Monday, September 9, 2002

Patient dearth dogs clinical trials
New drug approval slowed as a result

By Kevin Marron

Koenraad Blot is worried about an issue that few other doctors face – a shortage of patients.

As director of clinical research operations for Pfizer Canada Inc. of Kirkland, Que., Dr. Blot is concerned that the new drug-approval process may be slowed down because pharmaceutical companies are having a hard time finding enough patients willing to participate in clinical trials.

“With more and more drugs under development, we need to access more patients,” he says. “The regulators are asking for more data and rightly so. We could possibly come to a situation where there is some competition in getting the right patients in trial or getting enough patients in trial to get a drug approved.”

Dr. Blot says he has already encountered situations where research centres decline to participate in testing a new drug because they have too many other trials in progress.

“If we don’t get patients in our trials, we don’t get our trials to the point where we can submit then to authorities and that eventually means less drugs,” he says.

Encouraging patients to participate in clinical trials has become a major priority for the pharmaceutical industry, which can lose more than $1-million for every day that a single drug is delayed waiting for approval.

Failure to find patients in time is the cause of 85 to 95 per cent of all days lost during clinical trials, according to CenterWatch, a Boston, Mass.-based subsidiary of Medical Economics Co., a part of Toronto-based Thomson Corp.

Pharmaceutical companies are facing challenges not only in finding patients to participate in clinical trials but also getting then to stay in trials, according to Robin Kerbel, vice-president of Axon Medical Communications Group, a new company focused on clinical trial recruitment. “Patients are wary. They need enough information to make an informed decision,” says Ms. Kerbel, whose company is a division of National PharmaCom, a part of National Public Relations (Toronto) Ltd.

Few members of the public understand what is involved in clinical trials, says Dr. Blot. There are four phases of trial that new drugs go through, all carefully monitored under government regulations, scientific and ethical guidelines, says.

The first phase involves early studies, typically on healthy volunteers, who may be paid for their time as they submit to tests examining how the drug reacts with other medications.

The second phase involves the drug proving for the first time in humans that it does what it is supposed to do, says Dr. Blot, noting that patients participating in these trials are usually people who are sick and strongly motivated to try a new treatment. In cases of serious illness, they may be “grasping at the last straw because they know there’s nothing else out there,” he says.

The third phase involves comparing the new drug, either with a placebo (a pill that does not contain any medication) or with other existing treatments, to find out whether the drug offers any advantage over existing medication. These trials typically involve 10,000 patients and “they’re not always easy to find,” Dr. Blot says.

The final phase involves following up on the real-life use of the drug after it comes on the market; finding patients for these studies is not usually an issue, Dr. Blot says.

When patients participate in a phase-three trial, they are divided into two groups. One receives the new drug and the other is a “control group” that gets either a placebo or existing medication for the condition that the new drug treats.

A placebo is only used for minor ailments, such as mild hypertension, where it won’t harm patients if they go a few more months without treatment. For more serious illnesses, the control group must receive the best possible existing treatment, Dr. Blot says.

Patients participating in a trial of this type are not told which group they are in, says Dr. Blot, noting that there is something of a gamble involved, though the risk is minimized by researchers and the guidelines they work under.

“As long as a drug is being treated for efficacy, it doesn’t hold any promise of being better that what you’ve got – that is a gamble that a cancer patient who goes into clinical trial must face,” he says. “Either you get what everyone else is getting or something new that has at least the promise of delivering something better.”

Canada offers a good environment for conducting clinical trials because of the high standard of medical and scientific expertise available, but the existence of a public health care system takes away one incentive that motivates patients in many other countries to participate in trials, according to Dr. Blot.

That is that patients involved in a clinical trial invariably get the best possible care and attention, whether they are in the group taking the new medication or the control group – a huge motivating factor for people who don’t have access to high-quality care, he says.

Even in Canada, this could be a consideration for people interested in participating trials, according to Ellen Hodnett, a professor of nursing at the University of Toronto, who has been involved in many clinical studies.

“You’re likely to get better care than usual because the bar is set higher. Researchers have to show that they’re going to monitor your health and well-being systematically throughout the trial,” she says.

Until recently, it has been largely up to the clinicians conducting the trials to recruit patients, who are often people already under their care or referred to them by colleagues. But a shortage of volunteers is prompting may pharmaceutical companies to seek the help of marketing professionals to find patients and persuade them to participate in drug trials, says Ms. Kerbel, who adds that “scientists aren’t really the right people to communicate with the public.”

A key reason why the old referral system has broken down is that ethical bodies overseeing clinical trials now frown on the practice of paying physicians for referring patients, according to David Kaplan, a researcher at the Joint Centre for Bioethics at the University of Toronto and chief resident in family medicine at North York General Hospital.

“The loss of finders’ fees has closed up a large well of recruitment traditionally used,” he says.

In an attempt to fill this gap, Dr. Kaplan has started a business called myhealthCANADA.com that uses a Web site to put patients in touch with researchers conducting clinical trials. He says the site, which now lists 70 trials across Canada, charges researchers to put up their projects but is free for patients.

…Nevertheless, Marc Levine, a professor in the faculty of pharmaceutical sciences at the University of British Columbia and chairman of the research review committee at B.C.’s Children’s and Women’s Hospital, warns that many clinical trials are testing what he calls “me too drugs” – products developed to give pharmaceutical companies a slight edge in the marketplace, but offering no major improvement over existing medication.

He advises patients to ask questions before entering a clinical trial to make sure that the drug they will be testing offers a genuine prospect of benefiting themselves and others.

Still, the strongest motivation for entering a clinical trial is a sense of altruism, says Dr. Blot. “Participating in a clinical trial is very much a service to your community. It is a worthwhile cause to participate in something that can benefit if not you, then other people.”

Special to The Globe and Mail