FDA Approval process under fire–PML: Lethal side-effect–Tysabri: Multiple Sclerosis Drug

Biogen and Elan, the manufacturers of the drug, Tysabri, refused to release her medical records and imaging scans.  Inferno News reports: “Since the MRIs and any supporting records could establish the fact that Anita Smith never had MS, they may very well expose Biogen and Elan to a significant possibility of being found liable for her conscious pain and suffering and untimely death.” 

On March 1, 2005, The New York Times published an article in which a leading expert  on Tysabri, who participated in its original development in animal tests, stated that no one should have been surprised that patients being treated with Tysabri would contract PML (progressive multifocal leukoencephalopathy), a rare, but lethal brain infection.

As far back as 1992, based on animal studies and other in vitro experiments, scientists who developed Tysabri had concluded that it was far too dangerous to use in humans. By suppressing the immune system, Tysabri allows the JC virus, ordinarily latent in a patient’s kidney, to travel to the brain via the bloodstream, where it begins uncontrolled replication.

Based on all of the available data, many experts believe the manufacturers (Biogen and Elan) should have conducted long-term studies before ever testing Tysabri on human subjects. News Inferno reports: “It is alleged that at no time did either company disclose to the participants in the clinical trials of Tysabri that literature in professional journals questioned the use and/or safety of the drug in humans.”

Respected scientists and other experts, who had warned of such potential consequences associated with the powerful immunosuppressant, were not surprised. The complaint filed is extensive–64-pages with 14 separate causes of action reveals number of interesting facts and allegations:

An article in The Lancet discusses the pitfalls of current clinical trial selection criteria in which relatively healthy (asymptomatic) patients who are not disabled by a chronic degenerative disease like multiple sclerosis—are enrolled as test subjects of drugs that often are found to be highly toxic.
 “Lawrence Steinman, a professor of neurology and head of immunology at Stanford, said the F.D.A. should not have approved the drug on the basis of only one year’s data. He said the risk of serious infections like P.M.L. was ‘unfortunately logical’ given that Tysabri works by interfering with the immune system.”

There is disagreement about whether the drug should have ever have been approved. Within 3 months Tysabri was withdrawn from market. But there is a concerted effort to bring it back.

Meanwhile, Biogen’s unconscionable concealment of the data, outraged a Massachusetts judge who issued a Court order requiring the company to release the medical records: “Anita Smith was a human being and not a laboratory animal that belonged to Biogen. Thus, her records cannot be withheld at the company’s direction. To have argued otherwise was unconscionable.”
 
Jerold Parker, attorney for Anita Parker’s estate, assessment, unfortunately is not isolated—it describes the culture within the pharmaceutical industry: “It is simply amazing to watch Biogen and Elan insist on placing profits above safety. Clearly, they will do anything possible to recover their investment and turn a profit on this questionable drug.”

That immoral culture has infected academia and the highest ranking government oversight agency staff.  FDA policies have contributed in a major way to the erosion of concern for public safety.  The FDA, therefore, cannot be looked upon for a solution. 

Below: reports in Forbes and Business Wire about the points raised by The Lancet article and an in-depth overview of Anita Parker’s case and the evidence cited in the complaint filed with the court,

Contact: Vera Hassner Sharav
veracare@ahrp.org

http://home.businesswire.com/portal/site/google/index.jsp?ndmViewId=news_view&newsId=20060302005234&newsLang=en

Stanford Doctors Spotlight Fatal Flaw in Multiple Sclerosis Drug Trial

Business Wire March 2, 2006

When Anita Louise Smith enrolled in an experimental drug trial in 2002 in Colorado, she had a diagnosis of multiple sclerosis but no symptoms and was looking to reduce the chances of being ravaged by the disease. Last year, she died at the age of 46 from an infection linked to the drug.

