The New Battle of Algiers: Drug Quality

11/04/2013 02:59 AM |

Today's edition of Le Soir D'Algerie reports:

The themes for the Algerian Society of Pharmacy’s 22nd Journées Pharmaceutiques Nationales was health policy , intellectual property , self-medication and hospital pharmacy. A panel of national and international experts addressed the generic drugs and the pharmaceutical industry in Algeria.

According to Prof. P. J. Pitts , president of the U.S. Center for Medicine in the Public Interest, "We cannot replace quality with cost. Even a high quality generic does not always give the same therapeutic effect as the innovative product . The authorities should work with physicians and pharmacists to ensure that patients remain at the center of debate. The most expensive drug is the one that does not work. The most effective treatment is one that delivers good patient outcomes," he said.

The President of the National Council of the Order of Pharmacists , Dr. Lotfi Benbahmed, insisted on continuing education for pharmacists and also the establishment of a system to determine the traceability of drugs to determine responsibility.

"The door is open to counterfeiting and quackery. It is a great danger to public health if official medication is not controlled."

The complete article (in French) can be found here.

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ObamaCare's Green Stamps

10/31/2013 09:48 PM |

A small item from BioCentury that deserves more attention:

Drug companies will be able to provide copay assistance to consumers who purchase health insurance through the Affordable Care Act's exchanges. HHS Secretary Kathleen Sebelius announced the decision in a letter sent on Wednesday to Rep. Jim McDermott (D-Wash.), resolving a major uncertainty about the healthcare law. Under federal kickback laws, drug companies are not permitted to provide copay assistance directly to consumers insured by federal programs such as Medicare and Medicaid. According to Sebelius' letter, HHS does not consider qualified health plans purchased through federal or state exchanges to be federal health programs.

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Troy Bounce

10/30/2013 02:15 PM |

Mazel tov, Tevi!

Washington, DC—HR Policy Association, representing the chief human resource officers of more than 350 of the largest private sector employers in the United States, announces the selection of Tevi Troy, former Deputy Secretary of the U.S. Department of Health and Human Services, to lead the development of a health care initiative of the HR Policy Foundation.

 HR Policy Association member companies, all of whom are large employers, collectively spend more than $75 billion annually on health care in the U.S. and are in the process of assessing their company's current and future health care strategies in light of the growing instability of the American health care system.  They are seeking to establish a leadership organization dedicated to developing a more sustainable health care delivery system for the employees, dependents and retirees of large employers.

Dr. Troy is currently a Senior Fellow at Hudson Institute, where he will remain an Adjunct Fellow, and a writer and consultant on health care and domestic policy.  In 2007, he was unanimously confirmed by the U.S. Senate as the Deputy Secretary of the U.S. Department of Health and Human Services.  He was the chief operating officer of the largest civilian department in the federal government, with a budget of $716 billion and over 67,000 employees.  In that position, he oversaw all operations, including Medicare.

HR Policy Association CEO Jeffrey C. McGuiness said, “We are delighted to announce that Dr. Troy will be leading this critically important initiative.  He brings not only a wealth of understanding and expertise about health care, policy and the government, but a strong managerial and operations background.  Having successfully run the largest department in the government in terms of employees and budget, focused on all aspects of health care, Dr. Troy is uniquely qualified to help guide and lead this new organization.”

Dr. Troy has extensive White House and Capitol Hill experience.  During the George W. Bush Administration, he served as Deputy Assistant and then Acting Assistant to the President for Domestic Policy and was the White House’s lead adviser on health care, labor, education, transportation, immigration, crime, veterans and welfare.  Dr. Troy also served as the Policy Director for U.S. Senator John Ashcroft and as Senior Domestic Policy Adviser and Domestic Policy Director for the U.S. House Policy Committee.

In addition to his senior level government work and health care expertise, Dr. Troy is also an author and presidential historian.  He is a frequent television and radio analyst, and has appeared on CNN, CNBC, FOX News, FOX Business, and The Jim Lehrer Show, among other outlets.  He is currently on tour for his latest book, What Jefferson Read, Ike Watched, and Obama Tweeted: 200 Years of Popular Culture in the White House and is the author of Intellectuals and the American Presidency: Philosophers, Jesters, or Technicians? (Lanham: Rowman & Littlefield, 2002).  He has written over 100 articles, for The Wall Street Journal, The Washington Post, Forbes, The New Republic, Commentary, Reason, Investor’s Business Daily, National Review, Washingtonian, The Weekly Standard, and other publications.  Dr. Troy has a B.S. in Industrial and Labor Relations from Cornell University and an M.A and Ph.D. in American Civilization from the University of Texas at Austin.

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Up in Smoke

10/29/2013 03:06 AM |

Greetings from Moscow.

I'm in town to give a presentation on the importance of API and excipient quality, the urgency of advancing pharmacovigilance, and the evolution of both regulatory innovation and international regulatory fraternity.

The local english-language newspaper is The Moscow Times. It's what you get at the hotel. And amidst all the stories on NSA wire-tapping was an editorial that nearly made my heart stop. The title, "Dispelling the Smoke Screen." Here's the opening paragraph:

"The statement that smoking is harmful to your health is only a theory, not a medical fact."

Don't believe me? Read the article and then exhale. And then get angry.

This in a nation where non-communicable diseases (most notably alchohol and heart disease) are major killers. 50% of Russians smoke cigarettes.

I intend to discuss this article during my presentation.

Outrageous!  Read More & Comment...

Value Pack

10/25/2013 07:26 AM |

Check out Pfizer’s new “Value of Medicines: How Medicines Have Changed Our World” position papers. They’re actually concise and to the point (unlike many of the policy papers we see these days).

At the moment there are three to choose from:

* The Value of Statins

* The Value of Oncology Medicines

* The Value of Adherence

They can all be found here.

According to the website, “Papers will soon be available demonstrating value in a variety of areas including Vaccines, Diabetes, Rare Diseases, Atrial Fibrillation-Stroke, Pain, Renal Cell Carcinoma, Smoking Cessation, Breast Cancer, and more. Stay tuned!”

Kudos to Ian & Company for a job well done.

