Latest Drugwonks' Blog

The Pre-Sub Club

  • 07.13.2012

Medical technologists -- welcome to the world of "non-binding advice."

The U.S. Food and Drug Administration plans to provide medical device makers feedback before they apply for marketing approval to help companies identify regulatory requirements early in the device development process.

The new program, called "Pre-Sub," is in response to a MDUFMA that increases fees in return for more meetings.

"FDA's early feedback on studies can facilitate the development of a quality premarket submission and help industry avoid regulatory hurdles during the review process," said Christy Foreman, director of the Office of Device Evaluation in FDA's Center for Devices and Radiological Health (CDRH).

The FDA is seeking public comment on the Pre-Sub draft guidance.

Consider how Lilly’s social media presence grows.

Riding the success of its LillyPad blog and broader social media identity, Eli Lilly & Co. is branching out from the U.S. and Canada to Europe and south of the border in Mexico.

Lilly launched its LillyPad blog (http://lillypad.lilly.com) less than two years ago as a platform to discuss healthcare innovation and policy. On Twitter, the company tweets under the LillyPad handle about similar issues and has nearly 9,000 followers. Like most social media networkers in pharma, Lilly stays away from product-oriented issues and devotes attention to broader subjects in the healthcare realm.

With LillyPad branches in Europe and Mexico, the company can play by nation-specific rules and discuss off on the issues that are relevant to individual nations. Lilly also wants to give a tailored voice to specific business units. The company's clinical open innovation team, for example, has begun blogging and tweeting.

 Lilly’s emerging social media strategy appears to include establishing a wider presence in the global social media world while building targeted audiences based on factors such as geography and subject matter.  

New York Times Articles

I BEG TO DIFFER; The Fat Epidemic: He Says It's an Illusion

By GINA KOLATA
Published: June 08, 2004

 

Ask anyone: Americans are getting fatter and fatter. Advertising campaigns say they are. So do federal officials and the scientists they rely on.

But Dr. Jeffrey Friedman, an obesity researcher at Rockefeller University, argues that contrary to popular opinion, national data do not show Americans growing uniformly fatter.

Instead, he says, the statistics demonstrate clearly that while the very fat are getting fatter, thinner people have remained pretty much the same.

Let it be said that Dr. Friedman, a Howard Hughes Medical Institute investigator and the discoverer of the gene for leptin, a hormone released by fat cells, is not fat. He is tall and gangly, with the rumpled look of an academic scientist.

As an obesity researcher, he might be expected to endorse the prevailing view that obesity in this country is out of control. But Dr. Friedman said he was outraged by the acceptance of what he sees as a hurtful myth, one that encourages people to believe that if you are fat, it is your fault.


Dr. Friedman points to careful statistical analyses of the changes in Americans' body weights from 1991 to today by Dr. Katherine Flegal of the National Center for Health Statistics. At the lower end of the weight distribution, nothing has changed, not even by a few pounds. As you move up the scale, a few additional pounds start to show up, but even at midrange, people today are just 6 or 7 pounds heavier than they were in 1991. Only with the massively obese, the very top of the distribution, is there a substantial increase in weight, about 25 to 30 pounds, Dr. Flegal reported.

As a result, the curve of body weight has been pulled slightly to the right, with more people shifting up a few pounds to cross the line that experts use to divide normal from obese. In 1991, 23 percent of Americans fell into the obese category; now 31 percent do, a more than 30 percent increase. But the average weight of the population has increased by just 7 to 10 pounds since 1991.

Dr. Friedman gave an analogy: ''Imagine the average I.Q. was 100 and that 5 percent of the population had an I.Q. of 140 or greater and were considered to be geniuses. Now let's say that education improves and the average I.Q. increases to 107 and 10 percent of the population has an I.Q. of above 140.

''You could present the data in two ways,'' he said. ''You could say that the average I.Q. is up seven points or you could say that because of improved education the number of geniuses has doubled.''

He added, ''The whole obesity debate is equivalent to drawing conclusions about national education programs by saying that the number of geniuses has doubled.''

Not everyone agrees.

''It' s one thing to talk about statistics and another to talk about what's happening to individuals,'' said Dr. Marion Nestle, a professor of nutrition, food studies and public health at New York University. ''Everyone notices that there are more overweight people now.''