This tragedy — recounted in an article in the March 4 issue of The Lancet by two Stanford University School of Medicine neurologists — serves as a telling case study of what can go wrong in clinical trials. In their article, Annette Langer-Gould, MD, and Lawrence Steinman, MD, warn of the pitfalls of testing a drug with unknown side effects in patients who would do fine without the drug.

The drug in question is natalizumab, which has the brand name of Tysabri. In November 2004, the U.S. Food and Drug Administration fast-tracked its approval for use in multiple sclerosis patients following promising results seen early in two clinical trials. But within months of the approval, some patients taking the drug had developed a rare infection — progressive multifocal leukoencephalopathy, or PML — and Smith and one other patient had died.

Langer-Gould, a clinical instructor in neurology, treated a patient who was part of the clinical trial and developed PML after taking Tysabri; the patient survived. But that experience, coupled with an examination of Smith’s case, prompted Langer-Gould to approach Steinman about writing an article that would examine the appropriateness of testing a drug on people with no evidence of the disease and who are not disabled at the time of the trial.

"We are arguing that people with no disability should probably not enter into a clinical trial or be recruited into clinical trials, because where is the potential benefit to them if nothing is wrong?" said Steinman, professor of neurology and neurological sciences and of pediatrics.
"This situation represents a systemic problem," said Langer-Gould. "It is not just one company being a rogue, doing something out in left field."

Langer-Gould and Steinman argue that if a drug has a known risk of death, it should only be used on patients who are likely to suffer severe disability from the targeted disease — and for whom there are no other options. In other words, those who have tried all the other available therapies. That is almost the reverse of what happened in the Tysabri trial, which excluded the most severely affected patients.

"A big mistake was made in these trials that, in my opinion, is easily preventable," said Langer-Gould. "All they need to do is tighten up entry criteria into multiple sclerosis clinical trials and we could avoid similar types of problems in other trials."
Multiple sclerosis results when the immune system attacks the protective myelin sheath surrounding nerve cells, causing them to misfire and leading to loss of motor control and possibly paralysis. Tysabri appeared to block this effect and, after the first year of the two-year clinical trials, did not appear to cause more infections.

Steinman was involved early on in the development of the drug, publishing on its effects in 1992. Even then, he had suspicions that the drug’s mechanism of action — blocking the entry of immune cells into the nervous system — might also make patients more vulnerable to infections. Indeed, PML is an infection that usually affects people whose immune systems are compromised.
"It was a shocking development that a drug that had so much promise and so many potential benefits ended up causing two deaths and one very serious injury," said Steinman. "It is kind of a cruel Greek drama, something that may be more beneficial than anything yet developed for multiple sclerosis, but yet may be far more dangerous than those other approved drugs."

The FDA withdrew Tysabri only three months after its approval. The FDA is now considering re-approving the drug. On March 7 and 8, an FDA advisory panel is meeting about the possibility of bringing back Tysabri as a single therapy (in the trials, it was combined with another drug).
"I predict it will come back with really hellacious warnings," said Steinman. "I think the right course would be to have it undergo more testing, but I don’t think that is practical or fair to patients; they ought to have the opportunity to decide with their physicians if they are willing to take the one in a thousand risk of dying."

But Steinman and Langer-Gould expressed reservations about the drug returning to the market. They noted that its effects, while impressive, are in general not much better than what is seen with other available drugs: The risk of relapse dropped from an average of two relapses every three years using other approved multiple sclerosis drugs to one every three years with Tysabri.
"Do you want to expose someone to the risk of death for eliminating one relapse every three years?" said Steinman. "I say no."
"I’m not sure if it is wise to re-approve it," added Langer-Gould. "The question is, will the FDA rise to the occasion and admit their mistake and try to prevent future mistakes or are they going to ignore it?"

