Asking the right question

08/23/2011 09:22 AM |

I am currently attending (and speaking at) the Technology Policy Institute’s annual Aspen Forum.  It’s refreshing to listen to presentations on issues other than healthcare.  But, on the other hand, there are a lot of parallels.

One disturbing similarity was brought to mind by a talk given by FCC Commissioner Robert McDowell. The topic was regulation of the Internet.  McDowell commented that he wasn’t sure when the question of “Should the Internet be regulated?” morphed into “How should the Internet be regulated?

And he was very clear that this was a disturbing “iterative change.”

Sound familiar?  We should be asking ourselves the same thing about comparative effectiveness.  When did “Should we adopt a national comparative effectiveness approach to healthcare?” morph into “How should we adopt a national approach to comparative effectiveness?”

There’s still time and opportunity to robustly debate the former so that we can avoid the latter.

We can, in the words of Commissioner McDowell, “avoid a race to the bottom.”  Read More & Comment...

BioSimilar Fee for All

08/22/2011 09:25 AM |

The Generic Pharmaceutical Association never misses an opportunity to miss an opportunity. They are balking at continuing to negotiate the design of a biosimilar user fee program that is independent of other user fees and has its own baseline appropriations trigger.

 

The disagreement stems from a proposal by GPhA and a representative of potential biosimilar sponsor Momenta Pharmaceuticals that biosimilar reviews remain part of the Prescription Drug User Fee program through fiscal year 2017, the end of the first biosimilar program cycle, according to minutes of a July 18 meeting.

 

The tactic could be a way to lower the cost of a biosimilar application. If the agency is forced to include biosimilars in the PDUFA program, it likely would have a more difficult time arguing it needed a strong funding base to ensure the program functions properly.

 

GPhA said it could not continue “detailed negotiations regarding volumes and metrics without agreement to parity with the PDUFA user fee program.”

 

The position would seem to reverse one taken during a July 11 negotiation. Minutes indicated “industry stakeholders” and FDA agreed to support a flat product development fee of about 10% of the marketing application fee for the fiscal year while a biosimilar product was in the IND stage.

 

It is unclear whether FDA could send a commitment letter to Capitol Hill for approval without support from a major trade group involved in the negotiations.

 

If FDA went ahead with a commitment letter for a separate biosimilar user fee program and GPhA wanted to press the issue, the generic group would presumably need to convince legislators that its interpretation of the 2007 bill creating the new approval pathway was correct.

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Médecins Sans Facts

08/19/2011 06:47 AM |

“Facts are stubborn things” – John Adams

Médecins Sans Frontières (MSF) should be called Médecins Sans Facts.

MSF reports (correctly) that “while countries are rolling out new tests that will enable them to diagnose more patients with drug-resistant tuberculosis (DR-TB), a worldwide shortage of the drugs to treat these patients is likely.”

Not quite.

The news item generating this story comes from South Africa, which has the world's fifth-largest burden of multi-drug resistant (MDR) TB cases. According to Norbert Ndjeka, director of DR-TB, TB and HIV at the South African National Department of Health, the government will replace all microscope-based TB diagnoses with faster, more sensitive GeneXpert testing within two years, making it the world's largest user of the machine.

Good news.  But here’s the MSF spin:

But while more patients may get diagnosed, their access to treatment remains precarious as a limited number of approved drug producers keep many DR-TB prices high and supply uncertain, according to Dr Eric Goemaere, MSF's senior regional adviser.

It’s the familiar refrain from our friends at MSF: Blame industry! Blame international intellectual property (IP) protection! Convenient and consistent – and untrue. Médecins Sans Facts.

 

The truth of the matter is that the fault for shortages lies with all too familiar misguided government policies – in this case the government of South Africa and their myopic focus on lowest price.  Combined with a concerning lack of transparency, utter unpredictability and the exploding processing costs of their regulatory system, it all adds up to delays and drug shortages of not just medicines for TB – but for many other critical healthcare products.

 

Mr. Ndjeka has admitted that South Africa's regulatory Medicines Control Council (MCC) has been laboring for years under a backlog in drug registrations, including those of some fixed-dose antiretrovirals long available in other nations. South Africa now pays a private company to import the drug through a special application to the MCC.

So what does MSF recommend doing beyond their criticism of IP and the innovator pharmaceutical industry? Ignoring Economics 101, they recommend lowest cost "access to essential drugs"  -- which just further exacerbates the medicines supply problem.  

 

Médecins Sans Facts continues to call for countries to avert the looming crisis by “improving drug forecasting, negotiating better prices and accelerating national medicines registrations.”

As Mark Twain said, “Get your facts first, then you can distort them as you please.”

It would be helpful if groups like MSF took a longer term view -- encouraging multiple suppliers of medicines through more stable and predictable pricing versus their usual and customary (and wrong) focus on lowest cost. If MSF really wants to be part of the solution, they should consider combining efforts with industry to help streamline the complicated and costly regulatory process in South Africa (and in many other nations of the Developing World).  Harmonizing regulatory practices to align with evolving global standards (as called for recently by US FDA Commissioner Dr. Margaret Hamburg) and pressing domestic regulatory officials to respect timelines and transparent performance criteria, would make a huge difference for patients in countries like South Africa.

