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.
David Barboza contributed reporting.
Article source: http://www.nytimes.com/2013/07/23/business/global/drug-research-in-china-falls-under-a-cloud.html?partner=rss&emc=rss