Empower FDA By Eliminating CER

04/19/2012 11:39 AM |

My heart is with Mike Rogers and other members of Congress who want to expand FDA's mission to include  job creation and economic growth.   And I get the message they are trying to send to the public and the FDA about what's important.  CMPI has consistently made the case that medical innovation is the primary source of longevity and prosperity.  

But the way to change FDA to promote those broader objectives is to hold it accountable to new standards for product approval and oversight reflecting dramatic changes in the science sustaining innovation.   Congressman Rogers and others can help the FDA by getting them out of the comparative effectiveness business. Reauthorization of PDUFA will give the agency more resources and more direction with regard to increasing the predictability in the development process for drugs, devices, diagnostics and combination products.  However, the FDA would get a boost if legislation stipulated that any products that use biomarkers or other tools to target treatments and improve the ability to monitor disease progression or response would be automatically approved for use in Medicare, Medicaid, etc. 

The more we can defang what is an increasingly worthless CER enterprise the more FDA can achieve the mission the Congressman Rogers wants the agency to carry out.   CMPI will be releasing a study, supported by the Kauffman foundation, that estimates how much innovation and health value our nation will forfeit if CER becomes the focus of commercialization instead personalized medicine.   The estimates, even with conservative assumptions built in, are staggering.  

Every time someone at FDA has to pay lip service to CER it is a signal to companies that all the work put in on diagnostics, combination products and targeted treatments will go to naught because they have to wait for a bunch of underachieving health economists and other professionals to conduct systematic reviews or horizon scams, I mean scans, or clinical trials.   Then again, as I noted in my last post, it looks at though PCORI will be handing out dough to to figure out how to conduct patient-centered research and how to engage patients, though the last time I checked no one -- except the stakeholders who will also get the PCORI cash --  was asking for such government help. 

You want to make medicine patient-centered?  Produce patient-centered medicine.   Tools and treatments that reduce hassles, improve life, increase health. 

That's something FDA can, should and is trying to do in collaboration with companies.  If you asked people should we spend $3 billion on medical decision making or the same amount making better medicines more quickly available to people who need them, I don't have any doubt that faster approvals would win.

The FDA could do a lot with $3 billion over the next decade and do much more for our health and nation than PCORI ever will.  Just a suggestion if Congressman Rogers wants to amend his bill....



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And Rounding the Club House (and Senate) Turn ...

04/19/2012 08:05 AM |

Yesterday the HELP Committee released a draft version of PDUFA legislation and plans a April 25 PDUFA mark-up.

The Senate draft creates a new pathway for review of "breakthrough" therapies, requiring FDA to work with sponsors to expedite approval of products to treat serious or life-threatening diseases based on "preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints."

On the other side of the Capitol, the House Energy and Commerce Committee released a discussion draft of PDUFA reauthorization legislation on Wednesday. Both the House and Senate bills incorporate the Generating Antibiotic Incentives Now (GAIN) Act, which would extend market exclusivity by five years for drugs that treat antibiotic-resistant pathogens. The E&C version includes an additional six month extension for drugs approved along with a companion diagnostic; this provision has been deleted from the Senate version.

The House draft also seeks to permanently reauthorize two laws that create incentives for conducting clinical trials in pediatric populations, the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Similar legislation, the Better Pharmaceuticals and Devices for Children Act, was introduced with bipartisan sponsorship in the Senate on Tuesday; it is likely to be incorporated into the Senate PDUFA reauthorization bill.

House lawmakers said they were optimistic that any outstanding issues in the GOP draft would be resolved in the coming days, and full committee Chairman Fred Upton (R, MI) said he was convinced the panel is on track to meet his goal of approving the legislation by the end of June.

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PCORI's Maximum Feasible Participation (Of Consultants)

04/18/2012 06:38 PM |

I am sure that I will be one of the few that doesn't laud PCORI for focusing so much on patient-centeredness.  But I have two questions:  Just what is PCORI (and all the CER cronies they will pay through AHRQ to consult) doing? 

That PCORI was able to get JAMA to publish two fluffy and self congratulatory editorials that explain how patient-centered reflects the extent to which PCORI, AHRQ and the consultants it funds will be able to disseminate about any crap that it produces through the 'major' medical media outlets.   AHRQ, PCORI and cronies are able to get anything it produces published in medical journals.  It is spending hundeds of millions of dollars peddling CER to doctors who in exchange get CME credit just for clicking on to a website.   And PCORI will be spending hundreds of millions of dollars holding conferences, webinars, etc  to explain to 'stakeholders' how patient-cetered they are.

But what exactly is PCORI producing?