Why can't MSF advocate new drug approvals in places like South Africa within 90 or 180 days for products already approved leading regulatory agencies in Europe, Japan, and North America? Should South African patients really wait 2-5 years for access to promising new medicines that are already licensed for use in dozens of other countries?  Where is the activist outrage about these inexcusable regulatory delays?

Perhaps a better question (at least for starters) is why won’t MSF and their fellow travelers opt for a more collegial and logical agenda?

Perhaps the answer to that question was best addressed by George Orwell who wrote that “All political thinking for years past has been vitiated in the same way. People can foresee the future only when it coincides with their own wishes, and the most grossly obvious facts can be ignored when they are unwelcome.”

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Prior Proper Notification

08/18/2011 08:22 AM |

When I served at FDA we signed an MOU with PhRMA that required its member companies to notify the agency when instances of counterfeit medicines came to the attention of manufacturers.

 

It got the job done – minus additional federal regulation.

 

Today we face a different problem – drug shortages – but a similar decision tree:  regulation or public-spirited public health cooperation.

 

Minus the latter, we will get the former.

 

Senators Amy Klobuchar (D, MN) and Bob Casey (D, PA) have introduced legislation to require drug manufacturers to give “proper prior notification” to FDA when there is going to be a drug shortage.

 

Further, Klobuchar (D, MN) and Richard Blumenthal (D, CT) have formed a bipartisan group to work on the issue of drug shortages.

 

At their request, the FDA will hold a hearing on the matter September 21, and the General Accounting Office will review the problem.

 

It’s time for FDA and PhRMA to get the job done.

 

Legislation takes longer and leads to mission creep.

  Read More & Comment...

Now that's what I call priority review!

08/18/2011 08:17 AM |

BioCentury reports that the FDA has dentified eight priorities in the Strategic Plan for Regulatory Science: preclinical toxicology; personalized medicine; manufacturing; evaluation of emerging technologies; using information sciences to improve health outcomes; food safety; medical countermeasures; and communication with consumers and professionals.

 

The agency is seeking to improve the prediction of product safety through new animal models that consider both disease progression and co-morbidities. The plan also calls for FDA to collaborate with academia, industry and global regulatory agencies to develop and refine clinical trial designs. Such a collaboration would identify and evaluate improved endpoints and related biomarkers for areas where "optimal" endpoints are lacking, such as for osteoarthritis, gene therapy, ophthalmic indications, tumor vaccines and stem cell-derived therapies

  Read More & Comment...

Diagnostic Mission Creep

08/17/2011 08:32 AM |

CDRH has released two draft documents on approval process and guidance on its evolving approval process and planning clinical trials.

The first document explains the Center’s procedures for approving diagnostic and therapeutic devices -- how it weighs benefits and risks, judges the seriousness of a disease or condition, estimates how many people would use a device, and gauges availability of other devices for the same condition.

“Availability of other devices?”  Really?  Shouldn’t Shuren and Company stick to safety and efficacy?  Where’d this third leg come from?

Sounds like insidious mission creep of the comparative effectiveness variety.

The second document explains the agency's expectations for medical device clinical trials, and suggests companies pre-submit protocols for the design of pivotal studies. Both drafts are open to public comment for 90 days, beginning August 15.

  Read More & Comment...

"Temporary" My Aunt Fanny

08/17/2011 08:22 AM |

The IRS has "released what it's calling “temporary regulations” under which brand-name drugmakers must pay fees "to help fund" health-reform law provisions.

This was, as you will recall, part of “the deal.”

The regulations request payments of $2.5 billion in 2011 and are due by September 30^th. Additionally, IRS calls for $2.8 billion in each of '”fee years” of 2012 and 2013; $3 billion for fee years 2014 through 2016; $4 billion for fee year 2017; $4.1 billion for fee year 2018; and $2.8 billion for fee year 2019 and thereafter.

So what’s “temporary?” And what about those who are pounding the podium about rebates for dual eligibles?

Just asking.

According to reporting in Congressional Quarterly, although pharmaceutical companies have to "pay fees," they will garner "far more sales as millions of the uninsured gain coverage."

The requirement applies to companies with annual drug sales of "$5 million or more" to Medicare "Parts B and D"; Medicaid; and Veterans Affairs, and Defense Department and TRICARE programs.

  Read More & Comment...

The Dangers of Shorting Drug Shortages

08/16/2011 01:11 PM |

All of a sudden the Mainstream Media (highlighted by a much ballyhooed New York Times Week in Review op-ed by Zeke Emanuel) has discovered the problem of drug shortages.

 

Except it’s not a new problem.

 

According to a recent analysis, the frequency and impact of drug shortages have risen to critical levels, more than tripling since 2005, and affecting all segments of the healthcare community. In 2010, over 240 drugs were either in short supply or completely unavailable and more than 400 generic equivalents were backordered for greater than five days. In most instances, these did not progress to critical shortages, but point to instabilities in the supply chain that cause national concern. Many of the drugs identified in 2010 remain unavailable or in short supply in 2011.

