INN and FTC: Let it snow. Let it snow. Let it snow.

12/10/2013 03:02 PM |

Karma is a cruel mistress.

Today's FTC hearing on biosimilars cancelled because of safety concerns (snow day in DC).
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INN and the Green-Eyed Monster

12/06/2013 07:33 AM |

A good name is better than precious ointment.                                    
-- Ecclesiastes vii. 1.

U.S. approval of biosimilars promise to be a very good thing, but the devil is on the details. Unfortunately, we’re seeing a disturbing trend relating to one of those key details – naming nomenclature.

Advocates for nonproprietary names across innovator reference product biologics and the biosimilars associated with them dangerously miss the mark on the pivotal issues relating to naming. A new editorial in Nature Biotechnology demonstrates such misguided thinking. Wither their usual good sense?

Obviously much education remains to be done on this issue in the time between now and when FDA issues final draft guidance on naming. Because where FDA winds up on this issue  -- nonproprietary names, nonproprietary names + identifier codes, unique names or somewhere in between – will significantly impact patients, providers, manufacturers, pharmacists, safety experts and others. We need to all side firmly with what's best for patients.

If you’re for patient safety, you can’t be against distinguishable naming. The WHO established the International Nonproprietary Names (INN) system in 1953 before biologics were a figment of anyone’s imagination. Through the INN system, innovators and generics that share the same active ingredient also share the same generic name, also called the INN. It’s worked pretty well for chemical compounds but, as has been acknowledged by WHO and regulatory bodies of every developed nation, biologics are not chemical compounds – they’re infinitely more complicated.

We need to learn from these market-based experiences of nonproprietary names in the EU and Thailand, and distinguishable names in places like Japan and Australia. We can also take valuable lessons from how approaches specific to naming of biologics lend themselves to more effective safety monitoring, pharmacovigilence, data collection, clarity and transparency.

While the U.S. National Drug Code system will continue to serve a purpose for both small and large molecules, we can’t count on it to be the be-all-end-all solution for safety monitoring for biologics. Not even close. Payers don’t universally use NDC codes, they are rarely present in patient records and they are often inaccurately entered when they are. Distinguishable names provide a necessary safeguard to maximize safety and credibility. It’s really that simple.

The FTC is holding a hearing on the topic of biosimilar naming on Tuesday. They have stacked the deck (with exceptions) and no one is expecting anything other than the susual cost-centric care-verse-patient-safety drivel. I’ll be there all the same trying (from the audience) to interject occasional bouts of patient-centric sanity.

When it comes to biosimilars, we need to be extremely thoughtful about how we set policy relating to these promising medicines and strike a balance that promotes health and safety, rather than forcing a binary response that is driven by profits rather than patients. 

Here’s a non-biosimilar quote (with apologies to Mr. Shakespeare):

He that filches from me my good name
Robs me, enriches him,
And makes patients poor indeed   Read More & Comment...

From Little Blue Pill to Big Blue Button

12/05/2013 06:33 AM |

Pfizer has announced an update of its clinical trial data access policy that will “simplify and broaden access to information gathered in Pfizer-sponsored clinical trials. The updated policy builds upon and expands the company’s established methods of clinical trial information sharing, including Pfizer’s long track record of submitting for publication results from all interventional clinical trials in patients and its pioneering efforts to provide clinical trial results and data to study participants.”

Key elements of Pfizer’s expanded policy (effective January 1, 2014) are:

* Pfizer’s INSPIIRE public web portal for investigator-initiated research (iirsubmission.pfizer.com) will offer qualified researchers a standard form and process for requesting access to anonymized patient-level data from Pfizer-sponsored trials of approved (or discontinued) products/indications posted on clinicaltrials.gov that have been complete for 24 months.

* An external Independent Review Panel will consider all requests denied or only partially approved by Pfizer and make a final decision.

* Pfizer will publish (on Pfizer.com) synopses of clinical study reports (CSRs) filed with regulatory agencies for approved products for which basic results are posted in the clinicaltrials.gov registry (dating back to September 2007). These CSR synopses will include summary results for all primary and secondary endpoints; any data that could be used to identify individual patients will be removed.

* Pfizer will produce and distribute lay-language summaries of clinical trial results to trial participants who wish to receive them, starting with trials that begin enrolling in 2014, in countries where regulations permit.

* Pfizer is piloting the use of “Blue Button™” technology (launched by the U.S. Departments of Veterans Affairs and Health and Human Services) to enable Pfizer trial participants to download their own electronic clinical data collected in the trial.

According to Pfizer, their expanded clinical data access policy “also reinforces the company’s current practice of submitting for publication manuscripts for all interventional clinical trials in patients, regardless of outcomes, within 18 months of study completion, and the company’s commitment to register and post summary results for interventional human clinical trials to clinicaltrials.gov in the United States and to registries outside the United States as required.”

The full version of Pfizer’s expanded policy, the clinical data request form, the searchable CSR database, the Independent Review Panel membership roster and charter, and more information, including Frequently Asked Questions, are available at http://www.pfizer.com/TrialDataandResults.

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An Oscar-Winning Health Reform Idea: Electronic Prior Authorization

12/04/2013 07:52 AM |

According to the American Medical Association, cost estimates of inefficient health care claims processing, payment and reconciliation are between $21 and $210 billion. In the physician practice, the claims management revenue cycle consumes an unsustainable 10–14 percent of practice revenue.

