NIH finds ethics violations in 44 cases
Charges of fake research hit new high
Doctors accused of making up data in medical studies
7/10/05
On the night of his 12th wedding anniversary, Dr. Andrew Friedman was terrified.
This brilliant surgeon and researcher at Brigham and Women’s Hospital and Harvard Medical School feared that he was about to lose everything — his career, his family, the life he’d built — because his boss was coming closer and closer to the truth:
For the past three years, Friedman had been faking — actually making up — data in some of the respected, peer-reviewed studies he had published in top medical journals.
“It is difficult for me to describe the degree of panic and irrational thought that I was going through,” he would later tell an inquiry panel at Harvard.
'I made it up'
On this night, March 13, 1995, he had been ordered in writing by his department chair to clear up what appeared to be suspicious data.
But Friedman didn’t clear things up.
“I did something which was the worst possible thing I could have done,” he testified.
He went to the medical record room, and for the next three or four hours he pulled out permanent medical files of a handful of patients. Then he covered up his lies, scribbling in the information he needed to support his study.
“I created data. I made it up. I also made up patients that were fictitious,” he testified.
Friedman’s wife met him at the door when he came home that night. He wept uncontrollably. The next morning he had an emergency appointment with his psychiatrist.
But he didn’t tell the therapist the truth, and his lies continued for 10 more days, during which time he delivered a letter and copies of the doctored files to his boss. Eventually he broke down, admitting first to his wife and psychiatrist, and later to his colleagues and managers, what he had been doing.
Friedman formally confessed, retracted his articles, apologized to colleagues and was punished. Today he has resurrected his career, as senior director of clinical research at Ortho-McNeil Pharmaceutical Inc., a Johnson & Johnson company.
He refused to speak with the Associated Press. But his case, recorded in a seven-foot-high stack of documents at the Massachusetts Board of Registration in Medicine, tells a story of one man’s struggle with power, lies and the crushing pressure of academia.
The story is more common than most people might realize.
Fabrications exposed
Allegations of research misconduct reached record highs last year — the Department of Health and Human Services received 274 complaints, which was 50 percent higher than 2003 and the most since 1989 when the federal government established a program to deal with scientific misconduct.
Chris Pascal, director of the federal Office of Research Integrity, said its 28 staffers and $7 million annual budget haven’t kept pace with the allegations. The result: Only 23 cases were closed last year. Of those, eight individuals were found guilty of research misconduct. In the past 15 years, the office has confirmed about 185 cases of scientific misconduct.
Research suggests this is but a small fraction of all the incidents of fabrication, falsification and plagiarism. In a survey published June 9 in the journal Nature, about 1.5 percent of 3,247 researchers who responded admitted to falsification or plagiarism. (One in three admitted to some type of professional misbehavior.)
Some cases have made headlines:
On July 18, Eric Poehlman, once a prominent nutrition researcher, will be sentenced in federal court in Vermont for fabricating research data to obtain a $542,000 federal grant while working as a professor at the University of Vermont College of Medicine. He faces up to five years in prison. Poehlman, 49, made up research between 1992 and 2000 on issues like menopause, aging and hormone supplements to win millions of dollars in grant money from the federal government. He is the first researcher to be permanently barred from ever receiving federal research grants again. In 2001, while he was being investigated, Poehlman left the medical school and was awarded a $1 million chair in nutrition and metabolism at the University of Montreal, where officials say they were unaware of his problems. He resigned in January when his contract expired.
In March, Dr. Gary Kammer, a Wake Forest University rheumatology professor and leading lupus expert, was found to have made up two families and their medical conditions in grant applications to the National Institutes of Health. He has resigned from the university and has been suspended from receiving federal grants for three years.
In November, 2004, federal officials found that Dr. Ali Sultan, an award-winning malaria researcher at the Harvard School of Public Health, had plagiarized text and figures, and falsified his data — substituting results from one type of malaria for another — on a grant application for federal funds to study malaria drugs. When brought before an inquiry committee, Sultan tried to pin the blame on a postdoctoral student. Sultan resigned and is now a faculty member at Weill Cornell Medical College in Qatar, according to a spokeswoman there.
While the cases are high-profile, scientists have been cheating for decades.
'It's the character'
In 1974, Dr. William Summerlin, a top-ranking Sloan-Kettering Cancer Institute researcher, used a marker to make black patches of fur on white mice in an attempt to prove his new skin graft technique was working.
His case prompted Al Gore, then a young Democratic congressman from Tennessee, to hold the first congressional hearings on the issue.
“At the base of our involvement in research lies the trust of American people and the integrity of the scientific exercise,” said Gore at the time. As a result of their hearings, Congress passed a law in 1985 requiring institutions that receive federal money for scientific research to have some system to report rulebreakers.
“Often we’re confronted with people who are brilliant, absolutely incredible researchers, but that’s not what makes them great scientists. It’s the character,” said Debbi Gilad, a research compliance and integrity officer at the University of California, Davis, which has taken a lead on handling scientific misconduct.
David Wright, a Michigan State University professor who has researched why scientists cheat, said there are four basic reasons: some sort of mental disorder; foreign nationals who learned somewhat different scientific standards; inadequate mentoring; and, most commonly, tremendous and increasing professional pressure to publish studies.
His inability to handle that pressure, Friedman testified, was his downfall.
“And it was almost as though you’re on a treadmill that starts out slowly and gradually increases in speed. And it happens so gradually you don’t realize that eventually you’re just hoping you don’t fall off,” he told a magistrate during a state hearing in 1995. “You’re sprinting near the end and taking it all you can not to fall off.”
At the time he started cheating, Friedman was in his late 30s, married and a father of two young children. Following the path of his father, grandfather and uncle who were all doctors and medical researchers, he was an associate professor of obstetrics, gynecology and reproductive biology at Harvard Medical School and chief of the department of reproductive endocrinology at Brigham and Women’s Hospital.
His reputation was tremendous and his work groundbreaking. His 30-page resume highlighted numerous awards and honors, lectures in Canada, Europe and Australia, and more than 150 articles, book chapters, reviews and abstracts. Of those, 58 were original research articles, where he had designed studies, conducted clinical trials, enrolled patients, collected and analyzed data and made conclusions.
In the end, investigators found — and Friedman confessed — to making up information for three separate journal articles (one of them never published) involving hormonal treatment of gynecological conditions.
He testified that he was working 80 to 90 hours a week, seeing patients two days a week, doing surgery one day a week, supervising medical residents, serving on as many as 10 different committees at the hospital and the medical school and putting on national medical conferences.
He did seek help, both from a psychiatrist, who counseled him to cut back, and from his boss, who demanded Friedman increase his research and refused to reduce Friedman’s patient load.
As good as Friedman was as a doctor, surgeon and researcher, he was actually a lousy cheater. One thing that brought about his demise, in fact, was that the initials he used for fictitious patients were the same as those of residents and faculty members in his program.
Unlike many scientists who file immediate lawsuits when they’re caught, Friedman was repentant, resigning from his positions at both Brigham and Women’s, and Harvard.
In 1996, Friedman agreed to be excluded for three years from working on federally funded research. During the next three years he consulted with drug companies, he paid a $10,000 fine to the state of Massachusetts and surrendered his medical license for a year, became very active with the American Red Cross, donating more than 500 hours, and attended several lectures on ethics and record-keeping.
“Andy can never undo the damage that his actions have caused. However, he has paid the price — his academic career is ruined, his reputation sullied, and his personal shame unremitting,” wrote Dr. Charles Lockwood, then chair of obstetrics and gynecology at New York University School of Medicine, in a letter on Friedman’s behalf.
In 1999, after successfully petitioning to get his license reinstated, he went to work as director of women’s health care at Ortho-McNeil Pharmaceuticals. The job, which he still has, involves designing and reviewing clinical trials for hormonal birth control, writing package insert labels and lecturing to doctors. Lately he’s appeared on television and in newspaper articles responding to concerns about the safety of the birth control patch.
Mary Anne Wyatt, a retired biochemist in Natick, Mass., is one of several former patients.
“I think it’s not at all surprising that a drug company would hire somebody who is very comfortable with hiding the effects of very dangerous drugs,” said Wyatt, who unsuccessfully sued him.
Ortho-McNeil spokeswoman Bonnie Jacobs said the company was well aware of Friedman’s history when it hired him. “He is an excellent doctor, an asset to our company,” she said. Read
NIH finds ethics violations in 44 cases
July 14, 2005
WASHINGTON (AP) -- Forty-four government scientists who also worked as consultants for drug companies violated agency regulations designed to prevent conflicts of interest, a review by the National Institutes of Health shows.
The review centered on whether the scientists had properly disclosed their work for the drug companies on financial disclosure forms, whether they had prior approval to do such work from their superiors and whether they took personal leave to do private work. In the 44 cases, scientists were found to have violated one or more existing NIH rules.
In an additional 37 cases reviewed, scientists did have prior approval for their work, had properly reported the work on their financial disclosure forms and took approved leave when necessary, the NIH reported.
The House Energy and Commerce Committee asked for the review when it compared NIH records to consulting agreements maintained by 20 pharmaceutical companies. It found 81 cases between 1999 and 2004 where the agreements were not listed in the NIH records provided to the committee. It asked NIH to investigate those cases.
Even as NIH investigated those cases, NIH Director Elias Zerhouni issued a ban on NIH employees consulting with drug and biotechnology companies. The agency also issued ethics rules that it is monitoring before making permanent.