 

Seventy-seven percent of drugs in short supply in 2010 were sterile injectable products, critical in the acute care setting. Recent media coverage highlights the plight of patients and physicians faced with shortages for cancer drugs, anesthetic agents, and critical care medications that have contributed to delays in treatment and surgery, or changes in care plans. Drug backorders cause patients to receive substitute therapies that add expense to patient care.

 

A major reason for shortages is quality/manufacturing issues. However there are other reasons such as production delays at the manufacturer and delays companies have experienced receiving raw materials and components from suppliers.  Discontinuations are another factor contributing to shortages.  (The FDA can't require a firm to keep making a drug it wants to discontinue.) 

 

It is time not to fix the blame – but to fix the problem.

 

Let’s start with the FDA.

 

In 2010, there were 178 drug shortages reported to the FDA. Is that a solid number?  Hard to say, because current regulations do not require companies to notify FDA of shortages. The only requirement is that companies inform FDA six months in advance for discontinuations of sole source, medically necessary drugs.  

(In 2010, for example there were 38 shortages prevented due to companies notifying FDA voluntarily of potential issues that could lead to shortages and FDA was able to work with the company to avoid a shortage.)

Inside the FDA’s Center Drug Evaluation and Research (CDER) resides the agency’s Drug Shortage Program (DSP). The DSP was established to address potential or actual shortages of drugs that have a significant impact on public health. Through communication, facilitation and negotiation, DSP works with pharmaceutical manufacturers, review divisions, compliance and other components of FDA to manage product shortages.

For example, when the drug shortage is for a generic product (as it often is), the FDA works with other firms making the drug to help them ramp up production if they are willing to do so. Often they need new production lines approved or need new raw material sources approved to help increase supplies. FDA can and does expedite review of these to help resolve shortages of medically necessary drugs. 

But the FDA can't require the other firms to increase (or commence) production.

The agency tries to do the best it can with limited authority, spare resources and shared staff. In addition to direct communication with industry, the DSP also gets reports from healthcare professionals, patients/individuals, or professional organizations using the e-mail address drugshortages@fda.hhs.gov.

But, as you can imagine, there is not a lot of e-mail traffic.  And there is no social media effort to promote either its purpose or existence.

It’s a good start – but it’s not enough.  And you know what they say about good intentions.

The FDA’s Drug Shortage Program is a good start.  But it’s not getting the job done. The problem is getting worse. The FDA needs both more authority and greater resources. In short, more needs to happen.

The Institute for Safe Medication Practices reports that, according to survey of 1800 healthcare practitioners, more than half of respondents frequently or always encounter difficulties associated with drug shortages.

The top three problems fall squarely within the zone of appropriate FDA attention and action:

* Little or no information available about the duration of a drug shortage (85%)

* Lack of advanced warning from manufacturers or FDA to alert practitioners to an impending drug shortage and suggested alternatives (84%)

* Little or no information about the cause of the drug shortage (83%)

Survey respondents felt “unsupported by the FDA and are perplexed regarding why the US is experiencing drug shortages of epic proportion that are often associated with third-world countries.”

(More detail on the ISMP survey can be found here.)

Should the issues of both authority and funding for the FDA’s efforts to mitigate drug shortages be hung on the PDUFA Christmas tree or addressed in separate legislation?  Whether it’s one or the other, it’s an issue that must be addressed with alacrity before it becomes a political question of "Who lost drug shortages?"

And before it becomes a question of American lives.
  Read More & Comment...

The PDUFA Christmas Tree

08/15/2011 11:09 AM |

The EU Innovative Medicines Initiative (IMI), the world’s largest public-private partnership in health R&D, is calling for proposals across seven new health care areas.

 

The areas of focus are linking patients’ data to develop more targeted therapies; using knowledge management of experimental data for translation into drugs for patients; complications of obesity; predicting Alzheimer’s disease and other dementias; drug delivery by nanocarriers; sustainability of chemical drug production; investigating stem cells for drug discovery; and understanding the behavior of drugs in the human body.

 

The EU has agreed to contribute up to €105 million ($150 million) to this latest step in IMI's evolution, a figure that will be matched by "in kind" contributions – staff, access to databases and research activity and equipment – from the European Federation of Pharmaceutical Industries and Associations.

 

The new project phase comes weeks after IMI signed a Memorandum of Understanding with the U.S.-based Critical Path Institute, aimed at increasing collaboration between the two bodies. They have agreed to foster increased information sharing regarding each other’s programs and create a mechanism to exchange knowledge and develop scientific consensus regarding research and testing methods.

 

But, as our European cousins step up to advancing 21^st century medicine, wither our own domestic efforts?  What’s become of the Critical Path?  Where’s the Reagan/Udall Center?

 

Funding for the FDA’s Critical Path program and the Reagan/Udall Center is generally considered a “Christmas Tree” issue relative to PDUFA V. That’s a mistake.  Beyond the agency’s request to fund it’s Advancing Regulatory Science Initiative (ARSI), we are all talk and no action.