The current system is all too often manual. It must be replaced by automated, transparent, unambiguous, real-time health care transactions.

The full AMA white paper on this issue can be found here.

A new article by Robert Oscar, RPh,President and CEO of RxEOB, furthers that argument. According to Oscar:

Prior authorization (PA) is a complex process that is often daunting and monotonous for medical practice managers. It is also costly in terms of economics and human life, in particular when PA requirements lead to patient medication needs “falling through the cracks,” as some patients abandon their prescriptions due to the confusion and delay of the approval process.

Some other important points from Oscar:

The original goal of PA was to save money, requiring physicians to justify to health plans the need for medications, diagnostic tests and procedures, but it has led to pharmacists having to spend an average of five hours per week handling PA requests. This is non-reimbursable time that is better served on direct patient care.

A nationwide physician survey indicates that more than 69 percent of physicians typically wait several days to receive a PA from an insurer for a prescribed drug, while 10 percent wait more than a week. While more than 52 percent of office-based prescribers utilize electronic prescribing methods, most of them continue to use paper-based methods for obtaining PA of medications from health plans, causing unnecessary delays for patients.

The good news is that a growing number of physicians and office managers are taking proactive steps to solve these issues by taking advantage of electronic PA (ePA), a technology that enables them to submit an authorization request through hand-held devices or via a web portal prior to pharmacy adjudication.

ePA speeds up health insurer response time, minimizes resources associated with manual processes, and helps to enhance the quality and utility of the PA process.

For physicians and office practice managers who want to reduce manual PA workflow, improve the quality of the PA enforcement process, automatically document all activities, reduce the PA approval response time, and increase their understanding of lower-cost therapeutic alternatives, ePA technology is the way to go. The best solution can enable physicians and their staff assistants to submit the PA request online via EMR or e-prescribing workflow, thereby mitigating unnecessary delays, improving the quality of patient care and enhancing the patient’s overall experience with care delivery process.  

Oscar’s complete analysis can be found here.

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The Healthcare Tell

12/03/2013 10:45 AM |

Yesterday I participated in a conference on Content Marketing. (The complete program agenda can be found here.)

Content marketing?

As my sister (a mental health professional) asked me, “Content marketing? As opposed to what, bullshit marketing?”

Not a question I was prepared for over the Thanksgiving table but, from someone who we generically refer to as “a provider,” an honest and relevant one.

Rhetoric counts. Maybe a better phrase is “content management” – because then we can compare it to something more tangible – such as “financial management.” We certainly know what that is. You take a certain about of money (the “content”) and through a savvy understanding of the marketplace and using the legal tools and compliant instruments you seek to increase the value of your portfolio.

When it comes to healthcare, is it content marketing or content management – or is it yet something else?

Maybe a better way to ask the question is, if it’s content marketing, what is the content and to whom are we marketing it – and why?

Content marketing, as a business proposition, is about maximizing awareness, reputation, sales, market share – and the advancement of the public health. (And it needn’t be in that order.) Indeed, the purpose of content marketing is to maximize the potential of important, accurate and timely information.

So maybe we should be talking about content maximization – and a more three-dimensional agenda – that is to say, beyond sales acquisition to driving patient outcomes.

(Another reason to alter the nomenclature is to help recalibrate the corporate compass.)

Some important questions:

How can content maximization address the adherence/compliance quandary?

How can content maximization help healthcare communicators advance the use of new platforms and media?

Most importantly, how can content maximization help define healthcare communications in a post-blockbuster environment, specifically as it pertains to orphan diseases and the rise of personalized medicine?

Let’s consider how the goal of content maximization through the strategy of content management and the tactics of content marketing can help advance sales, corporate, and public health goals. (And, again, not necessarily in that sequence.)

The heart of content marketing is story telling. Savvy healthcare marketers need to move from ABC (“Always Be Closing”) to ABT (Always Be Telling).

In the world of 21st Century healthcare, companies must share their content from their own mouths – because in the ultra-transparent world of social media, you can't separate the story from the storyteller. And we shouldn't even want to.

Rhetoric counts. As Kurt Vonnegut wrote, we need to “transcend the bullshit.”

Amen.

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Small is the New Big

11/26/2013 07:30 AM |

It’s fast becoming an n of 1 world. A world where every disease is an orphan disease and success is measured by individual outcomes rather than large population studies such as CATIE or ALLHAT or the multitude of programs being funded by PCORI.

Small is the new Big means that we must also think differently about pharmacovigilance. While we must continue to capture adverse event data (and do a better job at that through social media channels and mobile apps), we must also strive to capture Substandard Pharmaceutical Events (SPEs). SPEs occur when a pharmaceutical product does not perform as expected – perhaps because of API or excipient issues. SPEs can arise because of an issue related to therapeutic interchangeability. When it comes to 21^st century pharmacovigilance, we have to both broaden and narrow our views about bioequivalence to the patient level. Small is the new Big.

And when it comes to drug development, adaptive clinical trials and companion diagnostics further define the outsized urgency of small-scale thinking.  Demonstrating outcomes on an n of 1 level is crucial not just for 21^st century healthcare technology assessment (think “value-based reimbursement”) but also for physician pay-for-performance measures and, last but not least, for the benefit of actual patients

There’s a lot of lip service paid to the comment that “the era of the blockbuster is over.” Now consider that statement from the perspective of another industry – in the 21^st Century would you rather be Blockbuster or Netflix?

