TCS Daily

The Harmful Side Effect We Never Hear About

By Henry I. Miller - February 13, 2007 12:00 AM

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

The old saying in Washington that 'when something has been repeated three times it becomes a fact' has been applied lately to supposed shortcomings in the safety of prescription drugs. The reality is that although all drugs have side effects - which can be serious and/or frequent - modern pharmaceuticals have wrought miracles in the control of pain; the treatment and prevention of infections; and the amelioration of the diseases of aging, such as arthritis and cancer.

Regulators need to balance patients' access to therapies with ensuring the safety of drugs. The consequences of poor decisions can be dire: Promote access at the expense of safety, and a dangerous product can cause incalculable harm; over-emphasize safety at the expense of access, and patients suffer from the absence of life-saving and life-enhancing medications.

Recently, beleaguered by congressional and other critics, the FDA has been pedaling as fast as it can to demonstrate its commitment to drug safety -- but without at all addressing a far more pervasive, more intransigent problem: unwise, unproductive, risk-averse regulation that itself has severe side effects.

In spite of increasingly more powerful and precise technologies for drug discovery, purification and production, during the past twenty years development costs have skyrocketed. The trends are ominous: 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 decreasing for more than a decade.

In January, the FDA announced new initiatives directed at the safety of new drugs, including a plan to perform a comprehensive assessment of the safety of some new drugs within 18 months after their introduction, and to issue a "report card" on their performance. Although this may sound plausible, it appears to be inconsistent with data which show that in fact newer drugs confer an advantage over older ones in reducing mortality. In a study of patients who took drugs during January to June 2000, those who took newer medications were less likely to die by the end of 2002. The estimated mortality rates were directly related to time that had elapsed since approval of the drugs: For pre-1970 drugs, the estimated mortality rate was 4.4 percent, while the mortality rates for drugs approved during the 1970s, 1980s, and 1990s were 3.6 percent, 3.0 percent, and 2.5 percent, respectively. Not surprisingly, drugs are getting better all the time.

A related point is the myth, often cited as fact by regulators and members of Congress, that rapid advances in science are outstripping regulation. Although some fields, such as human gene therapy, offer significant challenges, innovations such as improved gene-splicing and separation and analytical technologies have led to the manufacture of more highly purified drugs - especially vaccines, hormones and antibody preparations - which are less problematic for regulators.

The FDA's "cover" for these ill-advised innovations is that they are a response to a report on "drug safety" published last Fall by the quasi-governmental Institute of Medicine. However, the IOM's deeply flawed, one-sided analysis will remedy few, if any, of the FDA's shortcomings. In fact, many of their recommendations would make the agency even more risk-averse, reduce the number of drugs emerging from the R&D pipeline, and compromise public health.

Neither the Congress nor FDA (nor the IOM) is willing to admit that the agency's most significant problems are mismanagement and excessive risk-aversion. It's much easier to conclude that there is insufficient regulation and to throw more resources at the problem. (And recall economist Milton's Friedman's wry observation that only government responds to a failed program or project by expanding it.) Meanwhile, regulators keep raising the bar for approval, especially for innovative, high-tech products. The FDA is requiring ever larger numbers of patients in clinical trials, its demands for post-marketing clinical trials have proliferated wildly, and "risk management" plans for newly approved drugs have been inconsistently applied, punitive and often more appropriate for weapons-grade plutonium than prescription drugs.

Historically, the pendulum has swung back and forth about what kinds of problems predominate in the regulation of drug development. Thirty years ago, the concerns were primarily about "drug lag" - indolent reviews and approvals by the FDA that put Americans at disadvantage to consumers in other countries; but in recent years there have been repeated accusations about what might be called "drug leap" - a supposedly "too cozy" relationship between regulators and industry, and too little attention paid to drug safety, possibly as the result of regulators' struggling to meet arbitrary deadlines. No longer are federal regulators called to account for the unnecessary deaths of patients who don't get the new drugs they need in a timely way.

Unfortunately, these contemporary views are shared by many influential leaders of Congress. Given the long-standing, more-regulation-is-always-better prejudices of many of the new committee chairmen, including Senator Ted Kennedy (D-Mass.) and Reps. John Dingell (D-Mich.) and Henry Waxman (D-Calif.), hearings and new lawmaking will focus on alleged under-regulation and the need for additional power and resources for the FDA . User-fees on drug companies - another name for a discriminatory tax on a single industrial sector - will likely be increased.

Part 2 of this article will discuss two recent, wrong-headed legislative proposals introduced in the Senate. But even in the absence of new legislation (which could be vetoed by the president), oversight hearings will push the FDA to regulate more aggressively and punitively, and regulators will be only too happy to comply.

