University misled about drug University misled on attention deficit disorder drug

THE ethics committee of an Australian university gave the green light to a study involving a trial of a new ADHD drug after being wrongly told by a researcher that the US Federal Drug Administration had dropped a "black box" warning that the drug brought an increased risk of suicidal thoughts.

It has also emerged that Curtin University failed to disclose to the parents of the children in the study the full extent of involvement in the study by Eli Lilly Australia, the multinational company that markets the drug Strattera.

Concerns surrounding the conduct of the trial have emerged following a 15-month battle with the West Australian university and Eli Lilly to have details of the study released under Freedom of Information laws.

The trial, which has just concluded, compared the effects of the commonly prescribed ADHD stimulant drugs Dexamphetamine, Ritalin and Concerta with the new non-stimulant medication Strattera, on the educational and social outcomes for children aged between eight and 15 years who had been diagnosed with the condition.

The documents, the release of which Curtin fought hard to prevent, reveal that its ethics committee, which approved the research, was given incorrect Continued Page 8

From Page 1 information regarding the potential suicide risks associated with Strattera.

Curtin was ordered to hand over the documents to Western Australian Labor MLA Martin Whitely, a vocal ADHD medication critic, by the state ’s Acting Information Commissioner John Lightowlers.

"It ’s taken 15 months to get information that shows the university ’s Ethics Committee were given completely wrong information about the suicide warnings attached to this drug," Martin Whitely told The Weekend Australian.

According to the documents, Associate Professor Heather Jenkins, the university researcher who led the trial, told Curtin ’s Ethics Committee in June 2006 that the US Food and Drug Administration had revoked a black box warning about the increased risk of suicidal thoughts associated with the drug, citing an article to back up her claim which had appeared in the US medical journal Pediatric News.

"Since the study has been approved, there has been some publications related to the rare occurrence of suicidal ideation in some patients who were taking Strattera," Professor Jenkins told the ethics committee. "This initially led to a black box warning from the FDA, which was subsequently revoked following further investigations." This was wrong. The FDA black box warning the strongest it issues had been in place for eight months at the time Professor Jenkins advised the committee it had been lifted and the Pediatric News article she cited said so.

Further, Associate Professor Jenkins appears to have cited the incorrect publication she used to support her incorrect claim to the Ethics Committee that the FDA had revoked the Strattera warning. According to a summary document provided by Curtin University which details Professor Jenkins argument, she said it had appeared in the Harvard Mental Health Letter in April, 2006. No such article appeared in that issue but an article by the same name and by the same author does appear in the April 2006 edition of Pediatric News.

Australia ’s own drug regulator, the Therapeutic Goods Administration, had also placed its strongest possible warning on Strattera regarding the suicide risk two months prior to the university considering Professor Jenkins ’s application.

A separate document provided by the university to parents of children being considered for the study lists serious adverse events associated with the drug including liver damage, cardiovascular disorders and gastrointestinal problems. However, no mention is made of the increased suicide risk associated with the drug.

In 2006 Curtin was deliberating on whether to renew Professor Jenkin ’s drug trial application. They project had stalled because its research partner, Sydney ’s Childrens Hospital Education Research Institute (CHERI) at Westmead, had withdrawn from the project.

According to the documents, the head of CHERI advised Professor Jenkins that the Childrens Hospital Westmeads ethics committee had "too many objections to put in writing." The hospital refused to answer questions from The Weekend Australian about the nature of those objections.

Professor Jenkins did not respond to questions from The Weekend Australian but Curtin University has vigorously defended the conduct of the drug trial. In a statement its Acting Vice-Chancellor Professor Linda Kristjanson said Curtin ’s Human Research Ethics Committee was "fully informed and was not misled on any aspect of the study." "Before approving the study, the University ’s Human Research Ethics Committee conducted a rigorous independent review that complied scrupulously with the National Statement on Ethical Conduct in Research Involving Humans as prescribed by the National Health and Medical Research Council," Professor Kristjanson said.

She said information was given to parents by the pediatrician who diagnosed their children and prescribed the medication.

The extent of Ely Lilly ’s involvement in the trial of its own drug is also revealed despite Professor Jenkins claim in a statement to parents of children in the study that: "Eli Lilly has signed an agreement with Curtin University of technology that confirms that the university investigators are completely independent of their company. This means that Eli Lilly Australia has not influenced the design of the study." The documents show that a drug company employee was paid to work on the study as an investigator who would "contribute to the overall conduct of the study through advice on design and implementation." In an email from Ely Lilly ’s Director of Corporate Affairs and Health Economics to Professor Jenkins in 2002 during the set up phase of the project, he wrote: "We [Eli Lilly] would like the opportunity for our Clinical Research Physician, to look at the proposed protocol in more depth. We have some initial thoughts regarding a couple of additional instruments that may he worth including.." Eli Lilly contributed $145,000 in cash and inkind support to the trial. The trial also received a $500,000 grant from the Australian Research Council.

Parents of children who participated were told that Ely Lilly had supplied the medication free, that the company had made a financial contribution and that its medical staff would be available to the researchers and doctors for information purposes.

Eli Lilly Australia, which also fought the release of the documents said: "Lilly Australia feels that these documents, relating to the study, contained confidential information and their release is not necessarily in the public interest." Its spokeswoman said the company had early in the study provided "technical advice" on outcome measures on "as needed basis" but was dissociated from the study as a "Partner Investigator" in September 2004 and continued as an "Industry Partner Organisation" after that time.

Julie-anne Davies
Weekend Australian