Small is the new Big. And that means a focus on individual patient outcomes, which means a focus on the individual patient rather than the general population and on long term care rather than short term cost.

And it’s about time.   Read More & Comment...

RECORD Pace

11/25/2013 10:20 PM |

CDER Staff:

Today, FDA announced it will require the removal of certain prescribing and use restrictions for the diabetes drug, Avandia (rosiglitazone), to reflect new safety information regarding Avandia’s cardiovascular risk. The changes include modifications to the drug label about cardiovascular safety, changes to the Risk Evaluation and Mitigation Strategy (REMS), and the removal of a requirement for the drug’s maker to do another study of the drug.

In 2007, concerns had been raised about an elevated risk of heart attacks and strokes, and related deaths associated with Avandia. FDA issued safety recommendations to the health care community and initiated an intensive look into the cardiovascular risk of the drug. In 2010, GlaxoSmithKline (GSK) released a long-term study called the Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes (RECORD) trial, which evaluated whether patients are at greater risk of heart attack or death when taking Avandia, as compared to standard-of-care diabetes drugs. As a result of this study, GSK said it could find no potential elevated risk.

Questions continued to be raised both internally and externally about Avandia’s safety and the RECORD study. In light of the inconclusive scientific evidence, I made the decision that Avandia could remain on the market but with restricted access, until we had further data about the cardiovascular risk of this drug. An independent analysis, or readjudication, of the RECORD trial was conducted by the Duke Clinical Research Institute (DCRI) and confirmed the original findings by GSK, lending stronger evidence about the safety profile for Avandia. In June of this year, we convened two advisory committee panels to discuss the results of the DCRI review of the RECORD trial. The majority of the advisory committee panelists concurred with the findings and voted in favor of easing the 2010 restrictions on the drug. Our action today is consistent with the advice of those expert panelists.

I believe the Center’s work on Avandia is noteworthy for at least three reasons, as it:

1)     Exemplifies our lifecycle approach to drug regulation, and our ongoing work to monitor the safety and effectiveness of medications once they are on the market, and make necessary adjustments when the risk/benefit balance of a drug changes over time

2)     Underscores the complexity of our decision-making processes, and how as regulators, we must make decisions about regulated products -- even in the face of uncertainty or in the absence of complete information about a drug’s safety or effectiveness

3)     Reinforces the importance of our commitment to Equal Voice and our efforts to encourage viewpoints from our expert disciplines across CDER, and even when there is disagreement, to respect the views of each discipline and strive to make the best decisions possible based on the scientific evidence available and in the best interest of patients

A wide range of scientific disciplines and many people from a number of CDER offices have been involved in our efforts to characterize and communicate to the public the cardiovascular safety profile for Avandia. These offices include the Office of Surveillance and Epidemiology, Office of New Drugs, Office of Executive Programs’ Division of Advisory Committee and Consultant Management, Office of Communications, and statisticians in the Office of Translational Sciences. I greatly appreciate the work and professionalism of so many of our staff throughout this process and believe it can be instructive going forward in how we approach and attempt to resolve very difficult drug safety issues.

For more information about the changes announced today, visit FDA requires removal of certain restrictions on the diabetes drug Avandia

Janet Woodcock  Read More & Comment...

Basic Instincts

11/22/2013 07:33 AM |

Mom, Apple Pie, and NIH Funding

Is NIH funding really the be-all/end-all of healthcare innovation?

Mari Serebrov, Washington Editor of BioWorld writes, “With the sequestration blade set to indiscriminately shave federal programs again in January, a bipartisan group of senators is urging congressional budget negotiators to spare research dollars at the National Institutes of Health (NIH).”

But is NIH really the only game in town.

Such a singular focus on the basic research funded by NIH ignores the fact that other government agencies are doing important health care research, Peter Pitts, president of the Center for Medicine in the Public Interest, told BioWorld Today. That research also is getting nicked by the sequester razor.”

For instance, the FDA funds research into regulatory science and personalized medicine, despite a “very limited budget,” Pitts said. While regulatory science research may not seem as sexy as basic research into cancer cures, it’s necessary research, he added.

“Basic research is important,” Pitts said, “but it’s not the beginning, middle and end” of all health care research.

The concerns also ignore new government funding for other types of research. Pitts described the current U.S. funding of public health-related research as “a bigger pie with more people with knives and forks.” More research is taking place, but the NIH slice of the pie isn’t getting any larger.

A prime example of that growth was the creation of the Patient-Centered Outcomes Research Institute (PCORI) in 2010. Set up as a nonprofit under the Affordable Care Act, PCORI was charged with funding comparative-effectiveness research. While Congress began shaving NIH funding close to the jaw line, it mandated that $10 million be set aside in fiscal 2010 to fund PCORI’s activities, $50 million in fiscal 2011 and $150 million in fiscal 2012.

To date, PCORI, which is funded through transfers from two Medicare trust funds rather than general tax dollars like the NIH, has approved 197 research awards totaling more than $273.5 million. It also is committing more than $1 billion to research funding over the next two fiscal years. But that money will be used to “study other people’s research, rather than the basic research NIH promotes,” Pitts said.

Noting that all research is subjective, Pitts said it isn’t Congress’ job to approve individual research projects, but Congress makes the choices of how federal research dollars are spent in general.

The complete BioWorld article can be found here.

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Peggy gets personel

11/20/2013 10:12 AM |

According to Peggy Hamburg ...