 

For many involved in the reauthorization process, one statement that keeps coming up is -- ”The FDA is broken.” But what does that mean? Rather than making blanket statements that cause friction and promote areas of disagreement, one thing everyone can agree to is that the FDA’s must be both ally and accelerator in the advancement of innovation.

 

And that must be within the confines of PDUFA V – and it cannot be accomplished without moving forward the FDA’s Critical Path program and funding the Reagan/Udall Center.

  Read More & Comment...

The Cognitive Dissonance of Disinvestment

08/12/2011 09:39 PM |

Sander Flaum, the grand master of pharmaceutical marketing asks, “If you put the world’s top CEOs together in a room and asked them what challenges kept them up at night, what do you think you’d hear?”

The answer is shocking if not surprising/

According to the Conference Board’s CEO Challenge 2011 Survey – Fueling Business Growth with Innovation and Talent Development, most CEOs in the U.S. and Europe listed Business Growth as their top challenge.

According to Flaum there’s an even bigger concern. “Look down the list of the top challenges.  Where did these leaders consistently rank Innovation?  #3!  And guess what U.S. CEOs collectively viewed as an even more pressing challenge than the need for innovation– Government Regulation!” 

Flaum continues, “A CEO who is more worried about being handcuffed by regulations than coming up with the next big idea needs a priority readjustment. Sure, regulations can be a pain. But they can also be simply an excuse for failure. In Pharma, we’re always contending with the FDA in the struggle to bring innovations to market. And it’s not easy. But doesn’t the need for Innovation come first? If we don’t have something new and important to bring to market, then why complain about the regs?

Top 5 Global Challenges by Region

Rank	U.S.	Europe	Asia
1	Business Growth	Business Growth	Talent
2	Government Regulation	Cost Optimization	Business Growth
3	Innovation	Innovation	Innovation
4	Talent Cost Optimization  (tied)	Customer Relationships	Corporate/Brand Reputation
5		Government Regulation	Sustainability

Wither innovation? This crucial question becomes even more problematic when you consider the issue of “disinvestment” -- the processes of (partially or completely) withdrawing health resources from existing healthcare practices, procedures, technologies, or pharmaceuticals that are deemed to deliver little or no health gain for their cost, and thus do not represent efficient health resource allocation. “Disinvestment” is a more honest (and frightening) term for “comparative effectiveness.”

And leading the disinvestment charge (not surprisingly) is NICE.

Over the past 10 years NICE has identified over 800 clinical interventions for potential disinvestment. But, in the July 27^th edition of the British Medical Journal, Sarah Garner and Peter Littlejohns (both of NICE) report that although disinvestment will increase the opportunity for cash saving is unlikely to provide ways of controlling costs without cutting quality of care.

The authors write:

There is general agreement that stretched health services budgets should not be used to fund low value services. However international experience has shown that identifying and removing those services can be problematic and controversial.

Are you listening AHRQ?

Many suggestions for total disinvestment are based on a “social judgment” about whether it is appropriate for the NHS to fund the intervention rather than evidence of poor clinical or cost effectiveness. Others relate to “experimental” use of technologies outside their indications and evidence base.

Are you listening Dr. Berwick?

Opponents of a total disinvestment approach highlight the methodological flaws of using average estimates of effect drawn from populations; they argue that an intervention may be beneficial for an individual patient and should be an option, even if a last resort. An alternative strategy is optimal targeting: identifying subgroups in which an intervention is most clinically and cost effective.

Are you listening Dr. Pazdur?

Disinvestment is part of a broader agenda to improve efficiency and quality focusing on public health and prevention and ensuring that patients receive the right care at the right time in the right way.

Are you listening PCORI?

Although this approach releases resources in the long term, it may entail investment in the short term. It is very important to make the distinction between improving the efficiency of care and saving money.

Aha!

Without data, it is also difficult to identify the subgroups necessary to fully understand variation in care and therefore determine realistic potential savings.

Did somebody say “personalized medicine?” Did somebody say, “more and more targeted molecular diagnostics?”

The author’s conclude, “However, current evidence suggests that disinvestment is unlikely to achieve the huge savings required to meet tightened NHS budgets.”

We would be wise to learn from honesty of our transatlantic cousins.

  Read More & Comment...

The Avastin Spring

08/11/2011 04:20 PM |

By Dr. ROBERT GOLDBERG
Times Guest Columnist

Sometimes, profound change happens so swiftly it’s unrecognized and unappreciated. Such is the case with the response to the Food and Drug Administration advisory committee’s decision to withdraw the agency’s approval for using Avastin to treat metastatic breast cancer.

After the FDA Oncological Drug Advisory Committee declared Avastin to be unsafe and ineffective for women suffering from that incurable form of the disease, the headlines and pundits spun the decision — and the discussion — as one where science triumphed over emotional and desperate women.

Gary Schwitzer, a self-styled expert on objective medical reporting quoted the representative from the National Breast Cancer Coalition who at the ODAC hearing: “This decision can’t be driven by anecdotes. It must be driven by science.”

