All posts by Administrator

18Sep/06

Compounding Redux

By Daniel R. Matlis

Recently, I wrote an article calling for consistent federal regulatory requirements for the practice of compounding. Last month, the US District Court in Texas ruled against the FDA on this mater.

As I made clear in my previous article, I am a supporter of compounding. But in order to protect the public, it is imperative that the combination of FDA approved drugs into new compounds be tested for safety and effectiveness.

Critics may ask: Don’t two FDA approved compounds a safe new compound make?

Not always. Remember Fen-Phen?

Fen-Phen is the combination of fenfluramine or dexfenfluramine (marketed as Redux) and phentermine. All were prescription medications approved by the FDA as appetite suppressants. In 1996, physicians began prescribing the combination of Fen-Phen for use in weight loss programs. During that year, the number of prescriptions for Fen-Phen in the United States exceeded 18 million. The practice is known as “off-label use” since no studies are presented to the FDA to demonstrate the effectiveness or safety of the drugs taken in combination.

In July 1997, the New England Journal of Medicine published an article potentially linking heart valve disease with the use of Fen-Phen.  Later in that year, the FDA found that of 291 asymptomatic patients screened, about 30 percent had abnormal valve findings, primarily aortic regurgitation. Based on these data, the manufacturers agreed to withdraw the products from the market and FDA recommended that patients stop taking the drugs.

But this is not a recent phenomenon. In 1937 the manufacturer of “Elixir Sulfanilamide” was seeking a palatable solvent for its new sulfa drug. It decided to use a combination of diethylene glycol and water with raspberry flavoring.  Both the drug and the solvent are safe by themselves, but combined create they a lethal mixture that killed 107 people (mostly children) before the drug was recalled recalled.  Similar to Fen-Phen the combination compound had not been tested prior to release to the public.

By contrast before the introduction of Caduet, the combination of high blood pressure medicine Norvasc and high cholesterol Lipitor, the manufacturer conducted a double blind placebo controlled clinical trial of 1660 patients to evaluate the safety of the combination therapy.

I believe there are two approaches to address this issue; the first is to required safety testing for new compounds comprised of already approved drugs, regardless of who makes them, big Pharma or your neighborhood pharmacist.  This testing should focus on the safety and efficacy of the new compound.

The second alternative is to go the route of informed consent and experimental drugs.  I believe that doctors should have the right to prescribe compounded medicines, pharmacist the right to make then and patients the right to take them as long as we can evaluated all known risks and have meaningful  informed consent.

By the way, I checked with Andrew, my neighborhood pharmacist, and he will only mix in flavor for my kids prescriptions if the drug has been tested for safety in combination with the flavoring syrup.

28Aug/06

What’s More Sterile: the Band-Aid on Your Paper cut or Cardioplegia?

By Daniel R. Matlis

It’s a trick question. Technically both should be sterile. 

But you would think that cardioplegia, the solution used to stop the heart during bypass surgery, would be more stringently tested since it is infused directly into the heart.

According to a recent USA Today article, at least 11 cardiac surgery patients were stricken with an infection during a 10-month period from the end of December 2004 to September 2005, and three of them died at Mary Washington Hospital.  After a thorough investigation, tests confirmed the presence of several types of bacteria in the cardioplegia solution injected into patients’ hearts during surgery. 

I can already hear the cry from the trial lawyers: “Which Pharmaceutical Do We Go After? 

The answer? None, the reason is that the products leaving the Pharmaceutical companies were perfectly safe and sterile, but some drugs, including high-risk sterile preparations, are made in pharmacies under less-restrictive rules than those that drug companies follow.  Almost all hospital pharmacies do some type of drug making, called compounding. Pharmacist duties may range from low-risk procedures, such as grinding tablets to put them into liquid suspension, to high-risk work, such as making sterile treatments from scratch. 

I’m in favor of compounding, and cannot thank Andrew, my local pharmacist, enough for compounding prescriptions when my kids need them. Try to get a 3 year old to swallow an adult size tablet. It goes much smoother when it is ground and suspended in strawberry flavored syrup.

But there is a big difference between grinding tablets and preparing a sterile solution to be injected into the heart.  This is not an issue of qualifications, but one of oversight and facilities. Hospital pharmacies are regulated by each state, and the frequency and thoroughness of state inspections vary widely. The FDA’s role in oversight is hampered by questions of jurisdiction over what’s generally state matter. To make matters worse, in most states hospitals are not required to test the sterility or potency of products made in their own pharmacies or purchased from outside pharmacies.  So while a drug company could not sell saline solution without testing sterility, hospital pharmacies and their suppliers are not required to test for it. 

I am not a big proponent of government regulations, but this is a case of public safety and the proverbial “what’s good for the goose is good for the gander” theory of enforcement.  Having 50 different state statues regulating sterility and potency requirements for drugs is impractical, when the FDA has the mandate, know-how and capabilities to regulate them.  If hospital pharmacies and suppliers want to continue manufacturing sterile solutions, they ought to be held to the same standards as the Sesame Street Band-Aid I put on my kid’s “boo-boo”. 

