Montreal Clinical Trial Subjects Expoxed to Tuberculosis

The case involves SFBC, which runs the largest clinical trial site in North America, the site is Montreal, the trial involved testing Isotechnika’s– ISA 247. If it’s approved for use in organ transplants Roche Holdings AG, based in Basel, Switzerland, holds exclusive worldwide marketing rights from Isotechnika.

The trial involved a public health hazard–SFBC’s failure to screen prospective human subjects for tuberculosis.
  
 “The research community owes human volunteers at least the same fiduciary responsibility as it does to patients. This story suggests a serious lapse in the most basic care of patients exposed to a known communicable disease. The breach of responsibility is egregious.”  Saying so, doesn’t make it so.  There is no accountabilithy in the current research oversight system–all is left to the discretion of the stakeholders in the enterprise.

Bloomberg News reports that  SFBC Anapharm "allowed Participant 8 to remain with his fellow study participants for four days after he coughed up blood."  SFBC attorney York says:  “He was checked regularly and showed no signs of illness.”

"In a press release today, SFBC says its board of directors hired independent counsel whose internal investigation found that the Nov. 2 Bloomberg story was “wholly unsupported as to SFBC.” The report was written by two law firms, Miami-based Tew Cardenas LLP and Winston & Strawn LLP in Chicago."

What else should one expect from lawyers hired by SFBC ?  That is, if they want to be paid.

The chrade is a mockery and all involved know it.

Contact: Vera Hassner Sharav
veracare@ahrp.org

http://www.bloomberg.com/apps/news?pid=specialreport&sid=aPK9Hq1VxZn8&refer=news#
BLOOMBERG NEWS

SFBC Drug Testers Have Tuberculosis After Exposure (Update1)   

Dec. 15 (Bloomberg) — The drug test participant on the next bed was shivering and shaking and coughing up blood.

That’s what Mohsen, a 37-year-old man from Toronto, says he told a nurse on Sept. 1 at a Montreal testing center owned by Miami-based SFBC International Inc. Mohsen says he demanded to be moved.

SFBC, which runs the largest clinical trial site in North America, kept Mohsen and his roommate together for another four days, says SFBC lawyer Michael York. In November, Mohsen learned that his roommate had active tuberculosis, and that Mohsen himself had contracted latent tuberculosis. Eight other participants in the September SFBC drug trial also tested positive for latent tuberculosis, according to the Montreal Regional Health Department.

“Once they had a person coughing up blood, to allow him to expose others to TB is wrong,” says Steven Miles, a professor of medicine and bioethics at the University of Minnesota Medical School in Minneapolis and a co-author of a 2001 textbook about treating tuberculosis. “You assume TB until you exclude it.”

Tuberculosis is an infectious disease that kills 2 million people worldwide a year. Active tuberculosis is contagious and spreads through the air as people cough or speak. It develops from latent tuberculosis, which isn’t contagious and can be treated by a nine-month regimen of antibiotics.

Mohsen, who emigrated from Kuwait in 1990, asked that his last name not be published because he hasn’t told his family or friends that he has latent tuberculosis.

Rare Event

The Montreal Regional Health Department found that Mohsen’s roommate, an immigrant from Haiti, has active tuberculosis. That Caribbean country has the highest incidence of tuberculosis in North America, according to the Geneva-based World Health Organization, about 100 times higher than Canada.

In 2003, there were 386 cases of active tuberculosis in Haiti per 100,000 people, according to WHO. Canada recorded 4 people with active tuberculosis per 100,000 in 2003. The U.S. had 3 active cases per 100,000, WHO statistics show.

“I’ve never heard of this happening in a clinical trial before,” says Miles, 55. “I’ve seen TB spread like this in a prison.”

Daniel Federman, a senior dean at Harvard Medical School in Boston, who chaired a national panel on protecting people in clinical trials in 2002, says SFBC’s handling of the tuberculosis case is distressing.

`Breach is Egregious’

“The research community owes human volunteers at least the same fiduciary responsibility as it does to patients,” says Federman, 77. “This story suggests a serious lapse in the most basic care of patients exposed to a known communicable disease. The breach of responsibility is egregious.”

Health Canada, which regulates clinical trials in that nation, has started a probe of the tuberculosis event at SFBC’s center, says spokeswoman Jirina Vlk. “We’re investigating this incident and we’re taking it very seriously,” she says.

SFBC attorney York, 52, says company executives say they are sorry about the tuberculosis incident and that they hope to learn from it.

