GOV E R N M E N T

Drug Safety Is Relative, FDA Says Benefits must be weighed against risks in approving new drugs for market, Commissioner Larrick testifies

"There is no such thing as absolute safety in drugs. There are some drugs that are less liable to cause harmful reactions than others but people die every year from drugs generally re­garded as innocuous," George P. Larrick, Commissioner of the Food and Drug Administration, told the House Subcommittee on Intergovern­mental Relations. The subcommittee, headed by Rep. L. H. Fountain (D. -N.C) , is holding hearings on drug safety.

"There is an urgent need," Rep. Fountain says, "for a thorough and objective examination of the safety of new drugs in view of uncertainties created by recent articles in both the scientific and lay press." In his opin­ion, the hearings will provide an op­portunity for frank and open discus­sion of the problems and prospects of assuring the safety of drugs.

Balance. The administration of potent drugs involves a calculated risk where the presumptive benefit is bal­anced against the possibility of toxic effects or idiosyncrasies, Mr. Larrick says. To calculate wisely, it is neces­sary to know as accurately as possible what the risk may be in kind, degree, and frequency and the special condi­tions which may increase or decrease the chance or injury.

When a new drug is introduced, data on these side effects can often be learned only by experience. If the incidence is small, the injury may not become apparent for some time. On the other hand, one of the earliest cases may be one of the exceptions and so bring a valuable drug into disre­pute, perhaps depriving the public of an exceptionally valuable remedy, Mr. Larrick says.

In his opinion, no plan of clinical in­vestigation, even the most extensive, can be expected to give all the infor­mation that will be revealed by gen­eral marketing and use of a new drug. In fact, the early period following gen­eral marketing of a new drug must be regarded as a final step in its testing.

In deciding to approve a drug for

FDA Commissioner Larrick

The public must realize that use of any drug carries some risk

marketing, FDA must weigh the bene­fit to be expected from use of the prod­uct against the risk inherent in its use. This is the same type of decision a physician makes every time he pre­scribes a drug for a patient. But the Government must consider a number of factors not pertinent to the indi­vidual physician's decision, Mr. Lar­rick says. The Government must make a judgment as to the hazards likely to be encountered when the drug is employed by physicians of varying skills and abilities; in patients with a multitude of disease processes, many occurring concurrently; and in patients with maladies that are in­correctly diagnosed or inadequately tested with accepted laboratory pro­cedures, he says.

FDA physicians, pharmacologists, and other scientists evaluate the ac­cumulated body of data on a drug and make recommendations based on the broad picture of the relative merits of a drug for all of society, Mr. Larrick says. These recommendations are subjected to an administrative review which takes into account the applica­bility of existing law, and FDA ar­rives at an institutional decision on the merits of a drug, he says.

Public Opinion. "We seek to make decisions about drugs solely on the basis of scientific considerations. But, over a period of time, the direction of Government's decisions will inevitably be influenced by public reaction," Mr. Larrick says. The public has devel­oped a growing interest in drug mat­ters and is making judgments, he adds.

These judgments are not necessarily consistent with scientific facts; they are not always logical; they can be, and sometimes are, arbitrary. Even so, neither the executive nor the legis­lative branches of Government can long ignore them, he says. "If it should become the overwhelming pub­lic view that society should drastically limit the risk no matter how much good a drug can do, then we would be forced to remove from the market many drugs whose good far outweighs their harm. Carried too far, such de­velopments could seriously impede the progress of medicine," he warns.

In his opinion, public concern about drugs and drug reactions has not yet resulted in arbitrary decisions which damage medicine. However, he warns, the public needs to realize that the use of any drug carries some risk and that as science advances it will discover that some drugs quite prop­erly allowed on the market in the light of earlier scientific knowledge should be discarded either because more is known about the bad effects of these drugs or because new products have been developed which can accomplish the same good at less risk.

