In a rare move, federal regulators are seeking to disqualify a prominent Chicago HIV doctor from future drug studies after they discovered his clinic committed one of the most grievous sins of medical research: submitting fictitious data in a drug trial.
The Food and Drug Administration said Dr. Daniel Berger "failed to protect the rights, safety and welfare" of patients under his care.
Doctors' and patients' signatures were forged, even on forms where patients said they understood the risks of the trial and those where doctors said the patients weren't too sick to enroll, the FDA found.
Some falsifications were obvious. One patient's name was spelled differently in the trial records than it was in other medical records, the FDA said.
The most basic tests to protect the safety of patients who enroll in a study — physical exams and electrocardiograms, or EKGs, which measure the electrical activity of the heart — at times were not performed, the FDA found. More than 200 tablets of the investigational drug were missing, records show.
Berger acknowledges his clinic provided phony data to a drug company but blames a former study coordinator. That coordinator was a convicted felon who served time in prison for embezzling hundreds of thousands of dollars, but Berger said he did not check into his background before hiring him.
Patients who took part in the trial likely don't know about these problems. Berger told the Tribune that he never informed them.
In addition to being illegal, submitting false data can put lives at risk because the FDA relies on clinical trial results when it decides which drugs to approve, and the guidelines for using these drugs are based on trial results.
For the last six months, Berger and his attorney have tried to reach an agreement with the FDA that would allow him to keep participating in drug trials without major restrictions. Berger hopes for a final determination in the coming weeks. In the meantime, his drug trial work continues.
"I still feel disqualifying me is too harsh considering all the work that I've done and everything I've devoted myself to," Berger said in an interview with the Tribune.
Berger, who has been involved in drug research from the early days of the AIDS crisis, has served as a principal investigator on more than 100 clinical trials involving HIV drugs. With about 3,000 patients, his Northstar Medical Center describes itself as the largest private HIV treatment and research center in the Chicago area.
At times, he was involved with 20 investigational drug trials simultaneously — in addition to seeing patients who were not enrolled in trials, managing his medical practice and traveling around the country to lecture about HIV treatments.
The trials provided money to Berger's clinic and helped put him on a national stage. His work has been published in The New England Journal of Medicine, The Lancet and other prestigious medical journals. Pharmaceutical giants at times have hired him to be their spokesman and consultant, and the University of Illinois College of Medicine named him a clinical associate professor.
But now he faces one of the most serious actions the FDA takes. Of the thousands of researchers conducting drug trials in the U.S., the FDA launched disqualification proceedings against just five last year.
Once the FDA sends a notice like the one Berger received, the agency typically places serious restrictions on that researcher's work or disqualifies him completely, said Elizabeth Woeckner, who tracks these proceedings as president of the nonprofit Citizens for Responsible Care and Research. "These letters are like poison," she said.
The FDA cited Berger's inadequate supervision of a clinical trial testing a prescription drug that treats chronic diarrhea in patients with HIV.
Berger told the FDA that his former study coordinator "fictitiously created" records of lab tests, physical exams and electrocardiograms. That coordinator "fraudulently signed investigators' and patients' names" throughout the trial, Berger told the FDA.
But under federal law, a trial's principal investigator is ultimately responsible. Every time Berger joined a study, he signed an FDA form vowing to "personally conduct or supervise" the investigation.
Court and prison records show that the study coordinator for Berger was released from Illinois prison in 2003 after pleading guilty to the theft of $364,000 from the DePaul University alumni relations department. A basic Google search turns up a Tribune story on the employee's seven-year prison sentence. The coordinator also had prior felony theft and fraud convictions in Minnesota, records show.
Berger said the coordinator's description of his prior job — that he was a personal assistant to a wealthy man whose identity he couldn't reveal due to a confidentiality agreement — didn't strike him as odd at the time he hired him.
"You can lock your door at night, leave the house, come back and get robbed," Berger said in an interview.
When a drug company representative first showed Berger two falsified records in September 2008, Berger failed to look for other irregularities within that trial or in other trials that the research coordinator had handled, the FDA said.
"You admitted that had you reviewed the 'patient roster,' you would have noticed irregularities and been able to stop the study coordinator's violations," Dr. Leslie Ball, a top FDA official, wrote to Berger late last year.
She added that if Berger had been monitoring the trial well, "it would have been obvious from a review of the study documents that required EKG screenings were not being performed."
One fictional study participant had a real patient's name. While there were study records indicating he participated in the trial and received payments from the drug company for doing so, the FDA found that he never took part. The signatures on the forms saying he received stipend payments were forgeries, according to the FDA.
The FDA did not document a motive for the fraudulent activity. Ball wrote that her agency's review of records suggests the coordinator started falsifying documents in July 2008.
In September 2008, an employee or contractor for the drug company showed Berger two informed consent forms — documents patients sign showing they understand the risks of a trial — where the signatures "didn't look right," Berger told the Tribune.
Berger told the FDA that he confronted the study coordinator, who admitted to falsifying the records. The Tribune is not naming the former coordinator because he hasn't been charged with a crime. He could not be reached for comment.
After the confrontation, Berger gave the employee a written reprimand, suspended him for a week without pay and assigned a supervisor to monitor his work with studies, according to the FDA. In interviews with the Tribune, Berger said he took the trial documentation and locked it in a room where no one could tamper with it.
The FDA, which began investigating in March 2009, says that wasn't enough.
Berger said in interviews that the drug company sponsoring the trial said it would perform an audit. When asked why he didn't commission an audit of his own at that time, Berger said, "I didn't perceive that my own audit was going to be any better than theirs."
He added, "I was under the impression they were going to send out an auditor ASAP."
But it wasn't until that November — about two months later — that the drug company auditor came to Northstar, FDA records show. That auditor uncovered "further evidence of falsification," according to the FDA. That's when Berger fired the coordinator, according to Berger and the FDA.
Records show Salix Pharmaceuticals Inc., which acquired the rights to the anti-diarrhea drug in December 2008, dropped Berger's clinic as a trial site. Salix spokesman Michael Freeman said the company does not comment on trial sites. In general, Salix audits sites where fraud is suspected, reports any wrongdoing to the FDA and does not use data from sites that are under investigation, Freeman said.
Berger said he has taken steps to assure he, his patients and the drug companies he works with will never be involved in a similar mess. He hired a firm headed by a former top FDA official to scrutinize the records of the 12 studies in which the former coordinator had any involvement. That review found no evidence of falsified documents in trials beyond the one the FDA cited, Berger said.
He said he and his staff also went through training on how to spot fraud.
Even though he faces disqualification, Berger told the Tribune, "Pharmaceutical companies aware of my reputation and excellent track record are rooting for me and continuing to work with me on many levels."
Yet some of the biggest drug companies are backing away from Berger as a principal investigator — even those he has worked with for more than a decade.
Merck & Co., which has quoted Berger in news releases on its top HIV drug, reviewed trial records at Berger's office upon learning of the disqualification proceedings. While Merck spokeswoman Pamela Eisele said "the integrity of the data was not compromised," the company replaced Berger as primary investigator with another Northstar doctor at the request of its institutional review board, which protects the rights of patients in trials.
Gilead Sciences Inc., the nation's biggest seller of HIV drugs, went a step further. The company not only dropped Berger as principal investigator, but Berger said it also forbade him from seeing his own patients for study visits required for the trial.Copyright © 2015, Los Angeles Times