I'm not an expert in drug development, but even I was really skeptical when reading the Washington Post article on Pfizer "burying" the Alzheimer results. Derek Lowe (an actual drug discovery chemist) did put out on article with his thoughts on the article, which were similarly damning: https://blogs.sciencemag.org/pipeline/archives/2019/06/06/a-...
The impression the original article gave was that the company ignored compelling evidence because they couldn't make any money off of it. But the "compelling evidence" actually comes across more like the sort of thing you'd find here: https://www.tylervigen.com/spurious-correlations . As Derek Lowe puts it, "One of the biggest objections to the idea inside the company was that this finding was unlikely to be real because Enbrel doesn’t really penetrate into the brain."
A final coda: the actual data may not have been public, but the potential correlative results were published in 2010: https://www.ncbi.nlm.nih.gov/pubmed/20478733/. So much for being buried?
Exactly. People tend to overstate the importance of spurious, surprising findings that don't make scientific sense. Some of these may lead to breakthroughs, sure. But the overwhelming majority are just noise. And it takes experts to decide which are worth investigating. To wit, anti-vaxers love subgroup analysis without supporting scientific logic (ie more autism in this population of 5 boys from the study).
I'd hate to see old, frail people getting Etanercept (an immunomodulator) to prevent Alzhemier's based on very questionable evidence when all they really get are the costs (increased risk of serious infections leading to death-- an FDA black box warning).
There is an Awesome List[1] of open source healthcare projects. Also a quite nice blog[2] about various FOSS initiatives. Some of the important medical projects were accepted[3] in the Google Summer of Code this year.
Weirdly, this can also be true in FOSS software. Despite e.g. DBMSes like Postgres being open-source, SQL-the-standard costs ~USD$180 to read: https://www.iso.org/standard/63555.html
This is one of the better examples of where the use of 'open source' rather than 'free' distracts everyone from the end goal.
This particular case may well be a beat-up, but there's undeniably a regular habit within pharma to not publish neutral or negative results, and we don't know how useful those data may be simply because we don't have access to them.
AFAIK no country has laws requiring this, so it's not a regulatory / enforcement problem - it's a legislative one.
Believe me: if you had a drug that had any positive effect on Alzheimers you'd be rich beyond the dreams of Croesus. What possible incentive could Pfizer have to suppress something they thought could be useful?
Read the link to Derek's Loew's analysis in Science for deeper analysis: it's posted elsewhere on this discussion.
Pfizer has no incentive to axe a promising drug that would make tons of money, but journalists always have the incentive to kick up dust and make sensationalist articles.
> What possible incentive could Pfizer have to suppress something they thought could be useful?
Without seeing the results of the test it would be impossible to know.
But hypothetically the reason could be as simple as them not wanting to provide any kind of help to their competitors, no matter how small.
Their explanation that they did not release the data because it could lead to other scientists heading down another dead end path of research is just stupid.
The field of science is full of such dead ends and is exactly the scientific process that has got us to where we are now.
I would say it is more likely Pzifer did not release the data to help ensure their competitors would head down that same dead end should they try.
"I understand that AD affects many families who would very much like to have an intervention for the disease, and are anxious to see this trial clinical proceed. Nevertheless, I do not feel that this trial is warranted based on the existing data. Additional studies are needed to understand the mechanistic connection between HSV-1 infection and AD, and specifically to clarify whether infectious virus, or viral proteins are involved."
Sounds like it's not yet in the realm of proven effectiveness.
I think it will be cool if there's a pharma company that would use crowdfunding to decrease the medicine costs. So each tier/goal will unlock additional benefits.
For example, if they created drug X with the research cost of $10M. When sales/crowdfunding reaches:
- $1M: drug margin is reduced by 10%
- $5M: drug margin is reduced by 50%
- $10M: drug is sold at cost & recipe is now open-sourced
These clear goals will be big incentive for people and organizations to donate. A successful fundrasising could drive new medicine cost way down or open-source it.
But of course, the system can still be exploited by inflating cost numbers, etc.
Maybe it could work for a non profit, but the medical world has so many methods they start exploring but find are unfruitful (with many thousands to hundreds of millions invested). You essentially have to make boatloads of money on some products over a long time frame to continue the research and development efforts.
