Doctors Behaving Badly: FDA says UCLA cardiology chief botched clinical trial

Dr. Charles McKay understands the human heart better than most of us.

He has authored or co-authored hundreds of research papers about various aspects of cardiac care. He helped write the joint American College of Cardiology/American Heart Association guidelines for valvular heart disease treatment. Some of his work has been cited more than 1,000 times by other researchers.

He was named the chief of cardiology at Harbor-UCLA Medical Center in August 2002. He recently stepped down as chief but remains on the faculty. In October 2009, McKay received a warning letter from the U.S. Food & Drug Administration about a clinical trial that he was supposed to oversee while he was still chief. You can check out these letters yourself on the FDA's warning letters page.

Dr. Leslie K. Ball, director of the Division of Scientific Investigations for the FDA's Office of Compliance at the agency's Center for Drug Evaluation and Research wrote that McKay "did not adhere to the applicable statutory requirements and FDA regulations governing the conduct of clinical investigations."

The letter goes on to show how McKay had failed in his role as the "principal investigator," and, in fact, was in absentia for most of the trial, saying he had delegated responsibility to his staff and assumed things would run smoothly.

They didn't. One patient died. That should have been cause to tell the drug company and the Institutional Review Board so they could decide whether the trial should continue. No one told either of them until more than a year later.

On August 7, 2007, your site was informed that this subject had suffered cardiac arrest, had been hospitalized, and was not doing well. In the FDA investigators' review of your source documents for this subject, there was no evidence that you informed the sponsor of this SAE [Serious Adverse Event]. Subsequent to the subject's hospitalization, the subject died. Source records indicate that in September 2007 your site was aware of the subject's death. However, this additional SAE was not documented on the Serious Adverse Event Report Form with a documented causal relationship assessment, and was not reported to the sponsor until November 12, 2008.

Another patient was hospitalized multiple times during the study. The FDA could not find any evidence that the hospitalizations were reported. This was a big deal because these were two of only five patients in the study.

Why were patients falling ill? One reason might be that they weren't properly screened. The FDA found that patients provided lab samples, which usually means blood and urine samples, but that those samples weren't analyzed until after the patients already had been given the experimental drugs. Some of the patients weren't even given a routine physical exam. The patient who was hospitalized repeatedly had already been taking the drugs for a month by the time McKay's team got around to doing the screening exam. The study's protocols required that the patients be seen at a clinic every three months for the first year and then every four months, "to assess study medication compliance and accountability, concomitant therapy or intervention, and conduct of efficacy and safety-related assessments." That didn't happen.

For Subject #004, records indicate that after the 3-month post-randomization visit on October 16, 2007, your site staff did not see the subject for the 6-, 9-, and 12-month post-randomization visits.

You did not see this subject again until October 16, 2008. ... Given the length of time between clinic visits, we are unsure how you adequately protected the rights, safety, and welfare of the subjects enrolled into the study.

In addition to the visits, the study protocol required that all patients have their livers checked every four weeks to make sure the drug wasn't causing any damage. For some patients, the tests were done about once a year.

And for what?

The study itself was so poorly documented it likely will yield no usable results. For some patients, the FDA could find no information about how many drugs were given to them or how frequently.

Know your doctor: FDA warning letters to big names like McKay are about as frequent as the liver tests done during McKay's study. To make sure you don't miss one, you should check the FDA's warning letters page at least once a month.