Stanford University Medical Center integrates research, medical education and patient care at its three institutions — Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children’s Hospital at Stanford. For more information, please visit the Web site of the medical center’s Office of Communication & Public Affairs at http://mednews.stanford.edu.
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http://www.forbes.com/lifestyle/health/feeds/hscout/2006/03/03/hscout531359.html
FORBES
Controversial MS Drug Trial Flawed, Experts Say

FRIDAY, March 3 (HealthDay News) — Two experts are questioning whether a woman who died of a rare infection after participating in a trial for the multiple sclerosis (MS) drug Tysabri should have been included in the study in the first place.

The patient was suspected of having MS but showed no symptoms, and was later found not to have had MS. Now, a commentary in the March 4 issue of The Lancet paints a cautionary tale of what went wrong, and asks whether the woman should have received Tysabri at all, when other safe and effective agents were at hand.
The piece, penned by Stanford University neurologists Dr. Annette Langer-Gould and Dr. Lawrence Steinman, adds fuel to the debate over Tysabri (natalizumab), which has been linked to three cases of a rare, dangerous infection called progressive multifocal leukoencephalopathy (PML). Two of those cases proved fatal.

Researchers quickly halted the trial last February after the PML cases emerged. At the same time, Biogen Idec and Elan Corp., the drug’s makers, heeded a U.S. Food and Drug Administration advisory and withdrew Tysabri from the market, just three months after its fast-track approval for cases of especially tough-to-treat MS.
However, research published this week in the New England Journal of Medicine found the drug to be safe and effective, at least for the short term. And after a yearlong investigation, an FDA advisory committee recently announced that it will meet Tuesday and Wednesday to consider the company’s request to return the drug to the market.

In the Lancet commentary, Steinman and Langer-Gould criticize how the original trial was conducted.
"When you test a drug that is potentially dangerous and, in this case, carries a risk of one per 1,000 of fatality or serious injury, one ought to be careful that the subjects in the study have a fair risk-benefit balance," explained Steinman, a professor of neurobiology and neurological sciences who helped develop Tysabri.
In fact, the woman who died, Anita Louise Smith, had been diagnosed with MS, even though she had no symptoms. In the end, it was determined that Smith did not have MS. "But that can happen," Steinman said. "MS is a notoriously difficult disease to diagnose."

However, whether or not an asymptomatic patient such as Smith should have been included in the trial to begin with points to the crux of the problem, according to Steinman.
"One needs to reexamine the justifications for putting someone on an experimental MS drug when they have no disability," he said, adding that the criteria for including patients in such a trial needs to be re-evaluated.
Steinman does believe the FDA should let Tysabri go back on sale. "If I were the FDA commissioner, I would let it back — with warnings about the risk," he said. "I would leave it up to physicians and their patients to make the decision."

However, Steinman believes the drug will — and should — be used mainly for patients who are not doing well, and not for patients in the early phases of MS.
"It’s hard to justify looking a person in the eye and saying that ‘You have all these approved drugs that are safe — or [you have] this drug, which might be more effective. However, it carries a chance that you can die from it or have a really serious neurologic injury,’" he said.
Langer-Gould, who treated the MS patient who survived PML, believes the risk of developing the infection while receiving Tysabri is greater than reported. But, she explained, "all you need to have is three more cases, and the estimate becomes one in 500."
In addition, Langer-Gould doesn’t think Tysabri is significantly more effective than other, safer MS drugs. "This drug does nothing more than [add] a 4 percent reduction in disability, which is nothing," she said.

However, Langer-Gould said she, too, would like to see Tysabri back on the market. "I’d like to have this drug as an option for patients who are sicker," she said. "But I’d have to tell them that I have no data to support the use of the drug, because most of the patients at risk for disability were excluded from the trial."
"We have so little for these patients," she noted. If nothing else is working, Tysabri might be worth a try, she reasoned: "At that point in their disease, there is nothing to lose."

