Drug and Device Makers Can Expect Tougher Scrutiny of Clinical Trials

January 19th, 2010

On December 29, 2009, the acting director of the Center for Devices and Radiological Health said that FDA will soon urge device makers to set more rigorous standards for clinical trials.   Days later, the FDA published reviews critical of clinical trials involving implanted defibrillators and coronary stents.

Among the issues that manufacturers need to address are the the better refining of success metrics and end point definitions, closer patient monitoring, better defined treatment criteria and goals, safety goals, and adequacy of follow up.

Already a new Draft Guidance has been issued on the monitoring of clinical trials. This guidance, IRB Continuing Review after Clinical Investigation Approval, has been issued and is open for comments and suggestions. The guidance applies to Institutional Review Boards, Clinical Investigators and Sponsors.

Read more here: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM197347.pdf

Debarment

January 19th, 2010

In a recent post I pointed out that Charles Babbage thought that hoaxing was rare.

Were Babbage still alive he may want to revise his opinion in light of science’s newest Madoff, Scott Reuben. Dr. Reuben was the former chief of acute pain at Baystate Medical Center in Springfield, Massachusetts, accused of faking research for a dozen years in published studies suggesting Vioxx and Celebrex offered benefits after surgery.

Prosecutors allege that the doctor received research grants from drugmakers but didn’t perform the studies but rather made up patient data. Investigations later showed that 21 papers published between 1996 and 2008 used partially or entirely fabricated data.

Dr. Reuben has apparently agreed to plead guilty in exchange for a recommendation of a more lenient jail sentence of up to 10 years, a fine of $250,000 and forfeiture of assets received for the research.
The U.S. Attorney’s Office Report is here: http://www.justice.gov/usao/ma/Press%20Office%20-%20Press%20Release%20Files/Jan2010/ReubenScottPR.html

But this brings up another issue that is little talked about: debarment. Among the many enforcement tools available to the Food and Drug Administration is the ability to shut out people from any work in industries regulated by the agency.

Debarment action is intended to protect the public from those that would put unlawful profit ahead of consumer safety. The statute allows, and sometimes requires, that those convicted of certain crimes not be allowed to participate in regulated industries in any capacity. This includes not only direct employment but also consultation.

Read more here: http://www.fda.gov/ICECI/EnforcementActions/FDADebarmentList/ucm139627.htm

FDAs Position on BisPhenol A as of January 2010

January 17th, 2010

The FDA updated their stance on BPA. In short, they are pursuing additional studies as there are unanswered questions about the risks posed to certain populations, namely children and infants. Though they have not taken official action, they are supporting actions to reduce the use of BPA in food packaging articles, especially those for infants including bottles, infant feeding cups and the linings of infant formula cans.

http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm064437.htm

Science and Salami

January 7th, 2010

In 1830 Charles Babbage, wrote on the demise of science in Britain. Because I love the prose, allow me to quote him at length.

“Scientific inquiries are more exposed than most others to the inroads of pretenders; and I feel that I shall deserve the thanks of all who really value truth, by stating some of the methods of deceiving practised by unworthy claimants for its honours, whilst the mere circumstance of their arts being known may deter future offenders.

There are several species of impositions that have been practised in science, which are but little known, except to the initiated, and which it may perhaps be possible to render quite intelligible to ordinary understandings. These may be classed under the heads of hoaxing, forging, trimming, and cooking.” Reflections on the Decline of Science in England, and Some of Its Causes.

Hoaxing and forging are rare, overt deceptions. Trimming, according to Babbage, is that practice of ‘clipping off little bits here and there from those observations which differ most.’ Cooking is the art of giving ordinary observations the appearance and character of those of the highest degree of accuracy.

One wonders what Babbage would think of the ’salami slicing’ that went on with the drug of Cymbalta. As described in detail at the Pharmalot blog of January 6, salami slicing is the publication of separate, but similar articles that rely on the same set of data.

Such slicing and dicing of data may help researchers with their publishing output and helps drugmakers promote their drugs. Notwithstanding the ethical and legal considerations, this obfuscation serves no scientific purpose and erodes public confidence.

Design Defect Example: The Cornballer

December 13th, 2009

My last post introducted one type of product defect, the manufacturing defect.

Today’s topic is the design defect. A design defect is a flaw in the product’s specification or engineering, as opposed to the product’s unit or materials. Design defect issues are more complex than manufacturing defects and have no precise definition. Rather, most courts apply one of two tests to determine if a product’s design is defective.

One test is the “consumer expectation test” which considers whether the product fails to perform as safely as an ordinary consumer would expect when used as intended or in a reasonably forseeable manner. The second test is the “risk-benefit test” which evaluates whether the risks of danger inherent in the product’s design outweigh the benefits of the design.

