Threat Initiative, a foundation dedicated to reducing the threat to public safety from nuclear, chemical, and biological weapons.  A graduate of Radcliffe College, she earned her M.D. from Harvard Medical School, and completed her training at the New York Hospital/Cornell University Medical Center.

From 1997 to 2001, Hamburg held the position of Assistant Secretary for Planning and Evaluation, U.S. Department of Health and Human Services (HHS), serving as principal policy advisor to Secretary of Health and Human Services Donna Shalala.  From 1991 to 1997, she served as New York City Health Commissioner, a position in which she designed and implemented an internationally recognized tuberculosis control program that produced dramatic declines in tuberculosis cases, and created the first public health bio-terrorism preparedness program in the nation.  Between 1986 and 1990, she held a variety of positions within HHS, including Special Assistant to the Director, Office of Disease Prevention and Health Promotion; and Special Assistant to the Director, and later Assistant Director, of the National Institute of Allergy & Infectious Diseases at the National Institutes of Health.

A member of the Harvard College Board of Overseers and the Boards of Trustees of Rockefeller University and the Rockefeller Foundation, Hamburg is also a distinguished senior fellow with the Center for Strategic and International Studies, and a fellow of the American Association of the Advancement of Science.  She holds membership in the New York Academy of Medicine, and the Council on Foreign Relations and serves on the board of Henry Schein Company.  She has served on the boards of other organizations, including the New York City Health and Hospitals Corporation, the Nathan Cummings Foundation, the Primary Care Development Corporation, and the Board of Scientific Counselors for the National Center for Infectious Diseases of the Centers for Disease Control and Prevention.

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Agent Orange (Book)

01/29/2009 02:31 PM |

According to a new Harris poll, 81% of Americans say they prefer generics to brand-name drugs.

That’s good news.  It means the message that FDA-approved generic drugs are safe and effective is finally getting some traction.  And the cost savings are significant.

But, as usual, there are those who would use this news for their own selfish purposes.  In this case it’s the Generic Pharmaceutical Association (GPhA).

Earlier this month, the GPhA applauded the introduction of HR 573, a bill that would prohibit the marketing of authorized generics during the 180-day generic exclusivity period. Kathleen Jaeger, chief executive of the GPhA, sees the proposed legislation as a way to close a “loophole” in the 1984 Hatch-Waxman Act that allows innovator life science companies “to delay generic competition by discouraging generic companies from challenging weak and potentially unenforceable patents." She praised the bill’s sponsor, Republican Jo Ann Emerson, and colleagues for “working to close this loophole for the benefit of consumers struggling with health care costs during these difficult economic times."

Well, if we’re all in this to help consumers control costs – then this bill would achieve precisely the opposite.

If the GPhA gets its way, the category of medicines known as “authorized generics” (also referred to as “branded generics”) will vanish — and drug prices for millions of Americans could go up by as much as 17%. (This calculation is based on a comparison of what consumers actually spent on generics during the 180-day exclusivity period to what they would have spent to purchase the same quantity of generics at higher prices in the absence of a branded generic launch.)
 
Historical pricing data shows that brand companies launch their generics at a 50 percent discount off retail price compared to a 30 percent discount experienced when a generic drug has no competition. If HR 573 passes, consumers and taxpayers over the next two years would realize about $8 billion instead of $13 billion in savings.  Cui bono? The missing $5 billion will line the pockets of a handful of generics companies.  That’s quite a cui bonus. This end-run around Hatch-Waxman is an extended index finger to the FDA, the FTC and judicial precedent. (A Federal Appeals Court made it clear that Hatch-Waxman allows for authorized generics.)

Over the next few years about $60 billion in brand drugs will become generic; $30 billion of that will be sold without competition for 180 days if Ms. Jaeger and Representative Emerson get their way.

No wonder this “modest proposal” is being greedily embraced by the generics industry and Big Pharma bashers. And greedy is hardly hyperbole since profits on generic medicines exceed 45% -- even when there is a competitive branded generic on the market.