“The company very much regrets this happened,” York says. “It is committed to assisting those who have positive screen results. The company is taking steps to ensure this does not happen again.”

SFBC shares have lost 56 percent of their value since Bloomberg News reported Nov. 2 that bioethicists said the company’s consent process at its largest center in Miami inadequately warned participants in drug trials of the risks of injury and death.

Independent Investigation

In a press release today, SFBC says its board of directors hired independent counsel whose internal investigation found that the Nov. 2 Bloomberg story was “wholly unsupported as to SFBC.” The report was written by two law firms, Miami-based Tew Cardenas LLP and Winston & Strawn LLP in Chicago.

The report, which says “we continue to support SFBC’s management,” doesn’t refer to the tuberculosis in Montreal.

Independent counsel reports that SFBC’s consent forms are in understandable language, citing risk factors. It also says the company has resolved all issues raised by seven U.S. Food and Drug Administration reports of “significant objectionable conditions.”

The statement also denies that Chief Executive Officer Arnold Hantman took part in discussions with participants. The independent counsel didn’t interview three of four people who claimed SFBC employees pressured them into signing statements recanting what they told Bloomberg. Two said Hantman questioned them. The independent counsel says an SFBC employee “raised his voice and made reference to immigration officials.” The report found this behavior was “inappropriate.”

Senator Grassley Letter

U.S. Senator Charles Grassley wrote to the company on Nov. 17, saying his staff wanted to meet with SFBC executives to discuss safety in drug tests in the industry and at SFBC.

Those meetings haven’t yet been scheduled, Grassley spokeswoman Jill Kozeny says. SFBC’s test center in Miami, located at its headquarters, is the largest private clinical trial facility in North America.

Miami-Dade County health inspectors ordered SFBC to remove 325 out of 675 beds from its Miami center in November because it wasn’t complying with the county’s building code.

The Montreal test was sponsored by Isotechnika Inc., an Alberta-based company. The drugmaker hired SFBC’s Canadian subsidiary, SFBC Anapharm Inc. in Montreal, to study the potential for heart damage from its ISA 247, an experimental drug that lowers the body’s ability to fight off disease and is being tested to prevent rejection of transplanted organs and to treat psoriasis.

Company Requests

Roche Holdings AG, based in Basel, Switzerland, holds exclusive worldwide marketing rights from Isotechnika for ISA 247 if it’s approved for use in organ transplants.

Isotechnika President and Chief Operating Officer Randall Yatscoff says his company asked the SFBC test center to screen participants by asking them if they had tuberculosis or had recently traveled to a country where it was prevalent. The company also asked SFBC to do a physical exam to check for tuberculosis.

“The physical should have detected it,” Yatscoff, 52, says. “You leave a lot in the hands of the people at SFBC. They have a responsibility to carry out the trial the way the sponsor asked.”

SFBC’s York agrees Isotechnika asked for both verbal and physical screening. The physical exams didn’t include tests specifically for tuberculosis, he says.

The Montreal trial of ISA 247 began on Aug. 30, a day after the participants checked into the center. On the fifth day of the trial, Sept. 3, Yatscoff says, the center told him that one of the participants had been diagnosed with active tuberculosis. The participants left the trial on Sept. 6.

SFBC Didn’t Know

“We found out five days into the trial that the patient had active tuberculosis,” Yatscoff says. He says the test center told him the sick man was from Haiti.

SFBC attorney York, whom the company hired in November after receiving the letter from Senator Grassley, says the company’s management in Miami didn’t know about the tuberculosis situation when it happened. SFBC executives don’t recall when they first learned about it, he says. “They don’t know exactly what day they found out,” York says.

York says that Isotechnika reported the tuberculosis incident to Canadian officials. SFBC doesn’t have a copy of the report the drug company filed with the government agency, York says.

SFBC executives in Miami told their Montreal center General Manager Joanne Boucher-Champagne not to comment, York says.

`Patients Slip Through’

Yatscoff says he’s disappointed with SFBC. “Their explanation was `patients slip though sometimes,”’ he says.

Roche Canada spokeswoman Sabrina Paiva says, “I don’t have information on that study. We’re looking into it.”

On Aug. 29, Mohsen, the 37-year-old Canadian who later contracted latent tuberculosis, first roomed with the man who has since been confirmed to have active tuberculosis.