Dr. Friedman, however, begs to differ. The statistics let scientists get beyond impressions and focus on the evidence.

He is, in a way, an unexpected figure to insert himself into the highly charged politics of obesity. He left clinical medicine in 1980 after discovering that his true passion was the laboratory. By 1981, he had begun his scientific career, and within a few years he was taking on what seemed like an impossibly onerous task, finding a gene whose absence made mice grow massively obese.

He keeps mementos from those days. He still has the purchase order, from December 1986, for the first batch of mice he used for the experiment. Hanging on his office wall is a framed strip of white paper with black blotches, the data that on Sunday morning, May 8, 1994, revealed he had found the gene that he named leptin.

''To me, those data are as beautiful as the Mona Lisa,'' he said.

Over the years, Dr. Friedman says, he has watched the scientific data accumulate to show that body weight, in animals and humans, is not under conscious control. Body weight, he says, is genetically determined, as tightly regulated as height. Genes control not only how much you eat but also the metabolic rate at which you burn food. When it comes to eating, free will is an illusion.

''People can exert a level of control over their weight within a 10-, perhaps a 15-pound range,'' Dr. Friedman said. But expecting an obese person to decide to simply eat less and exercise more to get below the obesity range, below the overweight range? It virtually never happens, he said. Any weight that is lost almost invariably comes right back.

The same goes for gaining weight in general, Dr. Friedman argued. A person who has the genes to be thin is not going to get fat because portion sizes increase. It makes no scientific sense, he said.

But isn't it true that we can decide to eat or not, choosing to skip dinner, say, or pass up dessert? Isn't that free will? Not really, Dr. Friedman said. The control mechanisms for body weight operate over months, even years, not day to day or meal to meal.

''People live in the moment,'' he said. ''They lose weight over the short term and say that they have exercised willpower,'' but over the long term, the body's intrinsic controls win out. And just as willpower cannot make fat people thin, a lack of it does not make thin people fat.

No one, he says, can consciously calibrate their food intake as precisely as the body does naturally. Most people's weights remain steady, within about 10 pounds, year in and year out. But when people count calories, they typically err by about 10 percent. For someone who eats 750,000 calories in a year, that 10 percent error would add up to 75,000 calories, or about 25 pounds.

Obesity, Dr. Friedman says, is a problem; fat people are derided and they have health risks like diabetes and heart disease. But it does no one any good to exaggerate the extent of obesity or to blame the obese for being fat.

''Before calling it an epidemic, people really need to understand what the numbers do and don't say,'' he said.

 

Fizz Ed

  • 07.11.2012

Obesity is largely a question of calories in and calories out.

So why is Mayor Bloomberg only concerned about the “calories in” part?

Is the Mayor’s focus on Big Gulp Disease a sleight of hand to divert attention from the city’s inability (or is it unwillingness) to address the “calories out” part of the equation?

In its biennial survey of high school students across the nation, the CDC reported in June that nearly half said they had no physical education classes in an average week. In New York City, that number was 20.5 percent, compared with 14.4 percent a decade earlier.

That echoed findings by New York City’s comptroller, in October, of inadequate physical education at each of the elementary schools that auditors visited.

New York City has not filed a physical education plan with the state since 1982, though state officials recommend a new one every seven years. A spokeswoman for the city schools says one will be presented in September.

It’s time for Mayor Bloomberg to step down from the bully pulpit long enough to get our kids back into the gym.

Morning Joe

  • 07.10.2012

Kudos to the behind-the-scenes work of the FDA and the industry’s Opioids Working Group (OWG).

The FDA has approved a final class-wide REMS for extended-release and long-acting opioids that requires companies to make educational programs available to prescribers at no or nominal cost. The REMS does not require prescribers to participate in the training programs, though FDA said it is working with Congress to explore legislation to mandate prescriber training, including a prescriber education requirement as a condition of obtaining registration with the Drug Enforcement Agency.

The required educational programs must cover the content of an FDA-developed blueprint, which includes the dangers of misuse and abuse, directions for patient selection and how to recognize evidence of misuse and abuse. FDA expects the first educational program will be offered by March 2013. Companies will be required to track the number of prescribers completing the program and whether the program is adversely affecting patient access to medications.

In other news, the President signed PDUFA. The law reauthorizes both PDUFA and MDUFA and creates new user fee programs for biosimilars and generics along with a slew of other important codicils.