The difference between science and science fiction is a line that seems ever harder to distinguish, thanks in part to a host of astonishing advances in medical science that are helping to create a new age of promise and possibility for patients.

Today cancer drugs are increasingly twinned with a diagnostic device that can determine whether a patient will respond to the drug based on their tumor’s genetic characteristics; medical imaging can be used to identify the best implantable device to treat a specific patient with clogged coronary arteries; and progress in regenerative medicine and stem cell therapy using a patient’s own cells could lead to the replacement or regeneration of their missing or damaged tissues. Given these trends, the future of medicine is rapidly approaching the promising level of care and cure once imagined by Hollywood in futuristic dramas like Star Trek.

But these examples are not science fiction. They are very real achievements that demonstrate the era of “personalized medicine” where advances in the science of drug development, the study of genes and their functions, the availability of increasingly powerful computers and other technologies, combined with our greater understanding of the complexity of disease, makes it possible to tailor treatments to the needs of an individual patient. We now know that patients with similar symptoms may have different diseases with different causes. Individual patients who may appear to have the same disease may respond differently (or not at all) to treatments of that disease.

FDA has been playing a critical role in the growth of this new era for a number of years. Even before I became FDA Commissioner the agency was creating the organizational infrastructure and putting in place the regulatory processes and policies needed to meet the challenges of regulating these complex products and coordinating their review and oversight. It has been my pleasure to serve at FDA during this next exciting period and to help ensure that the agency continues to prioritize this evolution by anticipating, responding to, and encouraging scientific advancements.

I am very pleased to be able to present a new report by FDA as part of our ongoing efforts in this field. Paving the Way for Personalized Medicine: FDA’s Role in a New Era of Medical Product Development describes many of the exciting developments and looming advances in personalized medicine, lays out the historical progress in this field, and examines FDA’s regulatory role: from ensuring the availability of safe and effective diagnostic devices, to addressing the challenges of aligning a drug with a diagnostic device, to post-market surveillance.

Outside collaboration and information sharing is essential for this field to flourish. On Tuesday, the American Association for Cancer Research and AdvaMedDX held a fruitful daylong conversation on personalized medicine to treat cancer. I was one of the speakers, participating in a conversation with Dr. Francis Collins, the head of the National Institutes of Health. Our discussion focused in part on current status of drug and diagnostic co-development and the challenges and potential of whole genome sequencing, where data can be collected on a patient’s entire genetic makeup at a reasonable cost in a reasonable amount of time.

FDA is committed to fostering these cooperative efforts, as it will require the full force of government, private industry, academia and other concerned stakeholders to maximize our efforts and fully realize the promise of personalized medicine. Our new report outlines that commitment, and helps chart the way forward so that more people can live long and prosper.

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Thanks, Jenny!

11/20/2013 06:32 AM |

Julia Ioffe has a message for Jenny McCarthy and the other anti-vaccine zealots.

Via the New Republic:

It would be an understatement to say that pertussis and other formerly conquered childhood diseases like measles and mumps are making a resurgence. Pertussis, specifically, has come roaring back. From 2011 to 2012, reported pertussis incidences rose more than threefold in 21 states. (And that’s just reported cases. Since we’re not primed to be on the look-out for it, many people may simply not realize they have it.) In 2012, the CDC said that the number of pertussis cases was higher than at any point in 50 years. That year, Washington state declared an epidemic; this year, Texas did, too. Washington, D.C. has also seen a dramatic increase. This fall, Cincinnati reported a 283 percent increase in pertussis. It’s even gotten to the point that pertussis has become a minor celebrity cause: NASCAR hero Jeff Gordon and Sarah Michelle Gellar are now encouraging people to get vaccinated.

How responsible are these non-vaccinating parents for my pertussis? Very. A study recently published in the journal Pediatrics indicated that outbreaks of these antediluvian diseases clustered where parents filed non-medical exemptions—that is, where parents decided not to vaccinate their kids because of their personal beliefs. The study found that areas with high concentrations of conscientious objectors were 2.5 times more likely to have an outbreak of pertussis. (To clarify: I was vaccinated against pertussis as a child, but the vaccine wears off by adulthood, which, until recently, was rarely a problem because the disease wasn't running rampant because of people not vaccinating their kids.)

So thanks a lot, anti-vaccine parents. You took an ethical stand against big pharma and the autism your baby was not going to get anyway, and, by doing so, killed some babies and gave me, an otherwise healthy 31-year-old woman, the whooping cough in the year 2013. I understand your wanting to raise your own children as you see fit, science be damned, but you're selfishly jeopardizing more than your own children. Carry your baby around in a sling, feed her organic banana mash while you drink your ethical coffee, fine, but what gives you denialists the right to put my health at risk—to cause me to catch a debilitating, humiliating, and frightening cough that, two months after I finished my last course of antibiotics (how’s that for supporting big pharma?), still makes me convulse several times a day like some kind of tragic nineteenth-century heroine?

If you have an answer, I’ll be here, whooping, while I wait.

Read the full article here.
 

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Incident Dissent

11/18/2013 12:44 PM |

According to a new letter to the British Medical Journal, “Doctors may not report adverse events or speak up when they witness poor care because of fear of punitive action or lack of confidence that reporting will change anything.”

Whose responsibility is it to build confidence in both the pharmacovigilance process as well as the urgent importance of the proposition?  I believe it’s the job of the regulatory body that oversees the both the procedures and the actions that derive from post-marketing reports. That means (in the US), the FDA.

