INDEPTH: FAINT WARNING
From coloured tabs to computerized signals:
How Canada tracks dangerous drugs
Moore | CBC News Online
| February 17, 2004 (Updated Dec. 8, 2005)
It was a pill to help people sleep but it ended
up as a wake-up call to the world of drug regulation.
In the early 1960s, an abnormally high number of children
were born with severe deformities: limbs were missing, or
only half there, fingers and toes were found at the end of
what looked like flippers.
It turned out that a tranquillizer, marketed as the safest
ever, was causing the problems. It was commonly prescribed to pregnant women for morning sickness. The drug was thalidomide.
Devastating for the families affected, the discovery set
political wheels in motion around the world. Regulators realized
with tragic clarity that it was insufficient to establish
the safety and effectiveness of a drug before it went on the
market. A system was needed to track medications once the
general population had access to them.
In 1962, the year thalidomide was pulled from the market,
the Ministry of National Health and Welfare, as Health Canada
was then called, asked the Royal College of Physicians and
Surgeons to study Canada's drug approval process. The college
suggested some form of surveillance to track drugs already
on the market as a way of detecting potentially dangerous
The U.S. Food and Drug Administration, which had started
work on a reporting system in the late 1950s, implemented
a voluntary reporting system in 1963. (The U.S. had refused
to market thalidomide.)
The following year a Canadian parliamentary committee recommended
a similar system for collecting reports of suspected adverse
drug reactions (ADRs). In 1965, National Health and Welfare
established the Drug Adverse Reaction Reporting Program.
Three years later the World Health Organization
started the Collaborating Centre for International Drug Monitoring,
with 10 founding countries, including Canada, the U.S. and
the United Kingdom.
Canada's system of ADR reporting was set up by Dr. Ed Napke,
a man who liked to see what was going on. Although the reporting
system was computerized, Napke developed a system of "pigeon
holes" into which reports were filed. Coloured tabs were
attached to reports of severe or unusual reactions as they
Dr. Ed Napke filing reports in his system of "pigeon holes"
When clusters of coloured tabs began to emerge, Napke and
his small team had a visual cue that something might be wrong.
In the world of post-market drug surveillance, such cues are
called signals, and signals prompt investigations that can
lead to warnings, or even to a drug being pulled from the
Now, nearly 40 years later, the surviving thalidomide children
are middle-aged, and Canada's post-market surveillance is
run by the Canadian Adverse Drug Reaction Monitoring Program
of Health Canada.
Napke's pigeon holes are long gone, and the signals are now
contained in a database called the Canadian Adverse Drug Reaction
Information System, or CADRIS.
But critics complain that all is not well,
that Health Canada is reactive and not picking up on trends
There are some parents who say Canada's system of post-market
surveillance has failed them; notable among them are Susan
and Chris Atkinson. Their six-year-old daughter Ashley died
in February 2001.
Ashley went to the hospital with croup. She woke up one night
having difficulty with her breathing. Four days later, she
was dead. She had been sedated using a drug called propofol.
A coroner's jury didn't blame the drug, but in testimony
two medical experts linked Ashley's death to propofol toxicity.
Health Canada's CADRIS database, acquired by CBC News through
federal Access to Information laws, lists 13 reports of suspected
adverse reactions to propofol in children between 1993 and
2003. Three of those patients died. Ashley was the third.
"Why is it taking them so long to do something about
these drugs that are reported and flagged over and over and
over again?" asked Susan Atkinson after seeing the listings
from the database.
Dr. Supriya Sharma, Health Canada
According to Health Canada, that's a very complicated question.
When asked about how good the country's adverse drug reaction
reporting is, Health Canada spokesperson Dr. Supriya Sharma
split it into two considerations: quality and quantity.
Sharma and Health Canada concede that the ADR system receives
only a fraction of all suspected adverse drug reactions in
Canada, somewhere between one and 10 per cent.
Currently, 10,000 reports are entered into the CADRIS database
annually. In 2002, 450 of those involved a patient who died
as the result of a suspected adverse drug reaction.
But Sharma counters that it's not the number
that counts, it's the quality of the reports. Those reports
are made on a voluntary basis by health professionals, patients
and consumers. Drug companies, on the other hand, are required
by law to report any known serious or unexpected adverse drug
Health Canada says it determines the quality of the reports
by using the database in combination with other information,
such as medical literature, media reports, international databases
of suspected adverse drug reactions and statistics on drug
usage in Canada.
Health Canada also cautions that, due to underreporting,
it's impossible to project real rates of adverse drug reactions
based on the numbers found in their database. So for example,
just because there are database listings for three children
who reportedly died from a suspected drug reaction to propofol,
you can't definitively conclude that 30 children, or 300,
have died in Canada as a result of suspected drug reactions
to the same drug.
The database is used to find signals and warning flags. It’s
also used to corroborate trends found in other countries or
in medical literature.
While the quality of the data in the database may not be
perfect, it is an integral part of Canada's drug safety program.
Investigations started by those tracking Canada's ADR reports
can lead to labelling changes, a manufacturer issuing a Dear
Doctor warning letter, or the decision to pull a drug from
the market. (Health Canada can step in and do this, but the
usual practice is for the manufacturer to take action in consultation
with Health Canada.)
Critics complain that something needs to be done
to improve the system. Dr. Gordon Guyatt, a specialist working
at McMaster University, suggests mandatory reporting.
Others, such as Dr. Eric Wooltorton, say doctors need an
incentive to improve the quality of the reports. Faced with
a full waiting room, physicians will choose treating patients
before filling out a Health Canada form.
And still more critics, including the Atkinsons, say Health
Canada needs to track trends more aggressively in order to
pick up the warning signals. That's because, as the case of
Ashley Atkinson illustrates, the database of ADR reports,
blemishes and all, often contains the signals necessary to