Mohsen, who is five-feet, six-inches (168 centimeters) tall and speaks English with a Middle Eastern accent, says he was confined to a 10-foot-by-10-foot room with the sick man for eight nights. He says about 15 of the 20 participants were born outside of Canada, in South America, Africa, the Middle East and Haiti.

Five Confinements Planned

SFBC’s York confirms that most of the participants were from foreign countries. York says the varied backgrounds of participants are an important issue that needs to be addressed by the pharmaceutical industry and government health-care agencies.

“The mix of different populations from countries with varying rates of certain diseases presents a complex set of issues,” he says. “Anapharm and SFBC will seek a consensus for screening diverse populations for a number of diseases.”

The trial was planned to include five confinements totaling 31 days over 10 weeks, according to SFBC’s consent form. Participants in clinical trials must sign consent forms, which explain the risks of a test.

Confinement is the word SFBC uses to describe the time in which a drug-test participant spends 24 hours a day in the center.

Mohsen’s roommate, a Haitian whom the center called “Number 8,” appeared to be sick on the first day of the test, Aug. 30, Mohsen says. On Sept. 1, the third day of the experiment, Mohsen says his roommate was coughing up blood. “He was lethargic,” Mohsen says. “He spent most of his time in bed.”

Doctor Exam

Mohsen described the Haitian’s symptoms to a nurse that day, he says. Richard Larouche, the center’s medical director, then examined the man for about half an hour, Mohsen says. After that, clinicians brought the man back to the room, Mohsen says.

SFBC Anapharm allowed Participant 8 to remain with his fellow study participants for four days after he coughed up blood, SFBC attorney York says. “He was checked regularly and showed no signs of illness,” York says.

The day after Number 8 was examined, a female nurse whose name Mohsen doesn’t remember told Mohsen that the coughing man was okay, Mohsen says. He says the man’s condition didn’t improve. “He kept coughing and spitting up blood,” he says. “They didn’t take him away.”

Larouche, 48, the SFBC doctor, referred all questions to York.

Participants Sent Home

Mohsen says the center sent everyone in the clinical trial home after eight days of confinement. When the participants returned for a second planned confinement on Sept. 19, Mohsen says test center officials told participants that the study had been canceled because of a suspected case of tuberculosis.

Larouche, the center’s medical director, told participants about the disease, and said they would be tested for it, Mohsen says. Participants were paid the full promised compensation of C$6,800 ($5,868), SFBC’s lawyer York says.

Mohsen says he was tested for tuberculosis by Larouche on Nov. 1. He says Larouche also told him for the first time that participant Number 8 had been diagnosed with active tuberculosis.

Three days later, Mohsen says, the SFBC test center called him and asked him to come in. Mohsen says the center’s medical director told him that he had tested positive for latent tuberculosis. He told Mohsen that he’d have to take antibiotics for nine months to prevent the disease from becoming active in his body.

`They Don’t Care’

“I was shocked,” Mohsen says. “I reminded him I’d brought it to the attention of the staff. He said Number 8 deceived us. Why did they let him stay with me? I trusted their information. They never apologized. They don’t care. They don’t give a damn.”

SFBC’s lawyer York says Mohsen tested positive for latent tuberculosis. York says the company is sorry Mohsen is angry at SFBC. “Anapharm very much regrets that the subject feels this way,” York says. “They hope he recalls that Dr. Larouche apologized to him and to his fellow volunteers.”

Mohsen says he doesn’t remember any apology.

The Montreal Regional Health Department is now testing all SFBC employees who may have been exposed to tuberculosis, says the department’s Associate Medical Director Terry Tannenbaum. She says she can’t comment further. SFBC’s York says about 74 employees have been tested so far. The results aren’t yet available.

Tests for TB

Miles, the University of Minnesota Medical School professor, says SFBC mishandled the clinical trial from the start by failing to adequately screen participants for tuberculosis, which is more likely to develop when someone is taking an a drug like ISA 247, which suppresses the immune system.

Miles was chief medical officer for the American Refugee Committee treating 45,000 people on the Thailand-Cambodia border in 1981 and 1982. He co-authored, “Curing Tuberculosis: A Manual for Developing Countries” (Center for Blood Research, 2001).

Tuberculosis can be reliably detected only with a so- called “scratch test” and a chest X-ray, Miles says.

In a scratch test, a clinician sticks a small needle into someone’s arm. The needle contains a fluid that will cause a swelling if a person has latent or active tuberculosis.

