By Peter Aldhous
At around 7 p.m. on February 28, 2003, a 66-year-old woman showed up at the Pioneers Memorial Hospital in Brawley, a small Californian town not far from the Mexican border. She was seen by one of the doctors on duty in the emergency room that night, a man named Michael Berger. He learned that the woman, identified as “B.P.” in a later investigation, was in pain. A cramping sensation in her right thigh was radiating down her calf. Records show that she had a weak pulse in the same leg, and was short of breath. Her right foot felt numb.
Berger had options. He might have reviewed B.P.’s medical records, or tried to reach her primary care doctor to learn more about her history. He might have ordered an ultrasound or an x-ray. Either scan could have revealed the blockage in the artery in B.P.’s right leg. But Berger didn’t do those things. After consulting with a colleague, he sent B.P. home, with instructions to rest, drink plenty of fluids and take painkillers and blood-thinning meds. When she returned to the ER two days later, her leg was pale and cold—too far gone to save. She was flown to a larger hospital in San Diego, where surgeons removed the limb above the knee.
Berger’s career did not improve much afterwards. One day in 2004, he turned up for work impaired, a situation he blamed on taking sleeping pills. Other problems were noted when his employers asked a team of doctors to review his performance: failing to properly monitor patients after prescribing them dangerous drugs; prescribing excessive amounts of painkillers to his wife; a series of incidents while driving, which may have been related to his own drug use.
In 2008, the Medical Board of California put Berger on a seven-year probation. It was an unusually lengthy sanction, and it included limits on his ability to prescribe narcotics, and a requirement that he take regular blood tests to check for drug abuse. By then his career as an ER physician was effectively over: The California Emergency Physicians Medical Group, which employs ER doctors at Pioneers and dozens of other hospitals across the state, had handed him an indefinite suspension. Already his mid-60s, you might imagine that Berger would have taken these sanctions as a cue to slip into retirement.
But that’s not what happened. Instead, Berger secured a position at the helm of two high-stakes, high-tech cancer therapy trials. Dozens of patients with life-threatening cancers were entrusted to him. So was the responsibility for carrying out the complex procedures used to test the therapy. When the company involved—Immunovative Therapies—announced the first of these trials, its CEO enthused about the therapy’s potential to eliminate “every last” cancerous cell. In a photo accompanying the press release, members of the trial team stand in pristine white lab coats outside a building of concrete and tinted glass in Carlsbad, California, where the patients would later be treated. Next to the beaming CEO is Berger, wearing sandals and medical scrubs, a stethoscope slung over his shoulders.
I’ve reported before on doctors who fall foul of medical regulators. It’s been a sobering experience, partly because mistakes like those made at Pioneers don’t necessarily derail a career. Far from it—some sanctioned doctors find lucrative work with the drug industry. In 2010, for instance, I discovered that Pfizer, a pharmaceuticals giant, had made some questionable decisions when hiring physicians to talk to doctors about the company’s drugs. One recruit had been fined $30,000 for dangerous prescription of addictive narcotics, yet was hired to lecture others on how to use Pfizer’s leading antipsychotic drug. (Pfizer says it now screens potential speakers for disciplinary actions.)
Still, I hoped that companies would be more cautious when running clinical trials, the extensive tests that new therapies must pass before going on sale. These trials can be difficult to run; dense, jargon-filled instructions govern enrollment, administration of the treatment, and data collection. They’re also a step into the unknown. The point, after all, is to test a treatment that hasn’t been shown to work, and which might have unexpected side effects. Volunteers may rely on doctors’ advice when deciding whether to take part. If those same doctors are being paid to run the trial, there’s an obvious conflict of interest.
The challenges are so great that many experts argue that clinical trials should be run only by highly skilled doctors with impeccable personal integrity. “Standards for research have to be higher than for medical practice,” says Jonathan Kimmelman, a medical ethicist at McGill University in Montreal.