In the JAMA puff piece, Joe Selby and colleagues note:

"The institute's first funding announcement solicited projects focused on methods for engaging patients and other stakeholders in all aspects of the research process. "

They conclude that "The proposition that greater involvement of patients, clinicians, and others in the research process could help reorient the clinical research enterprise, reduce clinical uncertainty, and speed adoption of meaningful findings holds great promise, but remains to be tested. PCORI will test this hypothesis. The underlying imperative is to improve patients' care experience, decision making, and health outcomes. Patients as well as the physicians and other health care professionals who care for and about them are invited and encouraged to join in this effort. "
http://jama.ama-assn.org/content/307/15/1583.full?ijkey=2UlGCXlTXheck&keytype=ref&siteid=amajnls

This sounds alot like maximum feasible participation encouraged in community action programs during the 1960s.   In his book "Maximum Feasible Misunderstanding,"  Daniel Patrick Moynihan noted that the "war on poverty was not declared at the behest of the poor.  It was declared in their interests by persons confident in their judgment on such matters." 

The War on Poverty was not a war and did not do much about poverty.  But it did employ and give out grants to the policy entrepreneurs who conceived the War on Poverty in the first place.  That consisted of professional economists, professional social scientists, government officials and professional philanthropists.

Similarly,  PCORI was not created in response to an outcry from patients about the lack of inclusion of their "voices" in medical decision making.  It was a product of the same said professionals who supported PPACA and who believe that spending $3 billion on making sure the CER they produce is marketed and used is in the nation's interest.

The article by the Methods Committee on how it plans to spend money on grants reflects a similar disconnect between the needs of patients and the myopic goals of the CER community.  See if you can figure out the punchline of this paragraph:

"Ms M is a 45-year-old woman with depression (Box 2), whose situation similarly highlights the gap between existing research and the characteristics and concerns of patients. Little evidence exists about which sequence of treatments is optimal for Ms M's constellation of symptoms, adverse effects, or initial response. Despite more than 1000 trials on antidepressants and related treatments, most studies include patients with narrowly defined characteristics who are followed up for short periods, do not take place in settings in which care is routinely delivered, and include a limited spectrum of comparators, including drugs and other therapeutic approaches.^11​ How can clinical research focusing on much larger, long-term issues trials yield more personalized guidance for patients like Ms M?¹²"

http://jama.ama-assn.org/content/307/15/1636.full?ijkey=419QnSMR.MBDU&keytype=ref&siteid=amajnls


The Methods Committee presumes that since all manner of studies have never been able to identify what treatment is right for Mrs M that the solution is to spend more  money on methodologies that will be larger and more long term but at the same time yield more personalized guidance.  

Does anyone believe that bigger studies that take longer to produce will,  especially at a time when medical information is becoming digitized and atomized, yield personalized guidance that patients will abide by and obey?    Am I the only one who sees a social science scam in all this?  Is this too cynical on my part?

More later. 
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Survival of the Most Compliant

04/18/2012 08:24 AM |

They’ve got a list.  And they’re checking it twice.

The giant PBM Express Scripts is launching ScreenRx, a program that uses a computer to sift through hundreds of factors that affect patients and forecast who is most likely to forget a refill or simply stop taking their drugs. The company then plans to contact those patients to help them stick with their doctor's orders.

It’s estimated that about $317 billion in additional medical expenses were incurred by the U.S. health care system last year because people didn't comply with prescriptions. These additional expenses might include a heart attack for someone who stops taking cholesterol medicines or an amputation for someone who doesn't adhere to diabetes treatment.

The analysis, called predictive modeling sorts through more than 400 variables that could affect a patient to see which people have enough red flags to warrant concern.

Once a patient has been flagged, they receive a phone call. An Express Scripts representative will talk to the person to see if they need help. The PBM then might send the patient a pillbox if they have a hard time remembering their prescriptions or a special beeper that goes off when it's time to take medicine.

If the patient struggles to pay for the drugs, Express Scripts will provide information on assistance programs.

According to a report in the Washington Post, “Analysts say predictive modeling programs that aim to forecast patient behavior and improve care have been evolving in health care over the past few years, and the Express Scripts product is the latest evolution.”

Survival of the most compliant. Would Darwin have approved?

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Towards a Sustainable Innovation Ecosystem

04/17/2012 07:35 AM |

Eli Lilly’s John Lechleiter believes that the biopharmaceutical industry exists in an “innovation ecosystem.” A new study by the Tufts University Center for the Study of Drug Development (funded by PhRMA) confirms that notion by exploring the breadth and nature of partnerships between biopharmaceutical companies and academic medical centers (AMCs).

The full study can be found here.

The Tufts study examines a subset of public-private partnerships – more than 3,000 grants to AMCs from about 450 biopharmaceutical company sponsors. The Tufts report describes the various types of partnership models that exist, and recent trend as well as identifies next generation academic-industry collaboration models emerging from the public-private-partnership paradigm.

