The
short answer is this: To stop the pharmaceutical and device
industries from hiding the results of clinical trials
that did not show a benefit to their products. And to
stop them from withholding findings that indicate significant
harms associated with their products.
In
a perfect world, an independent group of researchers would
conduct the clinical trials designed to see whether a
new drug is safer or more effective than the drugs already
available for the same condition. A head-to-head comparison
would be conducted for at least one year. If the new drug
has no advantage over the older drugs, it wouldn't be
allowed on the market.
The
real world scenario, unfortunately, is far less than perfect.
To receive FDA approval, a drug company need only provide
two trials that proved its drug is better than nothing
(a placebo). Most trials last only a few months. In 2002,
Washington Post reporter, Shankar Vedantam , described
a new analysis of the trials conducted by drug companies
that made drugs to treat depression, such as Prozac, Paxil,
and Zoloft. The majority of these trials found that placebos
were just as effective as the antidepressants, and in
some trials, the placebos worked better. But the public
never learned about the trials that found antidepressant
were ineffective. The drug companies withheld their existence
and submitted the FDA-required two trials that did show
a benefit to their drug. The analysis described by the
Washington Post reporter also revealed that the makers
of Prozac had to conduct five trials to obtain two that
were positive, and the makers of Paxil and Zoloft had
to conduct even more.
The
issue of drug companies withholding negative trial results
has slowly become more acute in the last 15 years because
government funding of trials has decreased considerably.
The majority of all drug trials are now conducted by the
sponsoring drug companies. And it is becoming increasingly
evident that the drug companies get the results they want.
A 2003 review published in the BMJ (British Medical Journal)
found that studies sponsored by pharmaceutical companies
were far more likely to have outcomes favoring the sponsor
than were studies with other sponsors . The problem is
not limited to pharmaceutical research. For example, in
a 2003 review of all studies that looked at total hip
arthroplasty implants, 75% were commercially sponsored,
of which 93% reported positive outcomes; whereas independently
funded researchers reported good results in only 37% of
studies.
This
critical issue did not begin to penetrate the public's
consciousness until June 2004, when New York State attorney
general, Eliot Spitzer, filed a lawsuit against the British-based
pharmaceutical company, GlaxoSmithKline. The pharmaceutical
company, one of the world's largest, was accused of “persistent
fraud” for failing to tell doctors that some of its studies
of the antidepressant Paxil showed that the drug didn't
work in adolescents and might lead to suicidal thoughts.
The lawsuit has since been settled.
For
more than a decade, a small group of medical journal editors
and researchers has periodically offered a solution that
has only now gained serious attention: All clinical trials
should be registered at the onset. And the registry must
be publicly available. Only then will doctors and the
public have complete information about all the research
that has been conducted on a particular drug or device.
Predictably, there is a great deal of resistance to this
idea from industry. Congress is considering legislation,
entitled Fair Access to Clinical Trials Act, which will
mandate the early registration of clinical trials. Unfortunately,
there are many problems with this proposed legislation,
not the least of which is the failure to include more
than drug trials in the mandate.
Some
journal editors have taken a strong stand on this issue.
Last year, a new policy was announced by 11 editors of
the world's most prestigious journals, including the New
England Journal of Medicine, The Lancet, Canadian Medical
Association Journal, and the New Zealand Medical Journal.
They will not publish results of any trial that has not
been registered in a publicly available database before
the first participant is enrolled. The policy is aimed
at foiling researchers who change the goals of a study
while it is in progress and to stop drug companies from
withholding the existence of trials that show negative
results.
In
May 2005, the 11 editors, now called the International
Committee of Medical Journal Editors, updated its policy
about the registration of clinical trials. The journals
represented by this committee will not publish trials
that are not publicly registered by July 1, 2005. The
editors have given the drug companies until September
13, 2005 to register ongoing trials. Other editors from
other medical journals have now joined the committee.
The policy will be successful only when all medical journals
take a similar stand.
The
Committee defined clinical trial this way: "Any research
project that prospectively assigns human subjects to intervention
and comparison groups to study the cause-and-effect relationship
between a medical intervention and a health outcome.
By ‘medical intervention' we mean any intervention used
to modify a health outcome. This definition includes drugs,
surgical procedures, devices, behavioral treatments, process-of-care
changes, and the like.”
Consumers
have a major stake in this issue. We cannot make informed
medical decisions if we cannot trust the research. And
clinical trials cannot be conducted without us. People
who agree to participate in trial do so with the hope
of helping themselves or future patients. To participate
in a trial that never is made public means that people
have risked the harm of the treatment to no benefit.
The
Center for Medical Consumers recommends that people refuse
to take part in any clinical trial that is not registered
before recruitment. At present, the nearest thing to a
publicly available registry is www.clinicaltrials.gov
This Web site lists government-sponsored trials; it
has been criticized for having incomplete information.
Some pharmaceutical companies have begun to list their
clinical trials on their respective Web sites.
Maryann
Napoli, Center for Medical Consumers © July 2005
