Monday, June 04, 2007

Which Physicians Pharmaceutical Companies Choose to Participate in Clinical Trials

The New York Times published an article by Gardiner Harris and Janet Roberts about what sort of physicians participate in clinical trials sponsored by pharmaceutical companies in Minnesota. Using a data-base, unique to that state, of pharmaceutical company payments to physicians, they looked for physicians who were paid to participate in trials and had also been subject to medical board sanctions or criminal convictions. Surprise, surprise, they found some:

The Times's examination of Minnesota's trove of records on drug company payments to doctors found that from 1997 to 2005, at least 103 doctors who had been disciplined or criticized by the state medical board received a total of $1.7 million from drug makers. The median payment over that period was $1,250; the largest was $479,000.

The sanctions by the board ranged from reprimands to demands for retraining to suspension of licenses. Of those 103 doctors, 39 had been penalized for inappropriate prescribing practices, 21 for substance abuse, 12 for substandard care and 3 for mismanagement of drug studies. A few cases received national news media coverage, but drug makers hired the doctors anyway.

The Times included in its analysis any doctor who received drug company payments within 10 years of being under medical board sanction. At least 38 doctors received a combined $140,000 while they were still under sanction.

Drug makers refused to comment, said they relied on doctors to report disciplinary or criminal cases, or said they were considering changing their hiring systems.

Some of the more vivid anecdotes included:

A decade ago the Minnesota Board of Medical Practice accused Dr. Faruk Abuzzahab of a 'reckless, if not willful, disregard' for the welfare of 46 patients, 5 of whom died in his care or shortly afterward. The board suspended his license for seven months and restricted it for two years after that.

In cases involving Dr. Abuzzahab over 15 years in the 1980s and '90s, the medical board found that he repeatedly prescribed narcotics and other controlled substances to addicts, renewing one patient's prescriptions six weeks after the patient was jailed and telling another that his addictive pills should be thought of as 'Hamburger Helper.' He prescribed narcotics to pregnant patients, one of whom prematurely delivered a baby who soon died.

Separately, the F.D.A. in 1979 and 1984 concluded that Dr. Abuzzahab had violated the protocols of every study he led that they audited, and reported inaccurate data to drug makers. He routinely oversaw four to eight drug trials simultaneously, often moved patients from one study to another, sometimes gave experimental medicines to patients at their first consultation, and once hospitalized a patient for the sole purpose of enrolling him in a study, the F.D.A. found.

In June 2006, the medical board criticized Dr. Abuzzahab, this time for writing narcotics prescriptions for patients he knew were using false names, a violation of federal narcotics laws.

But Dr. Abuzzahab, a Minneapolis psychiatrist, is still overseeing the testing of drugs on patients and is being paid by pharmaceutical companies for the work. At least a dozen have paid him for research or marketing since he was disciplined.

Takeda, a Japanese drug maker, confirmed that Dr. Abuzzahab was doing a study financed by the company on its sleep medicine, Rozerem. Eisai, another Japanese drug maker, said that although Dr. Abuzzahab had signed a clinical trial agreement with the company to study its Alzheimer's drug, Aricept, it told him two days after a reporter asked for comment on the case that he was not qualified to be an investigator. And at AstraZeneca, for which Dr. Abuzzahab said he had performed clinical trials and still gave drug marketing lectures, a spokesman said the company was 'concerned' about Dr. Abuzzahab's disciplinary record.

'We have our own internal processes for dealing with these matters, which are under way,' said Jim Minnick, an AstraZeneca spokesman.

In an interview, Dr. Abuzzahab dismissed the findings as 'without heft' and said drug makers were aware of his record. He said he had helped study many of the most popular drugs in psychiatry, including Paxil, Prozac, Risperdal, Seroquel, Zoloft and Zyprexa.

Other examples were:

Dr. Barry Garfinkel, a child psychiatrist from Minneapolis who was convicted in federal court in 1993 of fraud involving a study for Ciba-Geigy. His criminal case made headlines across the state. From 2002 to 2004, Eli Lilly paid him more than $5,500 in honoraria, according to state records.

Dr. Garfinkel said in an interview that he had wondered why drug makers would hire him as a speaker considering his statewide notoriety. He decided that 'they're hiring me to influence my prescribing habits,' so he quit giving sponsored talks and taking money from drug makers, he said.

Dr. John Simon, a Minneapolis psychiatrist who for years shared an office with Dr. Abuzzahab and was told by the state medical board in 1994 to complete a clinical training program after it concluded in a report that he "frequently makes abrupt and drastic changes in type and dosage of medication which seem erratic, not well considered and poorly integrated with nonmedication strategies." He prescribed addictive drugs to addicts and failed to stop giving medicines to patients suffering severe drug side effects, the board concluded.