To add to Lechleiter’s phrase, the report discusses the importance for and a model of a sustainable innovation ecosystem. This is in keeping with the ethical and pragmatic policy of the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) regarding the disclosure of conflicts of interest:

“There is no inherent conflict of interest in the working relationships of physicians with industry and government.  Rather, there is a commonality of interest that is healthy, desirable, and beneficial.  The collaborative relationship among physicians, government, and industry has resulted in many medical advancements and improved health outcomes.”

Some findings from the Tuft’s study:

The partnerships examined in this report fall into three primary categories: joint clinical trials (75%), studies targeting public health priorities (14%), and health research and education projects (11%).

* 72 percent of the joint clinical trials are for pharmaceuticals.

* Studies targeting public health priorities cover a range of topics, including breakthrough-investigations involving multiple disciplines.

* Joint health research and educational activities ranged from basic medicine to translational research to new technologies, particularly nanotechnology and pharmacogenomics.

Tufts found that these relationships often involve company and AMC scientists and other researchers working side-by-side on cutting-edge science with advanced tools and resources, enabling the U.S. to rise to the challenge of various biomedical opportunities, such as personalized medicines and a growing understanding of rare diseases.

The report outlines the 12 primary models of academic-industry collaborations and highlights emerging models, which reflect a shift in the nature of academic-industry relationships toward more risk- and resource-sharing partnerships.

* Unrestricted research support has been one of the most widely used models. While these models have generally represented the most common form of academic-industry collaboration, Tufts research found that they are becoming less frequently used.

* The report found a range of innovative models emerging, from corporate venture capital funds to pre-competitive research centers to increasingly used academic drug discovery centers.

Examples of emerging academic-industry partnership models include:

* The Coalition Against Major Diseases, a consortium under the Critical Path Institute, involves biopharmaceutical companies, academic institutions, and others working together to facilitate the development of effective treatments for Alzheimer’s and Parkinson’s disease.

* Eli Lilly and Company launched the Open Innovation Drug Discovery program to facilitate research on molecules around the world that have the potential to ultimately be developed into medicines by allowing academic and other researchers to submit molecules for free screening as potential drug candidates.

* Sanofi has a strategic alliance agreement with the Massachusetts Institute of Technology’s (MIT’s) Center for Biomedical Innovation focused on advancing knowledge in the area of human health through basic and applied research and promoting scientific exchange between MIT and Sanofi researchers to support the development of health care solutions for patients.

The report highlights the mutual benefits of partnerships:

* Both academia and industry are facing increasingly complex scientific challenges. According to the report, as the scope of some of the scientific challenges is so large, collaboration is viewed as increasingly important to making significant progress.

* Partnerships benefit both industry and academia by providing the opportunity for the leading biomedical researchers in both sectors to work side-by-side to explore the promising new technologies and scientific discoveries that have the potential to treat the most challenging diseases and conditions facing patients today.

The report finds that the nature of collaboration occurs across all aspects of drug discovery. According to Tufts, companies are funding and working collaboratively with the academic component of the public sector on basic research that contributes broadly across the entire spectrum of biomedical R&D, not just for products in their portfolios.

The report concludes that academic-industry partnerships are growing in number and importance as “the translational gap between discovery and clinical development has become increasingly difficult to bridge.” The complementary nature of partnerships involving AMCs and biopharmaceutical companies increases synergies between the two sectors, ―enabling the nation’s R&D enterprise to tackle the most complex and challenging diseases and conditions.

How’s that for sunshine?

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Wanted: Clarity on Biosimilarity

04/16/2012 09:08 AM |

The official comment period is over and it's pretty clear that FDA’s February 9^th biosimilar draft guidance has sparked resistance among some industry players – specifically over certain definitions and requirements. No surprises there.

Stakeholders sent criticisms over the suggested protocols as well as several recommendations for change. The draft guidance, contained in three documents, represent FDA’s interpretation of the Biologics Price Competition and Innovation (BPCI) Act of 2009.

Biosimilarity

Two drug developers said that the agency should tighten its proposed biosimilarity standards. While commending FDA for “an excellent job drafting guidance on quality considerations for demonstrating biosimilarity to a reference product,” Genentech took issue with FDA’s proposed wording that manufacturers “should” thoroughly assess the analytical similarity of their biosimilars to their reference products, and  “should” perform in-depth chemical, physical, and bioactivity comparisons with side-by-side analyses of “an appropriate number of lots of the proposed biosimilar product and the reference product.” FDA also suggested that “where available and appropriate,” manufacturers compare their products with the reference standard for specific suitable attributes such as potency.

The assessment of the analytical similarity of a biosimilar product and the robustness of these methods are fundamental requirements for a biosimilarity assessment, and use of the word “should” implies that it does not necessarily need to be done, Genentech noted. “Please replace ‘should’ with ‘is expected to’ or ‘needs to,’” Genentech stated in a letter transmitted to the agency by Earl Dye, director of technical regulatory policy and strategy.

Novo Nordisk urged FDA to define biosimilars as products that are as similar as scientifically possible to their reference products, at least through sharing the same amino acid sequence, without exception, as their reference products. The company cited FDA’s emphasis on the importance the 3-D structures of proteins play in their biological functions and the ability of post-translational modifications to alter the proteins’ functions.

“FDA should never permit biosimilar applications for products that cannot be adequately characterized,” Novo Nordisk stated in its letter, signed by James C. Shehan, Novo Nordisk’s corporate vp, legal, government, and quality affairs.

Biosimilar producer Biocon counter-suggested that FDA should expect that the expression construct and/or the processing of a proposed product would result in the same primary amino acid sequence as the reference product. Some expression constructs may give a precursor protein that only after modification in the process will yield the same amino acid sequence as that of the reference product, Biocon noted in its letter, submitted by Siriam Akundi Ph.D., associate vp, quality, and regulatory.

Demonstrating Safety

Novo Nordisk also believes that biosimilar applicants “should always submit the results of comparative animal toxicity studies.” It added, “In the current state of science, some form of comparative safety and effectiveness testing will be necessary for almost all biosimilars.

“All biosimilar applicants should conduct at least one comparative clinical pharmacokinetic study and, where there is a relevant pharmacodynamic marker, at least one comparative clinical PD study,” Novo Nordisk added. “Similarly, a biosimilar applicant should always conduct at least one comparative clinical immunogenicity study.”

Two patient groups also called for FDA to promote greater safety. The Colon Cancer Alliance asked FDA to require “extensive” clinical testing of biosimilars, with a system capable of rigorously tracking and tracing them back to their product of origin. “It is critical to the safety of patients that these drugs be submitted to open and robust clinical studies and are marked with a unique and transparent product labeling system that will facilitate robust pharmacovigilance,” Global Healthy Living Foundation (GHLF) president Seth Ginsberg wrote in GHLF’s letter.

Interchangeability

Ginsberg noted that it is difficult to designate a biosimilar as interchangeable with their innovator products unless there is sufficient data. He expressed concern that decisions on interchangeability could be made by pharmacists or insurers through states’ automatic substitution policies. “We believe that the choice of product should be decided only by patients and physicians, who are ultimately responsible for patient care and have the full spectrum of a patient’s medical history,” Ginsberg added.

Novo Nordisk urged FDA to confirm that it would not designate a new biosimilar delivery device or container closure system as interchangeable with its reference product “where additional training on the new device or system is necessary to guide safe use, or where the proposed delivery device or container closure has inequivalent performance or critical design features.”

And miles to go before …

“The keys to success for the biosimilar pathway are informing and educating patients and physicians on the benefits and safety challenges of replicating biologic drugs, providing a unique and distinctive naming and labeling system, and understanding that the FDA’s approval of a biosimilar as a standalone therapy does not mean that it is interchangeable with its biologic counterpart,” the Colon Cancer Alliance stated in its letter to FDA written by CEO Andrew Spiegel.

The alliance urged FDA to adopt a system that uses individual nonproprietary names for biologics and biosimilars, enabling physicians, patients, and regulators to differentiate between products easily—a suggestion also made by Novo Nordisk and the National Association of Chain Drug Stores.

Biocon took issue with FDA’s requirement that sponsors provide “sufficient scientific justification” for extrapolating clinical data to support biosimilarity determinations for each condition of use for which a license is sought. “Once biosimilarity is established, and product is approved for one indication, no additional clinical studies should be expected for obtaining approval for other approved indications,” Biocon stated. “If the route of administration, dosing frequency, and dosage amount of the proposed biosimilar is identical to the reference product for each indication, any additional clinical studies should not be expected.”

Novo Nordisk also urged FDA to publish product-class specific guidance for biosimilar and bioequivalent applications for complex proteins, like the EMA has done. With all the discord that FDA’s draft biosimilar guidance has created, the agency will have to work to balance the interests of innovators, biosimilar developers, and patient groups. The agency will have to ensure that it does not tilt its final guidance toward developers of new drugs by rules that unduly impede biosimilars. Nor should it tilt its requirements toward biosimilar makers seeking less rigorous review. It won’t be easy, but balancing competing interests will ultimately benefit companies, researchers, and especially patients, by finally providing a biosimilar pathway in the U.S. 

And that's assuming the law that makes biosimilars possible remains on the books after the Supreme Court ruling.

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'Choosing Wisely' Replaces Hippocratic Oath With The Ethos of The Hunger Games

04/13/2012 12:23 PM |

http://spectator.org/archives/2012/04/13/obamacares-medical-mercenaries  Read More & Comment...

In Vitro Veritas

04/13/2012 07:24 AM |

In Vitro Veritas

A renegotiation of the EMA (European Medicines Agency) medical devices directives is imminent.  Our spies tell us that, for in vitro diagnostics, a line will be drawn between tests used as companion diagnostics -- where clinical evidence of their applicability will be required -- and other in vitro tests such as PSA for prostate cancer -- where no such evidence will be required.

Uneasy lies the head that wears a crown

Eric Abadie, the chair of CHMP (The Committee for Medicinal Products for Human Use) has resigned -- another victim of L’Affaire Mediator (the French anti diabetic /anti obesity drug remained questionably available in France and killed somewhere on the order of 5000 patients from pulmonary valve disease). The French Agency sacked him and the EMA opted not to pick up his salary.

Meanwhile on our own placid shores

Here’s an excellent article from the April edition of Nature Biotechnology on some of the key policy questions facing the US biotech sector pending PDUFA and presidential politics.

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First Person Risk Benefit

04/12/2012 08:19 AM |

Part of the FDA’s promise for PDUFA V is a more patient-centered approach to risk/benefit analysis. A timely new analysis provides a closer look at how much cancer patients value hope --with important implications for how insurers value treatment, particularly in end-of-life care.

The analysis by Darius Lakdawalla, director of research at the Schaeffer Center at USC and associate professor in the USC Price School of Public Policy, surveyed 150 cancer patients currently undergoing treatment, and is part of a special issue on cancer spending from the journal Health Affairs.

Lakdawalla and his co-authors found the overwhelming majority of cancer patients prefer riskier treatments that offer the possibility of longer survival over safer treatments: 77 percent of cancer patients said they would rather take a “hopeful gamble” — treatments that offer a 50/50 chance of either adding three years or no additional survival — to “safe bet” treatments that would keep them alive for 18 months, but no longer.

“Consumers tend to dislike risk, and researchers and policy makers have generally assumed that patients care about the average gain in survival,” Lakdawalla said. “But patients facing a fatal disease with relatively short remaining life expectancy may have less to lose and be more willing to swing for the fences. This analysis points to the larger ideal — that value should be defined from the viewpoint of the patient.”

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Drug Shortages and GPOs

04/11/2012 08:41 AM |

Reaching the wrong conclusion only makes a problem worse. Witness drug shortages and a bill pending in Congress that would require drug manufacturers to notify federal officials of a disruption to a drug supply six months in advance.

In theory, such a requirement would give the FDA an opportunity to prevent the shortage, notify health-care providers and develop a contingency plan. In reality, that’s not the problem.

 “What we’re trying to find out is whether there’s a pattern behind the shortages that we can address,” comment senator Richard Durbin (D, IL). “We’ve got to get down to what is really behind it and try to solve it.”

Precisely.

While earlier and more robust communications between drug manufacturers (largely generic manufacturers of hospital injectables) and the FDA is important – lack of such interaction isn’t the major cause of the problem. The issue at hand is that that, because of the way hospitals purchase medicines, there is no incentive for drug makers to update manufacturing facilities or build new ones. Hence, when a facility goes off-line due to quality concerns (the major cause of supply line disruption) or is retooled for a different (and more profitable) use – shortages can occur. In such an instance, should a manufacturer advise the FDA of potential shortages? Certainly.

But that’s not the real problem. The unreported problem is the role of Group Purchasing Organizations (GPOs). GPOs control the purchasing of more than $200 billion in drugs, devices, and healthcare supplies annually for some 5,000 private, acute care hospitals nationwide. And they keep costs low. That’s the good news. The bad news is that they are also permitted (by law) to charge a fee to hospital suppliers based on percentage of sales volume for a particular product. And sometimes it’s a hefty one – often as high as 35-50%. That certainly throws a spanner in the supply-and-demand proposition. Six months supply at ever-lower margins becomes a non-starter for many companies – further exacerbating the problem rather than solving it.

GPOs are a monopsony (a buyer’s monopoly) dominated by six firms that control about 90% of the goods purchased by hospitals via GPOs. The power of these organizations is such that they can often dictate which drugs, devices and supplies are used in hospitals – and which companies are allowed to sell them.

These practices have created a concentrated market that excludes other existing and would-be suppliers and distributors. So, with no other suppliers able or available to fill the gap, increases in demand for generic drugs have resulted in shortages and surging prices. It is no coincidence that the problem is generally limited to generics sold to healthcare facilities through GPO contracts rather than directly to consumers through retail pharmacies.

