Wednesday, April 22, 2015
Today the New York Times published an op-ed by Newt Gingrich where he calls for doubling the budget for the National Institutes of Health here in the US. Who can argue with that? Mr. Gingrich correctly points out that the NIH budget has been flat for years and that this has eroded the nation’s ability to carry out needed fundamental research. Of course, this situation is nothing new for antibiotic researchers. Having lived through decades of essentially no funding, there was relief starting in 2006 with at least some funding. I can’t put my hands on exact numbers, but I know that through the Drug Discovery and Resistance study section, through which many of the grants on antibiotics are funneled at NIH, and where I worked as a reviewer for a number of years, the paylines were only rarely over 10%. Most of the time, we funded only 6-10% of grants submitted – because of a lack of money – not because we had no good grants to fund.
Of course, the quality of grants was not always so good either. But with years of penury behind us, how could we expect anything else? With no funding, people leave the field and no one enters the field. Those that do may not be so well trained since they might have ended up in antibiotics research as a sideline of their thesis supervisor, who most likely knew little about the subject. Or, they may simply be scientists trained to do basic research trying to do the more practical drug discovery research with no particular training or background in this highly specialized field. This leads us to a situation where we have a tiny amount of money going to a tiny number of antibiotic researchers via the NIH.
And, to make things worse, in spite of many years of cajoling, the NIH still does not recognize the need for specialized training in this area. The NIH has yet to put in place a program that will train antibiotic researchers in the areas of drug discovery and development within the pharmaceutical industry – where the special knowledge still exists – at least for now.
What does Mr. Gingrich propose? He suggests a doubling of the overall NIH budget and he dreams of a world where we could boost research on Alzheimer’s, diabetes, kidney disease, cancer, strokes, and arthritis. All of these already receive more money from NIH today than antibiotic resistance. Yet according to the CDC, antibiotic resistance causes two million infections in US hospitals every year leading to 23,000 (a minimum estimate) deaths. This adds up to $20 billion in excess health care expenses and costs an additional $35 billion per year in lost productivity.
Another part of Mr. Gingrich’s proposal is that the NIH director be given the freedom of how to spend the money. The problem is that, at least within the National Institute for Allergy and Infectious Diseases (one of the institutes of NIH) where antibiotic research is funded, the director has deliberately chosen to prioritize other areas of research over antibiotics for decades. Is this a good idea?
So, like all of the presidential hopefuls this year, Mr. Gingrich ignores antibiotic resistance and antibiotic research and development in his appeal for more NIH money. On the other hand, it is remarkable that we have this proposal before us from one of the leading conservative politicians of our time. He actually wants to spend more government money. Wow. I’m just sorry that, once again, antibiotics are ignored.
Tuesday, April 14, 2015
This week Hilary Clinton and Marco Rubio announced their candidacies for President of the United States. This puts them alongside Jeb Bush, Scott Walker and I’m not sure who else. One thing all these candidates have in common is that not one of them has mentioned antibiotics – at least as far as I know. Do any of you know anything different?
So here we are. Antibiotic resistance is killing a minimum of 23,000 Americans every year according to the CDC. (I think that is a gross underestimate of reality.) The FDA just published a study showing large increase in antibiotic use on US farms – but they don’t know how or why the antibiotics are used. They have issued guidelines that ask industry to voluntarily withdraw growth promotion from labels for animal antibiotics – but they refuse to simply ban such use for reasons that are unclear (besides politics that is). Europe not only has instituted such a ban but does a remarkable job of following antibiotic use in animals. Have any of the candidates mentioned anything about the FDA and antibiotic use in animals?
President Obama has released a plan to combat antibiotic resistance that was enshrined in his congressional budget request where he asks for a doubling, but still completely inadequate, level of funding for his efforts. I have not seen any comments from any of the candidates on this plan.
No one is talking about one of the key tasks that lie before us globally and as a nation. We have to make sure that antibiotic research provides some sort of return on investment for those who engage in these activities and are successful. Many of the ways we can accomplish this have been discussed ad nauseum both here in this blog and elsewhere. Among them –
1. Support for R&D including the most expensive piece- late stage clinical trials. This has been mainly borne by BARDA in the US and IMI in Europe. Such support reduces the investment required to bring needed antibiotics to the marketplace.
2. Pull incentives
a. Guaranteed purchase upon approval.
b. Wild card patent exclusivity or patent voucher - where a company that achieves approval for a needed antibiotic is rewarded with six months to two years of added exclusivity for a product of its choice. A good example would be Lipitor from Pfizer where it was selling $15B per year at its peak.
From the lack of comment by candidates, I reach the following conclusions.
1. Antibiotic resistance is not a priority for the next President.
2. Antibiotic resistance is not viewed as a priority for voters.
3. The candidates do not view antibiotic resistance as an important public health threat.
4. The candidates’ desire to distance themselves from President Obama is greater than their desire to support or expand upon his programs.
5. We’re screwed!
Tuesday, April 7, 2015
A number of press reports have appeared, mainly in the UK, talking about Jim O’Neill’s predictions on the effect of massive resistance to antibiotics among common human pathogens. I’m sure this is done to justify, at a later time, the kind of money O’Neill is going to be asking government(s) to spend to support research on antibiotic resistance and the discovery and development of new antibiotics. I am of the opinion that these dire predictions are unrealistic and exaggerated – the word “hype” comes to mind. On the other hand, no one should doubt the public health threat of emerging resistance.