Langer-Gould is concerned, however, that if Tysabri returns to pharmacy shelves, there is a high risk of it being wrongly prescribed. "There are still many clinicians out there saying that they are going to use it as first-line treatment," she said. "They have a misunderstanding of both the efficacy and the safety of the drug."
"Physicians have to be willing and ready to accept the fact that it may kill or permanently disable their patients if they are going to use this drug," Langer-Gould said. "They need to ask themselves if that’s a decision they are going to be willing to live with."
One expert thinks the ongoing Tysabri controversy distracts from other promising work in MS treatment.

"Steinman and Langer-Gould make some interesting points," said Nicholas LaRocca, the director of Health Care Delivery and Policy Research at the National Multiple Sclerosis Society. "Over the years, the whole science of clinical trials in MS has been evolving," LaRocca said. "We are way ahead of where we were 20 years ago. This is not a field that is standing still." He added that there’s always been controversy as to whether or not doctors should actively treat patients who appear to be doing well. "If you talk to a number of neurologists, you will get differing opinions," LaRocca said.

One neurologist who took issue with the Lancet commentary illustrates that point.
"The accusation that this lady was put at risk inappropriately is specious, callous and vicious in its condemnation of standard of practice for clinical neurology research," said Dr. Norm Kachuck, an associate professor of neurology at the University of Southern California Keck School of Medicine. "It is sad and tragic that anyone is injured in medical care, in medical research. With the best of intentions, the most careful physician can do harm with the two-edged swords of our armamentarium."
"There is no reason except the obvious — that research is a search into the unknown, with only roughly estimated risks — that this woman, and all of the other courageous folks who contribute their bodies and souls to medical research, would not have been made a subject in this and other trials which we do to help understand and cure human disease," Kachuck said.

The amount of attention Tysabri has gotten is striking, LaRocca added.
"It sort of obscures the broader picture of MS research, and some of the other exciting things that are happening in MS research," he said. "We hope that we can get back to focusing people’s attention on some of the exciting things that are happening in the MS field."
More information  For more on MS, head to the National Multiple Sclerosis Society.
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http://www.newsinferno.com/archives/890#more-890
LEGAL NEWS
In Major Ruling, Massachusetts Court Orders Biogen to Produce ‘All Medical Records’ of Woman Who Died During Tysabri Clinical Test ‘Immediately’
Date Published: Saturday, February 25th, 2006
By Steven DiJoseph

Anita Smith died from a rare, and often fatal, brain disease while participating in a late-stage clinical trial of the MS medication, Tysabri. As it turned out, a number of other patients being treated with the drug also contracted the same disease.

Although she had been diagnosed with multiple sclerosis, an autopsy revealed that Smith never had MS, thereby making her enrollment in the trial problematic at best. Moreover, the unusually high incidence of the brain disease in Tysabri patients raised a serious question as to the drug’s safety. Although the potentially deadly side-effect caused the hastily approved drug to be pulled from the market on February 28, 2005, after only four months, the effort to have Tysabri re-approved began almost immediately.  Elan Corp. PLC (“Elan”) and Biogen Idec (“Biogen”), the manufacturers, immediately went to work reviewing medical records of patients who had taken the drug in order to find a way to justify seeking re-introduction of the drug from the FDA.

As we previously reported on July 1, 2005, despite the fact that Tysabri had been linked to five cases of a rare and often fatal brain disease, Elan (of Ireland) and Biogen (of Massachusetts) were simply unwilling to give up their quest to bring the drug to market and keep it there. Tysabri, which is designed to suppress the symptoms of multiple sclerosis and Crohn’s disease, has traveled a very rocky road from the beginning. Shortly after its withdrawal from the market, the FDA was informed by Biogen that a fifth person had developed progressive multifocal leukoencephalopathy (PML) after being treated with the drug.
Biogen and Elan, its development partner, had hoped to return the drug to the market despite three previously confirmed cases of PML (with two deaths) as well as a fourth unconfirmed case. Just before the report of the fifth suspected PML case surfaced in mid-June 2005, Biogen was hinting at a strategy for bringing the drug back to the market that included testing all patients for the virus that causes PML and stop treatment with Tysabri in time to allow the patients to recover.

