The bulk of Project AON-P7-304 took place in a large, windowless room located in an equally featureless building in Park Extension, a working-class neighbourhood in the northern part of Montreal. At 9 p.m., the 48 test participants were in their assigned seats facing a glass wall, behind which several medical technicians, who work for Montreal-based contract research organization (CRO) Algorithme, milled about in white lab coats. The test participants—always referred to as volunteers, though they certainly weren’t sitting there for free—behaved as strangers do when forced to socialize: they chatted politely, obsessed over their cellphones, read magazines, cast an eye to the TV in the corner.
When the technician yelled out “numéro 34”—the number written on the plastic bracelet around his arm and pasted on his chair—number 34 got up, walked into the laboratory, sat down in a chair and rolled up his sleeve. A technician then applied a tourniquet and extracted three millilitres of blood from a spot just below number 34’s right bicep. Number 34—actually a Maclean’s reporter participating in the study—will have 26 such extractions over the next three days, during which 89 ml of his blood will be harvested.
Most of the time, he can’t shower, drink water or go to the bathroom. His belongings will have been searched for contraband—cigarettes, drugs, bottled water. He will have a dose of atovaquone, an anti-pneumonia drug and the subject of Project AON-P7-304, sprayed into his mouth several times at regular intervals. He sleeps in a 60-by-six-foot room filled with bunk beds for the 30 other men in the experiment, and is given earplugs to cope with the snoring. He can’t eat until the technicians allow him; when they do, he must present his empty cafeteria plates as evidence that he ate everything, under threat of expulsion. He can smoke two cigarettes an hour, up to 10 a day, in the smoking room. He has the right to view one DVD a night.
For his trouble—that is, for playing a small but essential part in the costly process of getting atovaquone onto the generic drug market—he is given a “compensatory indemnity” of $1,400, tax-free. In 28 days, the mandatory waiting period between studies, he can repeat the process; if he is anything like the small army of roving “volunteers” who have made a career out of donating their time and bodily fluids for profit, he would.
These volunteers are in the right spot for this odd line of work: Montreal is the clinical testing capital of North America. It is so thanks to a confluence of favourable factors—comparably low salaries, generous tax breaks from various levels of government, industry-friendly federal laws governing clinical trials, not to mention one of the largest per-capita student populations on the continent. The city, according to a recent KPMG study, is the cheapest place to research, test and market a drug, and pharmaceutical companies have taken note: nearly 33 per cent of “healthy patient research” conducted in North America happens in Montreal. Over half of these tests are performed for drugs for sale in Europe, where in many cases stricter laws and higher costs make such testing prohibitive.
In Canada, a menu of name brand drugs that ring up annual sales of $28 billion are set to move to the generic market over the next three years, and each one must be tested on human guinea pigs beforehand. There is a booming industry ahead for Quebec’s contract research organizations, hired by drug companies to recruit volunteers and test their drugs, including Algorithme and competitors Anapharm and MDS Pharma Service, the three biggest in the country.
Yet critics of the industry say the Canadian and Quebec governments, in their quest to secure the lucrative clinical testing industry, have become more industry cheerleader than watchdog. Oversight of the industry, they say, is largely arbitrary and shrouded in secrecy, compromising the quality of research and endangering the safety of the “volunteers” on which the industry depends. Internal Health Canada documents, newly obtained by Maclean’s, show how the government agency was seemingly unaware of the extent of a tuberculosis outbreak in 2005 during a test until three months after the fact—when an American journalist called looking for answers. For many “volunteers,” the field is lucrative enough to weather the dozens of blood extractions and the often crushing boredom of the drug trials. Some are even willing to lie about how healthy they are for the privilege.