Strange that the White House is silent on this important piece of bi-partisan legislation. As Veep Biden once said, "It's a big, f--king deal."


Did you know that a recent study found " that most children and youth who consume soft drinks and other sweetened beverages, such as fruit punch and lemonade, are not at any higher risk for obesity than their peers who drink healthy beverages."

Or that a long term study tracking low income children (The Bogalusa Heart Study) that started in 1973 found a "positive association between diet beverage consumption and overweight resulted from the consumption of diet beverages and non-sweetened beverages. "   

Probably not.   Like me, you were too busy fixating on the proposed ban on soft drink servings over 16 oz in NYC.  

The Bogalusa Heart Study team also concluded  "eating patterns were associated with overweight in young adults. However, the eating patterns explained only 1–2% of the variance in BMI. Thus, 97% of the variance is unexplained. More studies are needed to better understand how eating patterns in combination are associated with overweight before policy changes are made. Targeting single eating patterns in obesity intervention programs may not be the best approach. This is possibly reflected in the modest-to no-effect being observed with this approachIn this study, eating patterns were associated with overweight in young adults. "

So why are lobbying organizations and interest groups and the CDC and NYC attacking soft drinks if it is -- at best -- only a sliver of that 1-2 percent explaining BMI variance?   

In part it's because attacking the eating habits of the poor -- especially the rural and minority poor -- is fair game.   But the more important reason is the belief that obesity is the underlying cause of every chronic disease and the cost of health care.   So under the guise of controlling health care costs it is now becoming legitimate to have governments tell people what to eat and drink.    You would  never know that around the world, people are living longer and healthier lives, a trend that has boosted income and prosperity over the last half century.   

Worse, a campaign is under way to claim that sugar -- or drinking soda -- is as deadly to humans as tobacco is.    That's not science.  That's the sort of fear mongering that has made people afraid of vaccinating their kids.   

BHAG in Beirut

  • 07.06.2012

Big Hairy Audacious Goals set doers apart from talkers.

Last week, “under the patronage of the Lebanese Ministry of Public Health,” I was honored to participate in the two-day “Drug Quality Forum” held at the American University of Beirut.

T
he focus of the event was on the impact of drug quality and safety with focused presentations on (among other topics) API quality, GMP requirements (as well as the often forgotten but hugely important GSDPs – Good Storage and Distribution Practices), data requirements and regulatory pathways. In attendance were senior health ministry officials from Lebanon, Syria, Jordan, and Iraq as well as representatives from the WHO and France’s Agence nationale de sécurité du médicament et des produits de santé  (ANSM) – née AFSSAPS.

Some brief verbatims:

David Holt (St. George’s University, London):  “There is nothing more expensive than clinical failure.”  He also cited the following from a recent paper in the British Journal of Pharmacology (2011;72:727-30)

“There are few prospective studies assessing potential additional risks associated with substitution and there are no established protocols by which switching is monitored or assessed.

This may make it difficult to know whether the money saved on the initial drug will still be saved as treatment outcomes on the substituted drug become apparent.”

Gilberto Lopes (The John’s Hopkins Singapore International Medical Center) pointed out that it’s not about the cost of pharmaceuticals but rather spending on pharmaceuticals – and that having more new therapies is a good thing.

Mark McGrath (Novartis) made the very important point that, “Quality cannot be implied.” This followed on my earlier comment that “Quality cannot be tested into a product. Quality is by design.”

At the end of the first day, Conference chairman, Dr. Joseph Simaan (Professor and Chairman, Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut), commented that public health officials are faced with “a moral dilemma” of wanting (and being under pressure) to approve locally manufactured generics – but cannot, in any way, allow sub-standard products onto the market.

As Khahil Gibran wrote, “Perplexity is the beginning of knowledge."

Day Two focused on topics ranging from bioavailability to bioequivalence and biowavers – highly technical presentations, but not without some humor. One example:

Q: Why were the two generic chemists so sad?

A: They were dissolutioned.

(Who said drug regulators don’t have fun?)

On that same topic, Soula Kyriacos (Pharmaline) gave a very informative talk on the correlation of product dissolution and bioavailability (in vitro vs. in vivo). And take my word for it – anything sounds riveting when presented by a smart woman speaking English with a Lebanese/French accent.

