Read an Excerpt
Chapter 1: A Suspicious Death
The morning of September 20, 2005, dawned like any other. My young children needed to be loved, entertained, fed, washed, dressed, and safely delivered to their respective schools and daycares, on time, lunches in hand. I was particularly anxious, and maybe even distracted, that morning as the hour of what I anticipated to be a very stressful meeting approached. My colleagues and I were meeting with SFBC Anapharm at its office in Montreal. SFBC Anapharm was a contract research company and long-standing client of our research ethics board. The purpose of our meeting was to provide SFBC Anapharm with an ultimatum: make efforts to reform its current research practices or we would pull our services.
The drive to the SFBC Anapharm test facility from my last offspring drop-off took only ten minutes. I parked at the back of the Wendy’s restaurant next door on Decarie Boulevard and entered through the test facility’s main doors.
I like to imagine that I encountered a lovely man as I entered the test facility, a man with a gentle demeanour and kind smile. I picture him holding the door open for me and the two of us engaging in casual conversation. He introduces himself as Henri, and I happily stop to speak with him. I notice that Henri seems unwell and is having difficulty maintaining his balance. As he clutches the handrail to stay upright, I ask him if he is feeling okay. He replies that he is having some trouble, and I guide him to a comfortable chair and summon help. Together we wait for emergency care to arrive.
Regrettably, I never met Henri. Our paths did not cross that morning, even though we were at the SFBC Anapharm< test facility at the exact same time, one of us entering and one of us leaving.
Henri at His End
In another part of the city, a woman named Jeanne waited in her living room. The house was quiet except for the tick, tick, tick of the pendulum swinging in the floor clock. Jeanne sat motionless, monitoring the passing time by the clock’s chimes and strikes. It was almost 10:00 a.m. She nervously held her coffee cup with both hands to resist the urge to smoke another cigarette. She was overwhelmed with concern for her loving Henri. He hadn’t been feeling well and had complained to Jeanne that he felt like he had the flu. That morning, he’d said he felt dizzy and that he was sweating and experiencing hot flashes.
Jeanne heard the key in the lock of the front door. Henri was home. Elated, she ran to greet him as the door opened. Henri, pale, stood in the door frame. It took every ounce of energy for him to remove the key from the lock. As he reached out to embrace Jeanne, Henri lost his footing and lunged toward her, causing them both to fall to the floor. Jeanne managed to wriggle out from under Henri to call 911.
Jeanne placed a cold cloth on Henri’s head. He was barely conscious. She spoke to him in her gentle way about family and upcoming plans, like their trip to Florida in the winter. Paramedics arrived at 10:28 a.m. and immediately began life-saving measures, which they continued all the way to the hospital. Henri’s death was marked at 11:20 a.m. at LaSalle General Hospital. The cause of death was recorded as a probable myocardial infarction, or heart attack.
Henri had walked into the SFBC Anapharm test facility that morning because he was participating in a clinical trial. Research participants like Henri are, to some, invisible, contributing to the clinical trial as sources of data points. But to those who know and love them, they are anything but mere statistics.
Henri at His Beginning
Henri was born on the first day of spring in 1930 in the community of St. Lupicin, Manitoba. He was the seventh of twelve children born to Ernest and Marie. Henri’s Manitoba lineage dates back to the province’s founding. In fact, Louis Riel was the godfather of Henri’s grandmother, Marie Alexandrine.
Approximately two hundred families, mostly first-generation Europeans, lived in the area surrounding St. Lupicin at that time. There was one Roman Catholic school in the town, where nuns taught the children, boys on one side of the schoolroom, girls on the other. Children started school when they were six years old, and since most families farmed, they usually began working weekends on the farm as early as twelve years old. During the Great Depression, Henri’s family was poor, like most families in the area. Ernest could produce approximately fifty bushels per acre of barley in those days, which was quite respectable. But with a family of fourteen to feed, their food supplies were close to depleted by the time spring rolled around, so meals were rationed.