Quebec has a long history of courting the pharmaceutical industry. In 1965, the federal government founded BioResearch, considered Canada’s first contract research organization. It employed about 30 people, and was one of the first North American labs to conduct trials on the psychedelic effects of marijuana. It also conducted studies on carcinogenic properties of bacon (in the mid-’60s) and cigarette smoke (in the early ’90s) before being sold off to pharmaceutical research giant Charles River. Today, the former BioResearch labs employ 1,600 people and are involved mostly in pre-clinical trials of drugs not yet on the market. “Here in Quebec, it’s the kind of work that is known and understood,” says Algorithme CEO Louis Caillé. “It’s nothing new. It’s been demystified. People are comfortable with it.”
Caillé, who started Algorithme in the 1970s, now oversees a multi-million-dollar company that has grown 400 per cent in the last four years. Nor is the availability of able and willing bodies for testing much of a secret. Investissements Québec, the province’s business development arm, touts “easy access to patient populations” and “a willingness among patients to take part in studies,” as well as “intense promotional activities that allow for quick subject recruitment” in its sales pitch to pharmaceutical companies. The federal and provincial governments sweeten the pot with generous tax holidays and credits—“the most generous in the world,” according to Investissements Québec. The results, according to the KPMG study: “Montreal ranks first in the world for its research and development fiscal incentives.”
Quebec accounts for over 40 per cent of the country’s pharmaceutical output. The 10 largest pharmaceutical companies in the world all have operations in Quebec, and with them have come dozens of generic drug companies, who, like the name brands, require fast, reliable, government-sanctioned testing of their wares. The federal government further obliged these companies in 2001, when the clinical trial review period was slashed; suddenly it took half the time for pharmaceutical companies to have their drug tests approved by Health Canada. The change, according to Health Canada officials, reflected the body’s two overarching objectives: “To strengthen protections for clinical trial subjects; and to attract and sustain investment in research and development in Canada.”
Health Canada’s oversight was put to the test in the fall of 2005, when a volunteer with tuberculosis infected 20 people during an Anapharm-sponsored study. As internal documents show, Health Canada officials didn’t seem to know of the outbreak until they were contacted three months after the fact by David Evans, a reporter for the Bloomberg news agency. Emails exchanged between Health Canada officials, obtained by Maclean’s, show how the agency scrambled to get information from Anapharm and from the reporter himself, who seemed to know more about the outbreak than it did.
In the of fall 2005, Anapharm had recruited 20 subjects in a clinical test of ISA 247, an experimental immunosuppressant drug produced by Alberta-based Isotechnika. The test subjects were promised $6,800 should they finish the five “confinement” stints totalling 31 days over 10 weeks, with the bulk of the payment coming at the end of the trial. Fifteen of the 20 subjects were born outside of Canada, including a man from Haiti who, according to his roommate’s account published in a report from the Bloomberg news agency, began coughing up blood on the first day of the trial. Though staff were apparently told the volunteer was coughing blood, they kept the subjects in the trial for four more days. The study was then halted and the patient eventually tested positive for tuberculosis, but some 20 people, including 11 Anapharm staff, later tested positive for latent tuberculosis.
Anapharm informed Health Canada of the single TB case within the mandated 15-day limit following the termination of the study. However, Anapharm didn’t report the subsequent spread of the disease; nothing in Health Canada’s regulations obliged the company to do so.
Then on Dec. 12, 2005, a media inquiry came in to Health Canada about the spread of tuberculosis at the trial. The request set off a flurry of notes. “Not aware of TB case,” wrote Yadvinder Bhuller, manager of Health Canada’s Office of Clinical Trials. “Do we have a record of this trial? Did we issue no objection letter? We need something definitive from HC [Health Canada] that we are aware of this trial,” wrote media relations senior advisor Jirina Vlk on the same day. “Who’s [sic] role is it to monitor this and ensure compliance? I guess this is what we need to know,” Vlk wrote. “What type of actions would we take?” Apparently starved for information, Health Canada officials asked reporter David Evans “to obtain more info” about the tuberculosis outbreak.