When we interviewed Jerrold S. Parker, a partner in the New York personal injury law firm of Parker & Waichman that represents the estate of Anita Smith, who died from a confirmed case of PML while taking Tysabri, he stated: “It is simply amazing to watch Biogen and Elan insist on placing profits above safety. Clearly, they will do anything possible to recover their investment and turn a profit on this questionable drug. This is a drug that simply refuses to die.”

Shortly after that interview, Parker & Waichman commenced a wrongful death action against Biogen and Elan on behalf of the estate of the 46-year-old wife and mother of two.
In February 2000, Anita Smith was diagnosed with multiple sclerosis (MS). By April 2002, she was enrolled in a clinical trial involving the MS drug, Tysabri along with 1,200 other patients. In November 2004, while Anita Smith’s health was rapidly deteriorating and she was experiencing severe neurological problems, Tysabri gained a coveted “fast-track” approval from the FDA. Anita Smith took her last IV infusion of Tysabri in January 2005. On February 24, 2005 she died of PML. Four days later, Tysabri sales were halted.

Respected scientists and other experts, who had warned of such potential consequences associated with the powerful immunosuppressant, were not surprised. A review of the extensive 64-page (315-paragraph) complaint with 14 separate causes of action reveals number of interesting facts and allegations:
A second MS drug, Avonex, also manufactured by Biogen was used jointly with Tysabri as an MS treatment during clinical trials. Anita Smith’s neurologist was already treating her with Avonex since February 2000. Significantly, Anita Smith’s treating neurologist was paid (as an agent, servant, or employee) by Biogen and Elan as an “Investigator” in their clinical trial of Tysabri.

While taking Tysabri and Avonex in the clinical trial, Anita Smith and others developed opportunistic infections including Progressive Multifocal Leukoencephalopathy (“PML”). PML is a typically fatal brain disease caused by the immunosuppressive effects of Tysabri or the immunosuppressive effects of Tysabri in combination with Avonex.
Smith’s treatment was comprised of 30 IV infusions beginning on April 12, 2002 and ending in January 2005. Tysabri had received fast-track FDA approval in November 2004, the same month Smith began to suffer severe neurological problems. She was hospitalized on February 12, 2005 and diagnosed with PML. Smith died on February 24, 2005.
Tysabri sales were suspended by defendants on February 28, 2005. An autopsy (participated in by defendants) confirmed that Anita Smith died of PML
An explanation of the mechanism of the infection is set forth in detail as follows:

On March 2, 2005, Forbes published an article about PML under the headline, “The Virus That Took Down Tysabri,” which described the virus’s latent virulence as follows:
“The JC virus, discovered in 1971 and named with the initials of the patient in whom it was found, is present in almost everyone but only destroys the brain when something damages the immune system and allows the virus to run rampant.” […]
As far back as 1992, based on animal studies and other in vitro experiments, scientists who developed Tysabri had concluded that it was far too dangerous to use in humans.
By suppressing the immune system, Tysabri allows the JC virus, ordinarily latent in a patient’s kidney, to travel to the brain via the bloodstream, where it begins uncontrolled replication.

Based on all of the available data, many experts believe Biogen and Elan should have conducted long-term studies before ever testing Tysabri on human subjects. It is alleged that at no time did either company disclose to the participants in the clinical trials of Tysabri that literature in professional journals questioned the use and/or safety of the drug in humans.
On March 1, 2005, The New York Times published an article in which a leading expert on Tysabri, who participated in its original development, stated that no one should have been surprised that patients being treated with Tysabri would contract PML. In this regard,the article stated, in relevant part:
“Lawrence Steinman, a professor of neurology and head of immunology at Stanford, said the F.D.A. should not have approved the drug on the basis of only one year’s data. He said the risk of serious infections like P.M.L. was ‘unfortunately logical’ given that Tysabri works by interfering with the immune system.