This is an unfair and lazy characterization of the debate over Avastin. The ODAC panel was stacked with members who already voted against Avastin’s use in MBC. The conflict was over the interpretation of clinical information and whether the FDA can pull an approval because, as it said in December of last year, Avastin doesn’t provide “a sufficient benefit in slowing disease progression to outweigh the significant risk to patients.”

But several other groups that looked at the same evidence came to a different conclusion, including the National Comprehensive Cancer Network and Europe’s equivalent of the FDA, the European Medicines Agency (EMA). Indeed, the EMA expanded approval Avastin based on the same “science” ODAC used in rescinding the drug’s FDA endorsement.

In any event, the speed with which both the Obama administration and private health plans announced they would still cover the cost of Avastin for the use the FDA rejected was stunning. When the FDA decided to yank Avastin’s approval in December 2010, several health plans and regional Medicare reimbursement contractors told women that Avastin would no longer be covered. Such decisions were reversed only after the FDA said it would review its revocation.

Last week, the same organizations — along with the Obama administration — rushed to distance itself from the FDA and assure women it would cover the drug.

The difference in response is a result of the rapid organization of patients through social media. While it culminated in the presence of hundreds of women at the ODAC hearing, that participation was only a part of an extensive, sustained and scientifically informed movement.

The FDA officials and the interest groups urging Avastin’s revocation were outgunned by individual patients who joined together, much as HIV patients did in the 1990s and MS patients did in pushing for the return of Tysabri to the market a few years ago.

This time however, the use of social media to share clinical information, organize support and express opinions was rapid, sustained and, above all surprising. The cancer advocacy “establishment” was outgunned and reduced to irrelevancy. This also happened after the Obama administration recommended not to cover mammograms for women under 50. The National Breast Cancer Coalition sided with the administration — and cancer patients, oncologists and radiologists everywhere told them go stick it.

That decision, like the FDA’s Avastin rendition, is being ignored in practice.

The uprising against the Avastin decision could signal a clear shift in power from the Beltway groups that claim to be patient or consumer “advocacy” groups - but are beholden to a particular party or just staying in favor with the powers that be — to individuals organizing on their own and in their own best interest.

More to the point, such movements are well informed and shaped by what the science says. They are often funding research to accelerate better treatment and detection of illnesses. The attempt to demean or diminish such movements as the expression of anecdotal experience and emotions reflects the arrogance of bloggers and pundits who have but a thimble full of the clinical understanding of the movement’s participants. And it suggests a contempt for any use of social media that does not seek to spread fear or skepticism of innovation.

Most immediately, the Avastin Spring has undermined the legitimacy of the effort to use comparative effectiveness research to delay access or payment for new technologies. Health plans and the government will have to expect ongoing challenges to their ‘expertise’ and claims that it is using the best evidence in determining what to cover. Consumers will be skeptical of one-size fits all judgments made by so-called “experts.”

Similarly, companies who develop new products will have to contend with consumers demanding credible and substantive clinical information.

The Avastin Spring suggests that resistance against bureaucrats telling the rest of us what treatments we can and cannot use will only grow. This is not an anti-science enterprise. Rather, these are movements that regard individual choice as an imperative as the science of personalized medicine advances. It means less authority for those claiming only they have science on their side en route to restricting access to innovations. Both changes bode well for our well being.

Dr. Robert Goldberg is co-founder and vice president of the Center for Medicine in the Public Interest. He is also author of the book, “Tabloid Medicine: How the Internet is Being Used To Hijack Medical Science For Fear and Profit.”

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No Pain. No Gain.

08/11/2011 07:55 AM |

Metrics for monitoring prescribing patterns to identify changes in access to opioid products may not be in place when FDA approves REMS for individual products.

 

The missing element is the methodology.

 

“It will take a number of months to develop detailed methodology with a research organization,” the Industry Working Group told the FDA in a communication seeking guidance on the agency’s expectations for the REMS. IWG is developing the shared implementation program for the risk management plan and has met with the FDA several times to clarify the agency’s expectations.

 

The access analysis is one of seven components of the assessment plan The FDA imposed when in April it unveiled its requirements for the opioid REMS. “The IWG has already proposed a high-level overview of the [prescriber pattern] methodology in the proposed REMS, with more detailed methodology to be developed after the REMS is approved,” IWG said.

 

The FDA seems willing to accept a staggered launch of the program. While the methodology may be only in draft form in the sponsors’ REMS submissions, they should provide a schedule “for expeditious completion of the methodology,” according to the agency.

 

Class-wide REMS and shared REMS assessment program do not eliminate the need to look at whether individual products are being used more safely.

 

The agency clarified that its request for drug-specific information does not refer to the active drug substance, dosage form or delivery method. Rather, the agency wants “as much detail as possible for each individual product, including each unique dosage form/delivery system.”

 

Industry is concerned about “providing comparative data on competing products and would prefer to perform general surveillance, looking at the changes in adverse events for the class or at the level of active drug substance, rather than for specific products.”