GPOs have their critics. Among them is former Wall Street Journal reporter Phil Zweig who writes that, “GPOs have concentrated production of generic drugs in a handful of drug makers and have forced some manufacturers to cease production of various lifesaving drugs altogether and distributors to slash inventories to the bone. In a nutshell, these cartels have undermined the laws of supply and demand in this critical industry.”

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IOM signs on to Regulatory Marshall Plan

04/10/2012 08:45 AM |

It’s time to actively and aggressively pursue FDA Commissioner Peggy Hamburg’s call for a regulatory Marshall Plan to help build, nation-by-nation, global systems for both quality and safety. A high tide floats all boats.

A new IOM report concludes the FDA should invest in advancing the regulatory capacity of developing low and middle income nations in order to secure the pharmaceutical supply chain and safeguard the American public.

The report, Ensuring Safe Foods and Medical Products Through Stronger Regulatory Systems Abroad, recommends 13 steps FDA and other regulatory bodies can take in the next five years to improve the regulatory systems of developing nations.

Rather than try to inspect all foreign establishments itself—something IOM conceded was unrealistic given FDA’s limited budget—FDA should instead invest in improving other regulatory systems to accomplish its goals of ensuring a safe pharmaceutical supply chain.

After all, as Peggy Hamburg has repeatedly said, ““We can’t inspect our way out of this problem."

The IOM reports, “The FDA should use partnerships to drive improvements in supply chain management. The committee recommends that the FDA work with strong regulators in other countries to plan inspections and pool data. There is no need for American and European inspectors to duplicate each other’s work, especially when a vast number of facilities go uninspected … One promising initiative is the two-year FDA Secure Supply Chain pilot program, which rewards firms that trace their products thoroughly from manufacture to entry into the United States.”

 “The report urges FDA and its technologically advanced counterparts in the European Union, Canada, Japan, Norway, Iceland, Switzerland, Australia, and New Zealand to plan a system for mutual recognition of one another's inspections, which would eliminate the wasteful duplication of effort,” wrote IOM in a statement.

FDA, the European Medicines Agency (EMA), Australia’s Therapeutic Goods Administration (TGA) and the World Health Organization have all announced their participation in a global active pharmaceutical ingredient inspection program that might go a long way toward accomplishing IOM’s recommendations—something IOM agrees with in principle.

IOM also called on industry association to “define a reliable way to share internal inspection results among their members within the next three years.

With scare resources, perhaps the best place to start is by committing to common standards for data capture and reporting.

After all, knowledge is power.

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If a tree falls in the forest ...

04/09/2012 07:44 AM |

It is rare that the words “progress” and “Alzheimer’s Disease” are used (positively) in the same sentence.

Maybe that’s about to change.

Last week the EMA's CHMP adopted a qualification opinion that positive/negative PET imaging of amyloid can be used as a biomarker to identify patients in clinical trials with predementia Alzheimer's disease (AD) who are at increased risk to have an underlying neuropathology. Now an Eli Lilly & Co. diagnostic that detects the presence of proteins in the brain that are related to Alzheimer's disease is FDA-approved.

According to a report in the Wall Street Journal, “The tool could enable clinicians to detect Alzheimer's earlier and more accurately in patients at the earliest sign of memory problems—a potential boon to treatment and developing drugs against the disease.”

A lack of ability to reliably diagnose patients in the early stages of the Alzheimer's disease has hampered research. Some experts believe that investigational drug trials have failed because patients enrolled in such studies already had progressed too far for the treatments to be effective.

Proponents of using florbetapir and similar agents that are being developed have said that such technology will accelerate research by helping to accurately identify people at high risk of developing the condition and to enroll such people in therapeutic trials.

The test uses a chemical called florbetapir, known by the brand name Amyvid, which is a radioactive agent that tags clumps of a sticky substance called an amyloid. Amyloid proteins are hallmarks of Alzheimer's disease. The chemical, which costs $1,600 per dose, then is detected using a brain imaging technique called positron emission tomography, known as PET scans.

The Journal raises an important point, “Some experts have questioned how useful the test is since no treatments are available that significantly alter the course of the disease. But some doctors believe that patients may find a diagnosis helpful for planning purposes or just to know for certain that they have Alzheimer's.”

Question – will payers pay?

If a tree falls in a forest …

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Remember when

04/06/2012 08:39 AM |

BioCentury reports:

EMA backs AD biomarkers

The EMA's CHMP adopted a qualification opinion that positive/negative PET imaging of amyloid can be used as a biomarker to identify patients in clinical trials with predementia Alzheimer's disease (AD) who are at increased risk to have an underlying neuropathology. CHMP also adopted a qualification opinion that the combination of low beta amyloid (1-42) and high tau in cerebrospinal fluid (CSF), and amyloid-related PET imaging, can be used to identify patients with mild to moderate AD who are increased risk of an underlying AD neuropathology. CHMP said the biomarkers are intended to enrich recruitment in trials aimed at studying products to slow the conversion to AD or severe AD.