Advances in medical science make it possible to assess the risk associated with a drug more accurately than ever before, Mr. Larrick says. So the safety judgments FDA makes today are better than those made five years ago and the judgments made five years ago were better than those made 10 or 20 years ago. This does not mean that FDA did a poor job five, 10, or 20 years ago; it means that it did the best job possible in the light of avail­able facts and the competence of the science of that day to evaluate the facts, he says.

Other Comment. There is always an element of risk, no matter how small, whenever a chemical agent is administered to a patient. That risk can be minimized by adequate animal testing and premarketing clinical trials; it can never be eliminated, Dr. Hugh H. Hussey, director of the American Medical Association's divi-

34 C&EN A P R I L 6, 1964

sion of scientific activities, told the committee.

AMA has always supported legisla­tion and regulations designed to strengthen the premarketing assess­ment of drug safety, Dr. Hussey says. However, AMA believes that no laws or regulations can ever be devised to forestall entirely the possibility of drug toxicity.

AMA recognizes the appropriate role of Government in protecting the public welfare; at the same time, free­dom of scientific research is necessary for the advancement of the nation's health, Dr. Hussey says. Thus, it is necessary to ensure that creativity is not harmed by the standardization of procedures through unnecessary and overly burdensome government regu­lation and supervision, he warns.

Dr. William S. Apple, executive di­rector of the American Pharmaceutical Association, told the committee that APhA is concerned that "the hysteria of the moment about drug safety could develop into an unwritten protocol of indecision and delay" on FDA ap­proval of new drugs. He urges a cam­paign to inform the public that a bene­fit-to-risk ratio will always exist in drug safety and that every effort is being made to reduce the risk and increase the benefit.

Representatives of the Pharmaceu­tical Manufacturers Association are slated to appear before the committee later this month.

NSF Starts Science Development Program The National Science Foundation has set up a program, the science develop­ment program, to increase the number of institutions "of recognized excel­lence" in the sciences. Under the plan, NSF will make grants to institu­tions which, in NSF's judgment, "have substantial potential for elevat­ing the quality of their scientific ac­tivities."

In applying for these grants, col­leges and universities will submit to NSF a five-year plan to develop their science activities. The NSF grant will cover the first three years of the plan and the university will be expected to finance the final two years. NSF says grants will be made to strengthen single academic science activities, groups of related science activities, or entire science programs. Also, in very promising cases, financial support will

be granted to set up new departments of science.

While all the details of approving or disapproving grants have not been worked out, NSF does have some gen­eral guidelines to follow. According to NSF, each institution must have suffi­cient scientific strength on which it can build a broader science program. Also, each university must have ade­quate financial resources to achieve and maintain the final goals of its plan.

A much broader program than the one which has been announced had been conceived by NSF in its 1964 budget request. In fact, NSF had requested $33 million for this program. Congress, however, trimmed the figure to $3 million. The foundation will ask for $25 million to run the program in its 1965 budget. Maximum grants will probably be about $5 million.

At present, there are about 15 to 20 institutions in the U.S. which have excellent science capabilities. Under the science development program, NSF hopes to increase this number. Since NSF's goal is to support schools with strong scientific potential, these top 15 to 20 schools will probably be excluded from the program. During the next year, NSF will award about 10 to 15 grants.

However, in carrying out the pro­gram, many problems arise. Some of these problems were brought out in a speech by Dr. Glenn T. Seaborg, Chairman of the Atomic Energy Com­mission, early in March. Dr. Seaborg was head of the President's Science Advisory Committee when it published its report on the need for more science centers more than three years ago. In his speech Dr. Seaborg asked: "How do we prevent the competition for establishing such new centers in the various regions of our country from degenerating into squabbles reminis­cent of our saltier pioneer political eras? How can we prevent a science pork barrel?

"We must not let our national sup­port of science and technology degen­erate to the point where no state-no Congressional district—is complete without a post office, a reclamation project, and a new science laboratory. . . . Any such program, however, should be both soundly conceived and wisely administered if we are to build new centers of excellence in new geo­graphical areas without tearing down or undermining other centers that have already achieved and sustained ex­cellence."

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