The President’s Council of Advisors on Science and
Technology (PCAST) has been busy preparing a report on Antibiotic Resistance
and what to do about it. Maryn McKenna
wrote a summary
after one of the PCAST meetings earlier this year. Another meeting is about to take place on
July 11. Basically, the PCAST has been saying things similar to what we have
all been hearing either at Pew or at Brookings or almost anywhere else. Some of the things we have to do are
completely obvious, even if hard to achieve in practice.
1.
Regulatory – Clinical Trial designs for
antibiotics meeting unmet needs (treating highly resistant bacterial
infections). As PCAST and everyone else,
including the regulators, has signaled, the trials must be feasible, small and
rapid. We all recognize the increased
risks associated with this approach (smaller numbers of subjects means less
sensitivity to detect adverse effects).
But I think we can all agree that the alternative – having no antibiotic
with which to treat such infections – is the greater evil. Even though the FDA
and Europe have made tremendous strides over the last few years in providing
guidance on this subject, what kinds of trials they will actually accept remains
somewhat obscure. Will they truly accept the kinds of externally controlled
trials (historical controls of various sorts) that most of us in industry
believe are the only feasible designs possible, or will they insist on
concurrent controls that will render the trials impossible? We probably have to wait and see – but a word
from PCAST in this regard couldn’t hurt.
a.
In addition – can we please have less
restrictive use of prior antibiotics and more clinically relevant endpoints for
our traditional trials? Is that too much
to ask?
2.
On the Regulatory front – what about banning the
use of antibiotics as growth promotants?
It is so obvious that this is what has to be done that any further
debate seems political. Any argument to the contrary is based on
pseudoscience. The vast weight of
scientific evidence demonstrates that antibiotic use in animals, whether for
prophylaxis, for treatment or for growth promotion selects for resistance. And the evidence is clear that these
resistant strains or the resistance genes involved can be transferred to humans
and human pathogens. Why we have waited since 1976 to do this is beyond my
comprehension (other than the politics involved).
3.
Money – Economics. For me, this is the final frontier. As they
might say in French – there are not 36,000 ways to solve this problem – and a
problem it is and PCAST has recognized it. If antibiotics to treat highly resistant
infections are going to have to be priced to compete with generic antibiotics,
we should prepare for the post-antibiotic era today because it surely will
follow. The industry as simply got to be able to see that they will be able to
make a reasonable return on their investment in new and effective antibiotics.
The reason AstraZeneca, with its sparkling pipeline of new antibiotics for
resistant infections continues to look for ways out of its antibiotic research
and development enterprise is that the company (the CEO specifically) does not
believe that they will ever be able to achieve such a return. The same is true
for every other company that ever abandoned the field and that has not yet
returned to the fray – and that is the vast majority of large pharmaceutical
companies.
There are several ways to address
this economic problem. One is with higher prices. In the US system, this might
be the best approach. The question is, what data will payers want to see,
either within the context of the feasible trial designs that we will conduct or
in addition to trial data in order to agree to pay these prices (up to $30,000
for a course of therapy)? An executive order requiring CMMS to add the cost of
these higher priced antibiotics (that don’t exist yet) to the usual DRG
reimbursement for hospital stay might be in order. There is a bill in Congress (DISARM) but
since nothing will pass this session anyway – an executive order might
help. Legislation in this case is better
because it will have an effect beyond the Obama administration – but let’s stay
real here.
Another approach would be to
establish an alternate business model for the industry. In this case, governments would guarantee a
certain amount of pre-purchase. The
greater the purchase, the lower the price the companies would be required to
charge to make their investment. This approach leaves open the possibility for
higher pricing, but softens it with the government purchase. In the US, this could be achieved via the
Veterans Administration and via BARDA for those drugs with implications for use
in the case of bioterror attacks. In any
case, I suspect that, again, legislation might be required – but the White
House will be able to figure this out (I guess). This approach might work better in Europe.
A disadvantage of the government
purchase is that the urgency for stewardship will be diminished. When an antibiotic is costing $30,000 for a
course, believe me, the antibiotic police will be at the bedside even over the
weekend.
The problem is, I’m not sure
everyone actually understands that if they want these antibiotics, they will
have to pay – one way or another.
Without them, the price will be something no one will want, but that we
will be stuck with for decades to come.
Lets not go there!
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