Government Brings Criminal Action for Improper Clinical Trials and Off-Label Promotion

The U.S. Attorney's office for the Eastern District of Pennsylvania recently announced the criminal indictment of Synthes, Inc., a second company that is a wholly owned subsidiary of Synthes, and four of its senior executives. In general, the indictment asserts that the companies and individuals conducted unapproved clinical trials, engaged in off-label promotion, failed to recall the product in question and mislead an FDA inspector.

This case involves the use of certain orthopedics bone cements for unapproved uses. According to the indictment, there were several serious patient injuries and deaths as a result of the off-label use of the product. The government alleges that the company and individuals knew that an IDE was needed, knew that they were engaged in off-label promotion, failed to file several MDRs and failed to conduct a recall of the product that caused the injuries. According to a company press statement, the company had net sales of only $400,000 for the product in question – clearly, no matter the outcome, the company is paying a hefty price for minor sales.

This indictment continues an apparent trend of the government to bring criminal and civil enforcement actions against what it perceives to be efforts to bypass the IDE system. For example, in a recent civil case, the government succeeded in obtaining an injunction against a company and two individuals for improper clinical trials and marketing of certain devices. See U.S. v. Endotec, 563 F.3^rd 1187 (11^th Cir. 2009).

The Sythnes case identifies certain conduct that the government may well find objectionable across the board.

• The government viewed the Synthes "test marketing" programs as shams and efforts to avoid the IDE regulations.
• Likewise, the government will not tolerate company-sponsored "seeding" studies designed to create publications and interest in off-label uses.
• The government objected to decisions not to file MDRs that were made without the involvement of company professionals.
• The government will closely examine all statements made and documents produced during inspections looking for false or materially misleading or incomplete statements.
• Training or education sessions for sales representatives or physicians on off-label uses can be high risk events.
• The government noted the presence of sales representative during off-label procedures and viewed that as evidence of company complicity.
• The government expects a company to conduct a recall – and notify the FDA of the recall – in any case in which the product is causing any significant unanticipated significant patient harm.

This case also highlights several interesting approaches being used by the government in such cases. Of potentially great significance, the government may be linking the clinical trial regulations with off-label promotion. In this case, the government looked at the one course of conduct and used that conduct to allege both off-label promotion and that such conduct constituted an unapproved clinical trial. If this theory gains credence, the government can go after off-label conduct under two theories – the traditional illegal off-label promotion prohibition and as being an illegal clinical trial. In the Synthes case, the government also alleges that the test marketing, education programs and related activities were an effort to avoid the IDE requirements.

It is also interesting to note that the indictment covers conduct that occurred 5-8 years ago and that the investigation lasted over three years. The investigation was a joint effort of the Department of Justice, FDA and the Department of Defense – perhaps highlighting an increasing role for DOD investigators due to the use of products for military personnel and dependents. So, what are the key initial lessons can be derived from this case?

• First, be very careful about "test marketing", "seeding" studies and similar stratagems on unapproved products and uses – the government may well view that as an effort to bypass clinical trial requirements and restrictions on off-label promotion.
• Second, the government is very wary of any sales representative and physician training or  education programs that include any off-label information.
• Third, FDA expects companies to conduct recalls as needed. The failure to do so is           viewed as putting profits ahead of people and as an effort to hide information from FDA.
• Finally, any inspection by FDA must be taken very seriously. All statements made and      documents produced must be complete and accurate.

We will continue to monitor this and similar cases.