As one British expert has noted:
The problem of suppression of facts is widespread. A typical case occurs along the following lines; a toxicological study has been conducted and gives an equivocal result, or a result unfavourable to the product. A second study is conducted and at times even a third in which the dose levels are adjusted or the protocols modified in such a way that eventually a result favourable to the applicant's product is obtained. Only the result favourable to the applicant's product is submitted to the regulatory authority. . . . Microscopical examinations of histopathological slides may be made by more than one pathologist each of whom may have come to different conclusions, yet only the conclusions favourable to the drug are submitted to the regulatory authority. On one occasion where such a situation has been detected the applicant with a dismissive gesture said 'that investigator gives the wrong results, we will not use him again'. [This attitude reveals the commercial pressure that can be brought to bear on an investigator by the threat of loss of future work.]. . . A case can be cited where some dramatic falls in haemoglobin of the order of 3-4 g/l(X) ml in two animals were attempted to be hidden by presenting the haematological data as means and standard errors and commenting in the text that overall the mean haemoglobin levels were only slightly reduced when before and after treatment values were compared (Griffin, 1977:29,31).
The boundaries between fraud, criminal negligence and civil negligence are obviously blurred. Concealing unfavourable evidence on the safety of a drug has rarely been the subject of criminal action, though in civil product liability matters it often becomes a central issue. The charges of involuntary manslaughter against executives of Griinenthal in Germany concerning the suppression of dangerous effects of thalidomide is one exception to the pattern of civil rather than criminal actions.1 This pattern would also have changed in the United States if Congressman Conyers and his Subcommittee on Crime had succeeded in its bid to have failure to report known dangerous effects of consumer products a specific criminal offence.2
There are many cases of drug companies concealing and
misrepresenting dangerous effects of drugs noted by their own scientists. In 1959 Wallace and Tiernan put a new tranquilliser, Dornwal, on the market despite the strenuous objections of its own medical director. Other company experts warned that Dornwal could cause serious and possibly fatal blood damage. They were right. Wallace and Tiernan failed to send to the FDA reports of side-effects which included nine cases of bone marrow disease and three deaths from using the drug (Johnson, 1976). The company was found guilty on criminal charges and fined $40,000 (Silverman and Lee, 1974: 97).
One could list a number of similar types of cases. Johnson and Johnson's subsidiary, McNeil Laboratories, was denounced by the FDA for concealing information on side-effects of Flexin which according to Johnson (1976) included the drug being associated with 15 deaths from liver damage. Such more blatant cases are merely the tip of an iceberg of selective misinformation.
The most dramatic recent case has been the disclosures in the British Parliament and US Congress that Eli Lilly and Co. knew of the dangers of Opren, an anti-arthritic drug associated with 74 deaths in Britain alone, 15 months before the drug was withdrawn (Sunday Times, 27 February 1983). Moreover, almost a year before the drug was withdrawn from the world market, an investigator with the FDA's Clinical Investigations office had recommended criminal prosecution of Lilly for failing to report adverse reactions to four of its drugs, including Opren. According to the investigator, 65 of 173 adverse reactions submitted to Lilly by doctors had not been reported to FDA at all, and not all of the side effects mentioned in an initial application to FDA were mentioned in its final submission, and not all of the side effects mentioned in its final submission had been mentioned in the initial application. The alleged combined effect was to have each document grossly understating the problem (Wall Street Journal, 4 August 1982).
The problem is not restricted to Anglo-Saxon countries. In November 1982, a Japanese company, Nippon Chemiphar, admitted to presenting bogus data to the Japanese Government with its application to market a pain-killer and anti-inflammation drug under the brand name of Norvedan. The company submitted cooked up data to the Government in the name of Dr Harcio Sampei, chief of plastic surgery at Nippon University. The good doctor had accepted 2.4 million Yen in cash from the company in return for permission to use his name. More disturbing are similar allegations on another Nippon Chemiphar product. The company denies cooking data on this second product. But the worrying aspect of the second scandal is that a former company researcher claims to have submitted a written report alleging fraud in drug testing by Nippon Chemiphar to the Japanese Health and Welfare Ministry; Ministry officials, he alleges, chose to ignore the report (Japan Times, 23, 24, 25 November 1982).
Data fabrication is so widespread in the pharmaceutical industry as to support an argot - the practice is called 'making' in the Japanese industry, 'graphiting' or 'dry labelling' in the United States.
The pioneering work of Morton Mintz