Help wanted: Human guinea pigs: A private Vancouver company tests new drugs on poked, prodded - and paid - volunteers

Friday, November 22, 2002
JOANNE BLAIN

Dennis Yano spent more than a week this March having blood and urine tests and being hooked up to a heart monitor.

He wasn't sick -- he was on vacation. And he wasn't running up bills for the provincial medical plan -- all the costs were covered by a private company, and Yano himself was being paid for his time.

Yano, a 29-year-old credit union employee, was taking part in a clinical trial, a key part of the lengthy process of taking a drug from the laboratory to the marketplace.

He spent 10 days and nights at at a clinic on the grounds of Vancouver General Hospital run by Prime Trials Inc., a private Vancouver company that conducts clinical trials for pharmaceutical and biotechnology firms, receiving low doses of a drug used to treat irregular heartbeats.

Yano earned $175 a day and the knowledge that being poked, prodded and constantly monitored might yield valuable information about how the drug works in people of Japanese ancestry, which was the focus of the study.

"It's a chance to earn some funds, and you're helping science," he said. "I have had relatives who have had heart attacks, and you think to yourself, you may not be part of a breakthrough, but it could help."

Before a company can apply for government approval of a new drug, it must go through a well-defined set of clinical trials to determine that it is both safe and effective.

They make up one of the most time-consuming and expensive parts of the drug-development process, said Dr. Jonathan Willmer, chief medical officer of Prime Trials.

"It's usually 10 years or more by the time the drug gets from discovery through final approval," Willmer said.

The cost of developing new drug is roughly $400 million to $500 million, he said, but it may run as high as $2 billion to $3 billion for some blockbuster drugs, especially those that are the first to treat a particular disease.

On average, he said, one-third of the cost of developing a new drug is spent on clinical trials, with the rest going to the initial drug discovery process, pre-clinical trials and other corporate expenses.

Prime Trials is mainly in the business of conducting phase 1 trials, the first to be conducted in humans. It has studied medications to treat everything from insomnia and arthritis to Alzheimer's disease and the rejection of transplanted organs.

It advertises in community and daily newspapers, on buses and on radio stations catering to specific ethnic groups to recruit volunteers, as well as through word-of-mouth referrals and the company's Web site (www.primetrials.com).

The ease of finding volunteers depends on the condition and the drug being studied, said Dr. Stephen Sacks, founder and CEO of Viridae Clinical Services. The private Vancouver company specializes in testing drugs to treat chronic viral infections, including hepatitis, herpes and HIV.

A trial Viridae is now conducting involves a drug to treat hepatitis C patients for whom existing treatments have failed. These patients "don't have too many good options" so recruitment hasn't been a problem, Sacks said.

But he said it was more difficult than he expected to find monogamous couples to participate in a recent study of a drug being tested to reduce the transmission of genital herpes, partly because the drug was already on the market.

Like Prime Trials, Viridae advertises in community and ethnic newspapers and on its own Web site (www.viridae.com). As well, Sacks said it may consider using online recruitment services such as... www.myhealthcanada.com in the future.

Viridae conducts all phases of clinical trials, but Sacks said "the specialty that gives us our reputation internationally is phase 2 and 3," the last two phases before regulatory approval. "We designed the gold-standard clinical trial model for studying viral infections in normal patients."

Willmer said there are two main motivations for taking part in a clinical trial.

"We get a lot of students, for example, and people who are living up at Whistler and want to ski all year and need some extra money to support themselves," he said.

"The rest are doing it for altruistic reasons. They tend to be an older group who might have a relative who has some sort of illness, and they feel they are doing something positive.

"And some of the older people even do it for social reasons," he said. "They develop some friendships -- it's sort of like summer camp for adults."

Some repeat participants "make it almost a career," said Willmer. One man from London, England was travelling in Vancouver and signed up for a trial to make a bit of money to pay for his trip, he said.

But there are ethical issues involved in offering compensation for participating in a drug trial, said Sacks.

"You don't want people participating in a study who are doing it just for money, because money may cause people to make decisions they shouldn't be making," he said. "It shouldn't be a primary motivator."