If I were to volunteer for a trial, I’d want to be sure that I was putting my welfare in the hands of someone at the top of their game. Yet what I knew about the business of clinical research made me pause. I use the word “business” because that’s what it is. The days when most trials were run by eminent researchers at prestigious medical institutions are gone. Costs have spiraled, and academic facilities have high overheads. Over the past couple of decades, work has been largely outsourced to regular doctors, often hired by firms that do nothing but manage trials for the drug industry. Some of these doctors are specialists; others are the family physicians who prescribe you antibiotics and administer your annual flu jab. They supply patients, and are usually paid according to how many complete the trial.
This trend has helped industry control its costs. But I suspected that it might have had consequences for patient safety. Finding out wasn’t easy. The U.S. Food and Drug Administration collects data on doctors hired to run clinical trials, but the records it makes public are censored and incomplete. Still, once I had the data, I was able to check it against disciplinary actions taken by the medical boards of the four most populous states: California, Texas, New York, and Florida. What I discovered confirmed my suspicions.
Among the doctors flagged by my search was a man named Robert Karns, a Beverly Hills physician whose clients once included Hollywood glitterati. Karns got involved in clinical research back in the 1980s, when Lovelace Scientific Resources (LSR), a drug-testing firm based in Albuquerque, decided to set up a satellite operation in Los Angeles. Karns’s busy practice offered a steady supply of patients. “They set up an office with eight to 10 employees, just adjacent to mine,” Karns recalls.
At that time, Karns’s record appears to have been clean. His problems didn’t begin until May 1993, when a movie actor later identified as “C.C.” showed up complaining of spinal pain. Karns examined C.C. and prescribed 100 tablets of Percoden, a combination of aspirin and oxycodone. Percoden is addictive, and medical board documents state that Karns knew C.C. had drug problems. Yet when the actor telephoned to ask for a refill a few days later, Karns obliged without seeing him. Further prescriptions followed. By late July, C.C. had received nine refills without returning to Karns’s office. Karns says that C.C. was abroad at the time of some of the refills, and that other doctors also prescribed painkillers to the actor. “I was just the fall guy,” he claims. But when the California medical board discovered what happened, it handed him a one-year probation.
A few years after the incident with C.C., Karns made a diagnostic omission that the medical board would later describe as “grossly negligent.” When patient S.R. arrived in Karns’s office, he told the doctor that he had been feeling tired, and that his friends described him as looking “ashen.” Karns ordered a chest x-ray, which, in the words of the medical board, revealed an “obvious abnormality” in S.R.’s left lung. Obvious to the board, maybe—but not to Karns, who failed to spot it. S.R. later died of lung cancer. (Karns admits his mistake, but suggests that S.R.’s prognosis would have been poor in any case: “Yes, I missed it. I’m responsible for missing it. But I believe it had little to do with his outcome.”)
For this omission, and for failing to properly plan the care of another patient, Karns was given a three-year probation in 2004. He’d only recently completed a similar sanction, this time for failing to follow proper procedure as a ringside doctor at a boxing match. It’s disturbing that a doctor can stumble from one probation to another in this way. More disturbing still is that these problems did not seem to hamper Karns’s work on clinical trials. The FDA’s records show 12 entries identifying Karns as an investigator on Lovelace trials between 2004 and 2009, when the company closed its Beverly Hills operation. Throughout this time, Karns can’t recall any concerns being raised about his disciplinary record.
By the time LSR departed Beverly Hills, Karns was beset by personal problems. In October 2009, he drove into oncoming traffic and broke his collar bone. When police arrived they discovered Demerol, an opioid painkiller, in Karns’s medical bag. In 2011, his son, Adam, locked him out of the practice they ran together, citing his drug abuse—a move that triggered a legal battle between the two. In May of that year, an administrator discovered a used syringe and a box of Demerol in a desk drawer in Karns’s office; the prescription for the drug was made out in Karns’s ex-wife’s name. That same month, CCTV footage captured Karns dumping used syringes, blood-stained gauze, and empty ampules of Demerol into the trash outside his office. When I ask Karns about his drug problems, he admits that he abused Demerol for three to four years, ending in 2011.