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The Fatal Conceit

10/24/2013 07:36 AM |

According to Friedrich Hayek, socialists are wrong because they disregard the fact that modern civilization naturally evolved and was not planned. Hayek refers to this fundamental error as “the fatal conceit.”

And on CNBC it’s what Larry Kudlow used to describe ObamaCare during a debate on the roll-out of the Affordable Care Act– the fatal conceit. The panel consisted of Jonathan Gruber (MIT professor and a designer of the ACA), Matt Welch (editor of Reason Magazine), and me.

Here are two clips to enjoy:

“ObamaCare already a huge turkey”

“Previous system of healthcare archaic”

Are we on a slippery slope to a single payer system? If we are, you can kiss investment goodbye, along with innovation, and any hopes for the future of personalized medicine. Is this a system that was designed to fail?

You be the judge.

We shall not grow wiser before we learn that much we have done was very foolish

-- Friedrich Hayek

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Demand for Supply

10/23/2013 01:14 PM |

Major Setback in US Cancer Drug Shortage

Factory Closing Means One Less Producer

Nick Mulcahy, MedScape

The already small number of producers of generic cancer drugs in the United States just got smaller.

Ben Venue Laboratories, a major manufacturer of generic chemotherapy injectables, announced the closure of its plant, in Bedford, Ohio, earlier this month, citing problems with both the facility and projected revenues. It will effectively depart the US market by the end of the year.

The loss is a significant blow to the recovery of the US marketplace for generic cancer drugs, said Erin Fox, PharmD, director of the drug information service at the University of Utah Hospitals and Clinics in Salt Lake City. Dr. Fox has been monitoring drug shortages in the United States since 2001.

"I really feel like it's a big step back," she told Medscape Medical News in an interview.

Our supply chain is that much more fragile.
 
The US market for generic cancer chemotherapy injectables has improved since the "crisis" of 2011, she said. But the loss of Ben Venue, which a company Web site touts as "one of the largest sterile injectable facilities in the world," is important. "Our supply chain is that much more fragile with the closing," said Dr. Fox.

"A significant portion of the ability of the market to meet demand is now gone," said William Greene, PharmD, chief pharmaceutical officer at St. Jude Children's Research Hospital in Memphis, Tennessee, who also spoke to Medscape Medical News about the Ben Venue closure.

"We are reaching a scary situation," said Sara Butler, PharmD, oncology clinical pharmacy supervisor at Barnes-Jewish Hospital in St. Louis, Missouri, about the loss of manufacturing capacity in an interview.

Another expert said that the impact of the plant closure is unclear.

"There's not enough transparency [from product distributors about the factory origins of generic drugs] to know exactly what [Ben Venue is] producing at this point," said Jeffrey Ward, MD, from the Swedish Medical Center in Seattle, who is chair of the Clinical Practice Committee of the American Society of Clinical Oncology (ASCO). "That's almost scarier than knowing what the impact is," he told Medscape Medical News.

Set Back of 4 to 6 Years

Before the news of the Ben Venue closing, Dr. Fox believed that the problem would see a significant improvement in ongoing and active shortages in about 2 years. Now, that time period doubles or triples. "I think it does set us back 4 to 6 years," she said.

Dr. Fox's speculative timeline was revealed earlier this week in the trade publication The Cancer Letter.

Ben Venue, which specializes in making injectable drugs, has been a major player in the US market for generic chemotherapy, Dr. Fox explained. There is no new manufacturer to take Ben Venue's place. "Nobody's jumping on board right now," she said.

We really need another supplier.
 
In the US cancer generics market, there are 3 "workhorse companies" that provide most of the generic chemotherapy injectables, said Dr. Fox. These are Hospira, Teva, and Bedford Laboratories, which is a distributor of Ben Venue products and products of other third parties. (Bedford and Ben Venue are both owned by Boehringer Ingelheim.) Pfizer is also in the market. Given this small circle, the loss of Ben Venue's manufacturing is significant, she believes. "We really need another supplier [of generic oncology products]," she said.

However, she emphasized that the situation is not as bad as it was 2 years ago. "People are not going without treatment, as in 2011."

A different opinion comes from Dr. Butler, who said that at Barnes-Jewish Hospital, there are still times when staff have to tell cancer patients that "we don't have certain drugs." She believes the situation has become "much worse in the last 2 years."

New Data on Chemotherapy Shortages

Currently, there are 31 cancer drugs actively in short supply, which is down from nearly 40 in 2011, according to Dr. Fox.

Also, there were only 4 chemotherapies that newly went into shortage in 2013, compared with 26 new chemotherapy shortages in 2011, according to data from a presentation that Dr. Fox made this week at a conference of hospital executives in Atlanta.

However, chemotherapies in short supply are just a small part of the overall drug shortage picture in the United States, Dr. Fox pointed out.

Notably, Ben Venue played a role in the cancer drug shortage crisis of 2011, Dr. Fox believes.

The production facility closed that year after a series of customer complaints about products and inspections from the US Food and Drug Administration (FDA) and other agencies. Subsequently, 2 very important mainstays of cancer treatment — doxorubicin and methotrexate — went into extremely short supply, said Dr. Fox. It turned out that Ben Venue was a producer of both drugs.

The marketplace eventually reacted, with some help from the FDA, and both dire shortages were alleviated.

Among other events, the FDA approved APP Pharmaceuticals as the manufacturer of a preservative-free form of methotrexate, and allowed an Indian manufacturer, Sun Pharma Global, to export generic doxorubicin to the United States.

After the 2011 closing, the Ben Venue plant resumed "limited" production in 2012. By that time, the drastic impact of the initial closure on the marketplace had passed, said Dr. Fox. "All of that pain has been dealt with in one way or another," she explained, adding that it holds true today, even with the news of the plant closure.

Immediate Problems

The closure nonetheless creates immediate clinical problems. For instance, Ben Venue and its sibling company, Bedford Laboratories, have been the sole US suppliers of thiotepa, Dr. Fox pointed out. The FDA is now allowing thiotepa, which is used in stem cell transplants and other settings, to be imported from Italy. "But that's very inconvenient for people; there's almost a month's delay," she said.