We all call the existing legislation by its inside-the-Beltway designation, “Hatch-Waxman” – but let’s not forget that the full name of the law that brought the generic industry into being is the Drug Price Competition & Patent Term Restoration Act -- not the Generic Drug Company Guaranteed Profit Act. When the media and generic drug lobbyists conflate suspicious stalling tactics with legal and consumer-friendly market actions, neither the truth nor the public health are served.

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Ends, Means, Medical Devices and Felonies

01/28/2009 04:32 PM |

You mean the ends doesn’t justify the means?

According to an article in today’s edition of the New York Times, “Nine dissident scientists at the Food and Drug Administration who say they were forced to approve high-risk medical devices sent a letter to President Obama on Monday stating that agency officials might have made them the targets of a criminal investigation into their complaints.”

The complete New York Times story can be found here.  

If the FDA has undertaken such an investigation (and the agency will not confirm or deny), the reason is that these nefarious nine leaked confidential agency documents to the media.  That’s a felony.

The Nefarious Nine are unhappy that their complaints about device approvals aren’t being addressed with greater alacrity.  So, in their righteous indignation, they decided that their purity placed them above the law.

Unfortunately, not only will their behavior not speed up the agency’s investigation of their brief – it may very well slow it down.

Breaking the law is the wrong path to better regulatory oversight of medical devices. The ends doesn’t justify the means.  

  Read More & Comment...

Kennedy on Cost Effectiveness

01/28/2009 11:32 AM |

Ian Kennedy that is.

According to a Reuter’s report, “The healthcare spending watchdog NICE said it was reviewing how it values new technologies, a week after an industry report called for such a move.” NICE's announcement followed an industry report published last week calling for an enquiry to assess the long-term impact of NICE on the cost and the uptake of drugs, along with a series of tax breaks and other measures to support the crisis-hit biotechnology industry

The study (due this July) will be led by Ian Kennedy, Emeritus Professor of Health Law, Ethics and Policy at University College London.  He’s an academic lawyer who, for the past few decades, has lectured on the ethics of medicine.  A long-standing member of the General Medical Council, he is a former president of the Centre of Medical Laws and Ethics, which he founded in 1978.

On a releated note, the Pink Sheet reports that, “Third-party payer policies appear to have an effect on clinical trial participation, but the impact "is difficult" to quantify, according to a draft report by Duke Evidence-Based Practice Center researchers prepared for the Agency for Healthcare Research and Quality.”

The draft report, "Horizon Scan: To What Extent Do Changes In Third-Party Payment Affect Clinical Trials and the Evidence Base?" was posted on AHRQ's technology assessment Web site. Comments on the draft are due Jan. 23. The topic is of interest because there is no consensus on financial responsibility for clinical trial-related health care costs, resulting in uneven reimbursement policies. A lack of adequate coverage for those costs may discourage patients from participating in trials, reducing the body of available clinical evidence.

A 2000 survey of nearly 6,000 cancer patients who were aware of clinical trial availability revealed that about 75 percent chose not to participate, with 20 percent of that group citing uncertainty about insurance coverage as the reason for declining participation. The top responses given for not entering into a clinical trial were: standard treatment was believed to be better (37 percent) and fear of receiving a placebo (31 percent).

Yet another unintended consequence of cost-based versus patient-centric reimbursement policies.

  Read More & Comment...

Partial Sunshine With No Sign of Clearing

01/27/2009 02:14 PM |

What’s better than 1 FDA?  How about 50.

That would be the result of language inserted into the 2009 version of the Kohl/Grassley Physician Payments Sunshine Act. 

New language in the bill proposes to give states authority to require disclosure or the reporting of information not required by the FDA.

Result:  50 state FDAs … and chaos.

Chaos for drug companies, certainly.  But even worse -- chaos for patients and physicians.  Imagine a doctor in New York getting different information on a medicine than a doctor in Michigan.  Imagine a patient in Vermont getting different treatment than a patient in Arizona because their physicians weren’t sure who to listen to or what directions to follow.

Talk about emasculating the drug label.

And who should pharmaceutical companies go to with data and questions?  50 state health commissioners who may or may not have ever even looked at clinical trial data?  Are there any state health commissioners who hold a technical candle to even a mid-grade FDA reviewer?  Is there a state in the Union that employs a biostatistician?  And how would states pay for these new professional employees?  Likely source is lucre from lawsuits.  And it's even more likely these professional services would be provided by outside “experts" --  the same folks who earn a nice living from being “expert” witnesses.