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And let loose the (watch) dogs of war

08/10/2011 08:00 AM |

From the pages of Medical Marketing & Media ...

Watchdogs bark as FDA relaxes rules on conflicts of interest

Matthew Arnold

 

An FDA move to relax conflict-of-interest rules governing advisory panels is meeting with heated opposition from watchdog groups and medical societies.

FDA commissioner Margaret Hamburg recently told Public Citizen that the agency may loosen a three-year-old policy aimed at keeping industry-funded physicians off FDA advisory panels because the resulting vacancies are gumming up the approvals process.

An FDA spokesperson told MM&M: “The new conflict of interest rules have, in some cases, made it more difficult for FDA to find expert advisors. In most cases, FDA has been successful in finding experts to meet our needs. However, in a few cases it has been necessary to delay holding advisory committee meetings in order to allow more time to contact and screen more experts for consideration or to begin the screening process with many more experts. This increases the work requirement for advisory committee preparation.”

As of March, 23% of the agency's advisory committee seats – 138 of them – were vacant.

FDA CDER director Dr. Janet Woodcock said at a conference in May: “There is no doubt it is difficult finding highly experienced people who do not have conflicts.”

Bull, said the Project on Government Oversight (POGO), arguing that the number of conflict-of-interest waivers granted FDA advisory members has never exceeded 5% and that the percentage of seats vacant is falling, having sunk from 30% in 2009.

“These rules do create an additional hurdle, but that is exactly the point,” said POGO head Danielle Brian in a letter to Dr. Hamburg. “We want expert advice that is as free as possible from the influence of industry.”

Like POGO, the National Physicians Alliance pointed to lists of conflict-free physicians.

“We understand and decry the increasing entanglement of many researchers and clinicians with industry and understand that finding reviewers without conflicts can be a challenge,” said National Physicians Alliance president Valerie Arkoosh, MD, who noted that almost half of the cardiologists who develop clinical practice guidelines for the American College of Cardiology and the American Heart Association do not have conflicts of interest.

In the FDA's corner on the topic is House Energy and Commerce Committee chair Rep. Fred Upton (R-MI), who said in July: “The rigid and unrealistic conflict of interest provision has prevented FDA and its advisory committees from utilizing some of science's best minds and left advisory committee slots unfilled,” and suggested that the rules have slowed approvals.

Another voice in favor of relaxing the rules is that of Peter Pitts, an industry PR man and generally pro-industry think tanker who, as FDA associate commissioner, was in charge of advisory committee oversight, in which role he had final say on what would-be panelists with conflicts made the cut and were granted conflict of interest waivers.

“Many did not,” wrote Pitts, “but those who did received their waivers because FDA professional career staff made a strong case that these people weren't just important to the advisory committee but critical. And we should all pay attention to the nomenclature. It's not about ‘conflict of interest' – it's about (as HHS Secretary Sebelius correctly says) ‘interest.' And having an ‘interest' is not necessarily a bad thing as long as you're transparent about it.”

“If we allow FDA adcomms to become the realm of the second best and the almost brightest,” continued Pitts, “What have we done to the advancement of America's health?”

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CER Sucks More $$ From Innovation

08/09/2011 10:04 PM |

Drug Companies Spend an Average $13,000 per Patient on Comparative Effectiveness Research in Phase IV

RESEARCH TRIANGLE PARK, NC -- (Marketwire) -- 08/09/11 -- The cost of running a comparative effectiveness trial is $13,087 per patient during Phase IV, according to a study by Cutting Edge Information.

Comparative Effectiveness Research (CER) compares drugs, devices or other medical tests and procedures to determine the most effective outcomes for patient populations. Drug companies often use CER studies to compare their products head-to-head against competitors. The study found that CER studies make up the second largest portion of the average Phase IV development program, at 29%. Data generated from CER studies can prove invaluable. Favorable results from a registered Phase IV comparator trial is a powerful marketing and sales tool and can eventually alter disease treatment patterns.

Cutting Edge Information's study, "Phase IV Clinical Trials: Best Practices in Post-Marketing Study Management," found that in the U.S., CER studies typically cost drug companies $14,924 per patient. But companies that conduct these studies in Europe can see a substantial savings. According to the research, European CER studies run an average $9,873 per patient.

"Comparative effectiveness research studies are some of the more costly Phase IV trials that companies can invest in," said David Richardson, research team leader at Cutting Edge Information. "They can also prove risky for companies when their drugs don't compare favorably. However, the risks may be worth the gamble as product teams face reimbursement challenges by payers who are unwilling to cover more costly treatments for unclear patient benefit."

CER presents an opportunity for drug companies to prove that their products are not only more effective than their competitors, but could also prove better patient outcomes -- such as longer life spans -- and more cost-effective in the long run.

"Phase IV Clinical Trials: Best Practices in Post-Marketing Study Management," available at http://www.cuttingedgeinfo.com/research/medical-affairs/phase-iv-clinical-trials/, contains per-patient cost benchmarks on comparative effectiveness studies, patients-per-site, patients-per-investigator and other key metrics for five types of Phase IV studies. It includes metrics covering the U.S. and Europe as well as major therapeutic areas.