The last session of the meeting was devoted to developing a series of consensus recommendations for the attendees to take back to their respective nations within the GCC (Gulf Countries Cooperative). I was pleased to help moderate this effort along with Dr. Simaan, Dr. Ghassan Hamadeh (Associate Dean for CME, Faculty of Medicine, American University of Beirut) and Dr. Ziad Nassour (President of the Lebanese Order of Pharmacists).

Here are those recommendations:

1. Ministries of Health (MOH) to develop criteria for approval of bioequivalence centers (CROs) in compliance with International standards (GCP, GLP) in line with FDA, EMA, WHO or ANSM mechanisms for inspection and approval.

2. MOH to ensure that complete, detailed, and well-documented files are submitted for registration of all drugs according to ICH guidelines.

3. Any biosimilar application for an imported product must include a prior EMA or FDA approval

4. MOH must insist on emphasis of the quality of the active ingredient with full information on sourcing, materials and manufacturer.

5. Information leaflets of generic and innovator drugs should be up to date and made accessible and include all safety information.

6. No marketing approval for drugs without stability, and bioequivalence studies according to ICH guidelines.

7. No marketing approval for drugs not approved or marketed in their country of origin.

8. MOH to initiate product specific pharmacovigilance systems.

9. MOH to set up an efficient communication system to be used by Health Care Professionals and the Public to report safety issues with drug products

10. Drugs should not be sold in dispensaries. (Note: In Lebanon, “dispensaries” are supposed to provide generic medicines for those who cannot afford to buy them at no charge.)

11. Create a Department for Quality Control within the Ministry of health to review, authenticate submissions and inspect dossiers as well as track batches and perform random testing of marketed products.

12. Ensure all drugs are available through controlled supply chain.

13. Build capabilities in the ministry of health through enhanced training in

Big Hairy Audacious Goals? Absolutely.

That’s precisely what makes them so exciting.

In a pithy commentary in Nature, Sir Alasdair Breckenridge, Chairman of the MHRA, (et al.) writes:

A life cycle approach to pharmaceutical regulation, in which the benefit–risk balance of new drugs continues to be robustly assessed following market approval, is emerging in both the United States and Europe.

Certainly.

But …

Whether the pharmaceutical industry joins in this consensus and whether companies will serve as willing or reluctant partners in an invigorated post-marketing drug regulation scheme remains unclear. Additional regulatory requirements are never welcome in the short term, and the post-marketing studies that may be required under the life cycle approach may impose substantial costs on manufacturers. However, industry has learned the hard way that inadequate responses to safety signals can have a serious detrimental impact not only on public health but also in economic and reputa­tional terms. The long-term interests of manufacturers and regulators in well-characterized benefit–risk pro­files are essentially the same.  

The complete article can be found here.

What’s in a name? That which we call a rose by any other name would smell as sweet.

No doubt. But a name also is an aspiration.

It is with that preface that I am pleased to share a bit of news that arrived with my July Drug Information Journal – the publication (the official journal of the DIA) is changing its name.

Transparency Alert:  I am an Associate Editor of this journal.

The new title, Therapeutic Innovation & Regulatory Science, is a stake in the ground. First, it’s not just about “drugs.” That’s a great leap forward. Second, it’s about innovation. That’s where the action is. And third, it’s not about regulation, but rather “regulatory science.” That’s a global topic -- from the FDA’s Critical Path initiative to the EMA’s IMI and beyond. And, dare we hope – one that might some day lead to greater harmonization.

Like I said – a name is also aspirational.

Bon Courage, Therapeutic Innovation & Regulatory Science!


Our aspirations are our possibilities.

-- Samuel Johnson

According to information presented at the American Society of Health-System Pharmacists Summer Meeting, health systems that rely primarily on voluntary reporting of adverse drug events identify as few as 6% of events." James M. Hoffman, PharmD, MS, BCPS, Medication Outcomes & Safety Officer, and Director, Medication-Use Safety Residency Program, and Associate Member in pharmaceutical sciences at St. Jude Children's Research Hospital in Memphis, TN, argued for using several different methods of detecting adverse events in order "to get a more complete understanding of opportunities to improve the medication use process … Underreporting is a key limitation of error reporting systems.” Hoffman proposed the use of four common methods: "incident reporting; direct observation; medical record review; and trigger tool." He also said that electronic health records can be "a key resource for event detection."

CMPI

Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.

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