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发帖数: 2761 | 1 中文版：内部审计暴露英国药商在华研发中心不当操作
http://cn.nytimes.com/business/20130723/c23drug/
http://www.nytimes.com/2013/07/23/business/global/drug-research
Executives at the British drug maker GlaxoSmithKline were warned nearly two
years ago about critical problems with the way the company conducted
research at its drug development center in China, exposing it to potential
financial risk and regulatory action, an internal audit found.
The confidential document from November 2011, obtained by The New York Times
, suggests that Glaxo’s problems may go beyond the sales practices that are
currently at the center of a bribery and corruption scandal in China. They
may extend to its Shanghai research and development center, which develops
neurology drugs for Glaxo.
The failings, some experts said, underscore the problems that can arise when
major drug companies export their scientific development to emerging
markets like China.
Since 2006, 13 of the top 20 global drug makers have set up research and
development centers in China, according to a report by McKinsey & Company.
“It’s cheaper to do research there,” said Eric G. Campbell, a professor
of health care policy at Harvard Medical School. However, “I have
absolutely no doubt that with cheaper research comes greater risk.”
Auditors found that researchers did not report the results of animal studies
in a drug that was already being tested in humans, a breach that one
medical ethicist described as a “mortal sin” in the world of drug research
. They also concluded that workers at the research center did not properly
monitor clinical trials and paid hospitals in ways that could be seen as
bribery.
Last year, Glaxo said, a more favorable audit found the concerns had been
addressed. But several outside experts said the problems outlined in the
initial audit were grave and painted a picture of an organization that
failed to keep tabs on a crucial research center as it expanded both in size
and scope. And it indicates that the problems there were more extensive
than were reported in June, when the company fired the head of research and
development in China after discovering that an article he helped write in
the journal Nature Medicine contained misrepresented data.
In a statement, Glaxo said it was committed to conducting “robust” audits
of its business practices, and in this instance, “the process worked
exactly as intended.” It added, “Patient safety is paramount and the audit
reports do not show that this was compromised.”
Glaxo’s research and development center opened in 2007 with lofty ambitions
not only to help the company’s drugs get approved in China, but also to
serve as one of its primary research hubs. The center grew quickly,
expanding from one employee in 2007 to 460 in 2011, according to the audit.
But as it grew, supervisors did not always ensure that the work done there
was of high quality, auditors found.
One of the most troubling lapses — a problem the report labeled “critical
” — involved a drug known as ozanezumab, which was being developed to
treat patients with multiple sclerosis and Lou Gehrig’s disease.
The report revealed that the drug’s project leader belatedly learned the
results of three studies of ozanezumab in mice. During their investigation,
auditors came across six studies whose results had not been reported, even
though early trials in humans were already under way.
Reporting such information is crucial, ethicists said, because animal
studies can identify safety risks and are among the main factors drug
companies use to decide whether to pursue human trials.
“If that’s true, it’s a mortal sin in research requirements,” said
Arthur L. Caplan, the head of the division of medical ethics at NYU Langone
Medical Center. He served as the chairman of an advisory committee on
bioethics at Glaxo from 2005 to 2008. “No one could approve human trials
without having that information available, scientifically or ethically. That
’s kind of a Rock-of-Gibraltar-sized ethics violation.”
The auditors said the results did not affect patient safety, but warned of
the high stakes involved, saying participants could be exposed “to
unnecessary risk or no benefit to the disease state.”
Glaxo said that “when the full range of data from all the studies was
reviewed, GSK determined that the efficacy would not be strong enough to
continue,” and it terminated a trial of ozanezumab in multiple sclerosis
patients. It is still studying the drug in people with Lou Gehrig’s disease
, or amyotrophic lateral sclerosis, according to the company.
In the follow-up audit, auditors said senior managers at the Chinese
research unit had “embedded a compliance culture that was not evident
during the prior audit,” and did not find any issues of concern, according
to an executive summary of the report that was provided by Glaxo.
Outside ethics experts said the report raised questions about whether
patient safety was adequately protected.
Auditors found that Glaxo employees failed to record whether research
participants had signed new consent forms during the course of clinical
trials. They also did not document whether participants were taking the
planned dosage of drugs, or whether they followed up when they learned that
participants were not following a clinical trial’s protocol.
In the statement, Glaxo said that employees were properly monitoring trials
but acknowledged that they were not adequately documenting their work. The
company said it had corrected the problem, and the later audit found that
practices had improved.
The 2011 audit report also raised alarms about the way the Shanghai office
was paying the people who were overseeing the company’s trials at outside
hospitals or clinics. According to auditors, Glaxo was paying many sites a
flat fee for the cost of a full-time coordinator, regardless of the number
of participants enrolled in the trial.
The report warned of “reputational, financial and/or regulatory action risk
where payments made to investigators regardless of actual work completed
are perceived as bribery or corruption.”
Chinese investigators have said that Glaxo participated in a widespread
bribery and corruption scheme in which the company used travel agencies to
funnel illegal payments to doctors and government officials to bolster drug
sales, and authorities have said they are also looking into the practices of
other pharmaceutical companies.
On Monday, Glaxo said that some of its executives might have broken the law.
Outside experts said the payment of doctors and other hospital employees
where trials were being conducted was tricky, because paying a fee based on
the number of people enrolled in a study could also be seen as inappropriate
.
“I’m much more concerned about people who are paid by the head to recruit,
” said Dr. Campbell. Still, he said, if large payments were being made for
little work, that could raise eyebrows. “It could be seen as simply another
way to put money in people’s hands,” he said.
Glaxo said it had since tightened the payment procedures for clinical
research coordinators. Referring to the current bribery investigation, the
company said, “we have zero tolerance for any kind of corrupt behavior
among our employees, suppliers and business partners and will take action
wherever and whenever we find it.”
In all, company officials said that appropriate steps were taken to address
the issues outlined in the audit. And in 2011, auditors noted that leaders
at the research center had recently tried to address the “significant
issues” there.
Dr. Jerry Avorn, a professor at Harvard Medical School, and others gave
credit to Glaxo for investigating one of its own research centers.
“It is good that they detected these problems and vowed to fix them,” Dr.
Avorn said, “but this report shows what can happen when a drug company
rapidly expands its clinical research programs overseas without adequate
quality controls.”
David Barboza contributed reporting. |
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