A few days ago I made
note of an article in the NEJM, about proposed changes in the
process for FDA approval of new medication. (A Proposal for Radical Changes in the
Drug-Approval Process, by Alastair J.J. Wood, M.D.)
At the time, it wasn’t possble for me to do justice to the
paper. It still isn’t but at least I will be able to make a
couple of points.
I’ve taken some shortcuts in this post, not explaining some of the
technical aspects of drug discovery and development as much as I
usually do. As a result, this post might not make a lot of
sense if you have not read the article that I am writing about.
Sorry about that. If there are things that are not
clear, Dr. Woods article should make them clear.
The author makes the following four suggestions:
- An extended period of exclusivity should be offered to drug
manufacturers after the completion of FDA-mandated studies that
demonstrate a drug’s long-term safety.
- Provide incentives for the completion of these [phase IV]
commitments by offering only a limited, shorter period of exclusivity
with accelerated approvals.
- [The] initial approval would provide only a limited period
of exclusivity during which the sponsor would have to demonstrate that
patients also benefited with respect to a clinically meaningful end
point (i.e., meaningful improvement in function or a reduction in
morbidity or mortality). The timely provision of such data would result
in an extension of the period of exclusivity.
- Once an area was designated as being high need and high
risk, an extended (i.e., longer than current) period of exclusivity
would be available to manufacturers of successfully developed drugs in
Greg, who blogs at Information is Free,
noted that nothing in these proposals addresses the high cost of
prescription drugs. At first, I was going to object, on the
grounds that the approval process is entirely separate from the drug
price issue. But of course, they are not separate at all.
For one, the potential for big profits can provide an
incentive to take shortcuts in the approval process, and to shirk
safety testing. At the same time, though, the potential for
big profits is the only thing that justifies the large investments and
great risks that are taken by pharmaceutical companies. So
there really is not any way to separate the cost issue from the
My suggestions are different from those of Dr. Wood. First, I
would do away with the current practice of starting the clock on
exclusivity at the time that the patent is filed. I would
give the company a set period of exclusive marketing rights, starting
from the day of final FDA approval. By starting with the date
of patent filing, there is a greater incentive for the company to rush
through the approval process. The more time they spend with
premarketing safety tests, the shorter the effective patent life.
That is not good.
While there always will be an incentive to get the drug to market as
quickly as possible, it would be good to take some of the pressure off,
and give companies some breathing room. We do not necessarily
want these things rushed to market. Admittedly, this is a
complex issue, but making this one change would get rid of some of the
I would not extend the patent life for companies that complete studies
on long-term safety. What I would do instead, is provide some
limitation on liability. Extending the effective patent life
would tend to drive costs up; limiting liability would tend
to drive costs down.
I am in complete agreement with proposals # 2 and 4. In many
cases companies have agreed to do phase IV (postmarketing surveillance)
studies, then simply failed to do them. The FDA does not have
the authority to punish companies directly, so there is little they can
do to enforce these agreements. Proposal #2 would,
presumably, make it unnecessary to enforce the agreements, because the
incentive would be so strong.
Having said that, it occurs to me that we should take a look at the
FDA’s lack of enforcement authority. I could be that they
need a little more bite. Or, what might be better, would be
to have a separate agency to do the enforcement. The FDA as
it stands seems to be highly susceptible to industry influence.
Therefore, having a separate agency might be better.
Proposal #4 gets to the problem of companies directing discovery and
development efforts to market “me too” drugs. Although such
products can be useful, the argument is that the development of second,
third, etc. drugs in an existing class should be a secondary goal.
It would be more beneficial to society, if those efforts were
redirected, toward finding new classes of therapeutic agents.
Dr. Woods explains why the current incentive structure favors
the strategy of developing “me too” drugs.