Dr. Greene said that procuring thiotepa from abroad is "exceedingly expensive and time consuming," and that St. Jude's is now looking for alternative drugs for chemotherapy regimens involving thiotepa. He is also concerned that daunorubicin, which is used in the treatment of leukemias, will fall into short supply because, now, only Teva will be producing the drug.

The Ben Venue plant has also been the world's sole manufacturer of Doxil, the branded version of doxorubicin hydrochloride liposome injection, which is owned by Johnson & Johnson. The product could disappear from the market for a time until a new manufacturer is found, as reported this week by Medscape Medical News.

Currently, Doxil is being evaluated in a number of clinical trials. Its potential disappearance from the marketplace puts the viability of these trials at risk because a generic substitution, which would be acceptable for patients in the clinic, is not possible in a research setting, ASCO's Dr. Ward pointed out.

The Murky World of Generics Manufacturing

Dr. Ward said he was surprised to learn that a branded drug, Doxil, owned by a major drug company, Janssen/Johnson & Johnson, was made by a generics manufacturer. But the cancer generics market is full of surprises and unknowns, he noted.

Take the example of Bedford Laboratories, which began as a division of Ben Venue in 1993. Both entities have been properties of Boehringer Ingelheim since 1997.

Unlike Ben Venue, Bedford will remain in business.

That's good news, because Bedford is the leading provider of cancer generic sterile injectables in the United States, with 30% of the market, according to an analysis led by Janet Woodcock, MD, head of the pharmaceuticals division at the FDA, and published earlier this year (Clin Pharmacol Ther. 2013;93:170-176).

But currently, Bedford is "out of stock" of a long list of sterile injectables, including many oncology products. The list, posted October 1 on the company Web site, includes Adriamycin, cytarabine, dacarbazine, etoposide, gemcitabine, methotrexate, paclitaxel, and vinblastine.

Some of these are very important products, said Dr. Ward. For instance, gemcitabine is part of the standard of care in pancreatic cancer.

"What you don't know from that list is how many of these drugs were manufactured by Ben Venue and how many come from elsewhere," he explained.

The company product announcement says these out-of-stock injectable drugs could be available "pending production as capacity permits."

"Bedford will continue to distribute products manufactured by Ben Venue Laboratories until that inventory is depleted," a company spokesperson said in an email to Medscape Medical News.

Generally, "there is not much transparency in this market," observed Dr. Ward.

He explained that producers of generic sterile injectables in the United States are regulated in terms of original licensure and the design of manufacturing processes. "But the FDA does not know who is having problems with a factory or profitability," he said, referring to the 2 reasons cited by Ben Venue for leaving the US market.

Generics companies can also switch their manufacturing from a drug that is not profitable to one that is, which can play havoc with the market availability of agents, said Dr. Ward.

He noted that the generics market, which includes chemotherapy injectables, is inherently volatile because profit margins are thin. Once on the market, "generics get very cheap very quickly," he said. Any variable that increases costs cuts into these already thin profits. This is exacerbated by that fact that the Centers for Medicare & Medicaid Services only updates the stated average sales price every 6 months, forcing companies to wait long periods for an approved adjustment in price. As a result, companies can feel a need to start and stop the production of certain products.

St Jude's Dr. Greene agrees that the generics market is a murky business in which many manufacturing and related planning details are not disclosed. "We just know when something is gone," he noted. The FDA Safety and Innovation Act, enacted in 2012, requires that drug manufacturers to notify the FDA as soon as they anticipate interruptions in drug production, and 6 months in advance if a product is to be discontinued. Although the law "improves the situation," Dr. Greene said, it has shortcomings.

Dr. Ward observed that the generics manufacturers managed to retain a number of loopholes in the law, which weaken its sentinel nature.

Seven companies supply 90% of the generic injectables market, said Dr. Fox. However, not all 7 make oncology products. Who manufacturers what product at what time is not publicly available information, and must be discerned through data detective work, she said.

The whole model is problematic, said Dr. Ward. "We have left it to business to ensure our drug supply."
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Adverse events and prevention

10/22/2013 03:50 AM |

A piece worth reading from a surgeon and blogger:

Medical errors are a real problem. I won’t deny that.

It was bad enough when the often-quoted Institute of Medicine figure that 98,000 deaths per year in the US are caused by medical errors was in vogue, but now a paper in the Journal of Patient Safety states that adverse medical events result in 210,000 to 400,000 deaths per year and 10 to 20 times those numbers of serious harms.

Since the paper disparages the medical profession, it has received a lot of media attention.

Most articles about it simply regurgitate the dismal estimates without any real attempt to dig into the paper’s methods.

Let’s take a closer look.

As is true of many papers, the abstract is a bit sketchy when describing how the paper arrived at its conclusion.

The full text of the paper reveals the author found four studies that looked at what are described as preventable adverse events in US hospitals within the last seven years. All four used the Global Trigger Tool which involves the screening of records for adverse events by nurses or pharmacists and a secondary review by physicians.

Based on opinions by “experts,” the author made a key, but erroneous, assumption that all adverse events are preventable.

Read the full blog here.


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Then and Now

10/17/2013 06:48 AM |

"It's about jobs. In its life, it [the health bill] will create 4 million jobs -- 400,000 jobs almost immediately."
 
- House Speaker Nancy Pelosi in February 2010
 
 
USA Today reports:
 
Hospitals, a reliable source of employment growth in the recession and its aftermath, are starting to cut thousands of jobs amid falling insurance payments and inpatient visits.

The payroll cuts are surprising because the Affordable Care Act (ACA), whose implementation took a big step forward this month, is eventually expected to provide health coverage to as many as 30 million additional Americans.

"While the rest of the U.S. economy is stabilizing or improving, health care is entering into a recession," says John Howser, assistant vice chancellor of Vanderbilt University Medical Center.

Health care providers announced more layoffs than any other industry last month — 8,128 — largely because of reductions by hospitals, according to outplacement firm Challenger Gray and Christmas. So far this year, the health care sector has announced 41,085 layoffs, the third-most behind financial and industrial companies.

Read the full article here.


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T Sells

10/16/2013 09:30 AM |

Ice T?

