TCS Daily


Powerful Medicine

By Henry I. Miller - September 18, 2003 12:00 AM

Transplants of a variety of human tissues -- among them cartilage, tendon and bone -- have become big business. Increasingly, they are being used to replace or reconstruct injured or aging body parts. Procedures such as the insertion of cartilage into joints damaged by trauma or inflammation, and bone used for spinal fusion, are performed more than a million times annually.

Documented problems are few and far between (the tally is one death and fewer than three dozen serious infections from contaminated tissue), but federal regulators have these products squarely in their sights. The FDA does not now regulate them but for several years has inspected and collected data on tissue banks. It found problems (many of them minor) at 51 of the 132 tissue banks it inspected in 2001, and at 48 of 165 in 2002.

The agency has proposed, but not finalized, the regulation of tissue banks, requirements for screening of tissue donors and testing of donated tissue, and standards for the manufacture, tracking and labeling of tissue products. In an op-ed article in the New York Times, Harvard professor Dr. Jerome Groopman decried the FDA's "apathy" and "lack of agility" in failing to regulate.

But, like antacids prescribed for arthritis, FDA oversight is the wrong medicine.

Orthopedic and neurosurgeons say the rules proposed by the FDA will increase the costs and reduce the supply of bone products for spinal surgery. Obstetricians and gynecologists complain that the rules will interfere with fertility clinics and sperm banks. Ophthalmologists worry that while offering no enhancement of safety, these regulations will compromise the supply of tissue needed for corneal transplants.

These fears are not without foundation. The FDA's notorious risk-aversion and mistrust of new technologies have made the American drug development system hugely expensive and caused the time and costs of drug development to spiral out of control. The total time required for drug development, from discovery of the product to marketing approval, has more than doubled (from 6.5 years to about 14 years) since 1964.

And in spite of more powerful and precise technologies for the discovery, purification and production of drugs, development costs have skyrocketed: According to the Tufts Center for the Study of Drug Development, companies' average expenditures to bring a single new drug to the end of clinical testing increased from $138 million in 1970 to $897 million currently. And while between 1970 and 2000, research-based drug companies' R&D outlays soared from about $2 billion to $30 billion, the number of approvals of new drugs barely budged.

An important reason is that the highly risk-averse FDA keeps raising the bar for approval, especially for innovative, high-tech products. This is not what Mark McClellan, the FDA's precocious and engaging new head, has been promising.

The FDA remonstrates that it's getting better and moving drugs through the pipeline more rapidly -- thanks, they say, to user fees paid by drug companies (a huge, discriminatory "tax" on one industrial sector) -- but the data tell a different story. Although the time required for the FDA's final approval of marketing applications for biopharmaceuticals has not changed appreciably during the past 20 years, the time required to meet the FDA's requirements for gathering clinical trials data has more than doubled: 32 months during the 1980s, 48 months during 1990-94, 64 months during 1995-99, and 72 months during 2000-02.

How does this happen? FDA officials arbitrarily and constantly introduce various obstacles to drug testing: They have directed researchers at biotech companies to begin trials at inappropriately low dosages; injudiciously limited early clinical trials only to single-dose, instead of multiple-dose, studies; demanded unnecessary, invasive procedures on patients; and required that foreign trials be completed and the results submitted before the U.S. trials could even begin.

What are we to do, then, about assuring that medical procedures like tissue transplants are safe and effective?

First, we need to realize that a government monopoly over product regulation is not sacrosanct. Non-governmental regulation of consumer products operates widely, efficiently and safely in the United States and abroad. In this country, Nationally Recognized Testing Laboratories, the prototype of which is Underwriters' Laboratories, certify more than 20,000 categories of consumer products, many of which, such as electrical appliances and equipment, automotive parts, and fire-resistant building materials, present inherent potential hazards to life and property.

Strong precedents for the evaluation of clinical data by independent organizations also exist. In a two-year pilot program (1992-1994) undertaken at the urging of the first Bush administration's Council on Competitiveness, the FDA contracted out reviews of submissions and compared the results of these evaluations to in-house analyses. The contractor was the Mitre Corporation, a non-profit technical consulting company. In all five of the submissions reviewed by Mitre, the recommendations were completely congruent with the FDA's own evaluations. Moreover, the time required for the nongovernmental reviews was two to four months, and the cost ranged from $20,000 to $70,000 -- fast and cheap compared to federal regulators.

Another example of successful nongovernmental oversight is the regulation of medical devices in the European Union, where the system relies heavily on various sets of product standards and normally does not involve government agencies directly in product oversight. And under pressure to improve its performance a decade ago, the FDA conducted a pilot program (which ended in 1998) that allowed private, third party review of most medical devices. Upon the termination of the successful pilot program, the FDA began to permit the review of specified medical devices by certain non-governmental "accredited persons." This approach should be expanded to drugs.

The most apposite model for tissue transplants, in particular, is the mechanism that regulates whole human organ transplants such as kidney, liver, heart, lung or pancreas. For many years, large segments of the domestic human-tissue industry have successfully self-regulated the quality and commerce of products through voluntary compliance with industry standards. Trade groups such as the American Association of Tissue Banks (AATB) and the Eye Bank Association of America (EBAA) sponsor voluntary accreditation programs that require adherence to standards and periodic inspections.

These kinds of third party, non-governmental oversight illustrate that there are attractive, proven alternatives to inefficient and expensive government agencies -- alternatives that should appeal to McClellan, the first FDA commissioner who is both an economist and physician. This approach to ensuring product safety should be expanded to the regulation of human tissues intended for transplants, as well as to conventional drugs. Such regulatory reform would be powerful medicine.

Henry I. Miller, a physician, is a fellow at the Hoover Institution and author of "To America's Health: A Proposal to Reform the FDA." He headed the FDA's Office of Biotechnology from 1989-1993.

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