We are constantly reminded that antibiotic resistance is not just a problem in hospitals. Recent experience in the US is a good example. According to the US CDC, the common GI pathogen, Shigella, which causes severe diarrhea, frequently bloody, has become resistant to the antibiotic most often used to treat the infection, ciprofloxacin. Shigella is estimated to cause about 500,000 cases of illness every year in the US alone and something like 100 million cases a year worldwide. Using molecular methods, the CDC identified a cluster of 243 cases of Shigella infection stretching from Massachussetts to California. Of the 109 isolates that tested by public health agencies, 87 were resistant. 22% of infected patients were hospitalized. The CDC showed clearly that, unlike in years past, these resistant strains can be acquired right here in the US – no travel is necessary.
It is important to remember that most cases of Shigellosis will resolve without antibiotic therapy. But occasional cases are more severe and require therapy or even hospitalization. The emergence of resistance to the most commonly used antibiotic to treat these infections right here in the US is an important warning. Its time to get our house in order.
Shigella can be a foodborne pathogen and can be transmitted from person to person via the fecal oral route. The origin of Shigella in food is human or animal excrement or the use of contaminated groundwater for watering or irrigation.
It is also important to remember that our food supply is now global. 20% of food consumed here in the US is now imported. 70% of seafood and 35% of fresh produce is imported. So not only do we have to pursue rational antibiotic policies for food here in the US, but we also need to partner with other countries who export their food to the US.
To keep ahead of this emerging resistance, many steps are required. Reduction of the unnecessary use of antibiotics for animals, crops and for us human beings is clearly required. This also means being able to monitor antibiotic use and the appropriateness of such use. We have not been very good at as yet – especially on the animal/crop side of things. We're also not good at tracking human antibiotic use. We could do a better job in hospitals and we are terrible in outpatients and in chronic care facilities.
We need to approach the entire food supply issue on a global scale. We’re not so good at this either.
We need to approach the entire food supply issue on a global scale. We’re not so good at this either.
We also need a constant pipeline of new antibiotics. To achieve this we need to stop the loss of antibiotic discovery and development within the pharmaceutical industry – especially among the larger companies that can drive such work at smaller companies and within academia. This will require two things; money and training. The world is sadly lacking both of these when it comes to antibiotics and the US and the UK are not exceptions to this rule. Like I keep saying - show me the money!
Tuesday, March 31, 2015
There has been much press lately about President Obama’s plan to address the growing crisis of antibiotic-resistant bacterial pathogens. And I agree with many that there is much to like in the plan. But I also find a number of key deficiencies that will lead us nowhere.
The goals of the plan are all laudable –
1. Slow the emergence of resistant bacteria and prevent the spread of resistant infections;
2. Strengthen national One-Health surveillance efforts to combat resistance;
3. Advance development and use of rapid and innovative diagnostic tests for identification and characterization of resistant bacteria;
4. Accelerate basic and applied research and development for new antibiotics, other therapeutics, and vaccines; and
5. Improve international collaboration and capacities for antibiotic-resistance prevention, surveillance, control, and antibiotic research and development.
Who can argue with that?
To achieve the first goal, the plan contains a number of key elements. Among them are strengthening of antibiotic stewardship in both inpatient and outpatient settings including long term care. Surveillance is to be strengthened by providing regional reference centers to detect resistant strains in clinical and veterinary settings. Importantly, there is a plan to streamline the regulatory process for approving susceptibility-testing devices such that they are available when a new antibiotic is marketed instead of the one to two year delay that now occurs. I like that one especially. Another piece of this plan is to establish a national database on antibiotic use. That’s another one I like, but man, will that be hard to implement.
An obvious goal is to eliminate the use of medically important antibiotics as growth promoters in animal feed. Wow. What a surprise. But the plan does not include an outright ban. Rather, it supports the FDA’s efforts, which could ultimately succeed, I suppose, to get the industry to back off. But why is there such consternation around an outright ban? I don’t know.
One piece of the plan calls for establishing a susceptibility-testing network for animal pathogens. It seems like this is aimed at providing better and more focused therapy for infected animals. Good idea. What this will require is an entirely new approach to animal pathogens including setting breakpoints for what is considered resistant or susceptible in different animal species. Right now, the assumption is that animals are humans – which I can tell you - physiologically, they’re not. Who is going to do all the sophisticated PK/PD experiments in the different species to establish these breakpoints? Is there going to be funding for this piece? Or is there no one but me who sees this as a possible pitfall?
The there is the section on establishing rapid diagnostic testing. See my blog on this. I say again. It has to be bedside and idiot-proof. This could take a while, folks.
Finally, there is the part on accelerating both basic and applied research aimed at finding new antibiotics, vaccines and other therapeutic approaches. But the way this is worded sounds like a way to let the NIH off the hook. For the last 50 years, the NIH has been shortchanging antibiotic research and funneling money into the study of vaccines and pathogenesis of infections. I don’t argue that these are not worthy of study. I just will state that antibiotic research has always gotten the short end of this stick. And, if I read the plan correctly, this is unlikely to change in the future.
What is glaringly absent from the plan is what was recommended by PCAST in terms of providing for a return on investment for companies who pursue the research and development of new antibiotics for resistant infections. Of course, that was the most expensive part of the PCAST report. That report would augment funding for BARDA in its effort to support applied research in academia and industry. It would also provide for various pull incentives such as an upfront purchase or so-called patent voucher system. Without this, as far as the development of new antibiotics is concerned, the plan is another piece of paper in a long line of such. Show me the money!!!
So here we are. There is much good here. But it is clear that the much-touted “doubling of funding” that the press is so excited about is less than it seems. Not only that, but what makes anyone think that the President’s budget, where this plan is enshrined, will pass? If it does, will it have to do so on the back of Medicare, Medicaid or food stamps? I’m sorry – but my eyes are on Jim O’Neill and the UK for now.