Still he continued to conduct trials. Karns can’t remember the companies he worked for, but I was able to establish that at least two were run for Cephalon, a pharma company based in Frazer, Pennsylvania, that has annual revenues in the billions. At least one trial involved opioid painkillers that, like Demerol, can be abused. In June 2011, shortly after barring his father from the practice, Adam Karns took over the last of these trials. Teva, the Israeli firm that now owns Cephalon, says: “To the best of our knowledge, Cephalon was not aware at that time that Robert Karns was under investigation for drug abuse.”
By December 2011, it had all become too much. The state medical board reviewed evidence of Karns’s drug use, and suspended his license. But they didn’t stop there. A few weeks later, an undercover operative working for the board visited the new solo practice Karns had established, a few minutes’ drive from his former office. The bogus patient complained of back pain and a cough, and was given prescriptions for both. The board’s account of the sting includes Karns’s immediate response to being caught breaching his suspension: “So I broke the rules … Guilty as charged.” He was later allowed to practice once more, under the supervision of another doctor, but it was only a temporary reprieve. In November 2012, Karns was finally stripped of his California medical license.
Almost to the end, Karns was being sought out for new studies. His final entry in the FDA database, submitted in March 2012, gives the address of his solo practice. Karns says that no clinical trials were actually run there. But evidently he was selected as a clinical investigator, and his paperwork was submitted to the FDA. Even after all the mistakes and the drug abuse and the disciplinary actions, there apparently was still a company somewhere that was prepared to employ Karns to run a clinical trial.
Karns may be an extreme case, but he’s far from alone. My trawl netted dozens of doctors selected to work on clinical trials over the past five years who had previously been censured by state medical boards. Thousands of doctors are hired each year to test experimental drugs, making this a small minority. But most doctors have clean records, so companies should have few problems finding recruits without red flags against their name.
It’s hard to know whether the doctors who were sanctioned caused problems in the clinical trials they ran, because the FDA rarely inspects trial sites. Karns was inspected in 2005, when nothing untoward was found, but there is no record of anyone coming to call during his later descent into drug abuse. (He denies ever putting trial volunteers at risk: “Was there any time I was impaired with a study patient? Absolutely not.”)
Yet there are good reasons for thinking that a doctor who errs once might do so again. A 2007 study found that doctors who were sanctioned by state medical boards in one five-year period were at least 10 times as likely as their peers to get in trouble over the following four years. More important, I came across several doctors who’d got into serious problems in both regular practice and clinical trials—including Michael Berger.
In April 2010, FDA inspectors arrived at Immunovative Therapies’ Carlsbad site. The records held there described a technically demanding study based on a radical idea. The treatment was known as AlloStim, and the idea was to take immune system cells from healthy donors, process the cells in the lab, and then inject them into cancer patients. The hope was that the cells would trigger an immune reaction aimed at the patients’ tumors.
Even enrollment was complex: blood tests and other analyses were used to assess whether patients met the extensive inclusion criteria. Once enrolled, they received three doses of AlloStim, followed by a procedure called tumor cryoablation. Using CT scans as a guide, Berger or a colleague had to pump chilled argon gas through a needle inserted into one of the patient’s tumors. The aim was to freeze the cancerous tissue, prompting it to release a chemical signal that would be targeted by the patient’s immune system. One hour later, another dose of AlloStim was to be injected straight into the tumor, followed a week later by a final dose into a vein.
As the doctor running the trial, Berger was responsible for ensuring that these procedures were followed. He had to oversee the collection of data, including MRI scans of patients’ tumors and tests of immune function, and verify that batches of AlloStim were sterile. These tasks apparently proved beyond him. FDA officials discovered that patients had been given AlloStim by the wrong method, or given numerous doses that they were not supposed to receive. One patient was enrolled despite not meeting the criteria. Some had received batches that were past their expiry date, or that had failed tests for bacterial contamination. Berger and his team had already treated 42 patients in one trial when the FDA visited, but the inspectors were so alarmed that they shut down the second trial he was running for Immunovative Therapies. The agency later told Berger that it would bar him from running clinical trials altogether—a lengthy process that ended with his disqualification in April this year.
