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.
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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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Why Being NICE is Deadly

01/20/2009 09:37 PM |

A study published today in the Annals of Internal Medicine deemed the use of warfarin gene testing prior to warfarin treatment as not cost-effective because the researchers said at $170K per one life year free of serious bleed for a $400 test was about $120K too much.  $50K is of course the "benchmark" produced out of thin air in 1985 for the value of dialysis for a 65 year old person. 

Now some facts for the likely consumer:

About seven percent of all patients who take the drug warfarin to prevent blood clots in the legs will have a major bleeding episode within one year of treatment, according to researchers who analyzed 33 studies covering 10,757 patients. About one in eight will die, 10% will bleed inside the brain, and half of these patients with an intracranial bleed will die.

Now let's administer the drugwonks comparative effectiveness test to the authors of the study:  Knowing this and assuming that a family member had to take warfarin to prevent blood clots, would you refuse to pay for a genetic test or give an AHIP thumbs up to denying coverage on the grounds that at $400 a pop, society and you are better off taking the risk of intercranial bleeding and death.  And that's just the leg mind you.   We haven't even gotten to other warfarin uses.

I thought we were all concerned about safety.
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Legal But Not Ethical

01/20/2009 09:02 PM |

NICE just keeps serving up examples as why it should be the "gold standard" for comparative effectiveness in the US...

NICE in the dock as Servier takes osteoporosis review to court

The UK’s drugs watchdog is being dragged into a legal battle over its osteoporosis ruling, which has been labelled as “unethical and short-sighted” by critics.

Drugmaker Servier is challenging the National Institute for Health and Clinical Excellence over draft guidance that recommends that doctors should prescribe cheaper drugs to women with early signs of osteoporosis, even though up to one in five patients cannot take the drugs, there are crippling side effects and in spite of more effective treatments being available.

According to the guidelines, sufferers would have to get 60% worse, based on a scoring system, before being offered the more expensive alternative treatment Servier’s Protelos (strontium ranelate).

Both Servier and the National Osteoporosis Society have criticised the guidance, labelling it unethical and claiming it will do nothing to reduce pain or prevent fractures.

In a bid to get the guidance changed, the organisations are taking NICE to the High Court, as part of a full judicial review, claiming lack of transparency and infringement of human rights by denying alternative treatment.

However, NICE denies any wrongdoing. Chief executive Andrew Dillon told The Times the recommendations had been “a complex set of guidance to produce”, but the Institute was “confident” NICE had acted lawfully.

WHY NOT 65 percent worse?  I guess that would be illegal.
                             
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Importing Hypocrisy

01/20/2009 03:52 PM |

This is too good to be true. The same pols who were pushing for drug importation are now demanding that meds be made in the USA:

From the NY Times...

Drug Making’s Move Abroad Stirs Concerns

"....now experts and lawmakers are growing more and more concerned that the nation is far too reliant on medicine from abroad, and they are calling for a law that would require that certain drugs be made or stockpiled in the United States.

“The lack of regulation around outsourcing is a blind spot that leaves room for supply disruptions, counterfeit medicines, even bioterrorism,” said Senator Sherrod Brown, Democrat of Ohio, who has held hearings on the issue."

Recentlly Senator Brown went to town on by claiming the company was outsourcing production and jobs to China to save money at the expense of patient safety.  Any proof?  None.  But, he pontificates:

"Are we supposed to believe that it’s just coincidence that China’s safety standards aren’t strong or enforced? Do we really believe that the lower manufacturing costs in Asia, depressed by slave wages, have no impact on patient safety?

“U.S. consumers are paying the highest prices in the world for prescription drugs as drug makers outsource American jobs and import tainted products. It’s safe to say that the drug industry is skating on very thin ice.”

But Sherrod and lots of other in Congress were pushing drug importation really, really hard in the past:

In 2004 Mark McClellan released a HHS task force report (that Peter Pitts helped coordinate which concluded it, "would be extraordinarily difficult to ensure that drugs personally imported by individual consumers could meet the necessary standards for a certification of safety to be made, especially if consumers continue to import prescription drugs in the same or increased numbers."

Sherrod and other pro-importation types responded:

"This one-sided report indicates no willingness to find solutions, instead dismissing importation using the same scare tactics employed by the pharmaceutical companies themselves." 

In a floor speech pushing importation after the release of the report, then Congressman Sherrod said:

“Thanks to Republican leadership’s stall tactics, the only thing that’s happened on importation is we’re all a year older.  The American people need to tell Senator Frist and the Republican leadership that they want an importation bill on President Bush’s desk before the November elections.” 