Neither a scratch test nor an X-ray was used to screen participants before the Montreal clinical trial began, says SFBC Miami-based Executive Vice President Greg Holmes, 49.

`It’s Disturbing’

Both SFBC and the institutional review board SFBC hired to monitor safety decided that it was sufficient to ask potential participants if they had tuberculosis or had been in a country where the disease was prevalent, SFBC’s lawyer York says.

Miles says SFBC failed to practice basic medical procedures by doing no scratch tests or X-rays during screening. “It’s disturbing,” he says. “I don’t understand their thinking.”

He also says that SFBC should have realized people may be dishonest when asked if they have tuberculosis so they can get into the test. “One point of a screening process in any trial is to watch out for people who might lie to get into a trial to make money,” he says.

The review board — Aurora, Canada-based IRB Services — had considered requiring a tuberculosis skin test to screen participants in the clinical trial, says its President Jack Corman.

The for-profit IRB decided against the scratch test because there’s a large Haitian population in Montreal, and many potential participants would have likely tested positive and have been excluded from the trial. “It’s clear the test has no utility,” says Corman, 57.

Lesson Learned

Miles is outraged by the IRB’s decision. He says people testing positive for TB should have been kept out of the study, for their own protection and the safety of others. “That statement doesn’t make any sense,” Miles says.

Miles says SFBC mishandled the situation after it learned a participant had been coughing up blood. “It takes 15 minutes to get a chest X-ray,” Miles says. “That’s just standard medical practice. They shouldn’t have waited for four days. I don’t understand why they let this guy in the study in the first place.”

SFBC attorney York says the company has learned from this experience. “I don’t believe this company will conduct this type of trial in the future without giving a scratch test or chest X-ray to screen for tuberculosis,” he says.

Financial Incentive

Miles says the clinical trial’s C$6,800 compensation to participants played a role in the tuberculosis incident. “It was a big wad of cash to poor people, and immigrants tend to be poor and unemployed and at higher risk for TB,” he says.

SFBC’s test center asked the 10 participants who so far have tested negative for tuberculosis to sign a waiver promising not to sue SFBC, York says.

The company also asked three participants who tested positive and haven’t agreed to begin taking antibiotics to sign a document giving up their right to any further compensation from SFBC, he says.

One person who tested positive and declined the nine-month course of antibiotics refused to sign the waiver, York says.

“The volunteer hereby grants Anapharm a full, complete and final release from any and all past, present or future claim he may have,” the form says.

York says SFBC sought the waivers on advice from its Canadian attorneys, whom he declined to identify.

`Waiver is Outrageous’

Trudo Lemmens, a law professor and bioethicist at the University of Toronto, says SFBC Anapharm’s efforts to get participants to sign the document are unethical. “The request to sign a waiver is outrageous,” he says. “They should offer compensation and offer to pay for any future health care costs associated with this mishap.”

York says SFBC believes it was fair and appropriate to ask for the releases.

The payment for the trial was backloaded, with 79 percent, or C$5,400, paid after the participant had spent 31 days in confinement.

“In my view, the IRB has approved an unacceptable payment structure that clearly induces people not to withdraw from the trial,” says Lemmens, 41. Just C$200 was to be paid for the first week of confinement, C$300 for the second week, C$400 for the third week and C$500 for the fourth week.

“This is even more troublesome in light of the significant side effects associated with the medication they are asked to take,” Lemmens says. “People are likely to feel pressured to continue the trial even when they are suffering significantly.”

`Not Entirely Happy’

The consent document provided to participants says potential side effects included vomiting, diarrhea and changes in kidney function. The consent document doesn’t mention tuberculosis. It also doesn’t include heart damage as a risk; the stated purpose of the test is to see if the drug causes heart damage.

Miles of the University of Minnesota says the consent form should have listed the risk of activating infectious diseases because the experimental drug lowers immunity. He says the form didn’t need to specifically cite tuberculosis as a risk because the test center should have screened out people with that disease.

IRB Services’ Corman says payments sometimes are backweighted to discourage participants from dropping out.

“We understand that research requires an incentive for completion,” he says. “We’re not entirely happy with that.”

Corman says he’ll advise SFBC to provide more compensation to the participants who tested positive for tuberculosis. Those people were subjected to inconvenience and possible long-term risk of the disease, he says. “What’s a few grand to protect your reputation?” he asks.

To contact the reporter on this story:
David Evans in Los Angeles at  davidevans@bloomberg.net.

Last Updated: December 15, 2005 09:03 EST

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