Editorial

The drug explosion

If the pharmaceutical chemists took the time to look back at the net result of their prolificacy, would they be shocked to discover that the point of no return may have been passed? Do they suspect that now, instead of helping mankind with new drugs, they may be making matters worse? Will they realize that there is such a thing as too many drugs, that as matters stand there are too many drugs for the patient, for the physician, and, surprisingly enough, for the pharmaceutical industry? Although no one would suggest that they cease or even slow the pace of their search for useful drugs, if they are at all interested, I suggest that they do take the time to follow the effect of their creativity to its ultimate conclusion.

Five years ago, in an article entitled "Hazards of Modern Diagnosis and Therapy-The Price We Pay," Dr. David P. Barr pointed out that to the already staggering total of about 140,000 medicaments in current use, of which an estimated 90 per cent did not exist 25 years previously and 75 per cent had been introduced within 10 years, some 14,000 new ones had been added during the current year. Untoward reactions to medication have also increased

at a staggering rate. This comes about primarily because of lack of experience with many different and entirely new active drugs and because of inability to master the full implications of these agents as rapidly as they are marketed and much less because of the unpredictable and unavoidable cases of hypersensitivity, which are relatively rare. Dr. Barr notes that on the medical service of one great hospital, 5 per cent of the patients-one of every 20-were admitted as the result of "sanctioned and well-intentioned" use of drugs. One needs only to read Moser's Diseases of Medical Progress (What an ironic title!) to realize the dimensions of this danger; Friend and Hoskins point out that there are now forty new diseases of this kind and that more are probably on the way.

As the number of new and active drugs increases and both knowledge and experience with each therefore become smaller and proportionately more difficult to ob tain, not only is it a mathematic inevitability that drug reactions will also mount, but since more than a single factor is involved, it is also a certainty that the incidence of reactions will increase at an even faster rate than the rate at which new drugs

emerge. Even now the situation is alarming; but the future looks dismal indeed.

If this was all a hazard inherent in medical progress, in the well-intentioned search for better treatment for mankind, there would be some justification for it, but too often this is not the case. Too often new drugs are not introduced for the only proper reasons: because there is a real or presumed need for them, because they are genuinely superior to those in current use. Too often they are turned loose on the public to horn in on a market which has been created by someone else's discovery, to compete with drugs which have recently been established as good and useful. Too often they are hurried into use to get in on a market before it vanishes. I know of a pharmaceutical company in possession of a series of congeners which kept what it deemed to be the best for its own use and licensed the inferior ones to other distributors, to be sold by them to the medical profession for use on patients. Thus, drugs are being marketed and promoted and advertised by precisely the same techniques used for soaps and detergents.

A large proportion of claims for superiority for new drugs are patently invalid. But in addition, it is impossible that of the huge number of new drugs available, each one is the "best" for a separate medical indication. Thus for the approximately forty-five different tranquilizers, the thirty different sedatives, the eighteen different psychic energizers, the twenty-five different antihistamines, the thirty-two different antispasmodics, the thirty different diuretics on the market at this writing (and this census accounts only for different chemical entities and not different brands), each manufacturer claims his to be the best. Is each of the 150,000 preparations on the market the "best"? The best for what? The best for whom? There is a manufacturer who sells one drug entity in this country and a congener in another country, making precisely the same claims in each case: namely that each is the best for the same purpose. We are accustomed to this in soap ad

vertisements, but drugs are not soaps. Since more than one drug cannot be the best for the same indication, we simply don't have enough diseases to go around. At the moment the most helpful contribution is the new drug to counteract the untoward effects of other new drugs; we now have several of these.

It is too bad that the American Medical Association gave up the publication of that small and masterful book, Useful Drugs. It provided a good, unbiased formulary for everyone. This, or its equivalent, is one way of ensuring both safe and effective use of drugs as well as limiting their number through authoritative suggestion. Is it the only way? Perhaps not, but how else clarify the confusion created by excessive numbers of unproved new drugs promiscuously and prematurely introduced into the drug market? Of course there would be no confusion if the pharmaceutical industry saw the immorality in claiming a drug to be the best when a better drug was in fact available, if the sole criterion for the introduction of a drug was the good of the patient.