And Sherrod just pushed Peter Rost (our fellow blogger) for FDA Commissioner who made a name for himself by pushing drug importation.  At the time Sherrod was still for allowing drugs made by slave labor and cheaper ingredients into the US, albeit through Canada, Europe and other areas and from FDA inspected facilities in India, China, etc. only and with pedigree, chain of custody and tamper resistant packaging all in place (all of which counterfeiters will be happy to comply with).  And at the time Peter (Rost) not Pitts   was a vice president of marketing at Pfizer and "the first" pharmaceutical industry executive to say publicly that reimportation "can be safe, rejected the administration's arguments about minimal cost savings," the Free Press reports. He said, "If importation didn't work, you wouldn't have had it in Europe for 20 years. This is so wrong" (Detroit Free Press, 12/22/04).

Well, I think Peter was wrong and still is.  But at least he is not a hypocrite. 

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The Same Game

01/20/2009 01:22 PM |

A final FDA rule (effective July 15^th) will require ANDA applicants to submit data from all bioequivalence studies conducted on a generic drug product formulation filed for approval, rather than just those that successfully demonstrate bioequivalence to the reference listed drug.

Currently, applicants submit studies demonstrating that the rate and extent of absorption of a generic drug meets bioequivalence limits, but additional bioequivalence studies conducted on the same formulation typically are not submitted. These include studies that failed to meet passing criteria, as well as multiple successful studies. The agency infrequently sees this additional data and is generally unaware of the existence of such studies.

Applicants also must submit data in an annual report on all post-marketing bioequivalence studies for an approved drug product formulation during the annual reporting period.

SCRIP World Pharmaceutical News reports that, “The agency notes that if it receives failed bioequivalence studies for a given application, it might make a different decision about whether to approve the generic than if it had received only the pivotal passing study.”

The FDA is limiting the additional studies to those conducted for the "same drug product formulation,” rather than requiring submission of all studies conducted with developmental formulations. "Same drug product" is defined as the formulation of the product submitted for approval, and any formulations that have minor differences in composition or manufacturing method but are similar enough to be relevant to the agency's bioequivalence determination. The FDA intends to issue draft guidelines giving specific examples of formulations it considers to be the same drug product.

Attention must be paid to the issue of bioequivalence -- particularly by those at the WHO and elsewhere who are toying with the idea of "clinical equivilence" for follow-on biologics.
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Will Innovation Survive This Administration?

01/19/2009 03:18 PM |

Forgive me for raining on the inaugural parade.   

I regard the incoming administration with trepidation.  Not because of it's agenda because on first, second and third glance it seems to have none.  But rather, it seems to worship at the altar of being perceived as effective.  What did Nick Carraway say about Tom Buchanan in The Great Gatsby being a "series of successful gestures."  Exactly. 

No permanent allies. No permanent friendships.  Just permanent interests. 

And to maintain it's interests the administration will toss biomedical innovation to the wolves.  Not because they want to but because the way it is done, in bits and pieces and in the dark of night and couched in cost containment and consumer protection it will be really easy to make it harder and harder to produce and bring to market any innovation.   Want your votes on the stimulus bill it will cost you a change to allow an override of pre-emption.  Want expanded SCHIP coverage?  Allow CMS to establish reference pricing for breakthrough drugs or special rebates.  Want more NIH funding?  Be prepared to require that anyone receiving NIH funding be allowed to collaborate with industry.  More funding for the FDA?  Be prepared to saddle the agency with regulation of tobacco, TV ads and drug importation.

Can we expect the media to analyze the impact of all this?  Not at all.  The journalists who believe that "science should not be for sale" and who work at newspapers that can't be given away have led the way in making people believe that the commercialization of medical discoveries is essentially a criminal enterprise no different than the one Madoff concocted.  

Sadly, many of those in the crosshairs appear oblivious or believe they can survive by engaging in accomodation or seeking what is known as a "seat at the table."

Ask the biotech industry in the UK and Europe if that's a recipe for success and prosperity.


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There's an awful lot of something in Brazil

01/19/2009 01:59 PM |

The Executive Board of the World Health Organization meets next week with significant discussion expected on a new secretariat report on counterfeit medical products

According to IP Watch, “The new report on counterfeit drugs released on 18 December also is likely to generate discussion, as some sources are concerned about what they see as contradictions between this report and earlier WHO statements on counterfeit drugs, and others are concerned about what they see as internal contradictions in this report.”