Speaking of expert witnesses, the Physician Payments Sunshine Act makes no provision for reporting fees earned for such activities.

That ain’t sunshine.  

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Sweden beyond the Welfare State

01/27/2009 10:18 AM |

As I mentioned in my presentation in Washington last October (“A Transatlantic Malaise”), politicians everywhere would do well to get the facts before referring to the Swedish model. As state provision of welfare services started earlier in Sweden, it also started creaking earlier, and alternatives emerged before relative to comparable countries.

New evidence of a healthy change in public opinion may be found in a survey released this week by our colleagues at Timbro. A positive result of the breakdown of the Swedish monopolistic health care system is that the young generation (especially age 16-29) looks with favour on private options in social services.

Try this for size:

- three out of ten people think that private financing may need to increase for health and elderly care
- about half of this population consider this a positive development, and the younger are the most positive: 55 per cent of people age 16-29, and 49 per cent of the age group 30-44 think this "rather or very good".

Perhaps more surprising is the figure for the population age 60 and above: 48 per cent (the same as for the overall population) of the oldest Swedes are rather or very positive (as a proportion of those who replied that private provision of welfare services will increase in at least one area).

Last but not least, 51 per cent also think it largely positive if citizens were able to access private insurance for welfare services, beyond what the state provides. (There was an ominous attempt in 2008 by the supposedly centre-right government to abolish this option.) And again, the strongest supporters are found among the 16-29 year-olds.

There is room for optimism in the home country of cradle-to-grave socialism.


  Read More & Comment...

Stupak P.I.

01/27/2009 01:59 AM |

Stupak food safety investigation expanded to include Salmonella in peanut butter

WASHINGTON - U.S. Congressman Bart Stupak (D-Menominee), chairman of the House energy and commerce subcommittee on oversight and investigations, and full Committee Chairman Henry Waxman (D-California), yesterday expanded the subcommittee’s food safety investigation to include the recent salmonella outbreak attributed to peanut butter.

The subcommittee on oversight and investigations held 16 hearings on food and drug safety over the past two years, including two involving a 2007 outbreak of salmonella from peanut butter.

Stupak issued the following statement:

“My subcommittee’s two-year investigation into the safety of our nation’s food supply essentially began when peanut butter contaminated with salmonella was discovered in February 2007,” Stupak said. “Today our investigation has been expanded to include the latest outbreak involving salmonella in peanut butter, which has sickened at least 448 people nationwide including 25 in Michigan.‬‪

“We have held 16 hearings over the past two years on food and drug safety, and have drafted legislation to provide the FDA the regulatory and financial tools to protect the American people. Food safety will remain a top priority for the Subcommittee and I remain committed to advancing legislation to address the weaknesses that allow 76 million Americans to be sickened by food borne illness every year.”

Good thing  he is on the case.  And good thing he has requested more money for the FDA in this latest disgorgement of tax dollars.

By the way salmonella happens all the time.  It's not the result of FDA oversight or lack thereof now or in the past...The idea that food borne illneses be prevented by putting more FDA cops in facilities is absurd.  And in terms of value per dollar spent how about investing in the Critical Path to pursue personalized medicine instead of spreading fear about peanut butter. 

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Dr. Offit Under Siege By Anti-Vaccine Zealots

01/26/2009 07:33 PM |

The New York Times reports that Dr. Paul Offit, the author of “Autism’s False Prophets,” is facing death threats for writing a book discrediting the supposed link between vaccines and autism.
  Read More & Comment...

Pfizer, Wyeth and "P-Value"

01/26/2009 01:15 PM |

No doubt there is much yet to be written about the Pfizer/Wyeth deal.  But going forward, it's good to see that the key word of the day isn't "profits" or "patents" or "promotion" or "PhRMA" (which will now have one less dues-paying member) -- but "patients."

