A radically simple idea may open the door to a new world of antibiotics
statnews.com
statnews.com
What we need to work towards is a large cash payment on approval of each drug or a guaranteed minimium annual payment. Once we have this we will start to get the new antibiotics we need.
There are millions of people in EU with anti-biotic illness.
These are serious, life-threatening, life-limiting illnesses where the seller can set high prices.
This is far from "near zero" sales.
http://www.who.int/mediacentre/news/releases/2014/amr-report...
We need to develop new antibiotics before we have a problem and where they will sit on the shelf, rather than wait until we have none and then panic.
> Treatment failure to the last resort of treatment for gonorrhoea–third generation cephalosporins–has been confirmed in Austria, Australia, Canada, France, Japan, Norway, Slovenia, South Africa, Sweden and the United Kingdom. An estimated 106 million people are infected with gonorrhoea every year (2008 estimates).
Only 1,000 people die a year from gonorrhoea worldwide, the vast majority of whom live outside the US and EU.
https://en.wikipedia.org/wiki/Gonorrhea
To the best of my knowledge, the anti-biotic resistant bacteria that currently poses the greatest public health risk is Methicillin-resistant Staphylococcus aureus (MRSA).
> Many of these infections are less serious, but the Centers for Disease Control and Prevention (CDC) estimates that there are 80,461 invasive MRSA infections and 11,285 deaths due to MRSA annually
https://en.wikipedia.org/wiki/Methicillin-resistant_Staphylo...
None of these are millions of people with life-threatening risks in the US.
> These are serious, life-threatening, life-limiting illnesses where the seller can set high prices.
This after referring to millions of cases. The response was that the only disease in your reference anywhere in that ballpark is gonorrhea. While I definitely don't want to get the clap, it is none of those things you mentioned.
He merely said that people with such needs are a few tens of thousands, and not many millions, so they don't constitute a viable market.
If your new point is that, "ok, they might not be millions, but they would still pay any price for a treatment", that would also be wrong: They might be WILLING to pay any price, but for most of them it wouldn't be possible to pay that much. There are lots of people that need stuff from surgeries to dental work, that are NOT happy not having them, but that nevertheless don't have them, because they can't afford them -- and expensive gonorrhea drugs wouldn't be much different.
Unfortunately not. The way that public payers (Medicare, Medicaid) pay for antibiotics levels very little room for high prices. Even private insurance is going in that direction.
If drug makers charged a high price, then hospitals would be left holding the bag.
Or having the know how to develop them on demand.
One thing I should mention is we don’t have to keep developing totally new antibiotics we can develop antibiotics that are tweaks of existing antibiotics. Antibiotic resistance is an arms race that we can never win, but we can stay ahead with continued investment.
What's the best way to quantify the failure? Like a chart showing the bacterial infection death rate for the past 100 years? Costs for the average antibiotic dose over time? Something else? Those data sets seem like they should be available, but are apparently harder for me to find than I would have thought, given the prevalence of all the information available on anti-microbial resistance that pops up for my collection of search terms.
Do you see this new work as a departure from, or a continuation of the antibiotics development of the past?
Here's one timeline I found in a paper: http://cmr.asm.org/content/24/1/71/F1.expansion.html
total number of efficacious treatments available per million infections, plotted over time? The million infections might need to be weighted by severity of clinical outcome.
Getting this data is likely to be really hard to get and be very labor intensive.
It is a continuation of some great science that doesn’t ever make it to market. There have been a lot of interesting new antibiotics discovered over the last 20 years or so that just have not been picked up.
I disagree.
Think of it this way. If it were truly laissez faire, then drug makers would charge a price high enough to still make it worthwhile. Unfortunately, the way antibiotics are paid for in US hospitals, the hospitals would lose money each time they used the drug.
Hell, we pay ~$80K to cure hepatitis C (millions have it in the US). If you have an antibiotic that cures a highly resistant infection that happens maybe a few hundred times in the US, why not charge something similar? What is the benefit to society to save someone's life?
Because a few hundred times 80k is still not much. And even so, many people still can't afford it.
All of this over-regulation is why medicine is declining in the first place. That shouldn't justify more regulation.
We put a price on human life all the time, not just for drugs.
Fixed. I also generally feel casual disregard towards human life and suffering as long as the human in question is not me, but lets call things with their real names.
With a price of drug per year being twice the average income in the richest country in the world - that creates impossible situation by definition for half of its populace.
Also value provided is not always correlated with value extracted - a janitor for a modest fee keeps my house clean. A hedge fund manager ruins the global economy just when I must enter my prime growing years in earnings and make sure I am at a disadvantage at both the cohort before and after me.
