Tuesday, July 7, 2015
Health Affairs Blog
July 6, 2015
Serious Risks And Few New Benefits From FDA-Approved Drugs
By Donald W. Light
Over the past year, the U.S. Senate and The New York Times have been
investigating the failure of the nation's auto safety regulators to
protect citizens from cars with occasionally dangerous faulty devices.
But neither august institution has paid attention to the Food and Drug
Administration's (FDA) failure to protect the 170 million Americans who
take prescription drugs from adverse reactions that are killing more
than 2,400 people every week. Annually, prescription drugs cause over 81
million adverse reactions and result in 2.7 million hospitalizations.
This epidemic of harm from medications makes our prescription drugs the
fourth leading cause of death in the United States. Including
hospitalizations and deaths from prescribing errors, overdosing, and
self-medication, drugs move up to third place.
Below I describe the biases that appear throughout the drug development
process, from initial research to FDA review and approval. I conclude
with recommendations that would reduce drug development costs and ensure
that drugs are only approved if they are safe and significantly more
effective than already existing medications.
Figure 1. Few Clinical Advances in a Decade and Hundreds of Other Drugs
Approved for Promotion
Number of New Drugs, 2002-2011
2 - Breakthrough
13 - Real Advance
61 - Some Advantage
918 - Little or No Improvement
(The exhibit focuses on France, a country whose consumer-oriented drug
market features an array of products similar to the U.S.)
Flooding the market with hundreds of minor variations on existing drugs
and technically innovative but clinically inconsequential new drugs,
appears to be the de facto hidden business model of drug companies. In
spite of its primary charge to protect the public, the FDA criteria for
approval encourage that business model. The main products of
pharmaceutical research are scores of clinically minor drugs that win
patent protection for high prices, with only a few clinically important
advances like Sovaldi or Gleevec.
This business model works. Despite producing drugs with few clinical
advantages and significant health risks, industry sales and profits have
grown substantially, at public expense. Companies spend 2-3 times less
on research than on marketing to convince physicians to prescribe these
The Center for Drug Evaluation and Research (CDER) is the FDA division
responsible for determining whether new drugs should be approved. Its
funding, however, now largely comes not from taxpayers but from the
companies submitting their drugs to CDER for review.
This clear conflict of interest and approving so many new drugs with few
clinical benefits serve corporate interests more than public interests,
especially given the large risks of serious harm. Direct and indirect
costs to society far exceed the cost of funding the FDA as a public,
independent review body.
Peer-reviewed studies already demonstrate how pharmaceutical companies
manipulate FDA rules to generate evidence that their new drugs are more
effective and less harmful than unbiased studies would show. The
industry then recruits teams of medical writers, editors, and
statisticians to select and repackage trial results into peer-reviewed
articles that become accepted as reliable medical knowledge.
Based on his investigations, Marc Rodwin concludes, "Scholarly studies
have revealed that drug firms design trials that skew the results and
that they distort the evidence by selective reporting or biased
New FDA policies to get more drugs reviewed faster so that they can
reach patients sooner result ironically in even more drugs being
approved with less evidence that they are either safer or more
effective. Faster reviews mean the chance that a drug will generate an
FDA warning of serious harm jumps from one in five to one in three.
To protect the public from unsafe and ineffective drugs and earn public
trust, the FDA and Congress must acknowledge the biases described here
that result from pharmaceutical corporations financing the public
regulator. They should also require two changes: that new drugs
demonstrate patient-based clinical advantages through comparative
trials, and that these trials be based on the population that will
actually take a drug.
These changes would reduce the flood of minor variations shown in
Exhibit 1 and the subsequent billions spent on them.
Comment by Don McCanne
Outrageously high pricing is not the only problem we face with new
pharmaceutical products. We are inundated with new drugs that provide
little or no improvement over existing products. This exposes us not
only to the higher prices driven by new patents, but also to the
potential of serious adverse effects that may not be recognized until
the new drugs have been on the market for a period of time.
Under a single payer system, drug formularies should include only those
products are reasonably effective, comparatively safe, and cost
effective. Since the industry does not provide us with those assurances,
it is the responsibility for the government to step in and do so.
at 5:57 PM