The FDA considers the details of trials of experimental drugs to be commercial secrets, and so wouldn’t tell me whether any patients were harmed as a result of Berger’s failings. Michael Har-Noy, Immunovative Therapies’ CEO, declined to comment, and Berger would not be interviewed for this article. (Documents reveal that Berger told the FDA that he notified and monitored the patients who received the batches of AlloStim that failed sterility tests, and that he had not detected any adverse events, but the agency described his response as “unacceptable.”) One investor in the company was prepared to talk, however. Ronald Lachman, a Chicago-based venture capitalist, contends that the FDA’s inspectors overreacted. Lachman’s late wife was one of the trial participants, and he’s convinced that the treatment helped her. “Things that show so much promise are few and far between,” laments Lachman, who put more than $1 million into Immunovative Therapies.
Since 2000, just 45 doctors have been banned by the FDA from conducting clinical trials. Yet among them I found four, including Berger, who had also been disciplined by state medical boards for problems unrelated to their work on clinical trials. They include Charles Runels of Mobile, Alabama, who was fined $5,000 in 2009 for his misuse of hormone replacement therapy—board documents mention two women who were “massively overdosed” with testosterone. Around the same time, the FDA was in the process of barring Runels from future clinical trials work, after finding serious problems with two studies he ran on a smallpox vaccine. The volunteers included 21 men from a homeless center; some didn’t understand what the trial involved, and others couldn’t be contacted for subsequent health assessments required by the trial.
Runels defends his actions, especially his use of hormones, which he contends helped his patients. He says that he wasn’t aware that the volunteers in the vaccine trial were homeless, as addresses were being checked by the company running the trial. But he was the one in charge, he admits: “At the end I was responsible for everything, which is why I got burned.”
It’s not hard to check a doctor’s disciplinary history: Just enter a state’s name and the phrase “physician license” into Google, and you’ll be directed to the relevant database. The veil of commercial secrecy surrounding drug trials ensures that it’s impossible to know exactly what checks are performed by the companies doing the hiring. But by searching clinical trials databases maintained by the federal government, I was able to identify several organizations that had green-lighted the hiring of previously sanctioned doctors.
Some didn’t want to say much. LSR’s current management, for instance, refused to answer questions about the company’s employment of Karns. I also alerted Bristol-Myers Squibb, a giant company with sales running into billions of dollars each year, to the fact that it had hired at least three censured doctors to test the company’s experimental drugs. The company declined to address specific cases, responding instead with a general statement about its commitment to “scientific, technical and ethical integrity.”
Another case raised questions about the screening employed by the biggest clinical trials company in the business. Quintiles, based in Durham, North Carolina, earned $3.8 billion in 2013, most of that through helping drug companies get their products tested and approved. In 2011, Alexander Jungreis was among dozens of doctors that Quintiles hired to test a new formulation of a painkilling drug. He had previously been fined by Florida regulators over two separate incidents, one of which left a patient in a long-term coma.
Purdue Pharma, the drug company sponsoring the trial, told me that although Jungreis’s disciplinary actions were not initially reported to Quintiles, he was removed from the trial when they came to light, and before patients were recruited. That didn’t gel with what I heard from Joan Cutillo, clinical research director at the National Pain Institute, the Florida-based chain of clinics where Jungreis is a director. Cutillo told me that details of Jungreis’s record were included in documents prepared for the study’s ethical review board, and which were sent to Quintiles. After Quintiles later raised objections, she said the institute withdrew in disgust. Quintile’s own questionnaire, she added, didn’t ask about disciplinary actions.
I exchanged several emails with Phil Bridges, director of corporate communication at Quintiles, in a bid to understand whether this was correct. Had his company—again, the largest of its kind—used paperwork that lacked questions about doctors’ disciplinary histories? He would not comment on the case, nor on the details of Quintiles’ questionnaires. “Quintiles follows a number of processes that help us to identify any issues that may make a potential investigator unsuitable,” Bridges told me, sending a list of databases that his firm checks when recruiting doctors. It did not include one that covers sanctions from state medical boards.