The family home was typical for its day, an uninsulated log structure with a sloping roof. On the first floor, the living and dining rooms were centred around an open fireplace. The living room doubled as a bedroom for Henri’s parents. The children slept two or three to a bed on the second floor, with a curtain separating the girls’ and boys’ beds. Attached to the house was Henri’s grandparents’ original house, which now served as a kitchen.
Life was very hard for Henri in St. Lupicin. For whatever reason a parent might despise their own child, Ernest despised Henri. From the time Henri was a young boy, Ernest capriciously deprived Henri of his education whenever he needed help on the farm. He worked Henri to the bone, giving him the most physically demanding and demeaning tasks. One of Henri’s jobs was to feed the pigs and clean their pen, which contained fifteen to twenty pigs at any given time. On one occasion, a pig escaped while Henri was cleaning the pen. Its speed and stamina led to a three-hour chase before Henri was able to return it to the pen. His accomplishment was not rewarded, though. After beating Henri, Ernest made him work in the dark to make up for the lost hours of chores.
To avoid getting caught by one of their father’s wicked blows, the other children stopped playing with Henri. Even his mother, Marie, displayed her love only during clandestine encounters with him. Winter mornings were especially comforting for Henri. He, his mother, and his sister Thérèse would rise before the rest of the house’s inhabitants to feed the wood stove and prepare hot chocolate, fresh bread, and porridge for the family. By the time Ernest was awake, Henri had already received the emotional and physical nourishment he needed to sustain himself for whatever the day had in store for him.
Henri retreated from the family, finding solace in books. He loved literature, poetry, and science. He had an amazing ability to memorize text, and his teachers often called upon him instead of reaching for a dictionary or encyclopedia or the Bible. He could speak English and French fluently. Henri was not a skilled farmer like his brothers. He was an artist, and this angered Ernest even more.
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SFBC Anapharm
Henri was seventy-five years old when he decided to participate in a clinical trial in order to be able to offer financial help to one of his children. He convinced Jeanne that it was a quick and easy way to make a bit of money. Although he didn’t recall the specifics of the study, Henri told Jeanne that he would be paid $1,160 for a two-night stay at the SFBC Anapharm test facility, located a short drive from their Montreal home.
In those days, SFBC Anapharm was a contract research company that specialized in the management of early-phase clinical trials out of its test facilities in Montreal and Quebec City. “Early-phase” refers to clinical trials conducted in the first two phases of drug development. Phase 1 drug trials are conducted to determine the maximum tolerated dose of the drug under investigation — that is, the highest dose that can be administered without causing unacceptable side effects. This is how researchers establish the appropriate dosage levels for subsequent studies. The goal of Phase 2 research is to determine how safe the drug is and how well it is tolerated and to get a preliminary picture of its therapeutic efficacy. Phase 2 trials are usually conducted in patients with the specific disease or disorder the drug is targeted to treat.
Every drug on the Canadian market, except generic drugs, has undergone early-phase testing. Generic drugs are replicas of brand-name drugs. They have the same active ingredients as the brand-name drugs, but may differ in how they are formulated and manufactured. In Canada, approximately three-quarters of all prescriptions filled are for generic drugs, and because generic drugs don’t have to undergo the costly, multi-phase clinical trials that brand-name drugs do, manufacturers can sell them at far cheaper prices. This doesn’t mean that generic drugs don’t undergo any testing at all, though.
For a generic drug to be approved by Health Canada for sale, it must undergo clinical trials to prove that it is bioequivalent to its brand-name counterpart. Two drugs are said to be bioequivalent if there are no clinically significant differences in their bioavailability. That is, the two drugs must release the same amount of active component into the bloodstream at the same rate and with the same quality.