The chairman of the committee, Rep. Joe Barton, R-Texas, said the agency's findings revealed the ethics problems at NIH were worse than he had anticipated.
"These findings indicate that the ethical problems are more systemic and severe than previously known," Barton said. "They also demonstrate the need for NIH to issue the final ethics rule as soon as possible."
Of the 44 scientists found to have violated agency rules, 36 are still employed at NIH and have been referred for possible disciplinary action. Nine of those thirty-six have also been referred to the HHS Office of Inspector General for investigation of possible criminal violations.
Zerhouni made the details of the NIH investigation known in a letter to the committee dated July 8. The findings were released, despite Zerhouni asking that they be treated as confidential.
"You have my pledge that I will continue to work with the committee on this matter as we move forward by correcting deficiencies and ensuring public trust," Zerhouni said.
Committee leaders released the data and letter anyway because of the compelling public interest, said Kevin Schweers, a spokesman for the panel.
Research: Third of study results don't hold up
July 13, 2005
CHICAGO, Illinois (AP) -- New research highlights a frustrating fact about science: What was good for you yesterday frequently will turn out to be not so great tomorrow.
The sobering conclusion came in a review of major studies published in three influential medical journals between 1990 and 2003, including 45 highly publicized studies that initially claimed a drug or other treatment worked.
Subsequent research contradicted results of seven studies -- 16 percent -- and reported weaker results for seven others, an additional 16 percent.
That means nearly one-third of the original results did not hold up, according to the report in Wednesday's Journal of the American Medical Association.
"Contradicted and potentially exaggerated findings are not uncommon in the most visible and most influential original clinical research," said study author Dr. John Ioannidis, a researcher at the University of Ioannina in Greece.
Ioannidis examined research in the New England Journal of Medicine, JAMA and Lancet -- prominent journals whose weekly studies help feed a growing public appetite for medical news.
Experts say the report is a reminder to doctors and patients that they should not put too much stock in a single study and understand that treatments often become obsolete with medical advances.
"The crazy part about science and yet the exciting part about science is you almost never have something that's black and white," said Dr. Catherine DeAngelis, JAMA's editor-in-chief.
Editors at the New England Journal of Medicine added in a statement: "A single study is not the final word, and that is an important message."
The refuted studies dealt with a wide range of drugs and treatments. Hormone pills were once thought to protect menopausal women from heart disease but later were shown to do the opposite, and Vitamin E pills have not been shown to prevent heart attacks, contrary to initial results.
Contradictions also included a study that found nitric oxide does not improve survival in patients with respiratory failure, despite earlier claims. And a study suggested an antibody treatment did not improve survival in certain sepsis patients; a smaller previous study found the opposite.
Ioannidis acknowledged an important but not very reassuring caveat: "There's no proof that the subsequent studies ... were necessarily correct." But he noted that in all 14 cases in which results were contradicted or softened, the subsequent studies were either larger or better designed. Also, none of the contradicted treatments is currently recommended by medical guidelines.
Not by accident, this week's JAMA also includes a study contradicting previous thinking that stomach-lying helped improve breathing in children hospitalized with acute lung injuries. The new study found they did no better than patients lying on their backs.
DeAngelis said she included the study with Ioannidis' report to highlight the issue. She said the media can complicate matters with misleading or exaggerated headlines about studies.
Ioannidis said scientists and editors should avoid "giving selective attention only to the most promising or exciting results" and should make the public more aware of the limitations of science.
"The general public should not panic" about refuted studies, he said. "We all need to start thinking more critically." http://www.cnn.com/
Attention Business Editors:
Protox signs exclusive Lung Cancer licence agreement and initiates Lung Cancer study
VANCOUVER, Aug. 9, 2005 /CNW/ - Protox Therapeutics Inc. announced today that
it has signed an exclusive licence agreement with the National Research
Council Institute for Biological Sciences (NRC-IBS) and the University of
Victoria (UVic) Innovation and Development Corporation (IDC). The licence
grants Protox exclusive worldwide rights to commercialize antibody targeted
PORxin(TM) (formerly known as Aerolysin) for the treatment of non-small cell
lung cancer (NSCLC). The financial terms of the agreement include an upfront
fee as well as milestone and royalty payments. Protox had earlier reported the
exercise of an option agreement on April 5, 2005.
"The licence enables us to develop a proprietary antibody targeted toxin
for non-small cell lung cancer, a disease for which existing therapeutics have
made little significant impact on overall survival. Together with our lead
product for prostate cancer, PORxin(TM) 302 (formerly known as PSA-PAH1), we
are exploiting the PORxin(TM) platform to create products to treat two of the
most common cancer indications", said Dr. Fahar Merchant, President & CEO of
the Company.
"By effectively 'weaponizing' the antibody using our PORxin(TM) platform,
we hope to localize a potent toxin at the tumour site thereby reducing the
side effects normally associated with conventional chemotherapies. Success
with this approach has the potential to open numerous development and
partnering opportunities with antibody companies to selectively target cancers
over-expressing membrane bound tumour specific biomarkers", added
Dr. Merchant.
The Company also announced today that it has initiated a preliminary non-
small cell lung cancer study with PORxin(TM) antibody fusion constructs at the
BC Cancer Agency. As reported earlier, this lung cancer project has received a
financial contribution of up to $340,000 from the National Research Council
(NRC) Industrial Research Assistance Program (IRAP).
ABOUT NON-SMALL CELL LUNG CANCER
In the United States alone more than 173,000 new cases of lung cancer
were diagnosed in 2004 and approximately 164,000 men and women died of this
condition. It has the highest mortality rate of any of the cancers and its
incidence in women is increasing. Of this category approximately 80% of the
patients had non-small cell lung cancer. Current treatments include surgery,
radiation and drug therapy alone or in combination. The median survival of
patients with advanced non-small cell lung cancer treated with the most
commonly used chemotherapeutic regimens is only 7.8 months.
ABOUT THE NRC INSTITUTE FOR BIOLOGICAL SCIENCES
The NRC Institute for Biological Sciences in Ottawa is a team of leading
life sciences researchers who are committed to making breakthrough discoveries
in immunochemistry and neurobiology and moving subsequent technologies into
the marketplace. Within the NRC, the Antibody Engineering group's goals are
the design and development of novel antibodies for use as diagnostic and
therapeutic agents.
ABOUT IDC
The Innovation and Development Corporation (IDC) at the University of
Victoria - one of Canada's leading research universities - was critical in
facilitating the transfer of the PORxin(TM) technology and it is a shareholder
in Protox. IDC's mandate is to move research and innovations into both the
public and private sector, through partnerships, licensing of technologies,
and the formation of new spin-off companies. Since 1992, IDC has helped found
37 new companies, based on UVic research or UVic student entrepreneurial
initiatives. In addition to Protox, these include BC businesses producing
vaccine and diagnostic solutions for aquaculture, secure electronic forms,
environmentally safe herbicides, laboratory information management systems,
and technology to design disease resistant plants and crops.
ABOUT BC CANCER AGENCY
The BC Cancer Agency, an agency of the Provincial Health Services
Authority, is committed to reducing the incidence of cancer, reducing the
mortality from cancer, and improving the quality of life of those living with
cancer. It provides a comprehensive cancer control program for the people of
British Columbia by working with community partners to deliver a range of
oncology services, including prevention, early detection, diagnosis and
treatment, research, education, supportive care, rehabilitation and palliative
care. The BC Cancer Research Centre conducts research into the causes and
cures for cancer.
ABOUT PROTOX:
Protox Therapeutics Inc. is developing novel therapeutics for the
treatment of cancer and other indications by engineering the naturally
occurring bacterial toxins such as Aerolysin, which kills cells by forming
pores in them ("PORxin(TM) platform"). The Company believes that its
engineering approach will produce targeted therapeutics that may have greater
efficacy and fewer side effects than existing treatments.
The TSX Venture Exchange has not reviewed and does not accept responsibility for the adequacy or accuracy of the content of this press release. This press release contains certain forward-looking statements respecting the Company's business, capital, research and development, and potential future products, which statements can be identified by the use of forward looking terminology, such as "expect", "to generate", "moving forward", "intends", "committed to", "moving", "developing", "believe" or the negative thereof or any other variations thereon or, or that events or conditions "will,", "can", "to", "may," "could" or "should" occur, or comparable terminology referring to future events or results. The Company's actual results could differ materially from those anticipated in these forward-looking statements as a result of numerous factors, including, without limitation, the need for extensive additional research and development, which is costly and time-consuming and may not produce anticipated or useful results; scientific research and development risks; the risk of technical obsolescence; intellectual property risks; manufacturing and marketing risks; partnership/strategic alliance risks; the effect of competition; the need for regulatory approvals, including without limitation, FDA approvals, which is not assured; product liability and insurance risks; the need for future human clinical trials, the occurrence and success of which is not assured; changes in business strategy or development plans; and the need for additional capital, which may not be obtained; and the fact that the Company may not produce any products or if it does, that such products may not be commercially successful; any of which could cause actual results to vary materially from current results or the Company's anticipated future results. See the Company's prospectus and other documents filed with the TSX Venture Exchange and the Canadian Securities Administrators at www.sedar.com from time to time for a further discussion of these and other important risks and uncertainties that could cause actual results to differ materially from results referred to in forward-looking statements. The Company assumes no obligation to update the information contained in this press release.
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