TCS Daily

New Drug Demagoguery

By Henry I. Miller - March 21, 2006 12:00 AM

"New Drugs Hit the Market, but Promised Trials Go Undone" and "FDA: Drug Companies Drop Ball on Studies," the headlines blared. Are Americans getting untested drugs? Are drug developers taking short-cuts, or worse? Are regulators incompetent, or impotent?

None of the above -- although it's hard to tell that from the press coverage.

As a condition of marketing approval of a new drug, the FDA often requires the manufacturer to perform additional studies to confirm efficacy or to look for previously undetected side effects. But according to a recent FDA report, which spurred the headlines, as of the end of last September, of the 1,231 "open post-marketing commitments" to perform clinical studies, only 14 percent had been duly reported to FDA, 65 percent were "pending" (that is, had not yet started), 19 percent were considered "ongoing," and two percent were "delayed."

However, the government's evaluation and approval of new drugs is an exceedingly complex and arcane business, and these statistics can easily be misunderstood or misrepresented.

American pharmaceuticals are the most intensively tested products in history. Moving a drug through laboratory studies and then animal and human testing requires on average 12-15 years and more than $800 million in direct and indirect costs. By the time a drug company applies to the FDA for marketing approval of a new product, on average it has performed more than 70 clinical studies on at least 4,000 patients.

Even after exhaustive clinical testing, questions may remain, particularly if efficacy has been judged by improvement in a "surrogate" endpoint, such as high blood pressure as a marker for heart disease, or shrinkage of a tumor as a stand-in for actual prolonged survival.

These kinds of criteria for measuring efficacy are both common-sensical and based on a scientific rationale -- and most often they do correlate with more definitive measures of benefit. Sometimes they're essential to efficient drug testing. I'm reminded of a cartoon in which two pharmaceutical scientists are contemplating a beaker that contains a new medicine. One says to the other, "It looks as though this drug will confer immortality. The trouble is, it will take forever to test it."

The FDA can require manufacturers to perform certain post-marketing follow-up studies, and according to the regulations, "once a post-marketing study commitment has been made, an applicant must report on the progress of the commitment . . . until the post-marketing study commitment is completed or terminated, and FDA determines that the post-marketing study commitment has been fulfilled or that the post-marketing study commitment is either no longer feasible or would no longer provide useful information."

That seems straightforward enough, but in practice widespread prescribing and use of a drug following FDA approval often make the mandated post-marketing studies moot. In other words, the availability of large amounts of data obtained from usage under real-world conditions -- sometimes from hundreds of thousands of patients within months of approval -- makes additional data from small clinical trials superfluous. In spite of that, the FDA seldom follows through to determine "that the post-marketing study commitment is either no longer feasible or would no longer provide useful information." Hence, the preponderance of post-marketing studies that are "delayed" or "pending."

Another related factor is that in recent years FDA regulators have tended to over-use the requirement for post-marketing studies -- mandating them not because they're essential, but merely as a way to inoculate themselves against criticism for too-rapid approvals.

The nuances of this phenomenon have eluded some who should know better. Congressman Maurice D. Hinchey (D-New York) claims mistakenly that the FDA's demands for demonstrations of safety "continue to be blatantly ignored by the pharmaceutical industry," so he and Senators Charles Grassley (R-Iowa) and Christopher Dodd (D-Conn.) have introduced legislation that would give the FDA added authority to require drug companies to carry out post-marketing studies.

Wrong diagnosis, wrong remedy.

Instead of bean-counting and indulging in demagoguery, we should be trying to ascertain what fraction of mandated post-approval studies is really necessary, and FDA should clean up its backlog of superfluous post-marketing studies.

Henry I. Miller, a physician and fellow at the Hoover Institution and Competitive Enterprise Institute, headed the FDA's Office of Biotechnology from 1989 to 1994. His most recent book, "The Frankenfood Myth..." was selected by Barron's one of the 25 Best Books of 2004.


I was in a drug study, made 3000 bucks.
It was great and they where extreamly carefull and monitored everything. (Allthough I think I got a placebo). The drug was Paxil.

It involved a lot of sex, and I had to log the quality of things. (that was kind of fun too.)

Make FDA approval voluntary.
I think we should just make FDA approval voluntary. This will do several things.

1. Patients at the end of treatment options who have little to no chance will have the option to try risky treatments that could save their life (although it could end it as well, but that would be the patients choice).

2. Private companies could enter the market of drug testing. Competition would lower cost and reduce times to market. Ultimately faster cheaper drugs save lives. New testing strategies could be tried, the possibilities are really endless.

3. Eventually the FDA could just be the FA. :)

I think #2 is a really big deal, but there is no market as long as the FDA has a monopoly on drug testing. Just think of how many lives are lost as a powerful new drug spends a decade or more winding it's way through the labyrinth of government bureaucracy.

Changing FDA to FA Miht Cost Us 10% of GDP

New Drug Demagoguery Font Size:

By Dr. Henry I. Miller : BIO| 21 Mar 2006

Make FDA approval voluntary. by smbell

American pharmaceuticals are the most intensively tested products in history. Moving a drug through laboratory studies and then animal and human testing requires on average 12-15 years and more than $800 million in direct and indirect costs. By the time a drug company applies to the FDA for marketing approval of a new product, on average it has performed more than 70 clinical studies on at least 4,000 patients.

