Today, The Guardian UK published a story that should be shocking–but isn’t: "More than Half of U.S. Drug Studies Never See the Light of Day." This serves as further proof–if we needed it– that pharmaceutical companies should not be allowed to control what doctors and patients know, and don’t know, about new drugs.
The story follows below.
More than half of US drug safety studies never see the light of day
Only 43% of the evidence of safety and efficacy that the US Food and Drug Administration uses to approve drugs is published in scientific journals. The authors of the survey say this amounts to "scientific misconduct."
James Randerson, guardian.co.uk,Tuesday September 23 2008 10:46 BST
The results of more than half of all clinical trials that demonstrate the safety and effectiveness of new drugs
are not published within five years of the drug going on the market,
according to an analysis of 90 drugs approved by US regulators between
1998 and 2000.
The researchers, who traced the publication or otherwise of 909 separate clinical trials
in the scientific literature, wrote that the failure of drug companies
to publish the evidence relating to new medicines amounted to
"scientific misconduct". They said it "harms the public good" by
preventing informed decisions by doctors and patients about new
medicines and by hampering future scientific work.
Sir Iain
Chalmers, who is director of the James Lind Library in Oxford and a
founder of the Cochrane Collaboration, a respected organisation that
reviews medical evidence, said that it was vital that all data on new
medicines be made public.
"Patients may otherwise suffer or die
unnecessarily," said Chalmers, who was not involved in the work. "The
people who participate in a trial have a right to expect that their
participation and their data will be made available publicly so that
people can take whatever decisions seem appropriate in the light of
that information."
The US researchers who carried out the study
searched the academic literature for publication of the trials that
drug companies relied on to convince the US Food and Drug
Administration that their new products were safe and effective and so
worthy of market approval.
Information that is used to convince
the regulators is not necessarily subsequently published for public and
scientific scrutiny, but the scale of the missing information was found
to be vast.
Five years after each of the 90 drugs was first
available for patients, only 43% of the studies supporting the drugs’
use had been published, with most publication happening in the first
one or two years. In the case of one product – an antibiotic – the
researchers could not find a single supporting trial in the scientific
literature, while five trials were published twice and one was
published three times.
The team also found evidence for a
"publication bias". Trials with statistically significant results were
more likely to be published than those with non-significant results, as
were those with larger sample sizes.
"In the years immediately
following FDA approval that are most relevant to public health, there
exists incomplete and selective publication of trials supporting
approved new drugs," Prof Ida Sim and her colleagues at the University of California, San Francisco, wrote in the journal PLoS Medicine.
One
possible explanation for the scientific data not being published is
that drug companies hold back publication of the results that are least
flattering to their new drugs. Another possibility is that academic
journal editors are less inclined to publish papers on trials that have
negative or ambiguous results.
"Regardless of the cause,
publication bias harms the public good by impairing the ability of
clinicians and patients to make informed clinical decisions, and the
ability of scientists to design safer and more efficient trials based
on past findings," the authors wrote. "Publication bias can thus be
considered a form of scientific misconduct."
The reporting of
clinical trial results should have improved since the period analysed
by the researchers, because the 2007 FDA Amendments Act mandated basic
results reporting for all trials supporting FDA-approved drugs and
devices. However, the researchers said it remained to be seen whether
clinical reporting would improve.
The new law could even have the
opposite effect. "Might sponsors feel less compelled to publish
equivocal trials because the basic results will already be in the
public domain?" they speculated.
What I find amazing is that doctors who prescribe medicines “off label” have no coherent mechanism to find out if this type of use works. They seem to depend upon word of mouth about anecdotal reports (and perhaps unvetted information leaked to them by drug reps).
The drug firms are happy with the mechanism, it boosts sales of their products without having them having to go through clinical trials. If the above report is correct, in some cases they may even know that a drug is ineffective, but by not reporting this, they allow such useless off label to continue.
A simple solution (in principle, not politically) is that every study that is undertaken has to place their results in a publicly available database, regardless of whether peer reviewed journals are willing to publish the results or not.
I think there is now a registry of drug trials underway, but nothing for the outcomes.
Everyday we seem to hear new ways that corruption has seeped into our society. From the financial markets, to health care, to environmental regulation, the public good gets sacrificed to greed.
A society can’t survive for long in this type of environment.
This is a difficult issue because academic journals are free to publish whatever they like. The medical science literature is vast and heterogeneous, running the gamut from high-impact, prestigious journals to the equivalent of the Weekly Shopper; the term “peer-reviewed” covers a lot of posssibilities. A key (and unobtainable) piece of information is the publication tracking of theses studies — how many journal submissions, to which journals, etc. It would matter a great deal to discover if, for example, many of the studies were never submitted at all for publication, or if the authors made initial submissions but did not persist in resubmitting rejected articles.
Chris and Robert–thanks very much–
Chris, you wrote: “It would matter a great deal to discover if, for example, many of the studies were never submitted at all for publication, or if the authors made initial submissions but did not persist in resubmitting rejected articles.”
I agree. And we need someone to track whether drug-makers are submitting their research–see my comment to Robert below.
Robert–
You wrote: “A simple solution (in principle, not politically) is that every study that is undertaken has to place their results in a publicly available database, regardless of whether peer reviewed journals are willing to publish the results or not.”
Yes, I agree. And then we need unbiased (no financial connections to manufacturers) people in the federal govt’ watching that database, pulling out negative results that haven’t been published, and publishing them them as widely as possible– through the mainstream media, medical journals and the blogsphere.
I agree that this is politically difficult–but not impossible. Most voters could understand that manufacturers shouldn’t be able to supproess negative findings about their products . ..
We just need to keep comparing medical products and treatments to automobiles. People are outraged about the idea of Detroit hiding information about potentially dangerous defects in cars.
We should hold the healthcare industry to the same standards of outraged.
This blog really more informative for safety and efficacy that the US Food and Drug Administration.
Great resources,Thank for information……….