David's New Book

Wednesday, May 25, 2016

Antibiotics, Politics, UK, EU, USA



Well, the UK’s O’Neill Commission released its final report on tackling antibiotic resistance. This is a very detailed report looking at all sides of the problem and trying to take a global perspective. I won’t review it today – but you can read it yourselves.  There is a nice review in The Atlantic. 
I want to talk about the relationship between our public perceptions, priorities and policies and provide a contrast between the US and the UK in that regard. The UK, under Prime Minister David Cameron and Chief Medical Officer Dame Sally Davies, has undertaken the battle against antibiotic resistance in a public and committed way.  News articles and press releases are constant. The Review on Antibiotic Resistance (I call it the O’Neill Commission) was undertaken under UK leadership. The UK has made enormous strides in educating the public on the dangers of inappropriate antibiotic use and the consequences of resistance. The UK has established strong guidelines for the stewardship of antibiotics and has provided teeth to help make sure physicians comply with these guidelines.  They have also carried out extensive public education campaigns to try and decrease patient demand for antibiotics for inappropriate indications. These efforts have begun to bear fruit with a demonstrated decrease in antibiotic prescribing. Combined with the general strategy proposed by the AMR Review under O’Neill to incentivize the antibiotic pipeline, the UK program show us all a way forward – at least in general terms.

How does the US look compared to the UK? Does our Surgeon General call for antimicrobial stewardship or incentives for antibiotic discovery or development?  A look at his website shows no headliners for antibiotics at all.  A search for articles on antibiotics on the website turns up older documents from previous surgeon generals. Although there are one or two articles on the need to reduce inappropriate antibiotic use, there is nothing like what can be found in the UK.
What about the presidential campaign in the US. I was unable to find anything meaningful from any of the candidates on the problem of antibiotic resistance by searching on Google. A search of the candidates’ websites shows nothing specific about antibiotics.  Hillary Clinton has posted her thoughts on HIV-AIDS, but not on antibiotics and antibiotic resistance.  Neither Bernie nor Donald have anything to say.

How about the use of antibiotics in animals?  Europe including the UK have essentially banned the use of antibiotics in animal feed for the purpose of growth promotion. The UK is now considering other proscriptions such as against the use of certain antibiotic prophylactic regimes for poultry and other animals as has been done by certain other EU countries. In the US – we’re still working on gathering data.  Again our candidates are silent.

Has the US really done nothing?  No.  President Obama has been more engaged in the problem of antibiotic resistance than any other US President in history. A number of important initiatives have been established under his watch. These include a report from his Council of Advisors on Science and Technology and a subsequent plan for implementing many of the suggestions from that report.  There has even been an increase in funding for NIH and BARDA to support these plans. Our regulatory agency has made great strides in providing feasible pathways for the development of new antibiotics, but they still lag behind Europe in that regard. The CDC website is replete with information, but we are just beginning to carry out surveillance for antibiotic use and we do not have the kind of teeth that UK and Europe do to alter prescribing habits. There has been nothing like the attention given to antibiotic resistance in the UK and in Europe. There is little discussion in the US of the kind of post-market incentives that will be so important going forward.

I am supposed to head to Amsterdam next week to attend a meeting of Drive-AB – the EU-funded effort to actually find ways to implement the strategies being promulgated by the O’Neill Commission. In thinking about this meeting, I am of two minds.  I am disappointed that the US is not more of a leader in this area.  But I also agree with President Obama (and, help me, Donald Trump) that Europe needs to do more to pull its own weight. 

Historically, the US has accounted for about 50% of the total pharmaceutical market.  As of 2013, it still accounted for over 40%.  That’s one country – 40% of the world dollar volume in prescription drug sales.  If you look at sales of new drugs, the US is responsible for 55% of sales.  When translated into pharmaceutical company profits, the US still dominates.  Since these sales are, to a certain extent, rolled back into research and development, one could conclude that the US has been subsidizing global pharmaceutical R&D for decades.

So I look forward to incentives for antibiotic R&D coming, to a large extent, from Europe!





Tuesday, May 17, 2016

Solving Antibiotic Resistance - The Longitude Prize

Guest Blogger Tamar Ghosh




The Longitude Prize is the UK’s biggest science prize, a 5-year challenge with a £10 million prize fund, and a 300 year legacy.  It commemorates the anniversary of the Longitude Act of 1714, the first British challenge prize, which offered the public £20,000 to solve one of the biggest global problems of the time, determining longitude at sea.  It was eventually solved when a little-known carpenter, John Harrison, invented the first marine chronometer, H4, surprising the establishment which expected a solution to come from the field of  astronomy,.  This early achievement demonstrated an early principle of prizes that we have seen time and again: if you create a public challenge, of reputation and profile, a far wider group of innovators are likely to get involved in finding solutions to the problem.


 In 2014, this new Longitude Prize, instigated by the Astronomer Royal in the UK, Lord Martin Rees, was launched after a public vote that selected resistance to antibiotics as the equivalent global issue to be resolved.  It aims to conserve antibiotics for future generations, revolutionising global healthcare. It is looking to award one prize of £8m to a team that can develop a transformative, accurate, affordable, rapid, point of care diagnostic test that is easy to use, anywhere in the world. The Prize is being developed by Nesta, supported by Innovate UK, and is open to entrants from any country.  This global Prize has the support of the UK Prime Minister and will be awarded by the Longitude Committee chaired by Lord Martin Rees and including Dame Sally Davies, Baron Peter Piot and Professor Jeremy Farrar, among other luminaries.


