David's New Book

Wednesday, July 2, 2014

PCAST

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!


4.  For other suggestions, see the article by Matt Metz in AAC.