360 



These and other new families of drugs have achieved unprecedented 

 orders of effectiveness and potency, and are credited witli major con- 

 tributions to the practice of modern medicine. The ability to construct 

 and modify complex organic molecules in purposeful ways re- 

 sulted in the production of tens of thousands of compositions, with 

 members of each group varying in slight degree, and with many subtle 

 differences in their effectiveness as drugs, and also in their side effects. 

 New m.olecules are continually being developed, in an attempt to re- 

 produce the therapeutic effect of a prototype drug, while minimizing 

 its adverse side effects. A wide range of individual responses of pa- 

 tients to these drugs is also characteristic, and a further complicating 

 factor. Elaborate trade-off calculations are thus involved in drug de 

 velopment. Among the variables involved in these trade-off calcula- 

 tions are (a) the statistical probability of genuine curative effective- 

 ness, (b) the statistical probability of any improvement in prognosis, 

 (c) the statistical probability of any benefit, (d) the statistical dose- 

 related toxicity, (e) the statistical probability of (sometimes dose 

 related) adverse side effects, (f) the seriousness of the disease being 

 treated in the light of the effectiveness and hazard of a particular drug 

 in question, in relation to alternative drugs or other methods of treat- 

 ment. Acceptance and sorting-out of all this new technology by the 

 medical profession has posed problems without precedent. 



Traditionally, the medical profession had learned to employ drugs 

 as a major tool of the healing art by the accumulated and recorded 

 experience of years of use in treatment. With perhaps 400 new drugs 

 and drug combinations appearinir on the market each year, this grad- 

 ual, careful, and evolutionary development of experience wath each 

 new drug was no longer feasible. The spectacular effectiveness of the 

 new antibiotics, compared with the slow and uncertain benefits of 

 previous drugs that they replaced, compelled their expeditious accept- 

 ance by the medical profession and the public. Similar pressures for 

 rapid acceptance occurred with other important categories of new bio- 

 chemical agents. 



The remarkable efficacy of some of the new drugs made tliem news- 

 worthy, attracting public attention to these medical advances. The pub- 

 lic began to expect, and even to demand, their benefits. To some degree, 

 tlie writing of medical prescriptions was reported to be responsive to 

 publicity about certain new "wonder drugs." A tendency was also re- 

 ported for the public to expect to be given these drugs for ailments or 

 conditiojis for which less potent drugs would suffice, and thereby to de- 

 velop sensitivities to the more potent drugs that would obviate their 

 use when they were really needed. Protection of the ])ublic against its 

 own eagerness to serve as guinea pigs become an important added 

 medical service. 



Testing procedures for new dnigs tended also to be less thorough 

 than established practice called for: innovations appeared that were 

 minor molecular modifications, or assertedly "synergistic" combina- 

 tions, of known and well-tested compositions; when their performance 

 conformed with expectations in some particulars, it was assumed 

 throughout. Testing procedures could not possibly be maintained at 

 optimal levels with so many candidate drugs for testing and only a 

 limited number of appropriate patients in a limited number of institu- 

 tions qualified to participate in drug trials. Even so, the reporting of 