13Jul/06

Doctors Don’t Treat Populations, They Treat Individual Patients

This week, Scott Gottlieb, MD Deputy Commissioner for Medical and Scientific Affairs at the Food and Drug Administration made an interesting speech before the 2006 Conference on Adaptive Trial Design in Washington, DC.Dr Gotlieb commented how today’s clinical trials are highly empirical. Drugs are tested on general populations for a response and a treatment effect that is statistically not likely to be a chance result. This approach is rigorous and focused, but inflexible. According to Dr. Gotlieb, “another problem with the empirical approach is that it yields statistical information about how large populations with the same or similar conditions are likely to respond to a treatment. But doctors don’t treat populations, they treat individual patients. Doctors need information about the characteristics that predict which patients are more likely to respond well, or suffer certain side effect. The empirical approach doesn’t tell doctors how to personalize their care to their individual patients.” This results in a highly empirical approach to the practice of medicine. Gone are the days of: Take two off these and call me in the morning. Gottlieb comments “Doctors prescribe treatments knowing full well that only a certain percentage of their patients will receive a benefit from any given medicine.” This approach is akin to: Take all of these and call me if you have a side-effect. 

But with the demands for personalized medicine and the advent of Pharmaco-genomics, there are potentially better alternatives. By enabling more trials to be adapted based on knowledge about gene and protein markers or patient characteristics, we can help predict whether patients will respond well to a new medicine. “These new approaches to clinical trials can result in trial designs that tell us more about safety and benefits of drugs, in potentially shorter time frames, exposing fewer people to experimental treatments, and resulting in clinical trials that may not only be more efficient but are more attractive to patients and their physicians to enroll in.” said Gottlieb. This is only a first step in the process to develop more adaptive clinical trials. This process will lead to more targeted therapies and in turn, Ii is my hope, more personal and personalized medicine.

04Jul/06

"Medicine is for the People, not for the Profits."

During my senior year, I was lucky to have a few job offers to evaluate. The top two were from Johnson & Johnson and Exxon. As part of my research I looked at how each company handled adversity. For me it was an easy choice when I compared J&J’s handling of the Tylenol situation vs. Exxon’s Valdez.  I was drawn by the impact I could make in people’s lives and by the industry’s reputation in general and J&J’s in particular.

But in recent years, our industry has gone though some tough times. We’ve have seen record FDA fines, product recalls and withdrawals as well as the erosion of consumer confidence.  In my opinion executives at some Life-Science companies lost focus on the patient and began to concentrate on profits for Wall Street.

It is in times like these that we must reach for our roots and reflect on the legacy left by our industry’s founders.

In the August 1952 Time magazine interview, George W. Merck said “Medicine is for people, not for profits.” He went on “…if we remembered that, the profits have never failed to appear. The better we remembered, the larger they have been.”

In 1943 General Robert Wood Johnson wrote: “We believe our first responsibility is to the doctors, nurses and patients, to mothers and fathers and all others who use our products and services.” This Credo is still etched in stone at the J&J world Headquarters.
In 1899 Charles Pfizer said, “Our goal, has been and continues to be the same: to find a way to produce the highest-quality products and to perfect the most efficient way to accomplish this, in order to serve our customers. This company has built itself on its reputation and its dedication to these standards, and if we are to celebrate another 50 years, we must always be aware that quality is the keystone.”

In this post Sarbanes-Oxley era, I am heartened to see that our industry is once again putting patients first.

Let us remember to chase after the cures for human ailments, then and only then will fair profits follow.

29Jun/06

I Lost the Cure for the Common Cold!

By Daniel R. Matlis 

It’s 3:00 AM and your newborn baby wakes up crying. You want to go back to sleep, but his circadian rhythm is set for Beijing, not Philadelphia, and he is wide awake.So you get a cup of coffee, turn on your laptop and start to do some work. In a moment of inspiration, you discover the cure for the common cold. It’s all there on the screen right in front of your eyes and then your baby kicks, the coffee spills on your laptop and, just like that, the cure is gone. Who do you call?

Monday, at the Corporate Computing Show in NY, I met the people for the job. DriveSavers Data Recovery is a company that recovers data from crashed and damaged media. They have been doing this for over 20 years and when James Bond looses the data in his laptop he doesn’t call Q. Instead he deals with Kelly Chessen, Data Crisis Counselor DriveSavers (Yes, Sean Connery is a client).

With the prospect of irretrievable information loss, many of the callers with whom Chessen deals are as distraught. The emotional trauma associated with the loss of critical data can be disruptive both at work and at home.

Chessen came to DriveSavers with a background in psychology that serves her well in her dealings with often-frantic customers. She worked with a suicide prevention hotline for more than five years, including one year as the manager and trainer. This is exactly the kind of training I want the person on the other end of the line to have under these circumstances.

In addition to the soft skills, DriveSavers has technical skills and facilities to back them up. They have recovered data from drives that have been damaged, dropped, deleted, burnt, crushed and drowned in the Amazon River. The company has a success rate of over 90%, and recovers data in as little as 24 hours from all operating systems and storage media including hard drives, disk arrays, floppies, CD-ROM, DVD, removable cartridges and digital camera media. They have they own calls 100 clean room, and if they work on your drive, the manufacturer’s warranty is still good, although I’m not sure that a drive full of Amazon River water is covered.

So the next time your husband, wife, son, daughter, dog, cat or self spill a cup of coffee on your laptop containing the cure for the common cold, or the therapeutic area you are working on, don’t sweat it, lay on the couch and call the Data Shrink.