E-DRUG: Public misinformed about seal of approval from US drug agency
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Between 2005 and 2011, nearly half of all new drug formulations in the US
were approved without companies having to demonstrate a tangible benefit.
*Public misinformed about seal of approval from US drug agency (23 January 2014)*
https://theconversation.com/public-misinformed-about-seal-of-approval-from-us-drug-agency-22319
Between 2005 and 2011, nearly half of all new drug formulations in the US
were approved without companies having to demonstrate a tangible benefit,
such as relieving disease symptoms, extending life, or improving someone’s
ability to go about normal activities.
What patients really want is evidence that the drug they are taking will
actually improve their condition. But the FDA, the American drug regulator,
doesn’t routinely consider this for new molecular entities (NMEs) – drugs
that have innovative chemical structures that have never been marketed
before.
The findings come in a new paper by Nicholas Downing of Yale University and
colleagues, part of a series on the drug approval process published in the
Journal of the American Medical Association (JAMA), that found there was
wide variation in the quality of evidence considered by the FDA. They also
found that nearly two out of five drugs approved by the FDA was brought to
market after a single pivotal trial.
A second paper in the series documented the lack of data required by the
FDA when it considers approvals for medical devices – the study found that
only 14% of high-risk medical devices, such as pacemakers and other
cardiovascular implants, were assessed in one randomised control trial.
Both studies strongly suggest that the FDA is approving products that may
not have accurate risk-benefit profiles, which could place patients at risk.
*Sleeping watchdog?*
While patients and physicians rely on the FDA to serve as an appropriate
gatekeeper and watchdog, opinion polls reveal the public is misinformed as
to what the FDA seal of approval actually means. For example, a national
randomised trial conducted in 2011 found that 39% of US adults believe the
FDA approves only “extremely effective” drugs, and 25% believe the agency
only approves drugs that do not have serious side effects.
In addition to debunking these commonly held myths, the Downing paper is
part of a long line of comprehensive studies that have highlighted the
limitations of the FDA’s review process for new drugs before they hit the
market.
Because pre-market studies are limited in duration and scope, they often
fail to capture later adverse events, or adverse effects that only happen
to a small percentage or sub-population of patients. At the same time,
pre-market studies often include research subjects who are not
representative of “real-world” patients. For example, studies typically
don’t include patients who are taking multiple medications.
The findings also affirm what commentators and FDA Commissioners have long
argued – that the FDA should take a more proactive role in reviewing drugs
and medical devices once they hit the market, to make sure adverse events
are logged and considered.
No one wants an approval process that drags on for a long time. So when it
comes to catching later problems, the only meaningful alternative is to
require that drug and medical device manufacturers actively review
post-market data and report their findings to the FDA – something that
needs manufacturers to actively engage with.
*Inside the FDA*
Since the 1960s, the total number of drugs approved has been falling on
average, according to data collated by The Conversation. This is happening
at the same time as the cost of research and development is going up. In
another study in the JAMA series, six FDA scientists looked at the reasons
why approvals for drugs might be delayed or denied. According to the paper,
between 2000 and 2012 a half of NMEs were approved when first submitted to
the agency and nearly 75% were ultimately approved. Some of the reasons why
new compounds failed to earn FDA approval included inadequate performance
and problems with doses.
It’s a hugely important paper because information from the FDA on why drugs
aren’t approved is limited, due to data sharing issues (despite
recommendations from its own transparency taskforce).
The study is sure to provide meaningful guidance to pharmaceutical
companies as they contemplate, prepare or conduct pre-market studies. At
the same time, however, the article raises complex questions as to the
proper role of the FDA as regulator, industry collaborator, and promoter of
public health. In many respects the FDA and industry are collaborators –
industry’s responses to new regulations are taken seriously by the agency,
and lobby groups have long had significant influence over the legislation
that sets the legal limits of FDA’s authority. Yet, the agency’s primary
mission is to ensure that marketed products are safe and effective, though
the FDA characterises itself as a public health agency that must “promote
health, prevent illness, and prolong life”.
As Marcia Angell, former editor of the New England Journal of Medicine, has
observed, “there is growing evidence that … [the FDA] has become the
servant of the industry it regulates.”
Taken together, the articles support calls for the FDA to be more robust in
the surveillance of marketed drugs and medical products. Simply stated, we
need to know if the products we are using actually work. As the Downing
study shows, the FDA’s pre-market review process isn’t clear on this and
the public remain none the wiser.
Jurgen Hulst
PSM Specialist
JHulst <hulst.jurgen@gmail.com>