Would it be nice if the FDA could get additional dollars to ramp up pharmacovigilance beyond MedWatch and Sentinel? Sure, but let’s get real – that ain’t gonna happen. What the FDA does have at its disposal is the bully pulpit. It’s time for Janet, Peggy, and Gerald to get up on their soapboxes and start preaching the urgency and importance of pharmacovigilance.

Such renewed efforts are called for since the focus is now increasingly on patient outcomes. If we can’t measure it, it doesn’t count – or counts for less. Perhaps it’s time for the FDA to create an advisory committee of pharmacovigilance issues – and hold meetings to focus on process improvement, greater stakeholder involvement (not just with physicians, but with pharmacists, hospitals and patients), and better ways to share post-marketing data in a transparent and timely fashion – and not just adverse events and label updates but also Substandard Pharmaceutical Events (SPEs), when patient’s don’t respond as they should when their therapy has been impacted by therapeutic switching or interchangeability/bioequivalence issues.

Can you say, “biosimilars?” It's an adverse event horizon.

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On the other hand, if you like your ObamaCare, you can keep your ObamaCare. Period.

11/14/2013 11:00 AM |

Sebelius & Co. have released enrollment numbers. Some key findings:

* 106,185 people have selected an Exchange plan (although not all have paid the premium).  This includes 26,794 people in the federal exchange states. 

* 396,261 people whose applications were processed by the Exchanges have been deemed eligible for Medicaid.  A little more than half of those people live in states with state-based exchanges.

* Surprisingly, of those deemed eligible for Marketplace plan enrollment, only 30% qualified for a premium tax credit.  CBO had expected about 80% of Exchange enrollees would qualify for a premium tax credit.

* About a million people have been deemed eligible for Exchange coverage but have not yet picked a plan.  It’s not clear if these people will pick a plan later on or decided not to enroll – especially if their “cancelled” plans are reinstated.

* The HHS release includes a long appendix comparing Exchange enrollment to Part D, Massachusetts Commonwealth Care, CHIP and FEHBP.  While Part D had about 10% enrollment in the first month, Massachusetts had just 3% enrollment in the first month (and the Bay State kept enrollment open for the entire first year so there was less pressure to enroll early).

* If exchange enrollment mirrors the same enrollment pattern as Part D, about 700,000 people would have to enroll by the end of November in order to meet the target of 7,000,000 people enrolled in Exchanges in 2014.

And speaking of exchanges, Gallup has found that just 18% of uninsured adults had attempted to visit an Exchange website.

Technical notes:

* This report only captures enrollment through Nov 2.

* Data includes applications submitted through methods other than the website (i.e. paper applications).

* There are state-by-state tables included in the release (see page 9).

The complete HHS release can be found here.

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FDA's new escape clause

11/13/2013 04:26 AM |

Context matters – but what, precisely, is “context of use”

The term “context of use” refers to a comprehensive description that fully and clearly delineates the limits of FDA’s qualification decision in terms of the manner and purpose of use for the DDT(s). The context of use statement should describe all criteria under which the DDT is qualified for use. The qualified context of use defines the boundaries within which the available data adequately justify use of the DDT(s). As data from additional studies are obtained over time, submitters of DDTs may continue working within the DDT Qualification Programs to submit additional data and expand the qualified context of use.

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugDevelopmentToolsQualificationProgram/

What is Qualification?

Qualification is a conclusion that within the stated context of use, the DDT can be relied upon to have a specific interpretation and application in drug development and regulatory review. Once qualified, DDTs will be publicly available to be used in any drug development program for the qualified context of use.  The qualified DDT can be included in IND or NDA/BLA submissions without the need for CDER to reconsider and reconfirm the suitability of the DDT as long as:

 *   There are no serious study flaws
 *   There are no attempts to apply the DDT outside the qualified context of use
 *   There are no new and conflicting scientific facts not known at the time the qualification was determined

Qualification may contribute to acceptance and application of DDTs across multiple drug development programs. Having qualified DDTs that can be utilized by many sponsors will aid in optimizing drug development and evaluation.

These Qualification Programs promote a collaborative setting in which there are advantages for multiple interested parties to work together in a consortium to develop DDTs for qualification. Resources and knowledge-sharing outside a specific drug development program can accelerate DDT development and facilitate availability of DDTs at critical milestones for future drug development programs. Early and continued interactions with FDA during the DDT development process are critical to the success of these programs.

Regulators love ambiguity because it gives them power. But flexibility is important. All this to say, it’s a tough balance.

And, once again, context matters.

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From those wonderful people who brought you ObamaCare

11/12/2013 09:09 AM |

From the pages of The Washington Examiner ...

Here comes the next big healthcare disaster, courtesy of HHS

And you thought the rollout of Obamacare was a catastrophe?

Here’s an immediate and critical pending national healthcare disaster — a new flu pandemic with nobody home at the Department of Health and Human Services.

This past April, a new strain of H7N9 avian influenza emerged in China and quickly spread throughout the region.

Though the H7N9 virus was only known to transfer directly from an avian source, numerous people were exposed to the disease’s devastating illnesses.

By the time the virus had momentarily vanished in August, a staggering 44 of the 134 infected had died, a 33 percent mortality rate.

At first, HHS took the necessary steps to address the new pandemic and prepare for the worst. Health and Human Services Secretary Kathleen Sebelius determined that the virus was a threat to U.S. national security and to Americans living abroad.