Again, the idea can be conveyed more readily by example. Any fans of the television show Arrested Development will recognize the invention of the Cornballer. This was a deep fat fryer invented by the Bluth family patriarch to fry cornballs. The defective dsign of the product was it’s burn hazard. In the show, it seemed any character that came close to the cornballer ended up with burns to their arms and hands. In fact the product was deemed so dangerous that it was ‘banned’ and sold only in Mexico- where it had also been banned. If you weren’t an Arrested Development fan, this won’t make any sense.

But without further ado, here is The Cornballer. Today’s example of a Design Defect.
The Cornballer from Arrested Development

Manufacturing Defect Example: treadmill gone haywire

November 27th, 2009

One of our specialties at Averture is creating highly defensible products. Our background in products liability work provided us insight to proactively situate products to be highly defensible in the event of a defect.

You may recall from torts that a product is defective when, at the time of sale or distribution, it contains a manufacturing defect, is defective in design, or is defective because of inadequate instructions or warnings. For the time being, I’m going to focus on the manufacturing defect.

A manufacturing defect is a flaw that occurs when the product, as built, doesn’t conform to the intended design. It is the easiest type of defect to identify. It is simply put, that product that sneaks through production and quality controls and gets out into the market. Something has gone amiss and the product doesn’t function as intended.

Many product defects that make it into the legal world have inflicted serious injury or even death, so it was difficult to find non-traumatic video of a manufacturing defect. However, Madison Avenue has provided an example, so we’ll use that. Apologies that it comes in the form of an advertisement.

Treadmill Gone Haywire

5 People and Their Ideas That Have Changed Our Health

November 27th, 2009

The onset of the holidays brings with it reflection on the past. Giving thanks for the blessings of the year prior, contemplation of the passing of another year and hope for possibilities in the year to come. I am not immune.

Given the national debate on health care reform, my thoughts have been focused on this issue. Not so much the issue of whether there should or should not be a public option or health insurance reform to prohibit pre-existing conditions. Rather, how much the science of medicine has evolved.

This is also a time for the multitude of lists published on the most influential people of the year, best inventions, best songs, movies, etcetera. So here is my list.

There have been remarkable discoveries and innovations in the last century or so. So much so that we often forget and take for granted some fundamentals. But here are my 5 best people and their ideas that have transformed modern medicine and its development.

5. Louis Pasteur and his work on germ theory. This microbiologist and chemist is probably best known for demonstrating how microbes caused fermentation. His work in proving germ theory (as opposed to spontaneous generation) led to advances in food science preventing spoilage and illness. If you’ve ever safely drank pasteurized milk (yes, eponymous), wine or beer or eaten aged cheese you have benefited by his work. Germ theory has also opened our collective eyes to this microscopic world with attendant dangers in the field of health care. From his theory we have developed aseptic techniques. All who have ever had surgery, had an IV inserted or given blood owe Mr. Pasteur a debt of gratitude.

4. Jonas Salk and the vaccine. Polio and smallpox are virtually eradicated in the U.S. Death by measles, mumps and rubella are relatively rare. We can be proactive against influenza. All because of Salk’s work with vaccines.

3. Sir Alexander Fleming and penicillin. This Scottish pharmacologist ushered in the era of antibiotics. It seems unfathomable in today’s world of antibiotics so ubiquitious that they are fed to feed animals by the ton but it was not that long ago that pneumonia, cellulitis, sinusitis and the like killed multitudes.

2. Thomas Jefferson and the patent system. While patents in some shape or form were in existence prior to our third president, Jefferson is credited with founding the U.S. patent system. (I’m aware this is a U.S. centric viewpoint and loved this commentary http://bit.ly/7nJlSn but I digress.) Our current health care system is largely dependent on drugs and devices. New drugs can sometimes cure and often times ameliorate diseases preventing invasive surgery. New medical devices allow life saving surgeries to be possible and to be done more safely. Most of these developments comes from innovations by companies in private industry. While there is plenty of room to debate whether companies are gaming the system or whether reform in some form should be instituted, the basic mechanism of protecting inventions for a limited time to allow return on investment at it’s basic level is a good one.

1. Sir John Harington and the modern flush toilet. The credit for the toilet is often given to Thomas Crapper. While he made improvements, along with Alexander Cumming and Joseph Bramah, Harington had the initial design. Toilets are so mundane and banal and the idea of human waste management is so distasteful that few of us ever give this modern contraption a second thought. But nearly 2 million people in the U.S. don’t have access to an indoor toilet. Over two-thirds of the world’s population is without sanitation and nearly 1.8 million child deaths each year are related to sanitation and clean water. Discussions of human waste are not comfortable in our society- we linguistically decontaminate the topic. Yet providing access to toilets and keeping feces out of potable water is the single biggest health threat in the world. If you’ve never had cholera, you can thank Sir Harington.