It is both unseemly and dangerous to public health for FDA officials to cavort like an organ-grinder's monkey trying to distract attention from the 800-pound gorilla. What the FDA needs is competent management, acknowledgement of its weaknesses, discipline in the ranks, more effective risk-benefit balancing, and a commitment to permitting patients and physicians to assume more responsibility for the risk of medical interventions..

Henry I. Miller, a physician and fellow at the Hoover Institution and the Competitive Enterprise Institute, headed the FDA's Office of Biotechnology from 1989-1993. His most recent book is, "The Frankenfood Myth."



Why is it so difficulty to sell
the idea of a UL (the electrical appliance testing service) for drug approval?

That one is doing a very commendable job.

The Endgame of Medical Serfdom
“Promote access at the expense of safety, and a dangerous product can cause incalculable harm; over-emphasize safety at the expense of access, and patients suffer from the absence of life-saving and life-enhancing medications.”

The above framing of the FDA “dilemma” is instructive. Since the answer must be NO and NO, it appears that other alternatives should be considered. Here are two:

1) The patient is sovereign.
2) See option-1.

If there must be a tax funded FDA, its role should be as advocate for the patient…a trusting source of fact and options. Congress should re-write the FDA charter and clarify its “omnibus” function. This would “moot” the no-win options now confronting the FDA community.

If the FDA-Congressional-Medical community continues down the path Mr. Miller fears, the black market will continue to expand in US and global markets. Soon we will have no choice but to bring the troops home from Iraq to keep Grandma from taking her “non-approved” meds. A police state for our own good…clearly supported in the Constitution…maybe we could clone Adolph, Joseph and Genghis as advisors.

Blame Aversion
I would characterize the FDA as blame-averse rather than risk-averse.

To me, risk-aversion implies that the FDA has evaluated drug mortality rates and has determined that the current rates are too high, that is we're taking too much risk by using potentially deadly drugs. I don't see that behavior. What I see is the FDA running like scalded dogs (FYI I've never actually seen a scalded dog) whenever a "news" story about a drug related death is broadcast. As soon as the specter of a Class Action Lawsuit arises all you hear from the FDA is "eek, eek, eek... run away, run away, run away".

Perhaps a good example would be Vioxx. I don't really know all of the details, perhaps somebody here has the facts rather than the trial lawyer spin, but in my view the proper response from the FDA would have been:
"How many deaths?"
"How many total patients?"
"The mortality rate is lower than we expected."
Instead, the klaxons sounded, hatches were battened, and the USS FDA dove for cover.

Frankly, I see no evidence that the FDA has any concern what-so-ever for product risk management. Their only concern is job security and that arises largely from a serious lack of management. How hard is it to build a slide presentation with all of the necessary drug test/trials/data in advance of a potential problem? Those of us in private industry know that the time to plan for the organic matter impacting the rotating air mover is before the disaster because afterwards you don't have time. How about a little disaster planning? Heck, how about a little planning, how about buying a clue from the clue store?

Irrational or Greedy?
One of the most tested medications in western pharmacopia, quinine, was an over-the-counter medication in the US until 1994, offering millions relief for leg cramps, particularly the form known as night cramps.

In 1994 quinine, recommended in western medical literature since at least 1633, was suddenly determined by the FDA to be too risky to be made available without a prescription, instantly raising the cost for this simple medicine, but prescribing it was considered relatively safe -- far more so, in any case, than alternatives -- so sufferers of this condition were still able to obtain relief.

This year, citing the 90 or so people who have succumbed to the careless use of quinine, the FDA restricted both the prescribing and the sale of quinine to malarial cases only, ignoring the fact that quinine's use as an antimalarial is almost insignificant relative to its use for leg cramps.

Quinine has no suitable replacement for relieving leg cramps; all other options are both less effective and more dangerous. And, of course, significantly more expensive.

What I do not see being discussed AND SHOULD BE in this forum..
In the past few years I have and my elderly mother has had the wonderful experience(you believe this I have some ocean front property in the Appal-mountains)concerning new drugs. Mostly the problem was potential serious effects not clearly put to find on the (leaflets) that come with drugs when you buy them. I could have died had I not jumped on the internet and punched in serious effects with k-plex or K-flex simular anti-biotics. When these are not prescribed properly by the physician the infection can and has often rebound in a more complex higher serious hard to treat condition of the patient. The other is some of these drugs can cause a swelling or tightening in the throat enough to choke off air passage, which you know what that air no live. I thought the infection was getting worse because my neck started swelling more and called the doctor who increased the strength and dosage that day. When night fall came and my breathing became more labored. I got on the internet found that info and immediately started drinking lots of water and coffee no caffine to flush my system and stayed up most of the night till my breathing was better than went to sleep.. I depend on the internet and very knowledgeable drugist at local business to keep me informed on serous effects. Not the doctors..

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