Dr. Simon earned more than $350,000 from five drug makers from 1998 to 2005 for consulting and giving drug marketing talks. Of this, Eli Lilly paid more than $314,000. Dr. Simon said in an interview that the board's action was a learning experience, and that drug makers continued to hire him to speak because 'I am respected by my peers.'

Asked about Drs. Garfinkel and Simon, Phil Belt, a spokesman for Eli Lilly, said that both doctors were licensed to practice medicine and that the company relied on doctors to report disciplinary actions or criminal convictions against them.

Dr. Ronald Hardrict, a psychiatrist from Minneapolis who pleaded guilty in 2003 to Medicaid fraud. In 2004 and 2005, he collected more than $63,000 in marketing payments from seven drug makers. In an interview, Dr. Hardrict said it was 'insulting' and 'ridiculous' to suggest that income from drug makers might influence doctors' prescribing habits.

Srikant Ramaswami, a spokesman for Johnson & Johnson, said the company removed Dr. Hardrict as a speaker in 2004 when, as a result of his conviction, his name appeared in a government database.

Asked why other drug makers continue to hire him despite a fraud conviction, Dr. Hardrict responded with an e-mail message stating only, 'I will pray for you daily.'

A US Food and Drug Administration official admitted that the Times' investigative reporting had found a significant problem.

Asked about the Minnesota analysis, the deputy commissioner and chief medical officer of the Food and Drug Administration, Dr. Janet Woodcock, said the federal government needed to overhaul regulations governing clinical trials and the doctors who oversaw them.

'We recognize that we need to modernize the F.D.A. approach in keeping people safe in clinical trials,' Dr. Woodcock said.

Drug makers are not required to inform the agency when they discover that investigators are falsifying data, and indeed some have failed to do so in the past. The F.D.A. plans to require such disclosures, Dr. Woodcock said. The agency inspects at most 1 percent of all clinical trials, she said.

Furthermore, there is no reason to think that the phenomenon uncovered by the Times is unique, or particularly prevalent in Minnesota.

The records most likely understate the extent of the problem because they are incomplete. And the Minnesota Board of Medical Practice disciplines a smaller share of the state's doctors than almost any other medical board in the country, according to rankings by Public Citizen, an advocacy group based in Washington.

Dr. David Rothman, president of the Institute on Medicine as a Profession at Columbia University, said the Times analysis revealed a national problem. 'There's no reason to think Minnesota is unique,' Dr. Rothman said.

'Clinical trial investigators must be culled from only the finest physicians in the country,' he said, 'since they work on the frontiers of new knowledge. That drug makers are scraping the bottom of the medical barrel is an outrage.'

We have posted recently about how the FDA approved a drug, (Ketek, Sanofi-Aventist) based in part on data from a clinical trial that included large numbers of patients enrolled by a physician who later pleaded guilty to criminal charges related to her management of that drug trial. At best, such sloppy management of clinical trials ought to lead to questions about the validity of their data. Decisions by the FDA about drug approval, and decisions by patients and physicians about whether to use a particular drug ought not to be based on such questionable data.

Yet this important NY Times article suggests that some, perhaps many of the physicians drug companies choose to enroll and manage patients in clinical trials have dubious clinical skills and/or ethics.

Not to sound like a broken record, but patients depend on their physicians to make decisions on their behalf based on the best scientific evidence. The principles of evidence based medicine suggest that physicians ought to make such decisions by weighing the possible benefits and harms of each possible clinical management option, taking into account their patients' values, derived from critical review of the best evidence from clinical research.

If such research is badly done, yet physicians and patients unaware of how the research is done use it to make decisions, they make make wrong decisions yielding bad patient outcomes. It appears that an unknown but probably important fraction of pharmaceutical (and perhaps other commercially) sponsored research may be badly done because the companies sponsoring the research chose unskilled, impaired, or even criminal physicians to participate in the research studies.

The anecdotes and data revealed in the NY Times article point to another major flaw in how clinical research sponsored by commercial firms is being done. We have previously discussed other concerns about commercially sponsored clinical research. Commercially sponsored clinical research may be designed, implemented, and disseminated in ways meant to favor the sponsors' commercial interests, not to advance science and medicine (see post here). Commercial sponsors may suppress research whose results do not favor their products (see recent posts here).

Putting these together suggests we should reconsider whether it is good for society to have any commercial firms sponsor, and thus control, clinical research done on real human beings.

ADDENDUM (4 June, 2007) - See also comments on GoozNews.

ADDENDUM (6 June, 2007) - See also this post on Clinical Psychology and Psychiatry.

No comments: