Grieving father spends $1 million nest egg to investigate Accutane

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http://www.usatoday.com/money/industries/health/drugs/2005-01-26-accutane-usat_x.htm

Grieving father spends $1 million nest egg to investigate Accutane
By Kevin McCoy, USA TODAY
Liam Grant says he's sure his son's Acne medication caused the Irish university student to commit suicide.

Liam Grant is '100%" convinced that Accutance led to his son's suicide death.
By Julien Behal, Getty Images, for USA TODAY

So sure he's spent roughly $1 million of his retirement nest egg on scientific research examining the effects of Accutane, the Acne drug manufactured by Roche.

So sure that he helped organize a Web site aimed at restricting use of the drug and investigating what the manufacturer knows about its safety.

And so sure that he rejected a settlement offer from Roche and several co-defendants that could total at least hundreds of thousands of dollars.

Early next month, Grant is scheduled to square off with a division of the Swiss-based pharmaceutical giant for a hearing in a Dublin court. If he prevails at the proceeding, which comes as a U.S. congressman seeks a Washington hearing on Accutane's safety, Grant could move closer to obtaining internal company records about the drug. That, in turn, could provide legal ammunition for plaintiffs in roughly 70 pending Accutane cases in the United States, where there have been few settlements involving suicide or depression.

The 57-year-old forensic accountant says he's optimistic about the David vs. Goliath confrontation. "How do you bring an elephant to the ground? Small bites," said Grant during one in a series of recent telephone interviews. "That's what I'm doing. Small bites."

In response, the company said: "Roche feels a great deal of sympathy for Liam Grant regarding the loss of his son, but according to a significant body of scientific evidence, there is no cause-and-effect relationship between Accutane and psychiatric events."

Accutane, introduced in the USA in 1982 to treat severe Acne that fails to respond to other drugs, is safe when prescribed and used appropriately, Roche says. Many dermatologists and acne patients also say it's more effective than other drugs.


By Tannen Maury, Bloomberg News
A 'significant body of scientific evidence' shows Accutane is safe, Roche says.


However, the drug has been linked to birth defects among children of pregnant women who have taken it. A Food and Drug Administration researcher told a Senate committee in November that Accutane was one of five drugs that should be studied for potential withdrawal from the market. Moreover, since the late 1990s Accutane's label has warned that adverse reactions reported by some users include "depression, psychosis, and, rarely, suicidal ideation, suicide attempts and suicide."

But regulators in the USA and Europe hadn't yet required that warning when Grant's 19-year-old son, also named Liam, went to his family doctor in November 1996 for acne treatment.

The younger Grant, one of four siblings, was an engineering student at University College Dublin. His father says Liam played guitar and drums in bands and hoped to launch a career recording music.

Medical records show that Liam did not suffer from the severe, treatment-resistant acne for which Accutane is prescribed. Dr. Pamela Mangal prescribed an antibiotic, then wrote a stronger prescription in December when Liam was unhappy with the results. One month later, she referred him to Dr. Gillian Murphy, a dermatologist, who prescribed Roaccutane, the drug's market name in Ireland. Liam started taking it in February 1997.

His father says he should have noticed the potential warning signs that ensued. Liam, previously outgoing and enthusiastic about his plans, increasingly spent time alone in his bedroom. When friends called, he asked one of his brothers to tell them he was unavailable.

Jury investigates

In June 1997, Liam was found dead, hanging from a tree outside Dublin. A jury, impaneled to investigate the case, ruled the death a suicide and called for more research on Accutane and its side effects.

Grant, backed by his wife, Loyola, and three surviving children, took on the mission.

First, he hired a local scientific researcher to check the drug's history. She discovered that France had added a suicide warning to Accutane's warning label in 1997, during the time Liam had taken the drug.

Grant said he wrote to dermatology associations asking them to conduct research on the possible brain effects of Accutane or urge Roche to undertake such studies. Receiving no response, he decided on an unusual scientific research program: He'd fund some study costs himself by selling two real estate properties he'd bought as part of his retirement portfolio.

He sought out scientific experts at universities in the USA, with the aim of prompting unprecedented research about Accutane. In Massachusetts, he made contact with the University of Massachusetts Medical School and the Eunice Kennedy Shriver Center. In Atlanta, he contacted Emory University.

Although rare, the move isn't unprecedented. Cure Autism Now is a group founded by families to raise funds and seek research that would help relatives suffering from the mysterious disorder. Similarly, Texas billionaire H. Ross Perot paid for research on illnesses afflicting U.S. soldiers who served in the 1991 Persian Gulf War.

So far, Grant funded two studies aimed at securing government grants for additional Accutane research. Results from one, published last April in the Proceedings of the National Academy of Sciences, showed that the active component of Accutane reduced cell creation in the brains of mice that had received clinical doses. In turn, that outcome appeared to impair the mice's ability to learn a maze task.

Could the medication have a similar effect on the human brain? "We can suggest it is a possibility, but we can't say that's the case absolutely," said Peter McCaffery, a University of Massachusetts Medical School researcher who worked on the project.

The second study is undergoing scientific peer review, a vetting process designed to spot any weaknesses or mistakes, in preparation for March publication in the American Journal of Psychiatry. Twenty-eight acne sufferers underwent initial brain scans, along with psychological tests that ruled out any connection between their acne and whether they felt depressed.