At Prime Trials, compensation for volunteers is based on "how much time we expect them to give up and how much of a hardship it is for them," said Willmer. "If they are there for only two hours and have just a blood test, they might only get $25, but if they stay overnight, they might get $175."

Viridae offers payment of $25 to $50 per visit in some studies, but in some late-stage studies that do not involve the use of placebos, Sacks said "the compensation is the drug." In some cases, he said, participants might be offered a year's supply of the medication after they complete the trial.

It's essential to make sure participants understand the experimental nature of the trial, Sacks said, and that in a double-blind trial, they won't even know whether they are getting the real drug or a placebo.

Yano said he was given a lot of information that allayed his early fears about taking part in a drug trial.

"You are kind of hesitant at the start," he said. "The first thing you think of is: 'Am I going to be a guinea pig? What is this going to do?'

"People joke around and ask you whether you're going to grow a third arm." But, he said, "the staff are great -- they are really supportive, they answer all your questions."

In addition to phase 1 studies, Prime Trials also runs early phase 2 trials and bridging studies, which compare how a drug works in a particular ethnic group.

The first trial in which Yano took part was to compare the effects of a drug to treat irregular heartbeats on different generations of Japanese-Canadians, both smokers and non-smokers.

He recently volunteered for a bridging study to compare how various medications, ranging from cough medications to sedatives, are metabolized by Caucasians and first-, second- and third-generation Japanese.

The stakes are high in clinical trials -- 46 per cent of drugs fail at some point in the process, Willmer said. By the end of phase 1 trials, a drug has just a 15-per-cent chance of making it to market, but that jumps to 70 per cent by the end of phase 3 trials.

Even after they win marketing approval, about 15 per cent of drugs will fail, he said, for reasons ranging from ineffective marketing to unanticipated side effects or drug interactions that in the most drastic cases can lead to a product being pulled off the market.

The industry is trying to improve its success rate by moving more quickly into phase 2 studies to establish drug's effectiveness, he said.

Canada reformed its clinical trial regulations last fall to speed up the process of testing new drugs, said Willmer. "We're hoping that's going to bring more business into Canada in terms of drug development work."

jblain@pacpress.southam.ca

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THE CLINICAL TRIAL PROCESS

Pre-clinical trials

These initial tests are designed to determine the toxicology of the drug and how it is metabolized by the body. They are usually conducted in animals because "we have to know all these kinds of things before we give the drugs to humans," said Dr. Jonathan Willmer of Prime Trials Inc. Animal testing is "a controversial area, and the industry is looking for ways of getting around that more and more." For example, he said, some drugs can now be tested on human cells grown in a lab rather than on animals.

Phase 1

These trials are the first to be conducted on people. Here, the focus is on "safety and tolerability" of the drug being studied and usually involve low doses of the drug, Willmer said. Researchers are looking at both the physiological effects of the drug (its effect on heart rate and blood pressure, for instance) and how it works in body (side effects and the length of time it takes to work and is eliminated from the body). Phase 1 studies are usually done on small groups of healthy volunteers unless the drug is known to be toxic even in small doses, such as drugs used to treat cancer or HIV.

Phase 2

These trials are "really where you prove that the drug works," Willmer said. They are meant to establish that a drug is both safe and appears to work the way it was designed to. These trials are the first test of the drug in patients with the condition it is designed to treat, he said, and may involve 100 to 300 patients in more than one city.

Phase 3

This is a multi-centre study involving thousands of patients that may take two or three years to complete, and it's the most expensive -- about 45 per cent of the cost of the entire clinical trials process. "These are what we call pivotal trials -- these are the ones that statistically show the drug is effective and safe, and these are required studies for the regulatory agencies," Willmer said.

Phase 4

These follow-up studies are carried out after the drug has received regulatory approval and is on the market. They look at whether the drug has any long-range side effects and whether it is more cost-effective than similar drugs. Provinces won't reimburse patients for a drug through plans like Pharmacare unless it is shown to be cheaper or more effective than other drugs to treat the same condition, Willmer said.