Subsidiary offices of HHS, the Biomedical Advanced Research and Development Authority and the Centers for Disease and Control, recommended producing a seed vaccine, conducting clinical trials and, if the threat of pandemic remained, contracting manufactures to produce vaccine stockpiles.

Once the virus was identified as a legitimate threat, HHS moved quickly to contract with vaccine manufacturers to produce a vaccine and prepare for mass production if the virus was to resurface, as influenza viruses typically do.

It seemed as though the government was taking on this threat appropriately — until Sebelius’ slogging bureaucracy, those wonderful people who brought you Obamacare, took over.

In September, BARDA contracted three vaccine manufacturers for $110 million to put in order a vaccine and prepare mass vaccine stockpiles once HHS gave them the go-ahead.

Reportedly, HHS was supposed to provide the manufacturers with further instructions by mid-October.

Yet today, HHS still sits on the very production orders that are necessary to stockpile the H7N9 vaccine to protect against a pandemic.

HHS’s timing could not be worse, with flu season already upon us. As of this week, there have been four newly reported cases of the H7N9 virus in China, leading a spokesman for the World Health Organization to conclude succinctly: "Winter is starting."

While experts have stopped short of guaranteeing a spike in H7N9 cases, the threat of a pandemic is anything but far-fetched.

If the second phase of this virus evolves from an avian-transferred virus to a human-to-human transfer, we will see devastating results.

Perhaps staff at HHS should heed the words of their colleague, Dr. Tom Frieden, director of the CDC.

In September, Frieden warned that “nothing has the potential to kill more people than influenza. A strain such as H7N9 could create a pandemic. When something with that much potential to cause widespread harm emerges, we must identify it in hours or days, not weeks or months.”

It will take, at minimum, 60 days to produce the first wave of vaccine stockpiles once an order is given to vaccine manufacturers.

And that is just the first wave, a quantity that would be wholly insufficient for the American public at large. Protecting the entire U.S. population would take many months, time that, frankly, we may not have.

Unfortunately, now HHS has again demonstrated gross incompetence in its obligation to best promote the public health. Its eye is not on the prize of pandemic preparedness.

If the federal bureaucracy continues to stall on producing the H7N9 vaccine, HHS could face a catastrophe that would make the healthcare.gov storm seem like a light spring shower.

Peter Pitts, a former FDA associate commissioner, is president of the Center for Medicine in the Public Interest.

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Risk/Reward: Failure is Often an Option

11/11/2013 09:14 AM |

From the pages of Law360.com …

Iclusig Deaths Won't Stall FDA's Speedier Drug Approvals

By Jeff Overley

The jarring death toll linked to leukemia drug Iclusig will force the U.S. Food and Drug Administration to revisit the science that won the product accelerated approval, but a growing willingness of seriously ill patients to accept risk means the tragic episode is unlikely to delay other fast-tracked medicines, experts say.

Sales of the chemotherapy drug, which earned FDA clearance in December, were halted last week after manufacturer Ariad Pharmaceuticals Inc. reported that at least 14 fatalities had occurred among 530 patients in two clinical trials. In addition, scores of other people suffered major side effects resulting from blood clots, including tissue death that led to amputations.

The dramatic circumstances add an important chapter to a long-running debate about FDA’s various “priority review” programs, which involve quicker analysis by regulators and may apply a relaxed safety standard.

While FDA is wary of risky medications, it’s increasingly under pressure from patients who say potentially dangerous treatments for deadly diseases are better than no treatments at all. That’s a trend with roots in the darkest days of the HIV/AIDS crisis, and it has only picked up steam in recent years.

“If someone has no options, it makes sense to try anything,” said Areta L. Kupchyk, a partner at Nixon Peabody LLP and former associate chief counsel for drugs and biologics at FDA.

Many drugs, even those approved on traditional pathways, are found to have more serious risks post-approval, but the Iclusig saga is particularly notable, as FDA rarely urges manufacturers to pull products from the market.

The development also comes at a time of rising scrutiny of whether the FDA has found the sweet spot in addressing unmet medical needs while continuing to protect patients from toxic medicines.

“It’s a very precarious balance,” said Peter J. Pitts, president and co-founder of the nonprofit Center for Medicine in the Public Interest.

For example, scholarly papers have explored whether standards are too loose. One article, published last year in the Journal of the American Medical Association, called particular attention to three products — AstraZeneca PLC’s cancer drug Caprelsa, Novartis AG’smultiple sclerosis medicine Gilenya, and Boehringer Ingelheim GmbH’s blood thinner Pradaxa — and asked whether their risk-benefit profiles made priority review inappropriate.

The safety record of the drugs raises the question “of whether it was good policy to approve three innovative new drugs with significant safety questions unanswered and with optimal doses not determined," according to the researchers Thomas Moore of the Institute for Safe Medication Practices and Dr. Curt Furberg, then of the Wake Forest University School of Medicine.

In a second article published just days before the freeze on Iclusig sales, the same authors found that drugs receiving expedited approval in 2008 typically used data from trials with less than one-fifth the usual number of patients and that progress was slow on completing mandatory post-approval studies.

In some recent years, nearly half the new drugs cleared by the FDA have used expedited pathways, raising the stakes should those routes be called into question by a review of Iculsig's approval.

“The question one has to ask is: Were there ... safety signals before this?” Kupchyk said. “That might be something that FDA and others wants to look at more closely.”