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HELP is on the way

04/05/2012 07:47 AM |

The Health, Education, Labor and Pensions Committee released a discussion draft of legislation aimed at accelerating patient access to innovative medical treatments for life-threatening diseases.

The bipartisan Drug Approval and Patient Access Plan would overhaul the FDA's Accelerated Approval pathways and create a new "breakthrough" designation to provide more flexibility and certainty for developers of new medicines intended to address serious or life-threatening diseases or conditions.

The draft includes legislation introduced last week by Sen. Michael Bennet (D-Colo.) that would expedite FDA approval and provide more flexibility when a drug or treatment shows dramatic responses early in development.

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Taking Pediatric Medicines Development off the 5 Year Plan

04/04/2012 07:55 AM |

We called it.

At CMPI’s November PDUFA without the Politics conference, each panelist was asked to bring one ornament to hang on the reauthorization Christmas Tree.  Tim Franson (President of the USP Convention and one of the “Fathers of PDUFA”) offered a little lifeboat.

What can we do for those with life threatening unmet needs? One thing, as was done in PDUFA IV, is adding renewal of the Best Pharmaceuticals for Children’s Act. That piece of legislation has done more for pediatric drug development than anything in the past. It’s been good for American children and it should be made permanent. I think the better policy argument is to make it permanent, because companies don’t invest in five-year cycles. (Note to reader: The Act is currently renewable every five years.)

If I’m looking for a return on an investment, I need certainty well in advance of five years on types of studies I should be conducting and I need to know the benefit I’m getting at the end. I think five years is far too short a period of time.

There’s an accumulated body of evidence, of companies fulfilling their commitments. Maybe its time we make it permanent. I think this point of holding up renewal like the Sword Damocles isn’t very persuasive even to sponsors.

Well, a bipartisan House bill now proposes to permanently reauthorize two pediatric-drug statutes that include marketing incentives and clinical-study mandates, which the drug industry supports, while also giving FDA recourse for unfinished pediatric studies and requiring drug sponsors to submit their plans to the agency earlier, measures advocated by pediatricians.

Reps. Ed Markey (D-MA), Anna Eshoo (D-CA) and Mike Rogers (R-MI) introduced the bill to permanently reauthorize the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act.

The bill would require drug makers to submit an initial pediatric-study plan by the end of phase 2 clinical trials. Currently, companies must submit the information when they submit an application or supplement to the agency. FDA must promulgate a rule and guidance on the new timing requirement, according to the bill. The plan should include an outline of proposed studies and any request for a waiver to defer the requirements.

Lawmakers backing the bill said the pediatric laws have led to pediatric studies for 180 new drugs and more than 400 updated drug labels.

“Government and private industry have worked together to fill an important void,” Eshoo said in a statement. “The laws have provided greater transparency and accountability in the programs, while improving communication between FDA and companies. I’m proud of how far we’ve come and look forward to a day when we know how all medicines will affect children.”

Now sponsors are looking for a little HELP.

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One man's ceiling is another man's floor

04/03/2012 07:51 AM |

In recent statements ANVISA, the Brazilian equivalent of the FDA, has put forward the proposition that (relative to raising the level of international drug quality and safety) there isn’t a way forward but rather “ways to move forward based on local situations.

While the solution must fit the problem, this poses an interesting question – can there be a floor and a ceiling for global drug safety and quality? Even as we move toward differential pricing, should we allow some countries to have lower standards than others “based on local situations?”

When it comes to the safety of pharmaceuticals and medical devices, can one man’s ceiling be another man’s floor.

And how does this fit into the debate over trade policy versus trade practice? Should medical products that are determined not to meet any given national standard be allowed to be exported to other countries? Should there be a “good enough for me, good enough for thee” standard for international trade in pharmaceuticals and medical devices?

For example, should Beijing allow substandard API -- illegal for use in the Middle Kingdom -- to be exported to, say, Nigeria?

When Paul Orhii, Director-General of Nigeria’s National Agency for Food and Drug Administration and Control, complained to the Chinese government that China was the origin of many of the counterfeit medicines in Nigeria, he was bluntly told Beijing was not responsible for the quality of medicines in Nigeria.

That’s the unfortunate distinction between trade policy and trade practice. Is this an issue for TRIPS? Should TRIPS Article 61 be amended to include punishments and penalties for those who export medicines and medical devices that do not meet a certain global standard?