Testosterone gels – do they provide an important treatment option? Is “Low T” a real disease or just a marketing opportunity? Do these two options need to be mutually exclusive? (The F.D.A. has approved testosterone gels “for use in men who either no longer produce the male sex hormone testosterone or produce it in very low amounts.”)

And what does this have to do with asthma inhalers and DTC?

Interesting article in today’s New York Times (see here).

One error that needs immediate correction. After reporting on the amount of money companies such as Eli Lilly and AbbVie spend on advertising their testosterone gel products, the Gray Lady reports that,

In response to an article Sunday in The New York Times on prescription drug costs for asthma medicines in the United States, a number of readers complained about the high price of inhalers, and that the costs were inflated by the millions of dollars pharmaceutical companies spend on advertising for them.

Except that assumption is not true. Whether or not you agree with the style or substance of pharmaceutical direct-to-consumer advertising, one thing that’s just an economic fact is that advertising budgets do not impact the list price of the product.

Study after study after study done by charitable foundations, the federal government and industry all show that the price of a drug does not correlate to the amount spent on advertising.

In other words, if you look at four medicines that treat cholesterol and compare their advertising budgets, the one that spends the most is not necessarily the most expensive -- and often the reverse is true.

Consider this: According to Tufts University it costs about one billion dollars to bring a new medicine to market. That's one billion per drug -- and those are the ones that make it to market.

Now compare that to the $2.5 billion per year the industry spends on advertising and you have a somewhat better perspective. Reducing direct-to-consumer drug advertising would not reduce the price of drugs.

A reduction in advertising wouldn't reduce the price of medicines, but it would most certainly reduce the number of people visiting their doctors, and I cannot imagine that anyone thinks that is a good thing.

Here's some data from an FDA research study: Doctors do not prescribe medicines just because their patients ask for them after seeing an advertisement. They're prescribing medicines because their patients need them. That's called progress.

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Biosimilars: Is it ever too early for safety?

10/15/2013 09:58 AM |

An excellent article from BioWorld on the continuing saga on biosimilars from Sacramento to Singapore.

Some snippets …

The U.S. Battle of Biosimilars Continues on Multiple Fronts

By Mari Serebrov, Washington Editor

While the first biosimilars to hit the U.S. are still in development, the battle over how and when the follow-on biologics should be marketed continues to rage on both the local and global fronts.

A skirmish in California ended Saturday when Gov. Jerry Brown vetoed a bill, overwhelmingly passed by state lawmakers, that would limit automatic biosimilar substitution to those the FDA deems “interchangeable.” SB 598 also would have required pharmacists to notify physicians when an interchangeable is substituted for a prescribed biologic.

“Obviously, the governor gave himself a little wiggle room here,” Peter Pitts, president of the Center for Medicine in the Public Interest, told BioWorld Today.

Pitts disagreed with the governor about the timing of the bill. “It’s never too early to say we need to educate doctors and patients about what’s going on,” he said, stressing the importance of promoting safety and pharmacovigilance in the use of biosimilars.

“The untrained ear hears ‘identical’” when biosimilars are mentioned, Pitts said, but the follow-ons are not the same as generic drugs. Noting that even generics, which are supposed to be identical to the reference drug, can have variants that could affect an individual patient’s response, he pointed out that due to their complexity, biosimilars could produce more variances.

Global Battle

While the substitution battle continues on the state level, another biosimilar war is raging on the global front as the countries negotiating the Trans-Pacific Partnership (TPP) push to finalize the trade talks this year. Despite efforts to have the agreement reflect the 12 years of data protection that biologic innovators enjoy in the U.S., the issue hasn’t made it to the 3-year-old negotiating table yet.

Opposition to including the data protection in the TPP is framed, once again, as an issue of increased access. But it really comes down to some of the partners wanting to maximize their own opportunities, Pitts said.

He noted that the 100 most essential drugs identified by the World Health Organization are all off patent, which means they’re available as generics. But people in many countries still don’t have access to those essential small-molecule drugs, so Pitts questioned the assumption that reducing or removing biologic data exclusivity would increase global access to biosimilars, which are more complex and costly than generics.

The complete article can be found here.

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Off the (Moon) Beam

10/14/2013 09:59 AM |

California Governor Jerry brown has vetoed SB 598, a bill (passed by both houses of the legislature with overwhelming bipartisan support) that would have allowed biosimilars to be substituted by pharmacists if the F.D.A. deemed the biosimilar “interchangeable” with the reference product.  

The California bill would allow substitution of a biosimilar for an innovator product only if FDA declared the biosimilar interchangeable for the specific use; the prescriber had not expressly prohibited use of a biosimilar; the substitution was communicated to patients; the cost to the patient was the same or less than the innovator product; and the pharmacist notified the prescribing physician within five days. The requirement for physician notification would sunset after three years Additionally, the California State Board of Pharmacy would maintain a list of biosimilar products FDA determines to be interchangeable on its website

Patient information? Pharmacist empowerment? Who could be against such a significant public health double play?

According to Governor Brown,

“Doctors with whom I have spoken would welcome this information. CALPERS and other large purchasers warn that the requirement itself would cast doubt on the safety and desirability of more cost-effective alternatives to biologics.”

(CALPERS is the California Public Employees’ Retirement System, which provides health benefits to more than 1.3 million people.)

“Case doubt on the safety …”

Perhaps the Governor should be made aware of what bioequivalence really means.

Per a report in the New York Times, “Ralph G. Neas, president of the Generic Pharmaceutical Association, celebrated the veto, saying that Mr. Brown had “demonstrated compassion for millions of patients and strong fiscal stewardship for the state of California.”

Nothing like celebrating the victory of cost-centric medicine over patient-centric care.

For shame.

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Pay to Play?

10/11/2013 10:21 AM |

The Washington Post reports that Senator Joe Manchin (D/WV),

... is calling for an investigation of “pay to play” allegations regarding a scientific panel that shaped the Food and Drug Administration’s thinking on painkillers and that, according to the organizer’s e-mails, was funded by major pharmaceutical companies that put up as much $25,000 to attend a meeting.