But while the events surrounding Iclusig are serious, experts say they don’t necessarily reflect poorly on priority review. FDA knew that blood clots were a risk at the time of approval and required a black box warning to that effect. It also ordered post-approval analysis that discovered greater-than-expected dangers less than one year after clearance, suggesting things worked largely as designed.

“What happened here seems to be consistent with the program, and I don’t see that FDA is going to pull back necessarily unless there is some evidence that they missed,” Kupchyk said.

FDA’s reaction with respect to its overall approach to expedited approvals is hard to predict because the amount of acceptable risk can vary greatly depending on which condition is being treated and whether there are any other effective drugs available.

“Safe is a relative concept. You wouldn’t approve a drug for allergies that is fatal for 30 percent of patients,” Pitts said.

Also, the prerogatives of distinct patient communities are influencing FDA more and more. Last year’s user-fee law directed the agency to refine its risk-benefit assessments, and a big part of that is so-called patient-focused drug development, which entails staging public meetings to gauge willingness to gamble on unproven drugs. Gatherings so far have covered chronic fatigue syndrome, HIV, lung cancer and narcolepsy, and more will take place involving fibromyalgia, sickle cell anemia and more than a dozen other conditions.

On Wednesday, an FDA spokeswoman defended the current system and did not directly answer a question about how the agency would decide whether any mistakes were made in approving Iclusig, which remains available in extremely narrow circumstances.

“We have a robust program for post-marketing surveillance and ensuring the benefits of a marketed drug outweigh its risks," FDA spokeswoman Stephanie Yao said. "If that profile changes in any way, we review and take appropriate action."

Regardless of whether anything should have been done differently with Iclusig, when dealing with the deadliest diseases and strong lobbying from people affected by them, experts say it may be inevitable that things occasionally go awry.

“When it comes to accelerated approval, it’s a high-risk, high-reward situation,” Pitts said. “The FDA’s not going to get it right all the time.”

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Generic Originals

11/10/2013 06:26 PM |

Taking bioequivalence and pharmacovigilance to new levels (and it's about time).

From the pages of the New York Times …

Label Updates May Be Allowed for Generics

By KATIE THOMAS

The Food and Drug Administration proposed a rule on Friday that would permit generic drug makers to update their labels if they received information about potential safety problems. The move puts the companies on equal footing with brand-name manufacturers, but it also opens the door to lawsuits against them for the first time since the Supreme Court barred such cases two years ago.

Until now, only brand-name drug makers had the ability to independently update their labels if important new information surfaced about one of their drugs. If the F.D.A. agreed that the new information warranted a change in the label, then generic companies were required to update their product information so that it would be identical to the branded drug’s labeling.

Dr. Janet Woodcock, the F.D.A.’s head of drug evaluation and research, said the proposed change would create better parity between brand-name drug manufacturers and generic companies, which is especially important given that more than 80 percent of prescriptions in the United States are currently dispensed as generic drugs. “Now, with the generic industry having grown up, most people are taking generic drugs,” she said in a telephone interview. “It’s really time to level the playing field.”

The rule would also pave the way for lawsuits from patients who could now claim that generic companies did not sufficiently warn them of a drug’s dangers. In 2011, the Supreme Court ruled that such lawsuits were not valid because generic companies were required to use the same label warnings as brand-name manufacturers and thus could not be blamed for failing to warn patients about the risks of taking their drugs.

Consumer advocates, who have long called on the agency to make such a change, praised the decision because they said the current situation was unfair to patients harmed by generic drugs.

“This is an important consumer protection provision,” said Representative Chris Van Hollen, Democrat of Maryland, who had supported such a change. “It’s a long time in coming.”

The Generic Pharmaceutical Association, the industry trade group, said it was still reviewing the regulation but was concerned that the change could create confusion. In a statement, Ralph G. Neas, the association’s president, said the group was “very concerned that multiple versions of critical safety information would lead to unnecessary confusion and uncertainty for prescribers and other health care professionals, with harmful consequences for patients.”

Mr. Neas also raised the question of whether the rule was legal. “The Supreme Court has repeatedly held that generic pharmaceutical manufacturers must duplicate the language on the brand pharmaceutical manufacturer’s labels and cannot make changes to a label without F.D.A. approval,” he said in the statement. “Therefore, the agency’s authority to enact a rule that differs from the federal law is unclear.”

The proposed rule, which is open to public comment for 60 days, would set up a website that would place all updates for a given drug in one place, minimizing such confusion, Dr. Woodcock said.

The agency said the Supreme Court decision, Pliva v. Mensing, altered the incentives for generic drug companies to conduct adequate monitoring of their drugs because it eliminated the threat of lawsuits from patients who were harmed by those products. In proposing the rule, the agency said it “intended to ensure that generic drug companies actively participate with F.D.A. in ensuring the timeliness, accuracy and completeness of drug safety labeling.”

Dr. Woodcock said she did not expect that generic companies would update their labels frequently, because by the time drugs become available as generics, they have been on the market for years. “It’s not to say that we won’t learn new things, but it becomes less likely to come across new serious adverse events,” she said.   Read More & Comment...

The Skinny on Type 2 Diabetes

11/08/2013 07:53 AM |

To address (one hesitates to say “celebrate”) American Diabetes month, here is the latest addition to Pfizer’s Value of Medicines series -- The Value of Medicine for Type 2 Diabetes.