While domestic standards are undeniably an issue of domestic sovereignty, shouldn’t there be transparency as to how any given nation defines safety and quality? “Market authorization” means one thing in the context of the MHRA, the FDA, the EMA, and Health Canada (to choose only a few “gold standard” examples), but how are we to judge the regulatory competencies of other national systems? Is that the responsibility of the WHO via a better-developed (and far more transparent) pre-qualification scheme? Or regional arbiters (such as PAHO)? Should there be “reference regulatory systems” as there are reference nations for pricing decisions? Should there be regulatory reciprocity?

All the more reason for “gold standard” nations to undertake a regulatory Marshall Plan to help build global systems for drug quality and safety.

The harmonization of global trade policy and practice is essential to the sinews of international medicines quality and safety.

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Is Obamacare Doomed?

04/02/2012 10:42 PM |

Even If It Survives the Court, the Health Care Law Is Doomed By Scott Rasmussen Media coverage now implies that the U.S. Supreme Court will determine the fate of President Obama's health care law. But nothing the court decides will keep the law alive for more than a brief period of time. There are three ways the health care law could meet its end. The first, obviously, is the Supreme Court could declare some or all of it unconstitutional in June. If it gets past that hurdle, the law also could be ended by Election 2012. If a Republican president is elected, the GOP will almost certainly also win control of the Senate and retain control of the House. While the details might take time, a Republican sweep in November would ultimately end the Obama experiment. But even if the law survives the Supreme Court and the next election, the clock will be ticking. Recent estimates suggest that the law would cause 11 million people to lose their employer-provided insurance and be forced onto a government-backed insurance plan. That's a problem because 77 percent of those who now have insurance rate their current coverage as good or excellent. Only 3 percent rate their coverage as poor. For most of the 11 million forced to change their insurance coverage then, it will be received as bad news and create a pool of vocally unhappy voters. Additionally, the cost estimates for funding the program are likely to keep going up. Eighty-one percent of voters expect it to cost more than projected, and recent Congressional Budget Office estimates indicate voters are probably right. But it's not the narrow specifics and cost estimates that guarantee the ultimate demise of the president's health care plan. It's the fact that the law runs contrary to basic American values and perceptions. This, then, is the third hurdle the law faces: Individual Americans recognize that they have more power as consumers than they do as voters. Their choices in a free market give them more control over the economic world than choosing one politician or another. Seventy-six percent think they should have the right to choose between expensive insurance plans with low deductibles and low-cost plans with higher deductibles. A similar majority believes everyone should be allowed to choose between expensive plans that cover just about every imaginable medical procedure and lower-cost plans that cover a smaller number of procedures. All such choices would be banned under the current health care law. Americans want to be empowered as health care consumers. Eighty-two percent believe that if an employer pays for health insurance, the worker should be able to use that money and select an insurance product that meets his or her individual needs. If the plan they select costs less than the company plan, most believe the worker should get to keep the change. It's not just the idea of making the choice that drives these numbers, it's the belief held by most Americans that competition will do more than government regulation to reduce the cost of health care. For something as fundamental as medical care, government policy must be consistent with deeply held American values. That's why an approach that increases consumer choice has solid support and a plan that relies on mandates and trusting the government cannot survive. COPYRIGHT 2012 SCOTT RASMUSSEN  Read More & Comment...

The Supreme Court and the Individual Mandate

04/02/2012 02:45 AM |

A lively discussion on the US Supreme Court and health care reform on "This Week":


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Drug Co-Pays and Asthma Rates

03/30/2012 06:44 PM |

I am quoted in this piece published in Medscape..

http://www.medscape.com/viewarticle/761255
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NRDC Rejects Science

03/30/2012 06:33 PM |

The gap between science and the National Resources Defense Counci's fearmongering is growing at an exponential rate.  Watch as NRDC pushes a legislative BPA ban and links it to their fundraising operation... 



http://www.nrdc.org/media/2012/120330.asp

FDA Rejects NRDC Call to Eliminate BPA from Food Packaging
NRDC: ‘FDA Fails to Protect Our Health and Safety’

WASHINGTON (March 30, 2012) --  The Food and Drug Administration said today it would allow bisphenol A (BPA) to remain in food packaging, an action that keeps the hormone-disrupting chemical linked to cancer, obesity and a host of other health problems in the food supply.

In rejecting a petition today from the Natural Resources Defense Council, the agency emphasized it was not making a final determination of BPA’s safety and instead will continue to examine the ongoing research of BPA’s effects on health.

The following is a statement from Dr. Sarah Janssen, senior scientist in the public health program at the Natural Resources Defense Council:

“BPA is a toxic chemical that has no place in our food supply. We believe FDA made the wrong call.

“The agency has failed to protect our health and safety ­ - in the face of scientific studies that continue to raise disturbing questions about the long-term effects of BPA exposures, especially in fetuses, babies and young children.

“The FDA is out-of-step with scientific and medical research.  This illustrates the need for a major overhaul of how the government protects us against dangerous chemicals.”
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