FDA responds that the sessions,

… amounted to what one agency officials described as “an essential collaborative effort.”

And, yes -- collaboration is essential. FDA must be both regulator and colleague. But should money have been charged (by a private, for-profit organization) for industry to have a seat at the table? That’s a good question.

It’s also important to clarify that these were not (repeat – not) advisory committee meetings.

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Planet Janet

10/10/2013 03:33 PM |

From: CDER Center Director
Sent: Thursday, October 10, 2013 02:33 PM
To: FDA-CDER-wide
Subject: Retirement Rumors
 
CDER Staff:
 
I want to assure you that I am not planning to retire as erroneously reported in the media today. In fact, quite the opposite is true. I am becoming more deeply involved in many of the Center’s issues, including the proposed reorganizations of the Office of Pharmaceutical Quality and the Office of Generic Drugs.
 
The inaccuracy of the media has unnecessarily raised concerns among Center staff, and even among my own family. My daughter emailed me this morning to ask if I’m retiring! I continue to be fully committed to the important work CDER does and to its staff who work so diligently to protect the health of the American public.
 
Janet Woodcock  Read More & Comment...

Detailing Adherence Part II: Oncology Nurses and the Wave of the Present

10/10/2013 10:58 AM |

In July 2013, the Oncology Nursing Society (ONS) held its annual Leadership Weekend. Each year, the organization collects information about oncology nurses, their interests, and their needs. This year, they asked about their membership’s experiences helping patients manage adherence to oral therapies and about their interest in non-CNE training on the topic. The results of the survey, completed by 127 nurses, show that:

• Oncology nurses are experiencing patient non-adherence to oral therapies

• Oncology nurses want and need specific clinical practice assistance to help improve adherence

• Oncology nurses want and will attend educational programs on adherence to oral therapies.

Some findings of interest and importance:

Most Nurses Observe Problems with Adherence

There is evidence that most nurses are observing problems with adherence. Forty-one respondents (32%) said that 25%–50% of their patients have trouble, and another 26 (20%) said that 51%–75% of their patients do. In other words, more than half the respondents said that at least 25% of their patients do not adhere properly to their regimens.

Nurses Highlight Most Common Barriers to Adherence

The nurses ranked various potential causes of non-adherence by their importance to their patients. Cost was viewed as very important by 73 (57%) and important by 31 (24%). Thus, of the 127 total respondents, 104 find that cost, including reimbursement issues and high copays, is a significant barrier to adherence to oral therapies.

Another barrier appears to be side-effect management. Fifty-nine percent said this is an important problem (45 [35%]) or very important (31 [24%]). Cognitive difficulties following instructions are another potential barrier, but perhaps less significant. Although forty-eight (38%) ranked cognitive difficulties as 3 on a 1-5 scale, or of modest importance, another 51 (40%) viewed cognitive difficulties as important or very important in interfering with adherence to oral therapies. Difficulty swallowing seemed to be the least significant barrier, with 55 (43%) suggesting that it was not important or of minimal importance. Twenty-eight (22%) said it was mildly important, and 41 said it was important or very important. Thus, although most of the nurses did not view swallowing difficulty as a critical barrier, it does affect a fair number of patients.

What Do Nurses Need to Help Manage Adherence?

The participating nurses were offered a number of options for possible practical tools or specific aid. They are listed below in order of popularity with the respondents.

• Co-pay and reimbursement assistance was the most positively received form of help with adherence to oral therapies. Here, 119 (94%) of the respondents said they would find the help useful or very useful (70%).

• Side-effect management guides/tear sheets were seen as useful or very useful by another 116 nurses (91%).

• Patient journals/calendars were seen to be useful or very useful by 103 (81%) of the respondents.

• Online resources for both nurses and patients were very positively received, with 100 (79%) respondents viewing them as useful or very useful.

• Patient refrigerator magnets with significant information were also popular, with 72 (57%) indicating they would be useful or very useful.

• Telephone or email follow-up services by drug company or pharmacy were viewed as useful or very useful by 73 nurses (58%).

• Tablet or smartphone apps might be an emerging area of opportunity for drug companies or pharmacies. Fifty-seven (45%) thought they would be useful or very useful.

It’s interesting that the current outreach efforts by pharmaceutical companies and pharmacies rank only one percentage point higher than refrigerator magnets. They’re both 20^th century technologies.

What’s also important is that the research differentiated between “online resources” and apps. While both are 21^st century technologies, “online” is the substrate -- apps are the wave of the present.

Apps remind, cajole, educate, praise, incentivize, and assist patients in their quest for better health. Apps are at the nexus of safe use, treatment outcomes, and patient satisfaction. And it’s not science fiction.

At present, there are some 17,828 healthcare and fitness apps and 14,558 that can be deemed “medical.” While some are better than others, these numbers tell us one thing – this is not a fad or a trend. It is reality.

I have been working with the Mobile Health Library to help develop their safe use and outcomes support platform. It’s delivered as an app (viable on all tablet and smart phone systems) specifically to address many of the issues called out specifically by the ONS study – facilitating co-pay cards, patient diary functionality, side-effect management, direct physician office communications (via phone, e-mail, and text) and, perhaps most importantly, providing educational services via app-enabled printed materials, website links, and video).

Will our socio-economic “technology gap” lead to a more pronounced “adherence/compliance gap?” It’s an important question. That’s why it’s crucial we remember there is no one-size-fits all solution. But that mustn’t mean we disregard the reality of the growth and pervasiveness of apps, mobile apps. Let’s face it, when it comes to mobile phones, any gap is rather narrow – and it’s getting narrower all the time, literally every day.

The ONS research refers to apps as an “emerging opportunity.” And that’s true. But maybe a better way to phrase it is as an “emergent opportunity.”

Apps are here now. People are using them – more every day, and that includes healthcare providers, patients, and care-givers.

And as Philip K. Dick wrote, “Reality is that which, when you stop believing in it, doesn’t go away.”

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Moose on the Loose

10/09/2013 09:40 AM |

The only thing that dies harder than a bad idea is a bad idea with political resonance.

