TCS Daily


Congressional Cures?

By Henry I. Miller - February 14, 2007 12:00 AM

Editor's note: This is the second of two articles.

Part 1 of this article series described the FDA's recent attempts to convince its critics that it takes drug safety seriously. In fact, no one who is familiar with the FDA culture and mind-set could possibly doubt that drug safety is paramount - if for no other reason, approving a product that proves to be dangerous can ruin a government career.

Although all drugs have side effects - which can be serious and/or frequent - modern pharmaceuticals have never been safer, more effective, more innovative - or more stringently regulated. But that seems to have escaped the notice of many members of Congress. This month senators introduced two separate bills that will further obstruct innovation and threaten public health.

Senators Edward Kennedy (D-Mass.) and Michael Enzi (R-Wyoming), the chairman and ranking Republican, respectively, of the Health, Education, Labor and Pensions Committee, proposed legislation that would grant the FDA new authority to impose safety requirements on medicines after they have been approved for marketing and would also would require registration of clinical trials and the reporting of their results in public databases. In addition, Senators Chris Dodd (D-Conn.) and Charles Grassley (R-Iowa) introduced legislation that would create within the FDA a center to oversee the safety of drugs after they go on the market.

These bills are the culmination of years of drug company-bashing by a small number of activists and members of congress who have seized on high-profile events such as deficiencies in the labeling of antidepressants and the discovery of previously unknown side effects of various widely used drugs. They will discourage drug development by making it more difficult and expensive and less profitable, at a time when an aging American population desperately needs new and improved (and cheaper) medicines, and when pharmaceutical R&D is already ailing. During the past twenty years the costs have skyrocketed, with direct and indirect expenses now exceeding $900 million dollars to bring an average drug to market. Other trends related to costs are ominous as well: The length of clinical testing for the average drug is increasing, fewer drugs are being approved, and the number of applications to FDA by industry for marketing approval has been declining for more than a decade.

The FDA is already the nation's most powerful and omnipresent regulator, but the Kennedy-Enzi bill would grant new authority, supposedly to ensure the safety of drugs. Among other unwise innovations, it would require the imposition of "risk management action plans (RiskMAPs)" when drugs are approved. Not only does the FDA already have the authority to require these when regulators feel that they are necessary, but they have been overused and abusive: At times the exhaustive (and exhausting) list of requirements for physicians, pharmacists and patients seems more appropriate for weapons-grade plutonium than a pharmaceutical. Some RiskMAPS have contained requirements such as mandatory enrollment in patient registries, limited distribution, and prescribed patient behavior (such as the use of two kinds of contraception, in the case of one drug).

The requirement that drug companies disclose advanced clinical trials in a public database is based on concerns that "negative" results are often obscured or simply not reported. It is intended to prevent companies from "cherry picking" studies, divulging only those that yield favorable results and suppressing the rest.

These concerns are exaggerated. Nothing in our society is currently more stringently regulated and monitored than drug development. During each phase of clinical testing, the FDA reviews and must grant permission for every clinical trial and has access to all of the proprietary information about the drug. When the manufacturer has accumulated evidence that the drug is safe and effective, as part of the application for marketing approval the results of every trial and everything else that is known about the drug, both in the United States and abroad, must be reported to the FDA. Statistical analysis must be performed in an appropriate and pre-specified manner. Moreover, the FDA serves as a repository for data on similar drugs made by other manufacturers. All of this prevents statistical "cherry-picking" or "data mining" that could mislead regulators.

Clinical trials databases are useful to individual patients who wish to ascertain whether they are eligible for a clinical trial that is under way - a function already served by www.ClinicalTrials.gov. But, except for offering a bonanza to plaintiffs' attorneys trolling for business, the benefit of a publicly available database of clinical trial results would be minimal.

There is also the question of the meaning of "negative results" in clinical trials. In the context of scientific and clinical experiments, the term has a meaning very different from the common usage. Such trials are seldom "negative" in the sense of revealing that the drug being tested inflicts harm but for a variety of reasons, they may not be useful or applicable to the indications (uses) for which approval is being sought. The reasons can include: insufficient statistical power (that is, number of patients) in the study; inappropriate choice of route, dose or frequency of administration, or in the stratification of subjects; or simply a failure of the drug to be effective for the indication for which it was tried.

The Dodd-Grassley proposal is even worse. It would create within the FDA an anti-drug entity with strong incentives to argue for the non-approval or withdrawal from the market drugs that have significant side effects even if they offer huge net benefits. (We have seen this already from certain factions within the agency.)

These proposed legislative remedies for the FDA's problems, with more planned for later in the year in both the House and Senate, are analogous to the discredited medical practice of bleeding the patient with leeches. By intensifying the FDA's notorious risk aversion, the new measures will inflate even further the costs, difficulty and uncertainty of drug development and reduce the number of drug candidates that begin and complete clinical testing. They will drain the life's blood from innovation and inflict harm on patients. If these pieces of legislation are enacted, they will validate yet again Will Rogers's observation about Congress: "Every time they make a joke, it's a law. And every time they make a law, it's a joke." And as usual, the joke will be on us.

