Over the last few years, as reports of liver failure began to surface among patients taking the antibiotic Ketek (telithromycin),
Sanofi-Aventis's story about the integrity of its clinical data began to unravel. Although the FDA approved the drug, it asked
Sanofi-Aventis (which was just Aventis at the time) to conduct additional safety and efficacy studies of the drug in several
indications. The company agreed and outsourced the pivotal postmarketing study 3014 to a contract research organization (CRO).
But when news of unscrupulous patient recruitment and significant underreporting of adverse events came to light, Sanofi-Aventis's
finger pointing couldn't make the problem go away.
The issue is, when it comes to collecting—and using—questionable data, the company is far from alone. Over the last few years,
there has been a growing number of instances of misconduct in clinical research. In fact, the number of allegations of research
misconduct rose by almost 30 percent from 2005 to 2006, according to the Office of Research Integrity. And that may be just
the tip of the iceberg: At least one study found that more than 40 percent of physician investigators (PIs) are aware of research
misconduct but have not reported it to the appropriate authorities.
Much of this increase may be attributed to a change in the way companies conduct clinical trials. Though the industry traditionally
contracted with academic medical centers to conduct sponsored clinical research, companies are now turning to physicians in
solo or group practices. According to a recent study by the American Association of Medical Colleges, industry-sponsored research
conducted in US academic medical centers decreased by 40 percent since 2004, in favor of community hospitals and independent
physicians in private practice. Companies are making the shift because it gives them better access to patients and because
private physicians and community hospitals have less infrastructure and overhead, which makes clinical research cheaper. But
despite these benefits, trials conducted by these investigators often lack the auditing, monitoring, and other controls that
are part of the academic medical center research environment, with their institutional review boards and clinical trial monitoring
units. This makes sponsors more vulnerable to using questionable data and to charges of research misconduct—not to mention
increased costs because they have to terminate and repeat those studies.
Companies began to recognize this issue in 2004, after the Chicago Tribune broke a story about a physician investigator in Kentucky who falsified the number of patients he enrolled in a clinical trial
to increase his compensation. A study coordinator for the multi-site sponsored trial reported the PI to the sponsor after
seeing the same lab results recorded for what were supposedly different human subjects on different dates.
In addition to falsifying data, physician investigators in private practice can also run into compliance issues associated
- research misconduct
adherence to human subject protection
- billing problems
- disclosure of financial relationships and other related conflicts of interest.
At first glance, these issues may seem like the physician investigators' problems—after all, they are the ones engaged in
the wrongdoing. But FDA's guidelines for Good Clinical Practice state that "ultimate responsibility for the quality and integrity
of the trial data always resides with the sponsor." Associate US Attorney Jim Sheehan reaffirmed the accountability of sponsors
for their clinical data during his talk at a compliance conference in September 2006 and noted that the Department of Justice
(DOJ) intended to increase its scrutiny of fraud and abuse in clinical research.
Scrutiny by regulators and the media often leads to delays in development, lawsuits, expensive remediation, and sometimes
irreparable damage to a sponsor's reputation. As a result, sponsoring organizations have a compelling interest in mitigating
and protecting against noncompliance. This article provides insight into two particular areas—billing and conflicts of interest—because
these are the areas most likely to be scrutinized in the near future.
Regulatory scrutiny of clinical research intensified in 2000, following the adoption of the National Coverage Decision (NCD).
The NCD defined new criteria for determining whether the government should reimburse medical procedures, items, and supplies
given to Medicare beneficiaries enrolled as subjects in sponsored clinical trials. While the NCD may sound like a simple procedural
change, it effectively meant that billing the federal government for non-covered services was considered fraud and abuse and
was subject to severe sanctions under the False Claims Act.