“I’m shocked that it happened so soon, but I knew it was going to happen sooner or later,” said Professor Steinman, who participated in an early animal study that led to the development of Tysabri. Dr. Steinman is a co-founder and director of Bayhill Therapeutics, a company developing competing drugs for multiple sclerosis.
“Dr. Steinman said he had expressed his apprehensions about the drug in speeches and in an article in the journal Science in July and had been asked by Biogen executives to tone down criticism of the drug.”

On March 9, 2004, the Los Angeles Times published an article providing specifics with respect to the infection rate and adding that FDA officials lacked sufficient information about Tysabri’s long-term effects. That article stated, in relevant part:
“In hundreds of pages of documents that offered the first detailed look at the FDA’s handling of the drug, reviewers noted that Tysabri appeared more effective than existing drugs, reducing relapses in patients by 66%, based on one year’s data. The reviewers said it was “reasonably likely” that the drug would provide long-term benefits.

“Nonetheless, the agency’s drug reviewers acknowledged they were unsure about Tysabri’s long-term effects.
“‘The clinical meaningfulness of a decrease in the incidence of relapses at one year is uncertain,’ the reviewers wrote.
“FDA reviewers found that Tysabri had an acceptable safety profile, though they noted that health risks ‘beyond one year are not known.’
“Infections, including urinary and respiratory, were seen with Tysabri, but they were ‘generally routine and did not have a complicated course,’ the reviewers said.
“Stanford University professor Dr. Lawrence Steinman, an MS specialist, had warned there was a clear risk of infection for patients taking such drugs, because they tend to suppress the body’s immune system.

“Steinman had helped discover the active agents in the drug, but later became concerned about potential side effects, and is working on a competing drug. He noted that the infection rate of Tysabri patients in one trial was 2.1%, compared with 1.3% in the placebo group.
“‘There were hints of an increase in the infection rate,’ said Steinman. ‘The FDA should have dug deeper.’”
While MS patients and parents of children with MS were concerned that what appeared to be a promising medication may never make it back on the market, many experts in the field of pharmaceutical development regard Tysabri as a dangerous drug that never should have been approved by the FDA in the first place.
There is also the claim that Tysabri should not have been used in human trials before thorough long-term studies were conducted.

Most of all, however, there appears to have been ample evidence in the form of test data and opinions from highly qualified and credible experts that this drug posed a serious risk of the very injuries (and deaths) that ultimately occurred.
Certainly, PML was always a possible risk due to the immunosuppressive quality of the drug. This factor made the combination therapy of two such drugs (Tysabri and Avonex) quite problematic and worthy of serious consideration (and appropriate warnings) before it was routinely prescribed to patients in the clinical trial.

Despite the serious concerns of many critics of the FDA’s (over 50% industry-funded) fast-track approval process in general, and the hasty approval of Tysabri in particular, the FDA announced, only last month, that it had decided to grant permission for the clinical studies of the drug to continue.

In its announcement, the FDA stated that it had “removed the clinical hold” on studies of Tysabri. “This will allow clinical trials to go forward.”
“In February 2005 Biogen-IDEC had announced suspension of marketing and clinical trials after three patients developed progressive multifocal leukoencephalopathy (PML), a frequently fatal infection of the brain, two following treatment with natalizumab for MS, and one patient being treated for Crohn’s Disease. Two of these cases were fatal.”
The removal of the clinical hold allows patients with MS who were previously treated with the drug under an investigational (IND) study to resume treatment “in an IND study following discussion with their physicians about the potential risks and potential benefits of treatment.”

Remarkably, the FDA stated that, “Although this treatment has been shown to have benefit in patients with relapsing-remitting MS, concern about the risk of PML associated with use of Tysabri remains.”