Here's the verbiage straight from the press materials:

For Patients Today – Broad Range of Health Care Solutions and Treatments: The new company will offer customers and patients a broad range of products for every stage of life.  Unique and valuable insights will be gleaned from a portfolio that spans wellness and preventive care, such as vitamins and vaccines, as well as therapies for a wide range of illnesses and diseases, such as Alzheimer’s disease and cancer.  We will leverage research across our portfolio and input from an extensive network of customer, physician and stakeholder relationships to accelerate, improve and expand the health solutions and treatments we offer.

For Patients Tomorrow – Robust Discovery and Development Program: The new company will have more resources to invest in research and development than any other biopharmaceutical company.  We will have access to all leading scientific technology platforms – enhancing the opportunity to produce significant breakthroughs in key disease areas.  As a result, we will be better able to help patients and invest in pursuing multiple avenues to address a wide range of unmet health needs.

At All Times – A Patient-Centric Business: We will operate small, distinct business units tailored to patients and customers that also benefit from being part of a premier global organization.  Each business unit will oversee product development from early stage research to clinical trials to commercialization.  This approach will allow for more customer input into the development process, rapid decision making and a better use of resources.  As a result, we will have the ability to invest in long-term opportunities while optimizing near-term patient access to existing products.

"Patients Today."  "Patients Tomorrow."  "Patient-Centric."  That's what I call real p-value.

The words are right.  Now let's see what happens. 

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California Dreamin' About Pre-emption

01/26/2009 03:14 AM |

The California Supreme Court is allowing a lawsuit to go ahead against Wyeth (soon to be Pfizer) for a drug that it invented but does not make.  

That is sort of like suing the Wright Brothers for every airplane crash. 

Here is a blog that puts this awful decision in perspective. As the blog notes:  "55 years of product liability law out the window." 

And that's just the beginning.   Ultimately, it's all about dinging the drug companies on labeling.
  Read More & Comment...

Accuracy in Media

01/24/2009 03:47 AM |

The other day Bob Grant of The Scientist interviewed me on who might be the next FDA commissioner.  He mostly got it right. 

There is one bit of reportage that does, however, need to be corrected.  Here’s what was written:

“Peter Pitts, president of the Center for Medicine in the Public Interest (CMPI) and former FDA staffer, confirmed those rumors, both on DrugWonks.com -- CMPI's blog -- and when I called him yesterday. Pitts, who has advised the Obama transition team, said that Sharfstein and Califf were the only two names receiving serious consideration.”

Almost right.  What I told Grant was that I thought the two most serious candidates for the job are Sharfstein and Califf.  Whether or not the Obama team is considering others is above my pay grade.

To view the complete interview in The Scientist, see here.

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Wither Clinical Excellence?

01/23/2009 12:01 PM |

A fair and consistent process is needed for dealing with absence of evidence

In England and Wales the National Institute for Health and Clinical Excellence (NICE) issues guidance on the appropriate use of medicines that is based on an assessment of evidence submitted by the manufacturer. The scope of the assessment depends on whether the appraisal concerned is a single technology appraisal or a multiple technology appraisal. NICE recently terminated four single technology appraisals of cancer drugs because it did not receive submissions from drug companies that met the institute’s specification of evidence (1).As a result, NICE was unable to recommend the use of the products for the clinical indications for which they were licensed, but it stated that, after considering the reasons for the lack of guidance, NHS organisations could still use the drugs. In contrast, the Scottish Medicines Consortium approves medicines only if drug companies submit evidence, so non-submission results in a recommendation not to use the drugs concerned in the Scottish NHS (2).

This situation is one consequence of NICE’s switch to undertaking more single technology appraisals, the main advantage of which is a shorter time between the drug’s marketing approval and a preliminary decision. However, in shortening the time allowed for the appraisal, NICE is largely reliant on information provided by the manufacturer, whereas under the original (multiple) technology appraisal process, the independent review group contracted by NICE also undertook an analysis.