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Open (Label) and Shut Case

08/09/2011 09:52 AM |

On July 5^th,  Eli Lilly, Johnson & Johnson, Novartis, Novo Nordisk, Pfizer, and Sanofi-Aventis filed a Citizen Petition with the FDA asking the agency to clarify its policies on how truthful, non-misleading scientific information not included in approved product labeling can be communicated.

 

According to the petition, communicating accurate scientific information about new research would enhance health care quality and potentially lead to better patient outcomes, but that companies lack precise guidance on how to communicate such information.

“Scientific exchange,” broadly defined, is the sharing of research and clinical information about investigational medical products or new information on approved products without representing the product as safe and effective for that use.  FDA said in a 1963 regulation that it does not intend to restrict “scientific exchange.”  The concept of “scientific exchange” however, is not precisely described in FDA’s regulations and therefore leaves ambiguity about the limits of what is permitted.

 

We now have, thanks to those wonderfolks at DDMAC, some clarity when it comes to one kind of scientific exhange – open label trials.

 

DDMAC has cited Nycomed for a flashcard that based many of its claims on articles that “describe the preliminary and follow-up efficacy results of an uncontrolled, open-label study in patients with actinic keratoses."

 

"Results from a single open-label trial with no control group do not constitute substantial evidence or substantial clinical experience to support these, or any other, efficacy claims," DDMAC said, referring to graphs purporting to show how effective Solaraze is at "clearance of target lesions" of actinic keratoses.

 

This study also was not acceptable as a basis for a claim about the effectiveness of Solaraze in treating subclinical lesions, the letter adds. The company also cited an open-label study - it is unclear whether it was the same one - to claim that "the majority of patients were compliant with treatment," which also was unacceptable, according to DDMAC.

 

DDMAC has sent several sponsors (Arbor Pharmaceuticals, Hill Dermaceuticals, AMAG Pharmaceuticals) letters recently making it clear that open-label trials are not considered to be acceptable evidence of clinical efficacy.

 

 

You ask for clarity.  You get clarity. 

 

For a change.

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Provenge: Poster Child For An Age of Decline?

08/08/2011 05:42 PM |

I have read several articles and posts about the how the use of Provenge -  the first vaccine to delay prostate cancer -- is well below expectations.   Most of the discussion surrounds whether the slow adoption of Provenge is a function of the company not being ready to roll and work with doctors to get reimbursement for the vaccine or whether doctors are finding the effort to get approval for the use of Provenge and getting paid for it, worth the hassle and expense. 

If you compare Provenge to a Benlysta, the first new treatment for lupus in 50 years, you can't help but conclude that the beating Provenge took and the uncertainty that swirls around it's reimbursement still -- some might call it fear -- is so significant among community doctors that even the best sales force couldn't ovecome it.   Benlysta was approved in March of 2011 and HHS issued a reimbursement code for the drug July 1.    Provenge not only took a year, it was the subject of a Medicare technology review committee hearing.   A big part of the difference is the beating Provenge took at the hands of Medicare and anti-innovation types.

Is Provenge a harbinger of how innovation will be handled?  I don't have the answer to that.  But there is a dramatic disconnect between what scientists are discovering and the ethos of most of the rent-seeking companies, regulators, health plans administrators, Commonwealth Fund/Soros funded researchers, etc.  That ethos is organized what Aaron Wildavsky called "radical eqalitarianiasm:"  the belief in the moral virtue of equalizing differences.  Medical innovation is regarded as a source of inequality:  the less we spend on new cancer drugs, the more we can spend on healthcare entitlements. 

The contributions of medical technology are denigrated and the harms of innovations --  cancer, heart attacks, autism --  as part of a narrative depicting commercialization of science as a corrupt and corrupting enterprise the place profits above people.  The healthcare stakeholders by and large are consumed with finding fault, imposing the precautionary principle, holding up each and every innovation to the benchmark of comparative effectiveness or tort action.   They view innovation as a source or vector for inequality or injustice and treat marketing of any form as a potential criminal activity.  And hence they regard all new technologies as expensive, potentially dangerous, while adding a teardrop of benefit to society at an enormous cost. 

The prevailing cultural view of "the stakeholders" towards innovation is one of deep hostility.   Opposing views of the relationship between humanity and medical innovation are hardly heard and barely represented.  When they are, those who regard commercialization as inherently corrupt and regard themselves as the annointed visionaries who know what is best for the rest of us, invoke the canard of conflict of interest.  

The radicals claim innovation won't wither because of requlation, it will only make companies more 'competitive.'     In one sense they are right.  Venture capital and IPO financing for medical technology and life science companies are at all time highs -- in China.   That may be part of the effort to respond to the growing demand for healthcare services in emerging markets.   But in China, new biotech and medical device companies are welcomed instead being treated as criminals or obstacles to human progress.

The gauntlet Provenge had to run through is a product of that hostility.   And there's more to come.




