383 



The manual included a word of caution to employees : 



Bear in mind that these are not basic clinical research studies. We have firmly 

 established the safety dosage and usefulness of Kevadon by both foreign and 

 U.S. laboratory and clinical studies. This program is designed to gain widespread 

 confirmation of its usefulness in a variety of hospitalized patients. If your work 

 yields case reports, personnel communications or published work, all well and 

 good. But the main purpose is to establish local studies whose results will be 

 spread among hospital stafE members. You can assure your doctors that they 

 need not report results if they don't want to but we, naturally, would like to 

 imow of their results. Be sure to tell them that we may send them report forms 

 or reminder letters but these are strictly reminders and they need not reply. 

 Their reports or names would not be used without getting their express per- 

 mission in advance. 



At the beginning of your interview, don't be secretive — lay your cards on the 

 table. Tell the doctor that present plans call for Kevadon to be marketed early 

 in 1961. Let them know the basic clinical research on Kevadon has been done. 

 Don't get involved by selling a basis [sic] clinical research program instead of 

 Kevadon. Appeal to the doctor's ego — we think he is important enough to be 

 selected as one of the first to use Kevadon in that section of the country. 



Attention of employees was directed, in the manual, to the require- 

 ment of FDA that a "qualified investigator statement" must be signed 

 by any clinician and be in the hands of the company before the com- 

 pany could legally ship Kevadon to the clinician. Moreover — 



One of the prerequisites for obtaining an NDA is that the application contain 

 full reports of investigations which have been made to show whether or not 

 such drug is safe for use. In order to allow for the investigational testing of 

 a drug, section 505(i) of the act was passed which provided that the Secretary 

 of Health, Education, and Welfare may promulgate regulations for exempting 

 from the operation of section •50.5(a) drugs intended solely for investigational 

 use "'by experts qualified by scientific training and experience to investigate the 

 safety of drugs." 



The Secretary has passed such regulations. The requirements that have been 

 set forth are that the investigational drug bear a label carrying the statement — 

 "Caution: new drug — limited by Federal law to investigational use," and that 

 such shipment be made only to a qualified expert investigator. A further stipula- 

 tion is made that the company that introduces new shipment into interstate com- 

 merce must obtain, prior to the shipment, a statement signed by such expert 

 showing that he has adequate facilities for the investigation to be conducted 

 by him. and that the drug will be used solely by him or under his direction. 



Successive bulletins and communications to the "special Kevadon 

 representatives" provide evidence that the company's estimate as to 

 the interest of the medical profession in thalidomide was correctly 

 foreseen. On November 8, 1960 it was announced that "In 1 week 

 you have already established 162 studies, totaling 6,648 patients!" 

 On November 15, the company had reached 55.3 percent of its "goal" 

 with 418 studies, involving a predicted 15,373 patients. On November 

 29, it was announced that the program had achieved 762 studies 

 involving 29,413 patients." 



The Humphrey subconunittee in its final report expressed criticism 

 of what it called the "peculiar aspects of the 'test'." The company had 

 distributed 2^2 million thalidomide tablets to 1,267 investigators, 

 who distributed them to 19,822 patients including 3,760 women of 

 child-bearing age, of whom 624 were pregnant. Fortunately, most 

 of tliese received the drug late in pregnancy."* However, said the 

 repoit : 



"3 Exhibit 43 (consisting of internal correspondence of William S. Merrell Co., provided 

 by FDA). In ibid., pp. 270-27.'',. 



''* Senate. Committee on Government Operations. "Interagency Drug Coordination " 

 Report. * * * S. Kept. 1153 (1966). op. cit., pp. 22-26. The figures are derived from an 

 FDA press release, dated Aug. 23, 1962, and are reprinted in full in Humphrey hearings, 

 op. cit., pt. 1, pp. 248-249. 