One concern is that, in the future, companies could terminate an appraisal by failing to submit data if they thought the chance of a positive NICE recommendation was small. Clinicians or patient organisations could then bring pressure to bear on local decision makers, whereas this would not be possible after a negative NICE appraisal. In most jurisdictions that use an evidence based approach to drug use, this situation cannot arise because a formal application must be made by the manufacturer for inclusion on the national formulary or "positive list." (3) In the United Kingdom, however, most licensed drugs are automatically available for prescribing on the NHS, unless guidance from NICE, the Scottish Medicines Consortium, or the All Wales Medicines Strategy Group limits their use. If terminated appraisals effectively delegate decisions to the local level, this could exacerbate the "postcode lottery" that NICE was created to tackle (4).

So what could be done? Moving towards a comprehensive approach for evaluating the clinical effectiveness and cost effectiveness of all new drugs, linked to listing for reimbursement, raises a wide range of questions, not least that of whether NICE could cope with the workload. Certainly, without substantial extra resources it would have to simplify its procedures greatly. In particular, it would need to limit stakeholder involvement and perhaps be less rigorous with its reviews, thereby increasing its reliance on manufacturers’ submissions.

Alternatively, NICE could follow the approach used by the Scottish Medicines Consortium and, in the absence of a submission, rule that the drug is not recommended for use. This approach would remove the incentive not to submit. However, this equates absence of evidence with evidence of absence (of clinical effectiveness and cost effectiveness), and it may deny patients access to drugs that might be cost effective. A third option would be for NICE to negotiate a "coverage with evidence" agreement with the manufacturer. Under this scenario, the drug would be available for use in NHS patients, but access would be conditional on a commitment by the manufacturer to provide evidence on outcomes and costs at a set date in the future when the NICE decision would be reviewed. This approach may be useful if non-submission reflects an absence of evidence for the relevant patient group (for example, the terminated appraisals on carmustine implants for recurrent glioma (TA149) and cetuximab for colorectal cancer (TA150)). However, it would be of little use if the drug company chose not to submit because the limited available evidence indicates that the drug is unlikely to be cost effective when assessed against NICE’s cost per quality adjusted life year threshold (for example, bevacizumab for breast cancer (TA147)). In such situations a coverage with evidence approach could provide a perverse incentive for companies to claim that no data exist, to increase the chances of market access for their product.

A fourth possibility, arguably more in keeping with NICE’s ethos, would be to commit to convert a single technology appraisal to a multiple technology appraisal if and when it becomes clear that the manufacturer is not intending to make a submission in accordance with the institute’s specification. This might lengthen the appraisal process and may be unsatisfactory if the manufacturer fails to give access to unpublished data. However, it is more likely to encourage submissions from manufacturers wherever possible, because the incentive to the manufacturer would be to ensure that its point of view was adequately reflected in the appraisal.

None of these strategies is without its drawbacks. Nevertheless, simply terminating appraisals runs the risk that the NHS in England and Wales will have to make difficult decisions in the context of an absence of evidence. The fourth option, of converting single technology appraisals to multiple technology appraisals when the manufacturer fails to make a submission, would be the best way forward.

Cite this as: BMJ 2009;338:a3182

Michael Drummond, professor of health economics, Anne Mason, research fellow in health economics
Centre for Health Economics, University of York, York YO10 5DD

Competing interests: MD and AM have worked on technology assessment reviews, for which the Centre for Health Economics at The University of York receives funding from NICE. They have also received funding for research from, and undertaken consultancy projects for, several drug companies. MD is chair of one of NICE’s guideline review panels.

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More Gossip From a Horse Named Jim

01/22/2009 12:58 PM |

More FDA parlor game gossip -- this time from Jim Dickinson's FDA WebView:

The inside-the-beltway crowd are speculating that two potential candidates for FDA commissioner remain in the running — Baltimore health commissioner Joshua Sharfstein and Duke University clinical trial researcher Robert Califf. On Saturday, Sharfstein, who was at an Obama rally in Baltimore, dismissed the rumor of possibly being selected for the top FDA post, telling a radio interviewer that he expects to continue as the city’s health commissioner. If so, this leaves Califf as the potential front runner. He’s no stranger to the agency and currently works with several top officials under the critical path initiative to help modernize clinical trials. The FDA/Duke co-founded Clinical Trials Transformation Initiative seeks to improve clinical trial quality and efficiency. It was formed in response to growing frustration among patients, consumers, the academic community, and industry over the difficulty of conducting high-quality clinical trials in a timely manner to produce information physicians need to define optimal patient treatments. During the firestorm after Merck withdrew Vioxx in 2004, Califf joined critics on NBC’s Today Show who questioned whether FDA should have acted sooner in requesting post-marketing safety data on the drug. At the time, Califf suggested Vioxx’s withdrawal illustrated certain regulatory shortcomings. He said “rules need to change” and FDA should require large outcome trials for drugs used to treat chronic conditions. Additionally, Califf has publicly said that the agency is starved for resources and needs a "nonpolitical scientific base for what it does,” and without these “we are going to see more catastrophes along the lines of what we saw in the past with thalidomide and even going back to the origins of the FDA, ‘the horse named Jim,’ whose illness at the time that tetanus toxin was being made led to the deaths of some children. They really got the FDA started. I think we're going to see some pretty major catastrophes if we don't repair the problem.” Califf has served on FDA’s Cardiorenal Advisory Panel and the Institute of Medicine’s (IoM) Pharmaceutical Roundtable. He served on IoM committees that recommended Medicare coverage of clinical trials as well as the removal of ephedra from the market, and its Committee on Identifying and Preventing Medication Errors. He is currently a member of the IoM Forum in Drug Discovery, Development, and Translation, and FDA’s Science Board.
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Initial Differences

01/21/2009 02:58 PM |

Congress is calling for the establishment of a “Federal Coordinating Council for Comparative Effectiveness Research.” What does this mean?  Is comparative effectiveness the same thing as cost effectiveness?  

No. Big difference. 

Cost effectiveness is what NICE (The United Kingdom’s National Institute for Clinical Excellence) does based on (among other things) the infamous $50,000 Per Year of Life QALY (Quality Adjusted Life Year).

Cost effectiveness assumes an additional year of life is worth about $50,000, the average price of a fully loaded Land Rover.

For example, NICE’s preliminary decision was that four new cancer drugs (to treat people with kidney cancer that has spread) -- temsirolimus (Torisel), bevacizumab (Avastin), sorafenib (Nexavar), sunitinib (Sutent) not be reimbursed by the National Health Service because, despite clinical evidence that these drugs can actually help, they weren’t “cost effective. In essence, NICE doesn’t think that these four drugs are a good value for the NHS.

(Currently, the only available treatment for metastatic renal cell cancer is immunotherapy. This halts the disease’s progress for just four months on average. But if people are unsuitable for immunotherapy, or it doesn’t work, that’s it. There’s no other treatment option.)

NICE agreed that patients tended to live longer when they were given these drugs. But when they put the data from the trials into their QALY-driven computer models, they found that the drugs cost a lot at £20,000 - £35,000 ($39,000 to $68,000) per patient per year compared to the benefit they brought patients - too much for them to recommend that the NHS prescribe these drugs.

Result?  The government saves money and patients receive an expedited death sentence.  And that’s not hyperbole.

That’s cost effectiveness.

Comparative effectiveness is different.  Key word:  “comparative.”

Comparative effectiveness strives to show which medicines are most effective for any given disease state.  Is there a “more effective” statin?  A “more effective” treatment for depression?  Most of the world refers to comparative effectiveness (often referred to as “CE”) as Healthcare Technology Assessment (HTA).

But how do you compare two molecules (or three or more) that have different Mechanisms of Action for patients (otherwise known as “people”) who respond differently to different medicine based on their personal genetic make-up?

Comparative effectiveness in its current form leads to a “one-size-fits-all” approach to healthcare – which means that it doesn’t fit anyone all that well.  The concept it good, but the tools are wrong.  Comparative effectiveness relies heavily on findings from randomized clinical trials (RCTs). While these trials are essential to demonstrating the safety and efficacy of new medical products, the results are based on large population averages that rarely if ever will tell us which treatments are “best” for which patients. This is why it is so critically important for physicians to maintain the ability to combine study findings with their expertise and knowledge of the individual in order to make optimal treatment decisions.