While the “drug is not being placed back on the market at this time,” the FDA has scheduled an Advisory Committee Meeting on March 7 and 8, 2006 to discuss an application for Tysabri for use in treating patients with relapsing forms of multiple sclerosis. “Aspects for discussion include the risks associated with the drug, its efficacy in the treatment of multiple sclerosis relapses and disability, its possible return to the marketplace, and its proposed risk management plan(s).”
In a Q & A with respect to the lifting of the “clinical hold,” the FDA stated that it was taking this action because an “extensive re-examination that Biogen and Elan undertook on all patients who had received natalizumab in clinical studies” revealed, “No additional cases of PML.” In addition, “Biogen has proposed a resumption of natalizumab administration under an IND study with very specific plans for close monitoring of patients.”

Although not mentioned in the body of the FDA release, the following statement was included at the end of the answer to the question: “Will Tysabri be available to all patients?” “Biogen has not proposed to administer the drug to anyone who had not previously been receiving it under an IND study. Biogen has submitted an application to FDA to resume marketing the drug for more widespread use. That application has a due date for a decision by FDA in late March 2006.”

To further justify what many experts see as an imprudent decision by the FDA, the agency stated that, while it “remains very concerned about the potential for PML associated with natalizumab use” the currently available information is “not adequate to clearly define the level of risk or the exact circumstances when this risk occurs.”
In addition, the FDA stated that “the existing efficacy data with natalizumab indicate this is a very effective product and multiple sclerosis is a devastating neurologic disease.”

Although the logic behind further testing makes sense to some experts, there are some that believe the drug should never have been approved in the first place.
As reported in HealthDay News (2/17): “A multiple sclerosis drug pulled from the market early last year due to safety concerns was initially approved too quickly and probably should not go back on the market, at least not without more data, according to an expert writing in this week’s British Medical Journal.”
The author believes Tysabri was approved too quickly in the first place. According to Dr. Abhijit Chaudhuri, a consultant neurologist for the Essex Centre for Neurological Sciences at Oldchurch Hospital, Romford, Essex, in England: “The rate at which Tysabri was fast tracked is absolutely unacceptable for a condition like multiple sclerosis, which can last for 30 years. They did not even look into the side effects and this is unbelievable. It’s a major failing.”

Dr. Chaudhuri agrees with the need for further study: “If a study is being conducted with ethical approval and physicians and participants are well aware of the risks, I have nothing to disagree about. Any scientific study where use of new product is closely monitored should go ahead.”
He was quick to point out, however, that he disapproves of the initial approval process for the drug.
“According to Chaudhuri, the FDA approved Tysabri only on the basis of short-term results from two unpublished trials, and before final data were available.” (HealthDay News 2/17)

“Based on what we’ve seen so far, there is no evidence to suggest that this is very effective for MS,” he said. “We’re talking about a condition that affects young people fairly early in life and which lasts for 30 to 40 years, so it’s a lifelong disease. Before you start using that, you must have convincing and compelling evidence that long-term disability is significantly reduced, at no cost for side effects. And I don’t think we have that kind of information.”
Specifically, with respect to Anita Smith, Dr. Chaudhuri stated: ‘’Because the pathology did not support the clinical diagnosis of multiple sclerosis in the fatal case, the diagnosis is questionable, and the decision to enroll an atypical patient is debatable.”
When we asked several litigation attorneys familiar with pharmaceutical products to comment on the Tysabri saga, they were unanimous in their skepticism concerning the FDA’s ability to protect the public from harmful drugs given the current state of the approval process.

Only two weeks ago, Jerrold Parker summed it up like this: “I certainly wouldn’t bet against Tysabri making it back to the market. If the FDA’s track record over the past several years tells us anything, it tells us that, with respect to the drug approval process, the bottom line usually wins out over concerns for the health and safety of the public.”

