Category Archives: Ethics

13Dec/06

My Body, My Choice?

By Daniel R. Matlis

No, it’s not what you think; I’m not going “pro” this or “anti” that on you.

I am referring to the Food and Drug Administration’s (FDA) proposal to make experimental drugs widely and easily available to seriously ill patients.

According to Dr. Andrew C. von Eschenbach, Acting FDA Commissioner “This proposed reform is carefully designed to balance several objectives.” von Eschenbach added “One goal is to enable many more patients who lack satisfactory alternatives to have access to unapproved medicines, while balancing the need for safeguarding the individual patient. Another equally important goal is to ensure the continued integrity of the scientific process that brings safe and effective drugs to the market.”

The proposed rule is a direct response to a 2 to 1 decision by the U.S. Court of Appeals for the District of Columbia Circuit overturning a lower court’s ruling in a case brought by the Abigail Alliance for Better Access to Developmental Drugs.

The court ruled that “barring a terminally ill patient from the use of a potentially life saving treatment impinges on the right of self-preservation.” Further, the court held that once drugs have passed safety trials, they should be made available if they might save someone’s life.

Judge Judith W. Rogers wrote “If there is a protected liberty interest in self-determination that includes a right to refuse life-sustaining treatment, even though this will hasten death, then the same liberty interest must include the complementary right of access to potentially life-sustaining medication, in light of the explicit protection accorded ‘life’.”

Dr. Janet Woodcock, FDA’s Deputy Commissioner for Operations stated “FDA hopes this proposal will increase awareness in the healthcare community of the range of options available for obtaining experimental drugs for seriously ill patients,” she added that “By clarifying and streamlining the processes, FDA also hopes to encourage companies to make such drugs available, and reduce barriers for healthcare practitioners in obtaining them.”

The proposed rules, which are open for comment for 90 days, are described in detail at the following FDA web address: http://www.fda.gov/cder/regulatory/applications/IND_PR.htm

I hope and pray that none of us ever face such a choice, but if we do, it should be our choice to make.

28Sep/06

FDA Drug Safety System Needs Fixing, IOM Report Says

By Daniel R. Matlis 

According to a report issued by the Institute of Medicine (IOM), the FDA suffers from a lack of clear regulatory authority, chronic under funding, organizational problems, and a scarcity of post-approval data about drugs’ risks and benefits.  

The report, entitled The Future of Drug Safety: Promoting and Protecting the Health of the Public”, was commissioned by the FDA and the Department of Health and Human Services in response to the growing public concern with health risks posed by approved drugs. The Agency asked the IOM to convene a committee to assess the U.S. drug safety system and to make recommendations to improve risk assessment, surveillance, and the safe use of drugs. 

“FDA has an enormous and complex mission — both to make innovative new drugs available to patients as quickly as possible and to assess the long-term risks and benefits of these products once they are on the market,” said Sheila Burke, chair of the committee that wrote the report.  “We found an imbalance in the regulatory attention and resources available before and after approval.  Staff and resources devoted to pre-approval functions are substantially greater.  Regulatory authority that is well-defined and robust before approval diminishes after a drug is introduced to the market.  Few high-quality studies are conducted after approval, and the data are generally quite limited.  Many of the report’s recommendations are intended to bring the strengths of the pre-approval process to the post-approval process, to ensure ongoing attention to medications’ risks and benefits for as long as the products are in use.” 

During its research, the committee found that

  1. There is a perception of crisis that has compromised the credibility of FDA and of the pharmaceutical industry.
  2. Most stakeholders–the agency, the industry, consumer organizations, Congress, professional societies, health care entities–appear to  agree on the need for certain improvements in the system.
  3. The drug safety system is impaired by the following factors: serious resource constraints that weaken the quality and quantity of the science that is brought to bear on drug safety; an organizational culture in CDER that is not optimally functional; and unclear and insufficient regulatory authorities particularly with respect to enforcement.
  4. FDA and the pharmaceutical industry do not consistently demonstrate accountability and transparency to the public by communicating safety concerns in a timely and effective fashion. 

To address these issues, the report offers a broad set of recommendations to ensure that consideration of safety extends from before product approval through the entire time the product is marketed and used.  
These recommendations include:

  • Labeling requirements and advertising limits for new medications
  • Clarified authority and additional enforcement tools for the agency
  • Clarification of FDA’s role in gathering and communicating additional information on marketed products’ risks and benefits 
  •  Mandatory registration of clinical trial results to facilitate public access to drug safety information
  • An increased role for FDA’s drug safety staff
  • A large boost in funding and staffing for the agency

“We have already called for making sure the FDA has adequate resources to perform its critical drug review, surveillance and monitoring functions: said Caroline Loew, Senior Vice President of the Pharmaceutical Research and Manufacturers of America (PhRMA), “Additionally, PhRMA supports recommendations for modernizing the post-market surveillance system for drugs, including more efficient use of the adverse reaction reporting system; maximizing use of large health care data bases; and building more expertise around epidemiological studies.”

I agree that the FDA and Industry need to do a better job monitoring medications’ risk-benefit profiles after approval. They must also improve communications to healthcare providers and patients on the uncertainties and potential risks associated with newly introduced drugs. 

However, as patients, we must recognize that there are no “risk free medicines”. Each patient must work with their healthcare provider to evaluate the risk-benefit profile associated with each recommended therapy and make an informed decision based on the facts available at that time. We must also remain vigilant and be ready to reassess those choices when new post approval data becomes available.

After all, our health is our responsibility.

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.

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.