Key dates in Accutane's history

1971: Roche develops Roaccutane, called Accutane in the USA.
1982: Food and Drug Administration approves Accutane to treat severe acne that is unresponsive to other treatments.
1986: Roche changes Accutane's package insert to say some users had reported Depression symptoms.
1988: Public Citizen petitions the FDA for a ban on Accutane.
1997: French regulators require Roche to list suicide as a potential side effect. A Roche doctor studies data on Depression in Accutane patients, leading him to recommend users be supervised for signs of Depression and, if necessary, referred for treatment.
February 1998: FDA says Accutane's packaging will include a warning that some users have reported adverse reactions including depression, psychosis and "rarely, suicidal ideation, suicide attempts and suicide."
March 1998: Health regulators in Britain and Ireland require warnings of Accutane's risk of psychiatric disorders.
December 1999: Roche prepares a "Psychiatric Disorder Issue Work-Up" for the FDA, concluding that none of the 168 reports of suicidal behavior can be directly linked to Accutane.
May 2000: Roche changes Accutane's package warning label to include possible side effects involving depression, rare suicidal thoughts, suicide attempts and suicide.
September 2000: During an FDA dermatology committee meeting, the agency confirms that Accutane patients were linked to 147 suicides and hospitalizations for depression from 1982 to May 2000 and says more research is needed to assess the drug's risks of birth defects.
October 2000: The Archives of Dermatology publishes Roche-funded research that studied 20,895 acne sufferers who took either Accutane or Antibiotics . The study found no link between Accutane and increased risk of depression, suicide or other psychiatric disorders.
June 20, 2002: Accutane's label is changed to warn of "depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors."
September 2003: The Journal of the American Academy of Dermatology publishes a Roche-funded study that found no significant increase in prescriptions for antidepressants among patients already taking Accutane.
Nov. 18, 2004: FDA scientist David Graham tells Senate panel that the drug should be studied for possible withdrawal.
Nov. 23: FDA announces registry of prescribers, patients and pharmacies for Accutane, requires women test negative for pregnancy before getting prescription.

Sources: FDA, Roche, USA TODAY research






For four months, the patients received either Accutane or an antibiotic. New scans conducted on the group afterward showed the Accutane patients had decreased activity in an area of the brain thought to be involved with regulating mood.

"What we can say is that Accutane affects brain function ... and the areas that are affected are the areas involved with depression," said Dr. J. Douglas Bremner, who led the research project at Emory University Hospital in Atlanta.

Grant concedes that some might argue that his personal stake could raise doubts about the integrity of the research. He said he tried to guard against that by channeling the funding through the respective universities involved and required that the study results be published, "no matter what the outcome."

"If you're a scientific researcher, you have a responsibility to do the best work you can while being objective," said Bremner. "In our case, the study showed a change in brain function. That's not something that's an interpretation one way or the other."

Roche responds

Roche, however, questioned the studies and Grant's advocacy role in funding them.

Commenting on McCaffery's research with mice, the company said: "It is widely recognized that animal studies are not predictive of human behavior as it relates to depression and suicide."

Roche said there is no scientific unanimity that the area of the human brain studied by Bremner definitely mediates depression. The company also noted that Bremner's tests showed no differences in severity of depression symptoms among the patients who received Accutane or an antibiotic.

While noting that it's common for pharmaceutical companies to fund drug research, Roche said, "It is quite another matter, in our view, for a plaintiff in a lawsuit to fund a study to support his allegations where there are no published studies that even suggest a cause-and-effect relationship between Accutane and psychiatric events."

Roche also cited three other scientific studies that showed Accutane was not associated with increased risk for depression, other psychiatric disorders or suicide. The studies, funded by Roche, include one that found similar risk rates among more than 7,500 acne patients who took Accutane and nearly 14,000 who took Antibiotics .

Grant has cited the differing results of the studies he funded — along with other scientific and legal information about Accutane — on a Web site (www.accutaneaction.com) that features contributions by individuals and families who say they have suffered serious medical side effects from the drug. Their goal, stated on the Web site, is to prompt a coordinated international investigation of Accutane.

"I don't let this take over my life," said Grant, who explains that he pursues his mission with the investigative approach he uses in his accounting work. He even stopped reading letters from families whose loved ones allegedly died or suffered other serious Accutane-related side effects, "because it got to be too much emotionally."

While preparing for next month's court hearing, however, he has kept in touch with others fighting Accutane battles. One is Rep. Bart Stupak, D-Mich., who is seeking a new congressional hearing on the drug he blames for his own son's suicide. Grant has also spoken with U.S. lawyers interested in any Irish court decision that could support their own Accutane cases.

In a Sept. 7 letter, a Dublin law firm representing Roche and other defendants said the group, though sympathetic about the death of Grant's son, bore no "responsibility for his death." But, even while predicting that position would ultimately be vindicated in court, the letter offered a settlement.

Under the deal, the defendants, including Roche, would pay the maximum damages Grant would be entitled to under Irish law, plus related legal costs. However, the letter stated the settlement would come "strictly without any admission of liability." Responding to questions from USA TODAY, Roche said, "It made financial sense to offer to settle rather than incur the costs of a protracted legal battle" because Ireland has a statutory limit on awards in such cases.

Grant estimated any settlement could total nearly $1.5 million, including the research costs — which Roche says it does not intend to pay. But he rejected a deal, even knowing that defense attorneys would likely seek a court-ordered end to the case on grounds he had turned down everything he might ultimately win in court. "That's wrong," says Grant. "Because what I can get from a court is a ruling that Accutane caused the death of my son and that Roche knew that the drug was a serious risk."

Even if the hearing goes his way, Grant faces at least a year of additional legal procedures before a trial that could produce the verdict he's seeking. He says he's determined to fight on, based on "a conviction that I'm 100% correct."

"The death of one person from this drug is too many," Grant said. "Somebody had to say stop. And that person happened to be me."

http://www.usatoday.com/money/industries/health/drugs/2005-01-26-accutane-usa...

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