I did eventually find a couple of companies that would defend a decision to knowingly hire a disciplined doctor. One of these cases involved Maurice Buchbinder, a cardiologist who was sanctioned by the California medical board over a 2007 incident. Buchbinder was inserting a stent into a 68-year-old man with a failing coronary artery when the patient became agitated and had to be restrained. According to eyewitnesses, Buchbinder returned when the still-distressed patient was restrained on a gurney, and called him an “animal.” Then he twisted the patient’s nose, pinched him several times, and bent his wrist. (Buchbinder did not respond to multiple requests for comment, but during his medical board hearing he argued that he used only sufficient force to protect the patient from harm.)
The prestigious Scripps Memorial Hospital in La Jolla, California, suspended Buchbinder, but the event did not dissuade the French firm Stentys from hiring him to lead a 2013 trial of an advanced stent. René Spaargaren, the firm’s chief medical officer, told me that Stentys would never hire someone who had been disciplined for negligence or fraud. In this case, the company weighed Buchbinder’s disciplinary record against his other attributes, including his strong medical and communications skills. Spaargaren pointed out that Stentys wanted Buchbinder to present the results of the study, and serve as a spokesperson with the FDA. Regarding the incident with the man on the gurney, he noted: “Everybody understands that sometimes you can lose your temper.”
Perhaps it shouldn’t be surprising that a company pushing for approval of its products might forgive a doctor’s indiscretions. But Institutional Review Boards are supposed to be different. They’re charged with looking for problems that might put patients at risk, and have to be consulted before a trial begins. Yet some are willing to approve previously sanctioned doctors even when they know about their disciplinary records. In the case of the Immunovative Therapies trial, for instance, I learned that the trial reviewers, BioMed IRB of San Diego, had discussed Berger’s disciplinary record and approved him anyway.
At least the BioMed IRB checked Berger’s record. In 2009, the Government Accountability Office, an investigative arm of Congress, submitted a fictitious trial protocol to three review boards. The application contained a number of land mines: the protocol was flawed and the doctor leading the trial was a work of fiction, backed by an invented résumé and falsified medical license. Two of the boards raised questions about aspects of the protocol, but one approved the trial—and its bogus investigator—with only minor modifications.
After spending months in the world of clinical trials, I’m left with an impression of a system that has evolved beyond the FDA’s ability to manage it. I’ve also been struck by the profound disconnect between the disciplinary system that governs everyday medicine, and the separate regulations meant to protect clinical trial volunteers.
Speed and efficiency seem to be what matters to industry, and at times these factors appear to trump concerns about the doctors who run trials. “The whole thing is profit driven,” says Michael Carome at Public Citizen, a consumer advocacy organization in Washington, D.C. “You can see where corners might be cut, looking the other way when there might be concerns about an investigator.”
Some experts argue that the FDA’s entire rulebook for clinical trials, with its talk of things like “institutional” review boards, reflects the academic past of clinical research—not today’s industrial juggernaut of for-profit clinical trials firms and for-hire review boards, which oversee a workforce of doctors drawn from regular medical practice. “They are regulations for a world that doesn’t exist anymore,” says Elizabeth Woeckner, president of Citizens for Responsible Care and Research, which campaigns for the safety of medical research volunteers.
When I presented the FDA with a summary of my reporting, I was told that the agency agrees that checking state medical board websites for doctors’ disciplinary actions “would be prudent.” So shouldn’t that be made an explicit instruction to companies and review boards? “We will keep your excellent suggestion in mind when we revise this guidance in the future.”
It hardly seems like a vigorous commitment to reform. All I can hope is that it won’t take a major scandal, a trial in which people die or are seriously injured, to get regulators to act.
This story is the second in a two-part investigative special on problems in the clinical trials industry. The first examines the use of homeless people in drug testing and is available here.
This second story was written by Peter Aldhous with additional reporting by Sandra Chung and Stephen Tung. It was edited by Jim Giles, fact-checked by Ben Kalin, and copy-edited by Lawrence Levi. Photography by Grant Cornett.
The reporting for this story is based in part on documents from disciplinary actions, a selection of which are available here.