Then, much to the surprise of Parker& Waichman (attorneys for the Smith estate) and Anita Smith’s husband Walter, who has become an outspoken critic of the drug and who intends to testify at the upcoming FDA hearing in March, it was learned that MRI films (and possibly other medical records) of Anita Smith existed and were in the possession of Colorado Springs Imaging.

The MRIs (taken on March 21, 2002, April 16, 2003, and April 21, 2004) and the records and reports relating thereto were not among the materials turned over in discovery by Dr. Fodor (Smith’s treating neurologist) or any other healthcare professional that had treated Smith. Since these reports (if any), and especially the MRI films, could be extremely significant with respect to the misdiagnosis of Smith (as having MS) and the improvident decision to enroll her in the Tysabri clinical trial, Parker & Waichman sought production of the records.

In an “emergency” motion to obtain these MRI films and any accompanying records, a number of unusual circumstances are alleged by Smith’s attorneys, Parker & Waichman (Jerrold Parker and Jason Mark) and their Boston-based counsel Robinson & Cole (Alex H. MacDonald, Michael D. Lurie, and Kimberly A. Dougherty).
When they became aware of the existence of these important and possibly pivotal records, Smith’s attorneys contacted Colorado Springs Imaging (CSI), an independent diagnostic center, and requested a copy of the MRI films and any other materials relating to them.

Under the law of every jurisdiction in the U.S., a patient is always entitled to a copy of their own medical record and once a properly executed authorization is delivered, a medical provider must release those records as directed by the patient or the patient’s legal representative. Here, Smith’s attorneys advised CSI that an authorization executed by Walter Smith, as administrator of the estate of Anita Smith, would be sent to them to permit the release of the records in question.

After initially agreeing to the release, CSI apparently contacted Biogen (or Biogen’s attorneys) and, as a result, reversed itself and refused to release the MRIs or any other records it had with respect to Anita Smith. CSI claimed Biogen’s consent was necessary before any exchange could take place. Although Smith’s attorneys strongly protested to CSI and Biogen’s attorneys, Biogen remained adamant that it could deny the release because the records belonged to the drug company and not to Anita Smith or her estate.

The emergency motion to compel Biogen to authorize the release of the MRIs and other records in CSI’s possession was submitted on extensive papers from both Parker & Waichman and Robinson & Cole and argued before Middlesex Superior Court Judge Julian T. Houston.

After a contentious hearing at which Biogen’s attorneys took a position that Judge Houston openly regarded as legally unsupportable, the court issued the following order:

“Motion # 14 allowed after hearing. Defendant Biogen- IDEC, Inc. is ordered to immediately direct the Custodian of films and medical records of the late Anita Smith, Colorado Springs Imaging is to release any and all medical records in its possession to the Plaintiff, Walter Smith, see General Laws chapter 112, section 12cc. The aforementioned records are to be released forthwith.”

Since the MRIs and any supporting records could establish the fact that Anita Smith never had MS, they may very well expose Biogen and Elan to a significant possibility of being found liable for her conscious pain and suffering and untimely death.

When reached for comment at a legal conference in Hawaii, Jerrold Parker expressed his appreciation for the prompt and definitive ruling by Judge Houston. Mr. Parker stated that it was “incredible” that any medical provider or law firm “could have taken the position that diagnostic tests like MRIs and any reports related to them could not be obtained by the patient. Anita Smith was a human being and not a laboratory animal that belonged to Biogen. Thus, her records cannot be withheld at the company’s direction.
To have argued otherwise was unconscionable.”

(Sources: FDA Press Release and Q & A; British Medical Journal; HealthDay News; The New York Times achives, Los Angeles Times achives; Complaint, motion papers, and court documents in Smith v. Biogen, et ano., Civil Action 2005-02527 – Middlesex Superior Court; and Newsinferno.com Archives)
This entry was posted on Saturday, February 25th, 2006 at 7:38 am and is filed under Legal News, Drug Side Effects, Health Concerns.

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