The situation is more serious now than it was 5 years ago when Dr. Barr pointed out that untoward reactions to drugs "could be regarded as one of the commonest conditions encountered." This is understandable. There are now more drugs; some are extremely potent and exert diffuse effects, others interfere with basic physiologic function; many are most unusual pharmacologically, hence poorly understood; many suffer from limited clinical trial; all are vigorously advertised. And, it seems, too many are used with little discrimination. In commenting on this situation in a lecture, "The Rational Era of Therapeutics," Dr. K. J. R. Wightman stated that if ever we were in danger of irrational and irresponsible behavior as therapeutists, it is now.

Are physicians characteristically irrational and irresponsible? No! But they may sometimes appear to be because of the sheer impossibility of dealing rationally and responsibly with so many new drugs

about which so little is known but for which extravagant claims are made and for the use of which pressure is exerted by the drug industry and by patients who have heard of new cures through newspapers, magazines, and other patients. Vigorous drug promotion even before the drugs are available helps build up pressure to use them. It is beginning to look as if the success of a new drug will depend less on how well it works and more on how well it is promoted. This is why physicians are led to use drugs when the indications are lacking, to use drugs that are not the best available or even those which do not apply. It is because of this that the rate of serious drug reaction is mounting. And it is because physicians are not irresponsible that they may be expected to react with some violence to this ever mounting hazard.

That the situation gives every indication of worsening is suggested by the title of a paper on steroids, "How to Win at Structural Roulette." The pharmaceutical industry has had a prolonged winning streak at this game, but every winning streak ends some time. Already it is abundantly clear that the medical profession is one of the losers. It is gradually giving over its initiative in choosing drugs for its patients to the detail man because it cannot deal with the plethora of new drugs expertly, safely, effectively. Obviously, the public is an even heavier loser.

What will happen when, as it eventually must, physicians refuse to gamble with their patients' lives and health or an enraged public demands that such gambling stop? Certainly the winning streak of the pharmaceutical industry will come to an abrupt end, but the rebound may well be excessive and may lead to unhealthy cynicism on the part of physicians and a state of therapeutic nihilism.

If the pendulum then swings as far in the other direction, as pendulums do, the medical profession will tend to lean more and more on the handful of proved, established drugs such as morphine, penicillin, and digitalis, about which it can read

substantial unbiased statements in textbooks, about which it will hear nothing from the detail man, and about which it will see nothing illustrated beautifully in drug house brochures, but on which it knows it can depend because of the accumulation of an enormous body of useful experience. And in this counterploy, surely important discoveries of our time will be overlooked and lost. How long before the public, medicine, and the drug industry are the losers to this type of gencral reaction?

What does the future hold if present practices continue? Twenty years ago the industry had already synthesized over 6,000 different sulfonamides; about a score or so were introduced and only about fifteen are in current use. There is no census on barbiturate synthesis, but although only about thirty were marketed in this country and about two dozen remain with us, the total number the chemists created certainly ran into many thousands. Several years ago one pharmaceutical company revealed that in its own laboratories it had synthesized and screened 1,000 nonphenothiazine tranquilizers. Thus there is a formidable stockpile of new and untried drugs which could be unloaded with very little notice. The present legal restraints could not effectively stop it, yet if all the active drugs available were introduced at one time, the result would be chaos.

In the past, the pharmaceutical industry has shown admirable restraint, but such restraint no longer exists. That drugs could be introduced still more rapidly is only a relative concession; it may be slow in relation to the rate which is possible, but otherwise it is far too rapid for the medical profession to acquire the knowledge essential for safe, effective use. Excessive numbers of drugs are now being introduced-excessive in view of the working capacities of those competent to test their safety and utility in man, excessive in view of the subjects available for the testing of their effects, dangers and uses in man, and excessive in view of the ability of those