Dr. Miller, a physician and fellow at the Hoover Institution and Competitive Enterprise Institute, was an FDA official from 1979 to 1994. His most recent book is "The Frankenfood Myth."


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5 Comments

Too Bad...
There is a real lack of cost-benefit analysis in the drug market. Yes, some drugs may have some pretty bad side effects. But maybe I would be willing to risk a doubling of my risk of heart attacks if a drug would totally eliminate my arthritis! (Just a hypothetical.) Everything we do carries some risk. It should be up to the individual to decide whether the benefits outweigh that risk, not some bureaucrat (or nosy Congressmen). Good and useful drugs have been removed from the market because of overblown fears, caused by lawyers and activists quick to find fault for something that was not faulty at all. Shame on them!

-Bob

Crises Help Government Grow
The FDA was created in response to a "crisis" in the meat packing industry.

Every time some wants to grow government, we create a crisis.

What needs to stay, whant needs to go?
It seems to me that the FDA has neither a clear idea of what makes a drug "safe," nor a strategy for limiting the chilling effects of FDA regulation on new drug development.

As far as the definition of "safe," even the libs on here seem to agree that there should be some sort of recognition of the beneficial effects of a drug before pulling it due to potential harm. HobNobBob just cited the example of Vioxx, and notes that crippling arthritis can be much worse than a minor increase in the risk of heart attack. The same could be said for the MS drug Tysabri, recently returned to the market, that made the lives of many MS patients much, much easier. That is, until the FDA banned it because of the potential to cause a rare brain disorder in a tiny number of patients. It was only after the ban that the FDA took a real look at the benefits that the drug provided for those taking it, and instituted a new bureacracy to deal with its prescription and distribution.
(http://www.mayoclinic.com/health/tysabri/DI00059)

This tendancy to ban or hyperregulate any drug that looks like it might cause even the slightest harm to patients is the natural response of a bureacracy that is charged with protecting public safety. Harms that occur because burecrats permit something are visible, and result in political consequences. Gains that are lost because of red tape are never seen and therefore are not missed. The motivation for an agency like the FDA is clear: Throw up as much red tape as possible in the way of every drug, in order to avoid angry congresspeople.

Add bloodsucking lawyers suing the drug companies because of unknowable risks, and leftists demanding price cuts or controls. Suddenly, developing new drugs suddenly seems like a less-than-stellar idea.

So how do we fix it?

- What is the definition of "safe," who should make the call about safety, and who should make the call about the availability of drugs that are potentially unsafe?

- Is there any way to fix the FDA's motivations so that they will do some rational cost-benefit analysis on both new drugs drugs and drug-approval procedures, or does the agency need to be scrapped? Can the private sector do this, or do we need government intervention?

I've seen a lot of good ideas on this discussion forum over the last year or so, and I hope a few of you have suggestions as to how to answer these questions...

Some thoughts
- Appoint the head of the FDA similarly to the FBI (10 yr term?) to insulate the agency from some political pressure. Of course, as the FBI shows, such a change doesn't guarantee competence.

- Reform the tort system and make it harder to aggregate cases into a Class Action Lawsuit.

- Reform the tort system by placing limits on real damages and stripping punitive damages from most cases. If you're 65 years-old and in poor health your life isn't worth $50 million (sorry to have to break the news, but it's not). Additionally, the drug company didn't intend for you to suffer side-effects so punitive damages shouldn't apply.

- Require the FDA to hire at least some people with a forward thinking brain cell. Why is it that every problem becomes a crisis? You'd think, using your examples, that Vioxx was the only drug that ever had side-effects, until Tysabri came along, and until the next drug comes along. The utter inability of the FDA to explain the "hows and whys" of side-effects simply erodes what little trust the public has in them. The more they flail about, the more they resemble bureaucratic clowns.

- Require the FDA to publish projected results of Congressional and Regulatory Actions. If a drug is pulled how many lives are potentially saved and how many are potentially lost. As you point out, it does little good to prevent 1 potential death if it might lead to 100 potential deaths. Force the "leaders" to be accountable.

- Follow Shakespeare's advice and kill all the lawyers.

Chances of any of the above happening... zero

A possible answer... loser pays and undetectable side-effects?
I get a little worried whenever people talk about limiting damages of any sort. After all, there does need to be penalties for companies that actually go over the line. However, I wonder if we could get around the question of damages by putting in place two rules:

- The general rule I suggest is a "loser pays" system for allocating court costs. This will dramatically reduce the number of junk lawsuits, and will encourage people to file only when they have a real and legitimate case. Most medical malpractice, product liability and junk-science cases will disappear overnight.

- The specific rule would be in the area of medical malpractice cases and liability for drug makers. Here, there are frequently cases where side-effects are undetectable during drug trials because they are very rare, take a long time to develop, or are hard to detect. Tysabri is an excellent example of this sort of thing. In cases where this sort of side-effect exists, patients would not have any standing to sue for damages. Drug companies would be wise to cover their medical expenses, but that is a PR question. After such side-effects have occured in a large enough percentage of patients, drug-manufacturers would be required to disclose them prominently. This rule would result in substantially greater numbers of vaccines and antibiotics being manufactured in America (where liability and price controls make their production economically unviable now.)

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