Bioavailability is a measurement of the rate and extent to which the active component of a drug is absorbed into the bloodstream and becomes available at the site of action. Once the drug has entered the body, a series of accurately timed blood samples are collected in order to create a graph of the amount of the active component in the blood versus time. These data are used to reflect how quickly the active component is released and how quickly it is absorbed from the gastrointestinal tract, as well as how quickly it is metabolized, distributed, and eliminated. Two main pharmacokinetic variables are measured from these data. Based on international consensus, for most drugs, the generic and brand-name drugs are considered bioequivalent if there is no more than a 20 percent difference between their ratios of these pharmacokinetic variables. It is important to recognize that this test of bioequivalence only concludes that the drugs are not different from one another, not that they are the same. In other words, bioequivalence studies provide indirect evidence of the safety and efficacy of a generic drug.
Henri was slated to be enrolled into a clinical trial that would examine the bioequivalence between two types of fifty-milligram tablets of bicalutamide, a drug used to treat prostate cancer. One, the reference formulation, was a brand-name formulation called Casodex. The other, the test formulation, was a generic formulation made by Genpharm Inc. For the trial, SFBC Anapharm needed to enrol forty-eight “healthy volunteers,” all men eighteen years of age or over.
Before the clinical trial commenced, Henri was screened to see if he qualified. This session took place on September 3, 2005, at 10:00 a.m. After signing an informed consent form for the screening, Henri was asked questions about his general health, his medical history, and any medications he was taking. His vital signs, including blood pressure, pulse rate, respiratory rate, and oral temperature, were taken. An electrocardiogram and various blood and urine tests were also performed, and SFBC Anapharm determined that the results were normal or not clinically significant.
In my opinion, however, one test result was noteworthy: the presence of inspiratory rales. Inspiratory rales are crackling sounds that can be heard through a stethoscope. They correspond to the opening of collapsed airways in the lungs due to the presence of fluid. There are many reasons why fluid could be present in the airways, including heart disease and pneumonia. In Henri’s case, inspiratory rales were present on September 3, but they were deemed to be not clinically significant at 5:03 p.m. on September 9, the exact time and day that Henri was enrolled in the clinical trial. Henri did not disclose to SFBC Anapharm that he had a heart condition that was stabilized by medications.
In the late afternoon of September 9, Henri arrived, overnight bag in hand, at SFBC Anapharm’s test facility on Decarie Boulevard. After signing an informed consent form for the study, Henri was taken to his allocated sleeping area and was cautioned that he could not eat anything until the following day. In the morning, Henri ate his assigned breakfast, and a blood sample was taken. At 9:12 a.m., Henri was administered a fifty-milligram oral dose of bicalutamide. Although he did not know which formulation he was receiving, Henri was randomly assigned to the reference group and given Casodex.
Sixteen blood samples were taken from Henri over the next thirty-six hours, and then he was allowed to go home. Unless Henri had smuggled his heart pills into the facility, he would have missed seven doses of the medication he needed: three doses each day for just over two days. Henri returned to the facility to have blood samples taken on September 12, 13, 14, 15, 17, and 20, but he was not required to stay overnight. At each of these visits, Henri was asked a number of questions about his general health condition. He was asked if he had eaten or drunk anything that contained specific prohibited products; if he had experienced any new health problems or taken any medications he hadn’t reported at the start of the study; if he had donated blood or plasma during the study; and if he had smoked more than twenty-five cigarettes per day. It was recorded that Henri answered no to all of the questions at each visit.
Even though SFBC Anapharm had a medical doctor on site, Henri was not given a physical examination nor were his vital signs assessed at any of these study visits. The report from his last visit, on September 20, the day of his death, states that Henri provided a blood sample at 9:12 a.m. It would have taken him between twenty-five and thirty minutes to get home from the SFBC Anapharm facility after the visit. Henri collapsed as soon as he walked through his front door, at around 10:00 a.m., and he was pronounced dead at 11:20 a.m. It is very difficult to believe that Henri showed no signs or symptoms of distress at the SFBC Anapharm test facility that day.
Jeanne told her family that Henri had not been feeling well since September 11, just one day after he’d received the dose of bicalutamide. She described Henri as having the flu, yet he also complained of frequent hot flashes, dizziness, and sweating. He joked to Jeanne that maybe he was going through menopause.