The Wall Street Journal reports:

AUGUSTA, Maine—The hunt for cheaper prescription drugs long has led consumers to reach beyond U.S. borders, but under a Maine law set to take effect Wednesday, their search now will have the state's blessing.

The law, the first of its kind, sanctions the direct purchase of mail-order drugs from some foreign pharmacies. It has ignited a court battle with the pharmaceutical industry and set the stage for a broader fight over access to less-costly medication.

Vendor of choice – CanaRx.

This is particularly appalling since the drugs being sent to U.S. customers from CanaRX are most certainly not “the same drugs Canadians get.” That bit of rhetoric is just plain wrong. CanaRX – by their own admission – sources their drugs from the European Union. And while they may say their drugs come from the United Kingdom, let’s not conveniently forget that 20% of all the medicines sold in the UK are parallel imported from other nations in the EU – like Spain, Greece, Portugal, and Lithuania.

PS/ The drugs CanaRX sells to Americans aren’t even legal for sale in Canada.

Once again -- a brief primer on why drug importation is a bad idea 

 
(1) It doesn’t save money.

(2) The drugs being sent to U.S. customers from Canadian Internet pharmacies are not “the same drugs Canadians get.”

(3) The state experience has been dismal and politically embarrassing.

(4) National Security concerns.

 Let’s look at each of these four items.

(1) It won’t save any money. Let’s not forget the non-partisan CBO study that showed that such policy would reduce our nation’s spending on prescription medicines a whopping 0.1% -- and that’s not including the millions of dollars the FDA would need to set up a monitoring system.

(2) The drugs being sent to U.S. customers from Canadian internet pharmacies are not “the same drugs Canadians get.” That bit of rhetoric is just plain wrong. In fact, drugs sold to Americans by Canadian Internet pharmacies aren’t even legal for sale in Canada. This isn’t about the quality of Canadian drug regulation. Canadian Internet pharmacies – by their own admission – are sourcing the drugs they're sending to the United States from outside of Canada. And while they may say their drugs come from Great Britain, let’s not conveniently forget that 20% of all the medicines sold in the UK are parallel imported from other nations in the EU – like Spain, Greece, Portugal, and Lithuania.

And the important political point here is that when Americans are asked if they want drugs from nations other than Canada – the answer is a resounding “no thank you.”

(3) The state experience has been dismal and politically embarrassing. Remember Illinois’ high profile “I-Save-RX”program? Over 19 months of operation, a grand total of 3,689 Illinois residents used the program -- which equals approximately .02% of the population.

And what of Minnesota’s RxConnect program? According to its latest statistics, Minnesota RxConnect fills about 138 prescriptions a month. That's for the whole state. Minnesota population: 5,167,101.

That's not a surprise considering that Minnesota, state officials observed Canadian Internet pharmacies engaging in dangerous practices.

One pharmacy had its pharmacists check 100 new prescriptions or 300 refill prescriptions per hour, a volume so high that there is no way to assure safety.

One pharmacy failed to label its products and several others failed to send any patient drug information to patients receiving prescription drugs.

Drugs requiring refrigeration were being shipped un-refrigerated with no evidence that the products would remain stable.

One pharmacy had no policy in place for drug recalls. Representatives of the pharmacy allegedly said that the patient could contact the pharmacy about a recall "if they wished."

The FDA launched an investigation, confiscating thousands of drug shipments headed for the United States. Some of them were headed for Minnesotans who ordered them over the state's Web site.

When opened, nearly half claimed to be of Canadian origin, but "85 percent of them were from 27 other countries including Iran, Ecuador and China." And 30 of them were counterfeit.

One Minnesota resident discovered that one of his "Canadian" drugs came from Greece, and another came from Vanuatu, a small island in the South Pacific. "I never heard of the place," he said.

Wisconsin also has an importation program, modeled on the one in Minnesota. It too hawks its promise and hides its dangers. All of the legalese buries the fact that the state doesn't accept any responsibility for the safety or effectiveness of any medicines bought on the state's Web site.

The state won't even guarantee that the drugs ordered are what the customer will receive. Not only that, but the state also says that it will not accept any legal responsibility or liability should any of the drugs cause a problem.

And remember Springfield, MA and “the New Boston Tea Party?” Well the city of Springfield is now out of the drugs from Canada business.

(4) National Security concerns. According to a report from the federal Joint Terrorism Task Force, a global terrorist ring with ties to Hezbollah, is importing counterfeit drugs into America by way of Canada. They are doing so for profit today - but could just as easily do so for more nefarious and deadly purposes. And legalizing importation would only facilitate such actions.

And then there are those politically pesky safety issues.

Adding fuel to the reality is a new by the European Alliance for Access to Safe Medicines.  The title says it all, “The Counterfeiting Superhighway.”

The report reveals the scope of the unregulated trade of fake pharmaceuticals. Through extensive research and examination of over 100 online pharmacies and over 30 commonly purchased prescription-only medicines, the report makes one thing very clear – we’re not winning the battle.

Key findings from this report

* 62% of medicines purchased online are fake or substandard (including medicines indicated to treat serious conditions such as cardiovascular and respiratory disease, neurological disorders, and mental health conditions).

* 95.6% of online pharmacies researched are operating illegally.

* 94% of websites do not have a named, verifiable pharmacist.

* Over 90% of websites supply prescription-only medicines without a prescription.

* 78.8 of websites violate intellectual property.

My favorite anecdote is the report’s example of an Internet pharmacy whose products came wrapped in pages from the Mumbai Daily News.  The most frightening fact, though, is most of the fake medicines “were delivered in seemingly authentic boxes, accompanied by patient information leaflets in good condition and ostensibly trustworthy blister packs.”

"Those who cannot learn from history are doomed to repeat it."

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Haile Selassie, call your office

10/08/2013 09:28 AM |

Another way the Republic of South Africa is trying to reinvent itself is in the way it regulates and reimburses for medicines. “BE” means not only “Black Empowerment” (in the post-apartheid sense) but also “bioequivalence.”

I’ve just returned from the “New Developments in Drug Regulation” conference in Pretoria, and there was a lot of serious discussion as to how government regulators can do a better job in a uniquely South African situation.

