Staff Writer

SAN DIEGO - Government investigations of the drug industry - which once centered on big pharma sales and marketing infractions such as off-label promotion, kick-backs and reimbursement fraud - now are focusing on biotech clinical trials.

That was the conclusion of "Emerging Enforcement Trends: Clinical Trials and Sponsored Research," a panel held Wednesday during the 2008 Biotechnology Industry Organization meeting.

Joan McPhee, partner with law firm Ropes & Gray LLP, said the pharmaceutical industry is the largest source of settlements for the Department of Justice, generating $6.1 billion in revenues for the government between 1990 and 2007. And clinical trials are "coming under increasing government scrutiny," she said, from both the DoJ and various state attorneys general.

Jesse Witten, deputy associate attorney general with the DoJ, confirmed that investigations into clinical research are "very important" to his agency because they involve patient safety and affect public confidence in the health care system. He added that the DoJ also sees clinical trial cases as an "opportunity to leverage" the substantial amount of publicity that usually follows such investigations in order to change behaviors of others in the industry.

The conduct of overseas clinical trials is one emerging area of interest for DoJ investigations, Witten said. If an American biotech company "greases the wheels" by bribing a foreign government official to facilitate approval of a trial, that company has just violated the Foreign Corrupt Practices Act, he said. Ditto if a company gives money or gifts to a foreign physician as incentives to serve as an investigator in a trial, since many foreign physicians are government employees.

Another clinical trial-related practice of interest to government is the way study results are communicated. High-profile cases against GlaxoSmithKline plc and Merck & Co. Inc. for the suppression of clinical data regarding Paxil and Vioxx, respectively, led to a push for mandatory registration of clinical results. That push culminated in the FDA Amendments Act of 2007, which requires nearly all clinical trial protocols to be listed on www.clinicaltrials.gov and will begin to phase in mandatory reporting of trial results beginning later this year.

But will that protect the biopharmaceutical industry from future litigation?

"Maybe not," said Paul Weissman, staff vice president of compliance for Schering-Plough Corp. He explained that the way in which trial results are reported will be of the utmost importance, since a trial in which one arm had two adverse events and one arm had three adverse events could be reported as having 50 percent fewer adverse events. "One person's statistical analysis is another person's distortion of the facts," Weissman said.

Data reporting investigations can reach even beyond companies and affect biotech executives. In the case of InterMune Inc., a DoJ investigation into a company's interpretation of clinical results led to a criminal indictment against the CEO for allegedly making false statements in a press release.

Another data reporting issue of interest to government prosecutors is the practice of ghost-writing scientific articles and paying prominent physicians to add their names at the top. Weissman said such cases could be the basis for a claim that a drug was prescribed under false pretenses. Additionally, if the underlying research causes a hospital or doctor to submit a false reimbursement claim, the drug company could be liable.

Beyond data reporting and publishing, the government also has "begun to pull the lid off the clinical trial process itself," McPhee said, launching investigations into issues such as financial conflicts of interest on institutional review boards (IRB) and data safety monitoring boards (DSMB), adequate warning of the risks involved in a trial and any situation in which "commercial considerations may affect scientific accuracy."

Priscilla Adler, director of research compliance and regulatory affairs at St. Jude Children's Research Hospital, said her facility has a separate monitoring plan for each study that includes unbiased external expert advisors. Although the FDA does not require a DSMB for most trials, she advised that a DSMB can provide a company with protection if compliance issues arise.

Adler also recommended that all DSMBs include a statistician, and that the DSMB and IRB communicate with each other. Communication with the investigators also is key, although she admitted that investigators can be a difficult bunch to regulate because "their science comes first."