Government sponsored studies that conduct head-to-head comparisons of drugs in "real world’" clinical settings are regarded as a valuable source of information for such coverage and reimbursement decisions -- if not for making clinical decisions. Two such studies, the Clinical Antipsychotic Trials in Intervention Effectiveness (aka CATIE), study and the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study were two such “practice based” clinical trials, sponsored in part by the National Institutes of Health, to determine whether older (cheaper) medicines were as effective in achieving certain clinical outcomes as newer (more expensive) ones. 

The findings of both CATIE and ALLHAT were highly controversial, but one thing is not – even well-funded comparative effectiveness trials are swiftly superseded by trial designs based on better mechanistic understanding of disease pathways and pharmacogenomics.  And, since most comparative effectiveness studies are underpowered, they don’t capture the genetic variations that explain differences in response to medicines by different patients.

But it’s important to move beyond criticizing comparative effectiveness in its current form, and instead focus on creating a policy roadmap for integrating technologies and science that is more patient-centric into comparative effectiveness thinking.

Much the like the U.S. Food and Drug Administration created something called the Critical Path Initiative to apply 21st-century science to accelerate the development of personalized medicine, another national goal should be to create a Critical Path Initiative to apply new approaches to data analysis and clinical insights to promote patient-centric healthcare.

Why? Because comparative effectiveness should reflect and measure individual response to treatment based on the combination of genetic, clinical, and demographic factors that indicate what keep people healthy, improve their health, or prevent disease. First steps have been taken. For example, the Department of Health and Human Services has invested in electronic patient records and genomics. Encouraging the Centers for Medicare & Medicaid Services to adopt the use of data that takes into account patient needs would complement such efforts. 

We need to develop proposals that modernize the information used in the evaluation of the value of treatments. Just as the key scientific insights guiding the FDA critical path program are genetic variations and biomedical informatics that predict and inform individual responses to treatment, we must establish a science-based process that incorporates the knowledge and tools of personalized medicine in reimbursement decisions: true evidence-based, patient-centric medicine.

For instance, the FDA, in cooperation with many interested parties, has developed a Critical Path opportunities list that provides 76 concrete examples of how new scientific discoveries in fields such as genomics and proteomics, imaging, and bioinformatics could be applied during medical product development to improve the accuracy of the tests used to predict the safety and efficacy of investigational medical products.

We need a Critical Path for Comparative Effectiveness to begin the process of developing a similar list of ways new discoveries and tools (such as electronic patient records) can be used to improve the predictive and prospective nature of comparative effectiveness.

It’s a complicated proposition—but such a body’s goal is as simple as it is essential—cost must never be allowed to trump care, and short-term savings must not be allowed to trump long-term outcomes Just as we need new and better tools for drug development, so too do we need them for comparative effectiveness measurements.

Today, comparative effectiveness is a short-term, short-sighted, politically-driven policy that results in one-size-fits-all medicine. While it may provide transitory savings in the short-term, current strategies result in a lower quality of care that result in higher healthcare costs over time.

Restrictive formularies and health care systems that deny patients access to the right medicine in the right dose at the right time but pay for more invasive and expensive procedures later on have their priorities upside down. Attention must be paid. If the devil is in the details (and it is), it’s time for a deep dive beyond simplistic and self-serving “comparative effectiveness.”

A health technology assessment model for the 21st Century should reflect and measure individual response to treatment based on the combination of genetic, clinical, and demographic factors that indicate what keep people healthy, improve their health, and prevent disease. A rapidly aging society demands a new healthcare paradigm capable of providing for its needs in the 21st century. Equality of care must be matched with quality of care. 

In an era of personalized medicine, one-size-fits-all treatments and reimbursement strategies are dangerously outdated. We are early in this debate, but at least we can all agree that this is not, and must not be exclusively, a debate about saving money. It must be about patient care.

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Let It Bleed

01/20/2009 10:16 PM |

Per NICE's decision that it's not cost-efficient to spend $400 on a diagnostic test to determine whether a patient should be given Warfarin (see "Why being NICE is deadly"), consider this:  conservative estimates project that using the diagnostic (specifically called out in the amended FDA label) will prevent 85,000 serious bleeding events and 17,000 strokes annually – and that’s just in the United States. And this “safer use” is estimated to save $1.1 billion annually.  And that’s the mid-range.

NICE should think twice.
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