Some memorable moments …

Tomas Salmonson (Chair of the EMA’s CHMP) told the audience that, while he is a strong believer in transparency, he is not in favor of patient representatives on decision panels. Such representation, he said, “would be like having an elected parliament and then additional members.” He also does not believe that these meetings (akin in many ways to an FDA advisory committee meeting) should be open to the public. I pointed out that having patient reps and open adcomm meetings was a crucial part of the FDA process. Salmonson commented, “I know.”

Transparency translates in different ways. Salmonson noted that one way the EMA promulgates transparency is through its EPARS (European Public Assessment Reports System). The European Medicines Agency publishes an EPAR for every medicine granted a central marketing authorization by the European Commission. EPARs are full scientific assessment reports of medicines authorized at a European Union level. 

Salmonson also made the point that a transparent process behind benefit/risk allows consumers and healthcare providers to trust the regulator. FDA – attention must be paid.

Peter Bachmann, head of the Germany’s BfArM (Federal Institute for Drugs and Medical Devices) Coordination Group Unit, spoke to the EMA’s philosophy of being “united in diversity” (a theme that certainly resonated in Pretoria). He also discussed the EMA’s program of mutual recognition, detailing the agency’s methodology of “work-sharing” – a process of cross-national regulatory peer review that should be studied by FDA policy panjandrums for many reasons, not the least of which is quality control.

Ngokoana Khomo, Vice Chair of South Africa’s MCC (Medicines Control Council – the South African version of the FDA) honestly spoke of the tension between “the policy and the practice” of medicines regulation in South Africa. Unspoken was the obvious under-current of a third “p” – politics. And perhaps a fourth – “Potemkin Regulation.” She spoke of the MCC’s mission as “access, equity, efficiency, quality, and sustainability.” Dr. Khomo wisely said that “transparency takes away all suspicions.” But saying and doing is not always the same thing. She also spoke about the rational use of medicine. After all, you can’t spell Ngokoana without NGO.

Ekkehard Baader (Senior Director, Head of EU Regulatory Affairs at Teva) addressed the importance of (and distinctions between) consultation, communications, and cooperation.

Speaking of Teva – there was no discussion of generic drugs during the conference. Not a single mention of API sourcing and quality, not a word about excipients. Disturbing considering the venue and the reality.

BfArM’s Birka Lehmann (a member of PDCO, the EMA’s Paediatric Committee) spoke about issues surrounding informed consent for children (“What if the baby is crying?”) as well as the need for a Paediatric Investigation Plan (PIP) at end of phase 1. Clearly an area ripe for FDA harmonization conversations. Clearly the pediatric train is moving – but EMA and FDA should be on the same track.

At this point you may be wondering what any of this has to do with regulatory reform in the Republic of South Africa. That question was also on the minds of many in the audience who asked questions like, “how much does all of this cost?” and “how many people do you need?” and “how do you train staff?”

Day 2 began with a focus on biosimilars and the successes and failures of the EMA experience – as well as a nod to the work being done by the WHO.

The presentation by Chris Holloway (Group Director of Regulatory Affairs & Chief Scientific Officer at the ERA Consulting Group) was the first person to use the word “quality” – and “process.”  He spoke about “balancing needs against expectations.” And it was a welcome addition to the conversation. A breath of real-world reality vs. regulatory theory.

Elwyn Griffiths (WHO) likened his organization’s attempts to develop criteria for biosimilars to the League of Nations – but in a good way.

Haile Selassie, call your office.

Max Wegner (VP, Head of Global Regulatory Affairs, General Medicine at Bayer AG) addressed the unintended consequences of the EMA’s PRAC (Pharmacovigilance Risk Assessment Committee), specifically the impact of public reports of adverse events that had yet to be investigated. I added that the FDA had similar issues with Early Safety Signal Communications and the resultant unintended (but not entirely unsurprising) over reaction by the media and the ensuing leap in non-adherence.

Finally, Marc Blockman of the host Medicines Control Council (MCC) spoke on the issues surrounding both the importance of and difficulties with pharmacoviginance in South Africa. Two of his comments stand out: “Pharmacovigilance is a public service” Bravo. And, “Yes, we have a yellow card – but the form is as much the problem as it is the process.” Sounds familiar.

The conference was, as Pierre Abélard might have put it, a “sic et non” experience. Lots of good advice – but not a lot of applicable next steps. What makes this all the more urgent is the South African position on medicines reimbursement and intellectual property – which shares many philosophical underpinnings with that other bastion of IP protection – India.

Just as there are issues relative to South Africa’s need for regulatory capacity building, so too is capacity building and investment important for the future of intellectual property issues. One frightening passage in South Africa’s proposal states, “The Draft Policy proposes adopting strict patenting rules to “exclude diagnostic, therapeutic and surgical methods from patentability, including new uses of known products, as is the case under the TRIPS Agreement.” Not a good start for a nation that wants to be the “s” added to BRICS.

Further, South African law currently provides no regulatory data protection and the Draft Policy does not include any.  Moreover, it explicitly rejects the utility of “blanket data protection” for innovator data and emphasizes the importance of “access to knowledge.”  Uh oh. And, of course, there’s a magic rain dance call for compulsory licensing.

The Draft Policy encourages the use of parallel importation to improve access to medicines. Been there. Done that. A clear and present risk to patients.

And these are only a few examples. It gets worse.

The policy disconnect is profound. In April, South Africa sent a sizable delegation to the mega BIO convention with the message that they were “open for business,” and aspires to be a player in global life sciences.

At the same time, local generics manufacturers and the usual suspect activists are whipping up frenzy over intellectual property issues. The same old song. And a dangerous one considering that Scientific American ranks South Africa in the bottom 20% of its life science/innovation index.

(PS/ Under the current regulatory regime, it takes the MCC between 3-5 years after EMA or FDA approval t bring innovative therapeutics to South African patients – the slowest among “advanced” MEA nations. What’s wrong with this picture?)

Rather than looking to emulate the EMA, perhaps South Africa should adopt a reference basket of maybe five to six countries. A good model is Singapore. Everyone’s favorite city-state reviews seven countries—USA, Canada, Australia, NZ, Japan, Switzerland and the EMA.  If any two of the seven have approved, then approval is basically a formality.