Obviously only very big corporations could ever hope to bring any treatment to market, and then only if the drug had patent protection and the profits sufficiently large to make the $800 million investment profitable. Such a system precludes any treatment which cannot be patented and any treatment whose sales are less than $1 billion.

Make FDA approval voluntary. by smbell

Much evidence suggests that the FDA’s power to exclude non-patentable remedies and to grant monopoly rights over an above that granted by the patent system is the main cause of ever rising health care costs. The existence of the FDA, along with government mandated non-risk rated health insurance, heavily proscribes freedom of choice and speech and the operation of the free market system in American health care.
Recall that the main public excuse for Congress to confer the power to determine the efficacy as well as the safety of a drug or device to the FDA was the Thalidomide scare. Yet such an excuse was baseless. The FDA had never approved use of Thalidomide in the U.S. Americans had to go offshore to get the drug. The FDA had very effectively prevented use of the baby deforming drug Thalidomide in America.
So exactly what problem did adding the hurdle of efficacy to the FDA’s mandate solve? Well, arrival of the polio vaccine 10 years earlier did in fact virtually eliminate polio. However, it also closed down the polio wards of hospitals, scraped their iron lungs and other treatments, put a lot of people out of work, cut incomes, and in general hurt the bottom line of the health care establishment. Adding efficacy to the FDA mandate gave the agency the power to prevent further cures. Indeed, there have since been no further far reaching cures such as the polio vaccine. Nor can there be.
But there were other problems it solved. Efficacy gave the FDA the power to shut down efficacy claims of producers of non-monopoly products, thus ensuring the monopoly of FDA approved products. It created an insurmountable burden of proof of efficacy on the producer. Only with the potential of monopoly production could the cost of proving efficacy be afforded.
Efficacy also gave key FDA officials expanded power to do favors for drug companies in return for favors and jobs with the drug industry. It is not coincidental that drug companies have more and better financed lobbyists in Washington that any other group. Add to the problems solved are the ever increasing needs of the best Congress money can buy and industry needs for insurance against competition.
Health care is projected to rise to 20% of GDP and higher in the next decade or so. Even so, it is a safe bet that there will be no corresponding increase in the efficacy of treatments of either existing or new diseases except those that threaten the entire population (why leaded gasoline was banned and substitutes like fluorides and aspartame approved by the FDA). There will be no cures for any major disease unless, like AIDS, it involves the need for lifelong treatments.
Cures or preventions for a number of diseases exist which will never receive official testing or approval because they are not patentable and allow people to use them on their own, bypassing the monopolists. The current war on vitamins is just another attempt to shake by confusion and deceit the belief which 70% of Americans continue to have in the efficacy of vitamins.
As we keep reading, the urgings of drug company reps are being substituted for the independent decision making of doctors. More and more, the drug salesmen are becoming the de facto diagnosticians of the medical profession. Diagnosis is a rare gift in any event except for the specialist, who has a tendency to be lost if the condition lies outside the specialty. In that event, the patient had better hope the specialist knows a really good general diagnostician.
Health care is now 16% of GDP. Changing the FDA to the FA might very well reduce health care to 5% to 10% of GDP, multiplying the economic effect of the polio vaccine on the health care bottom line perhaps 1,000 fold. Forget about it. The FDA and health care growth are here to stay until enough people get wise and adopt the many effective non-prescription remedies in the public domain (better educated people see the weaknesses of the system, go around it and find more effective alternative remedies). Jury trial verdicts instigated by trial attorneys have been shown to be far more effective in checking the deadly, fraudulent tobacco company claims than the FDA.

Hurt the economy be making things more efficient?
"12-15 years and more than $800 million"

This is a huge part of the problem if not 'the' problem. Overly long, overly costly required phases and tests to get a drug to market.

Your main argument seems to be that there could possible be a cost of "10% OF GDP". In order to believe this you would have to assume first that there is some illness, or maybe a group of illnesses, currently costing us that 10% of GDP, and that by removing the FDA from it's currently mandated role those illnesses would be cured.

This flies in the face of medical consumption trends where we have more and more money going to 'preimium' care, such as expensive tests that may not really be needed, and usful, but not life saving, drugs.

This is not to say that prescription expenditures are small, they are considerable, but they are not nearly the full 16% of GDP that is spent on health care.

Prescription Drug costs in the US are $144 billion (2004) which is roughly 1.5% of GDP.

So your 10% GDP loss by allowing competition in drug testing is not only laughable, but absolutly ridiculous.

I'm not going to defend the 10% figure
because I have no means of estimating how much any of these factors cost.

1) The direct cost of drugs.
2) The need to go to a doctor, then wait in line at the pharmacy adds up to a lot of wasted hours. Some drugs need to be prescribed by a physician, many do not.
3) Because of cost, some symptoms are not treated, resulting in longer or more intense illnesses, which result in lost productivity.
4) Chronic conditions, such as allergies, are not treated, resulting in lower productivity.

Probably a few others.

Add all of this together, and the current mechanism for approving drugs could add up to a non-trivial fraction of the economy.

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