So far we have 130 teams working on ideas from 29 countries, however we want to ensure the Prize is helping as many teams as possible enter the Prize from a range of countries, sectors and disciplines, and through new collaborations.  We already have a mix of entries from industry large and small, academia, individuals and many collaborations. However, we want to make sure everyone who is able to take part can do so, and to address some of the concerns we hear from current teams who have hit a barrier in the development of their ideas.

For this reason, on Monday 16th May we launched the Longitude Prize Discovery Awards.

These are small seed grants to help individuals or teams to further develop their ideas to win the Prize, hopefully enticing more of the greatest minds across the world to take part.  The total current fund for the Discovery Awards is just over £200,000.  From this total pot we will look to make grants of around £10,000, rising to maximum of £25,000 for exceptional ideas.  These are small grants and our teams tell us they are likely to use these to access labs for testing, evaluating the feasibility of their test in communities, securing expertise to help them to develop a business plan, or acquiring new specimens to develop their concept. We want to make as many awards as possible, and these may be very early stage ideas coming from very different areas of science. The current awards are being funded by GSK and by the Biotechnology Industry Research Assistance Council (BIRAC) in India. We hope the awards will attract more entries from the UK and around the world.

Dame Sally Davies, Chief Medical Officer for England, has said of these Awards: “I'm delighted to see the launch of the Discovery Awards, providing support for teams that have great ideas to be further developed. We need the best minds in the UK and around the world to work on this and find us all a diagnostic that will help reduce the misuse of antibiotics.”

Applications for a Discovery Award can be submitted from 6pm BST 16th May until midnight on the 26th August BST, and awardees will be announced in late November.   

Applicants need to demonstrate that their overall idea is in the scope of the prize and that the activity they are putting forward for funding is feasible and will help them to move forward with their idea.  Some of the teams working on ideas have told us that by winning a Discovery Award they may be able to access far higher levels of funding, through reaching proof of concept or through credibility attached to this. .

We hope this will help us to broaden the range of innovators and innovations into the race, so we can make sure the equivalent of the present day John (and Jane) Harrisons do get involved.





Wednesday, May 11, 2016

Big News - FDA Delays Again

Well, here we are again talking about the FDA and the use of antibiotics in animals. The FDA just finalized its long-awaited rule requiring industry to report how the antibiotics marketed for use in animals are actually used (see the report by STAT).  The FDA will now have actual data about how much and which antibiotics are used for growth promotion, prevention of infection and for therapy. Of course, one could ask how long it will take for them to collect all this information and then decide whether to act on the data or not.
 
To me, as those of you who follow my blog already know, this is nothing more than a delaying tactic.  In my view, as I have expressed on multiple occasions, the argument as to whether antibiotic use in animals leads to resistance in pathogens that infect humans was settled back in the 1980s. Once again, I think the FDA is maneuvering to avoid congressional pressure.  They also have received cover in this regard from none other than the President’s Council of Advisors on Science and Technology who stated in their report that the data showing the link between use of antibiotics in animals and resistance in humans has not yet been convincingly shown.  This is a view I could not disagree with more strongly.

All the FDA need do is look at data from Europe where halting the use of antibiotics as growth promoters in animals has clearly led to decreasing levels of resistance in human pathogens. Europe leads the way once again!

While there is nothing wrong with collecting more data – the time for the FDA to act has long passed.  But what else is new?




Wednesday, April 27, 2016

Australia, Antibiotics, Head in Sand


A recent news article from Australia that quoted my friend and colleague Matt Cooper caught my attention. The article notes the potential for an onslaught of antibiotic resistant superbug infections and talks about ways to counter this threat.  One topic discussed was addressing the market failure for supporting antibiotic R&D. That is, the market size remains too small for pharmaceutical companies to invest in antibiotic research.  Hence the pipeline of new antibiotics active against these resistant pathogens is nowhere near what it needs to be. Matt is quoted as saying that Australia needs to be paying into a sort of insurance fund that will go towards providing government support for an improved antibiotic marketplace. 
 
I wrote Matt to ask him what was happening in Australia. I noted my skepticism.  My doubts are based on Australia’s long history of fighting the pharmaceutical industry tooth and nail over pricing and patent exclusivity.  Australia has one of the shortest patent exclusivity periods for new drugs in the world.  It also requires companies to accept exceedingly low prices to be allowed to market their drugs in Australia.  Now the latter depends on how innovative a drug might be – but my experience is that now matter how active a new antibiotic is against resistant pathogens, it is never innovative enough to garner a reasonable price in Australia. Is a lower frequency of dosing for an antibiotic innovative enough? How about an expanded spectrum of activity including resistant superbugs?  Would a safer antibiotic be innovative enough?  In Australia – not necessarily. With a population of only 23 million, many companies are happy to walk away from the Australian market with their low prices and short exclusivity periods.

Back to the article in question. Given the threat of new and more resistant superbugs, what is the Australian government willing to do? The answer can be found in their strategy – here. Like most other government authorities, antimicrobial stewardship, surveillance for resistance and other such measures figure prominently in the Australian plan. Australia would also like to increase research funding for Universities and basic research – but Matt informs me that has not really happened yet. What is missing from the report is the very sort of incentives that the rest of the world, especially Europe, is considering seriously.  That is, providing incentive payments to those companies that do bring needed new antibiotics or other therapies to market that successfully combat superbug infections. Europe is looking at plans to provide payments of around $2 billion or so to companies who succeed as a way of guaranteeing that they will have a market.  The idea is to incentivize companies already in antibiotic R&D to continue, to provide a motivation for those who gave up antibiotic R&D to come back and to provide impetus to investors to support new company entrants to the field.


Whether Europe plans to do this on its own or whether they will be seeking other global partners is not totally clear yet. But - will Australia be participating?  As a country that has a long history of being part of the problem, it seems unlikely it will become part of the solution.