Talk is cheap.

There is nothing like returning to a place that remains unchanged to find the ways in which you yourself have altered. – Nelson Mandela

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Words from the Wise

10/04/2013 06:47 AM |

                 At CMPI’s recent Capital Hill conference ,Personalized Medicine and Responsible Access to Pain Medication, Dr. Charles Inturrisi, professor of pharmacology at the Weill Cornell Medical College, laid down the gauntlet:

I want to make a distinction that really does make a difference.  And this is the distinction between efficacy and effectiveness.  We know that opioids can provide analgesia for some chronic pain patients.  We don’t know what percentage but we know that some, and you’ve heard from them this morning, at least one of them.  But we also know the treatment outcomes with opioids are variable and not predictable.  And this is the take home message if you have to leave.  At present, there are no well-validated means of identifying optimal candidates for effective long-term chronic opioid therapy.  That’s the problem.  That’s the gap in our knowledge.  That’s the gap in our evidence base. 

We need to learn who will experience good analgesic effectiveness at stable dosages with limited side effects and low risk of abuse.  So the critical question there is are there phenotypic or endo-genotypic characteristics that we can associate with better or worse outcomes that will help us to predict which patients might benefit and so that the cost-benefit ratio will be favorable rather than unfavorable. 

Now I’m going to talk about personalized medicine in general and in particular.  This refers to this emerging concept approach that uses patient-related factors including the phenotype, that is what information you can observe about the patient and a lot of that information now is contained in the electronic medical record.  Also genotypic information that you can gain by collecting a sample and it can be either a sample of blood, or in some cases even a sample of saliva and by going through and looking at snips of DNA and creating biomarkers that select optimum medication and dosage for individual patients.  It’s been estimated, on average, that prescription drugs are effective for only about half of those who take them.  And for some drugs like anticancer drugs and antidepressants, the so-called non-responder rate is even higher.

Personalized medicine can reduce the non-responder rate because you can focus in on individuals who are highly associated with being respondersand you can eliminate the trial and error inefficiencies that inflate healthcare cost. 

An audio recording on Dr. Inturrisi’s full comments can be found here (at the 1:03 mark) and the panel discussion that followed here.

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A Strike Against Sustainable Innovation

10/02/2013 07:40 AM |

On Friday CMS issued its final decision on beta amyloid imaging. It’s similar to their draft decision in that they ignored the recommendations of the medical community that was calling for full coverage for the Appropriate Use Criteria (AUC) population and imposed Coverage with Evidence Development (CED). CMS will only pay for Alzheimer's imaging tests used in clinical research or to exclude Alzheimer's disease when diagnosing patients in narrow circumstances. There are some slight changes from the initial draft, but from a patient access perspective, we are in the same boat as we were previously, which is non-coverage.

The Alzheimer's Association noted that, in the past, it has taken as long as seven years for CMS to move from a CED designation for new medical technologies to full coverage.  

CMS’ move is just the latest example of cost-based thinking trumping patient-centric care

And, as per a recent article in BioCentury, there are significant unintended consequences that will impact the future of personalized medicine.

The cost of demonstrating clinical utility, along with the lack of clear or consistent standards, is killing a business model that had made it possible for small companies to commercialize molecular diagnostics quickly and cheaply. The fate of these laboratory-developed molecular diagnostics companies, and especially the conclusions investors draw about the viability of the space, could shape the future of personalized medicine.

According to research by the Tufts Center for the Study of Drug Development, without clinically useful diagnostics, personalized medicine growth will occur at a relatively slow pace.

And personalized medicine represents the future of healthcare around the world.

Let’s cut to the chase, if we are going to take meaningful strides both in addressing Alzheimer’s Disease specifically and in personalized medicine more broadly, we should not rely on Coverage with Evidence Development (CED) criteria in cases where the FDA’s approval process has expressly evaluated and endorsed the use of a drug or biologic in a specific patient population.

Fact: The evidence on amyloid imaging supports coverage for the population as identified by the Amyloid Imaging Task Force through Appropriate Use Criteria (AUC). A task force, convened by the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging, recommends coverage in this population based on a comprehensive review of the literature and expert consensus.

Fact: CMS currently covers similar PET technologies to aid in the diagnosis of Alzheimer’s Disease and other forms of cognitive decline. The agency has not previously required evidence of health outcome improvement as a condition of such coverage.

Fact: Using CED alone will deny Medicare beneficiaries adequate and rapid access to this technology, as the path to implementation is unclear. Such uncertainty in the reimbursement process strongly dis-incentivizes future investments in research and development. And without innovation there will not be advances in personalized medicine.

Wither “sustainable innovation?”

Why even bother with expedited review and similar FDA pathways? Clearly closer FDA/CMS coordination is required to address both the will of Congress – and the future of American healthcare.

The future ain’t what it used to be. – Yogi Berra   Read More & Comment...

FDA: The Shut Down Details

10/01/2013 10:57 AM |

In the absence of either an FY 2014 appropriation or a Continuing Resolution for FDA, beginning on October 1 and continuing until the date of enactment of an FY 2014 appropriation or Continuing Resolution ("lapse period"), agency operations will be limited to the following:

• Emergency work involving the safety of human life or the protection of property;
• Criminal law enforcement work; and
• Activities funded by carryover user fee balances, including user fee balances under the Prescription Drug User Fee Act (PDUFA), Generic Drug User Fee Amendments (GDUFA), Medical Device User Fee Amendments (MDUFA), Animal Drug User Fee Act (ADUFA), Animal Generic Drug User Fee Act (AGDUFA), and Family Smoking Prevention and Tobacco Control Act. Carryover user fee balances will only be spent on activities for which the fees are authorized under the Federal Food, Drug, and Cosmetic Act (FD&C Act).  

With respect to medical product user fees, during the lapse period, FDA will not have legal authority to accept user fees assessed for FY 2014 until an FY 2014 appropriation for FDA is enacted. This will mean that FDA will not be able to accept any regulatory submissions for FY 2014 that require a fee payment and that are submitted during the lapse period.   

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