The development of medicines is complicated -- explaining their value should not be. Pfizer's straightforward efforts put the facts in perspective -- and in plain English. Their Value of Medicines series provides highly valuable tools for healthcare policy professionals, practitioners, and patients. Additional materials can be found here.

Knowledge is Power.

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From Eugene to Eugenics

11/07/2013 07:20 AM |

From the pages of the Oregon StatesmanJournal

From Eugene to Eugenics: Oregon's new cost-cutting strategy is to deny care to cancer patients

In an ad for the Affordable Care Act, local folk singer Laura Gibson plucks her guitar and muses about how the “Oregon way” is to “care for each one, every daughter and son.” Though a little corny, the song delivers a worthy message: Oregon is committed to providing everyone access to health care.

The commercial is part of Oregon’s new ad campaign to boost enrollment in the newly created “Cover Oregon” health insurance exchange.

But the reality strums a different, far less organic tune. Even as Oregon drops $3.2 million to spread their “each one” message, the Beaver State is also taking measures to that would deny life-saving treatments to desperately sick citizens.

In August, Oregon’s Health Evidence Review Commission issued an update to its guidelines for providing cancer treatment to low-income individuals covered by the state Medicaid program. These new guidelines require that Medicaid deny coverage for certain cancer treatments for patients that have been deemed “too” sick, haven’t responded well to previous treatments, or can’t care for themselves.

Through these new rules, Oregon state bureaucrats are severely restricting access to care and dooming potentially thousands of local patients to a premature death.

What’s worse it that these new Medicaid guidelines are not grounded in the medical literature or best clinical practices, according to Kenneth Thorpe, chairman of the Partnership to Fight Chronic Disease. Rather, according to Thorpe, they’re based “on the odds of survival observed in a group of patients.”

It’s true that for some late-stage cancer patients, the odds are long than any additional treatment can help. But without access to the latest that medical science has to offer, a patient’s survival rate simply drops to zero.

As B.J. Cavnor of the Northwest Patient Education Network powerful puts it: “Cutting patients off from cures means patients who could have beaten their illness will no longer have that chance.”

It’s a frightening move from Eugene to eugenics. These guidelines dictate that Medicaid only provide “palliative” care – painkillers, acupuncture treatments, wheelchairs, drugs for nausea, and the like.

So while Oregon won’t let Medicaid patients have access to cancer medicines that could prolong or save their lives, it will pay to make their deaths slightly less painful. Is that what Oregon considers compassionate care?

About 19,000 Oregonians are diagnosed with cancer each year. Over 640,000 state residents are covered by Medicaid -- that’s about one in five of the total state population. And the state Medicaid ranks will swell next year, when the Affordable Care Act will raise the program’s income threshold up to 138 percent of the federal poverty line.

Oregon’s new Medicaid guidelines take treatment decisions out of the hands of doctors and patients and put them in the hands of distance state bureaucrat willing to cut costs no matter the human toll. It’s the practice of cost-centric controls over patient-centric care.

Even supporters of the President’s healthcare law have taken to calling these treatment restrictions a death knell for poor cancer patients.

Cavnor, the patient advocate, has described them as “extremely frustrating and morbidly ironic, especially for those of us who have tried to argue that the Affordable Care Act doesn’t allow for ‘death panels.’”

Is this really change we can believe in? Promising to expand access to health care to all while denying it to those who need it most is brazen hypocrisy. Oregon should expect more from itself.

At the end of her song boosting the state’s health exchange, Laura Gibson sings “live long, Oregon.” That’s a good aspiration. Oregon’s state bureaucrats should live up to it.

Peter J. Pitts, a former associate commissioner at the FDA, is president of the Center for Medicine in the Public Interest.

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Unlucky Seven

11/06/2013 07:42 PM |

Substandard Subcontinent.

On its Tuesday broadcast, the CBS Evening News reported on former Ranbaxy executive Dinesh Thakur, who “was asked by his boss to investigate allegations of fraud at the company” in 2004. He soon “uncovered disturbing problems with the data required by the FDA to prove the effectiveness of Ranbaxy drugs.” According to Thakur, the company had “gotten approvals from the FDA to sell drugs that were based on no data, or data that was fraudulent.” After presenting his finding to Ranbaxy executives in 2005, Thakur “says nothing was done,” so he “blew the whistle to the FDA.”

The CBS News  website reports the FDA investigation uncovered a “persistent ... pattern” by Ranbaxy of submitting “untrue statements.” Auditors found that the applications of at least 15 new generic drugs contained over 1,600 data errors, leading the FDA to conclude the company’s products were “potentially unsafe and illegal to sell.” The investigation that was launched in the wake of “Thakur’s allegations led Ranbaxy to plead guilty to seven felonies.”

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PutinCare

11/05/2013 01:36 PM |

I’ve just returned from Kiev, Moscow, and Algiers where I spoke on pharmaceutical quality, bioequivalence, and generic interchangability. (And, yes, I did get a chance to tour around a little too.)

Two comments worth sharing.

* In Algiers, the head of the domestic generic drugs manufacturers, told me that the issues of generic quality and therapeutic substitution were “obsolete.” It was a laugh line – because that’s how the audience responded.

* In Moscow, at a meeting of federal and provincial healthcare officials, one comment (relative to patient choice vs. limited formulary options) was, “The only patients who give us trouble are those who want more expensive treatments.”

In Russia -- if you like your insurance, you can keep it. If you don't like it, you can keep it ... quiet.

Think of it as a healthcare safety nyet.

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