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The Bully Pulpit

08/08/2011 08:05 AM |

Witness the prescient wisdom of Ralph Waldo Emerson who wrote, “Democracy becomes a government of bullies tempered by editors.”

Now consider the story of HHS v. Forest Laboratories.

When the Wall Street Journal pointed out the utter outrageousness of HHS threat of debarring Forest Labs CEO Harold Solomon (Kathleen Spitzer, 5/2/11), the department sent a BSD letter to the editor (if you don’t know what these letter to the editor restating, for all intents and purposes, “look out, there’s a new sheriff in town.” (PS/ If you are not familiar with the acronym “BSD,” please ask a friend to explain.)

But the Journal was right and the U.S. Department of Health and Human Services was wrong.

 

The gist of the Journal editorial can be summed up in these two excepted paragraphs:

 

HHS says its action is about holding corporate CEOs accountable, but it looks more like the Administration's latest bid to intimidate the health-care industry into doing its bidding on prices, regulations and political support for ObamaCare. This is the same agency that has threatened insurers with exclusion from new state-run health exchanges if they raise their premiums more than Mrs. Sebelius wants, or if they spread what she deems to be "misinformation" about the President's health bill.

The hammer on Forest Labs "reinforces everybody's worst fears—that this Administration won't do business with anybody that doesn't completely agree with its policy initiatives. Not only will it refuse to even have the argument, it will actively destroy these people," says Peter Pitts, a former Food and Drug Administration official who now runs the Center for Medicine in the Public Interest.

 

But, just like any other blustering bully, when you stand up for what’s right – the bully folds like a house of cards.

 

On Friday, HHS dropped its foolish efforts to force the resignation of Harold Solomon after protests from the company and major business groups.

 

In another letter, this time to Mr. Solomon, the office of the inspector general of the Department of Health and Human Services said, "Based on a review of information in our file, and consideration of the information your attorneys provided to us both in writing and in an in-person meeting, we have decided to close this case."

 

Oops.  Sorry about that.

 

A statement from the HHS inspector general's office Friday said: "We remain committed to investigating and, when appropriate, sanctioning executives" who engage in health-care fraud. "This includes individuals who directly committed fraud as well as executives who were in a position of responsibility at the time of the fraud.”

 

As they should.  And when the fraud is an attempt by the current residents of the Humphrey Building to cow healthcare companies into obsequious servitude – they should, equally and publically and aggressively, be called to task.

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FDA Not Relaxed About Lazy Cakes

08/05/2011 05:32 PM |

When you think of the FDA the last thing that comes to mind is an agency ready to protect kids from overdosing on brownies baked with melatonin in them. 

"Public health advocates and some mayors are sounding the alarm over Lazy Cakes, a brownie adorned with a lackadaisical cartoon character and laced with a powerful sleep aid that has sold millions nationwide.

“Children are attracted to brownies,” said Dr. Caroline Apovian, director of the Nutrition and Weight Management Center at Boston Medical Center. “I don’t think it’s appropriate to put herbal things that are actually drugs in brownies or food items that are attractive to children. I think that’s heinous.”

One Lazy Cake, which is wrapped in plastic with a photo of a smiling cartoon brownie, contains 8 mg of melatonin, a sleep-inducing supplement not regulated by the federal government. Apovian said 10 mg of melatonin would cause an adult to abruptly fall asleep."

Alarm? Heinous? 

To see the breathless coverage and comments from Nannystaters you would think that the FDA was racing to head off some terrorist plot.  The contraband in question is lazycake brownie advertised as having "relaxation baked in".    I mean they are brownies for goodness sakes, not ground turkey or Avastin...

Of course, all it took was one stupid grown up to spoil snack time for America's youth:

"Earlier this year, a 2-year-old Tennessee boy was hospitalized after a relative gave him a portion of a Lazy Cake, according to news reports."

The brownies have about 10 mg of melatonin in them.  Melatonin pills have about 3 mg of the stuff.  Apart from the toddler from Tenn this is no evidence that the the brownies harming kids or turning them into zombies.  And it's not as if the Lazycake guys are the first to make something quasi-therapeutic taste good too:  Flinstone vitamins anyone? Or how about fruit flavored zinc lozenges?   Maybe we should ban making any medicine flavorful because that would make them "attractive".

I am trying to figure out what alarm is...  Maybe some people believe that if you market brownies laced with melatonin and stress how relaxed they make you feel and well, the next thing you know they'll be selling Chips Ahoy cookies with Valerian root will become the next gateway snack. 

Apparently the FDA will demand changes in the labeling and marketing of the product or else..  Maybe they should require Lazycake to be stored behind retail counters like cough medicines and the morning after pill.   Oh wait, that's a serious proposal under consideration.    So too, I bet, is a lawsuit sometime soon. 

Maybe everyone should just.... chill.  But not with a brownie. Unless there's some perspective and common sense baked into them.



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Part D Success

08/05/2011 04:23 PM |

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A Political Headline if Ever We Saw One

08/04/2011 08:07 AM |

An instant classic inside-the-Beltway headline:

"FDA Approves First-Ever Treatment For Scorpion Stings."
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