Which of those two lives is more valuable to me?
Even worse. There are a few gigantic outliers at the upper end of the scale. That means that the number of people below average income will be >50%. What you want to check against in such cases is the median (50:50 split by definition).
"Also value provided is not always correlated with value extracted"
That is exactly one of the main problems society is struggling with. How do we even measure value provided? It's a subjective measure to begin with. In the case of the hedge funds manager, it's probably net-negative for most people (but I'm sure her friends would disagree).
No, but the other side of it is that for the money that they had invested, before shutting it down, they got very little at all. That is the other explanation here — that they invested money into antibiotics research and simply couldn't make it work. E.g., http://blogs.sciencemag.org/pipeline/?s=antibiotics
There is some evidence that some of these divisions weren’t very good at finding new drugs, but even when they were found they weren’t brought through to market because there was no profit.
Also, Radiolab recently noted[0] that antibiotic resistance can often be found in the wild within just a few years after a drug's discovery.
Antibiotic resistance was found in the wild to penicillin before it was even widely used by the public.
Others had a few years (or sometimes months): Streptomycin ~5 years Linezolid ~2 years Clindamycin ~1 year Piperacillin ~1 year Meticillin 11 months
Why burn through 10 years of development for 1 year of sales? It doesn't even take very wide use before resistance gets around...
The researchers they interviewed postulate resistance wanes when a treatment leaves the population for a while.
The conclusion at the end was that it would be beneficial to have a big bevy of antibiotics and such, that we could rotate through as immunity came and went.
In this ^ way, it would seem these pharmas, and the pharma market, needs to adopt a second perspective on antibiotics. They should look at a new drug not for revenues over the next 6 quarters, but over the next 6 decades. In that time frame the drug would hit, be shelved, hit, and repeat.
Perhaps this would be one place that more permissive or advantageous patents would help, by encouraging growth in the antibiotic industry. That probably sounds unpopular given the general "no patents!" sentiment, but I there could be reason in it for at least some period of time.
It's when the first line antibiotic stops working that you need to go to the newer antibiotics.
Of course, this solution ignores issues of varying toxicity and side effects (not every antibiotic is equally appropriate for front-line use) and anti-trust issues. If an ordered schedule for reserve antibiotics was used, the same principle would apply, just one step farther up the reserve schedule. So, if no one wants to use your antibiotic because it is very harsh, but if your antibiotic is first choice among the harsh reserve antibiotics in some region, it will at least get used some, perhaps enough to pay for development. Anti-trust issues could be dealt with by splitting the regions along jurisdictional lines, or by international agreements. Because this proposal is pro-competition (because new entrants are granted new territories) it also may suffer less regulatory ire than most collusion agreements.
Huge deal, expect much more to come from microbiologists using this culturing technique.
In addition, we actually have quite a bit of trouble culturing bacteria that might be pathological (our inability to culture them is quite related to our inability to determine their pathological status).
Didn't most antibiotics come from fungi? All of the -mycins came from fungi.
If we could simulate what's happening in just a single bacterium, we could pre-screen drugs in a virtual petri dish. Promising compounds could then be put to real-life tests.
There was an article about the standardization of laboratory mice - it allows large scale, reproducible results but guarantees you won't things that can't be learned from the single, genetically uniform mouse type that is used.
Slightly off topic the traditional divisions between different areas of biological sciences that built up in the 20th C have all broken down with the rise of molecular biology. Once biochemistry was a different field to say microbiology, now both are part of the super-field of molecular sciences.
We have considered and discarded a lot of candidate drugs with great potential before starting human testing. As a rule, if some molecule would cure an important disease but for whatever reason doesn't work on the popular strains of mice, then our current process would cause us to discard it.
I don't think this is really true. Perhaps that makes it unlikely genetic differences are the cause of a relatively large apparent treatment effect, but not just any difference.
None of this would matter if we were developing cures for diseases of C57BL/6 mice [1], but we are actually interested in developing cures for humans who are not inbred (well in most places). We need our animals models to match as closely as possible to humans and using inbred mice is not a good match.
This is a misrepresentation of the state of mouse biology research.
We use many different strains of inbred mice (check out the JAX Labs list of available inbreds)[1]. Inbreeding reduces the genetic variability of our mice, allowing us to control more of the variation in an experiment. This allows us to perform pilot studies with smaller samples sizes while still reaching sufficient statistical power. This is important -- mouse biology is expensive, and we try to discover as much as possible with limited funding.
If a result merits generalization to multiple backgrounds, it is often tested in multiple inbred strains and an "outbred" strain that is genetically diverse.
[1] - https://www.jax.org/jax-mice-and-services/find-and-order-jax...