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Reform the FDA!

By Chris Rangel MD ⋅ January 6, 2006 ⋅  Email this post ⋅  Print this post ⋅ Post a comment

REFORM THE FDA!

An FDA pundit defends the “vetting process” for new medications.

Former FDA regulator Dr. Henry Miller in his TCS op-ed article lashed out against recent calls for the FDA and the drug companies to be more open in exposing problems with new medications. Dr. Miller points out that allowing people to comb through every part of the development process would risk exposing a drug company’s sensitive proprietary data and trade secret and besides;

“Nothing in our society is more stringently regulated and monitored than drug development.”

I tend to agree. What is to be gained by having a thousand self appointed “inspectors” going through every document regarding a drug’s development? Sure, there would be plenty of “do-gooder” consumer safety advocates but there will also be tons of corporate spies, plaintiff lawyers, and intrepid reporters looking to break and thus benefit from the next big Vioxx story! But not every new medication is a Vioxx disaster waiting to happen and some new medications are desperately needed despite the risks. Take the following example from Dr. Miller.

“By filing a Freedom of Information request, an analyst at the stock brokerage firm Morgan Stanley obtained a list of adverse-events reports made to the Food and Drug Administration related to Tysabri, a multiple sclerosis drug withdrawn from the market by its manufacturers in February. (Following an FDA priority review of new data, the drug should again become available in 2006.) After analyzing that data, the analyst released a brief report noting that a number of Tysabri patients had died of rare infections. Are “published” opinions about the safety of drugs destined to have only the level of reliability as the average blog?”

Tysabri (natalizumab) is a monoclonal IgG antibody that has been shown in pre-FDA approval studies to reduce the annual incidence of relapse in Multiple Sclerosis patients by about 20-25% compared to placebo. The two infections turned out to be multifocal leukoencephalopathy (PML), which is very rare and typically associated with immunosuppression. Upon further evaluation the infections were found to be linked to concurrent or recent use of interferon treatments in MS patients taking Tysabri. The drug is expected to be reapproved by the FDA this year with a warning to avoid concurrent use with other immunosuppresents like interferon.

I’m not sure that anything was gained by pulling Tysabri off the market. It is even less clear that Tysabri has been made “safer”. Even before the discovery of the PML cases, Tysabri came with warnings to use with caution because of the risks of infection. Tysabri is an immunosuppressent. Every one of these types of medications has a risk of the development of rare and often fatal opportunistic infections. This is completely unlike Vioxx, which exposed a previously unheard of link between NSAID use and cardiovascular events.

The problem is obvious. With information on drugs in development widely available for public consumption we risk the type of over reaction that we saw with Tysabri. Even worse we risk sending the message that new medications should be completely safe (come have a look at the data yourself!) and that any adverse effects or death is grounds for pulling the drug out of development or off the market. But such a notion is ridiculous. This is like pulling a new car off the market after reports that it was involved in two fatal accidents!

And then there are the lawyers who would like nothing more than to have every single American believe that medications should be completely safe. Take these two geniuses who climbed onto the Tysabri bandwagon and declared the drug to be “dangerous“. Of course it’s dangerous! It’s an immunosuppressent! The only way to make it completely safe is to eliminate all infectious diseases from the world!

Besides, are we really going to leave it up to people like these who have serious self-interest issues to decide what is acceptably safe and what isn’t? The decision to pull a drug is an exceedingly complex one. There are many questions that must be satisfactorily answered. Do the risks outweigh the benefits? Is the evidence for the adverse effects solid or does much more research need to be done? Should certain indications for use or use of the drug in specific cases be limited? Are there effective alternatives without the risks that are already on the market? Seems like these decisions should be left up to the FDA. Oh look. We came full circle!

The decisions of Merck (Vioxx) and Elan/Biogen Idec (Tysabri) to pull their products from the market represents the worst of the recent trend to regulate medical products outside of the control of the FDA. I still occasionally have patients who have significant gastric problems and severe chronic arthritic pain but no cardiovascular history for whom once a day Vioxx was the only medication (short of addictive narcotics) that worked for them.

Now I have to tell my arthritic patients that their treatment of choice was taken away by overzealous consumer advocates, narrow-minded academic cardiologists (to the hammer everything is a nail), an impotent FDA, and Merck executives who wrongly believed that pulling Vioxx would limit their liability and protect their share holders. The decision to pull Tysabri was even worse since this drug adds a very effective treatment option with fewer side effects for sufferers of multiple sclerosis (and possibly Crohn’s Disease) and now it might not be available for months.

In our recent drive to make medications as risk-free as Rocky Mountain spring air we risk a backwards progression in pharmaceutical development in this country. The FDA needs to be reformed (maybe by the next administration) to exclude corporate influences in the way lobbyists influence Congressmen. In addition the FDA needs to be insulated from hysterical external political pressure that has nothing to do with proven risks or safety of a medical product (silicone breast implants, RU486, Plan B). If these people want to ban a medication for political reasons then they can go screaming to Congress.

The FDA needs to be given more power to require drug companies to conduct further safety studies and investigations when such concerns crop up following FDA approval. The idea that the safety concerns can be 100% evaluated by the point of approval prior to the use of a new medication in large and varied populations is a complete fantasy and the FDA and patients need to wake up to that fact. Perhaps also there needs to be a period of protection from liability for the drug maker during which further safety evaluation can be carried out. As we have seen, voluntary withdrawal of a medication protects neither the consumer nor the company but only takes treatment choices away from patients.