According to spokesperson Gary Holub, Health Canada launched an investigation into the outbreak before the media requests. However, a timeline in Health Canada’s internal documents show Health Canada scheduled its compliance verification of the Anapharm site on Dec. 21, a week after the Bloomberg article appeared. The ensuing investigation uncovered several violations at Anapharm’s testing site, including the lack of a “cleaning procedure for clinical areas where subjects are confined and for the equipment used by them,” of training “for personnel responsible for the cleaning,” as well as a lack of a proper signed record “of all personnel who were implicated in the study.” Anapharm says it has since rectified the problems, and has changed its policy on TB testing. “We do all the required testing, including for tuberculosis, when an immunosuppressant is involved,” Anapharm president and CEO Johane Boucher-Champagne told Maclean’s. “This happened in 2005. It’s an old story.”
Perhaps so. Yet apart from a Health Canada list of non-binding guidelines suggesting companies should test patients for tuberculosis, little has changed since. “Health Canada didn’t change anything. They recommend that companies should test for tuberculosis when conducting a clinical trial for a drug that suppresses the immune system,” says Martin Letendre, director of ethics and legal affairs at Ethica, a CRO. Its non-profit division, Veritas, was the independent review board that until August 2005 oversaw Anapharm’s testing protocols. (According to Health Canada regulations, contract research organizations must have an independent review board oversee their clinical trials.) “It’s a guideline, so if you aren’t doing the TB test you aren’t actually breaking the law.”
Part of the problem, Letendre says, is simple disclosure. In the U.S., the Food and Drug Administration posts the findings of its inspections on its website. Anyone, prospective volunteers included, can view the history of CROs. Health Canada doesn’t disclose its inspection findings. Anyone curious about Anapharm’s tuberculosis outbreak, for example, is out of luck. “You should call the company to get more info,” is how one Health Canada official responded when asked about the number of people infected.
“There’s not enough questions about how the sausage is made, as long as you have hot dogs at the other end,” says Martin Letendre. He frequently uses words like “broken” and “conflicted” when describing the profession in which he himself works. “There is room for someone to abuse the system and no one would know about it.”
Overseeing trials is certainly a challenge, one often made more difficult by the volunteers themselves. During a recent visit to an Algorithme clinical trial, Maclean’s found several participants who drank alcohol and took prescription medication when both are explicitly forbidden during the testing period. Many of these participants, some who were decades-long veterans of the trade, were well versed in what the company tested for—and what it didn’t. “You learn how to say ‘no,’ ” says Anthony (not his real name), referring to Algorithme’s questionnaires over consumption of alcohol and drugs.
Anthony spent the downtime between his confinement and return visits celebrating a birthday. He was worried more about the ensuing hangover than about getting nabbed by Algorithme’s tests, which would have meant forgoing most of his $1,400 paycheque. He knows from experience that the company wouldn’t test for the booze swishing around his system. Other testers in the study were taking prescription medication—even though, like alcohol, doing so might affect Algorithme’s study results. “Nobody tests for anything except for illegal drugs, and that’s only when you first get here,” Anthony says. “Other than that, you can do what you want.”
Algorithme’s Louis Caillé defends the integrity of his firm’s research, saying people like Anthony are the exception to the rule. “We have rules to follow but we can’t enforce all the time,” he concedes. “We don’t do follow-up tests [for alcohol or drugs].”
Others still blame the media. After all, “no one died,” says Jack Corman, president of IRB Services, the independent review board contracted to review Anapharm’s testing for the ill-fated 2005 study. “There is an agenda to do harm to Anapharm and us,” Corman says without elaborating. “I think Health Canada could have done better [but] I think we did everything we could.” The clinical testing industry as a whole, Corman says, has been unfairly tarnished as a result of the TB outbreak—which he is loathe to even call an outbreak. Tales of outbreaks and half-drunk volunteers are media concoctions, Corman says, designed to blemish what is a made-in-Canada success story. “We have highly trained, highly qualified, highly ethical scientists and physicians who conduct world-class research in this country. The industry is a success for Canada, and for Montreal.”