The counterfeit drugs report will be the “big IP item” on the agenda next week, a developed country source predicted. A developing country source predicted a “very difficult discussion” on the document.

Several nongovernmental sources have expressed concern over the use of the term “counterfeit” in general - saying that legally speaking it is associated with violations of trademark law, a legal association which is confirmed in international law by its definition in the World Trade Organization Trade-Related Aspects of Intellectual Property Rights (TRIPS) Agreement relating it specifically to trademark violations. They also say that even statements within the report itself that “legal instruments related to intellectual property rights have a broad scope and are not focused on the protection of public health,” cannot take away the fact that the terminology is focussed on IP and not on healthcare.

A Brazilian delegate agreed with this assessment, saying “we do not want to see WHO as an agency of enforcement related to trademark,” and the use of the word “counterfeit” automatically brings in discussion of IP, especially given its presence in TRIPS. Further, the delegate added, the work of IMPACT was done outside the WHO and therefore “and we cannot simply import IMPACT recommendations without discussion.” It should not be legitimized as though it were an intergovernmental process, the delegate explained.

A meeting of the International Medical Products Anti-Counterfeiting Taskforce (IMPACT) – a taskforce of anti-counterfeiting stakeholders, including pharmaceutical industry associations and drug regulatory authorities, international agencies and non-governmental agencies, and enforcement bodies, launched by the WHO in 2006 – in Tunisia in December 2008, for instance, defined counterfeits in such a way that “disputes about patents” would not be accidentally equated with counterfeits. However, the new report contains the broader statement “recognizing that disputes about IP rights are not to be confused with counterfeiting.” A developed nation delegate said that the patent definition is preferable, but expected disagreement on the issue.

The definition IMPACT agreed on is: “a product with a false representation of its identity and/or source. This applies to the product, its container or other packaging or labeling information. Counterfeiting can apply to both branded and generic products. Counterfeits may include products with correct ingredients/components, with wrong ingredients/components, without active ingredients, with incorrect amounts of active ingredients, or with fake packaging.”

The definition by IMPACT adds that “violations or disputes concerning patents must not be confused with counterfeiting of medical products,” yet there is much concern – particularly on the part of developing countries and non-governmental agencies – that disputes concerning trademarks could still be conflated with counterfeiting.

The International Federation of Pharmaceutical Manufacturers and Associations (IFPMA)’s director general Alicia Greenidge approved of the report, saying it “touches on some key issues concerning the fight against counterfeits, including the appropriate definition of a counterfeit medicine,” and endorsed the IMPACT definition. She added that “generic medicines play an important role in ensuring global health and are unfortunately themselves widely counterfeited, [therefore] it is important to have a definition which provides guidance that authorized generic medicines are not counterfeits and which also assures that patent actions are not confused with counterfeit actions … this will help authorities in both developing and developed countries to identify and address counterfeits of trademarked products, including the many authorized branded generics.” 

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Yes we can ... have NICE in the USA

01/16/2009 08:40 PM |

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

APPROPRIATION OF $1.1 BILLION FOR CER RESEARCH

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

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

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

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

    o Encourage development of networks that can generate outcomes data

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

• Public Accountability:

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

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

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

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

ESTABLISHMENT OF ‘FEDERAL COORDINATING COUNCIL FOR COMPARATIVE EFFECTIVENESS RESEARCH

• Council shall coordinate and assist government agencies with conducting CER

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

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

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

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

What does all this mean?

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

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

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

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

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

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

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

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

No thank you.

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Onions on pizza or blood pressure control?

01/16/2009 06:59 PM |

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Minefields Along the Innovation Highway

01/16/2009 05:36 PM |

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

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

He found:

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

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

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

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


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Of Mice and Meds

01/16/2009 10:56 AM |

Talk about pharmaceutical direct-to-consumer advertising!

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

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

According to an article in the Financial Times,

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

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

To view the commercial, click here.

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

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

The complete CNN story can be found here.

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

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

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

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

$1.4 Billion for a Misdemeanor?

01/16/2009 01:18 AM |

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

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

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


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Got Guidance?

01/15/2009 05:37 PM |

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

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

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

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

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

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

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

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

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

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

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

01/14/2009 09:36 PM |

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

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

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

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

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

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

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

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

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

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

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

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

(Editing by Maggie Fox and Vicki Allen)

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