There is currently a monopoly in electronic prescriptions in the US. Surescripts runs the only network that connects electronic health records to pharmacies. (over 99% of electronic prescriptions are sent using them) They dictate that you must have a contract with an approved commercial prescription drug database vendor.
I want the industry to come together and make an open source drug database so that it can become the world standard. This way a lot of legacy businesses will no longer have a reason to exist and charge exorbitant licensing fees.
I am still having trouble understanding the specific problem you want solved, and what an additional open drug database would add that DrugBank lacks but that is required to accomplish your solution.
It seems like your frustration is mostly with the Surescripts monopoly on electronic prescribing. You say that they dictate an approved commercial vendor. This is a very different problem, and would have very different solutions, than the problem We don't have any open source drug interaction database, which is where this thread started.
The difference is quality. The existing open source solutions are frankly not good enough. Industry should come together to sponsor an open version that matches the quality of vendors which will become the canonical source of truth for the world.
What's the monetary benefit to the industry in doing that?
The open source solutions aren't good because validating and fixing this data is very time consuming (read: expensive) and carried legal liability (read: expensive). Open source tends to not be good at requiring many people to do tedious things (see: most open source documentation). Companies could pay people to do it but then you've recreated a commercial vendor except competitors who don't pay get a benefit. Companies tend to open source things which are not direct competitive advantages for others in the same industry while this would be exactly that.
The commercial databases aren't great either, the information sure scripts has doesn't match first databank for example in many cases. it's not wrong just formatted slightly different so it's hard to compare against.
Ah, thank you for clarifying.
What are the issues with currently available open drug information resources compared to commercial ones? I can imagine they might have information about fewer drugs, or less up-to-date information, or not enough of some kinds of information, etc.
I know it's off-topic, but with all the attention FOSS and other Open-Source projects get these days, I've been thinking about the final consequences and paradigm changes they impose on businesses and societies. In a world where FOSS has won, what new businesses emerge and how do they operate? It's an interesting question for me, because I believe one reason we're not there yet is not that business owners have philosophical problems with the idea of Open-Source, but rather most don't know how that'll be profitable for them. I know there are successful examples in which Open-Source has helped the business model (RedHat, etc.), but the bigger question is how can it be successful in other businesses and contexts (such as medicine)?
It's basically communist/collectivist, it's not going to be a profit producing model in the long run; those profiting are selling other services around their OSS AFAICT.
How it can help in medicine is by saving people's lives or improving their quality of life, it can't line people's pockets - indeed that goal is contrary to the aforementioned benefits.
There are some understandable reasons, some of them related to them containing potentially export controlled models. Even then, you could strip out those bits but for some reason, no one does it because they see no need to once they have access to the code. Often a hefty (for academics) license of 4 figures a year gives them access to modify the source code but they can't share their modifications with others.
“According to industry watchdogs, reducing clinical trial costs will not help curb list prices because those prices are not determined by investment costs; they’re determined by what the makers think the market can bear, which helps explain why profit margins are so high.”
isn't that a bit circular? If investment costs (lets include capital, time, and risk)were low, wouldn't there be a influx of motivated innovators to create a greater selection of new drugs, which would either drive down price of equivalent drugs (or produce better drugs with are more efficacious/less toxic)? If investment costs/risk aren't limiting abundant new drugs, what is?
Often the most expensive drugs you hear about are lifesaving drugs. Imagine you could charge whatever you wanted for a lifesaving something that only you are allowed to sell. Is it really that common for a competitor to come up a unique (patentable) invention to treat the exact same niche disease? It should be no surprise that drugs are expensive.
The article also says: “Another thing federal officials can do is to use independent cost-benefit analysis to set a drug’s list price. The United States is the only developed country in the world that doesn’t do this”
I’m not saying pharmaceutical companies should not be able to profit off of their drugs. I think we should decide on some reasonable limits.
Also, what are you going to do to loosen regulation? Get rid of several years of clinical trials and let consumers decide for themselves whether a drug works? There’s too much of an incentive for drug companies to misinform consumers for that to work.
I’m also not trying to say the FDA is perfect. There are probably things they could do to speed up the process. I think the FDA is not the root of the problem though.
The Gilead Hepatitis C case study mentioned elsewhere in this thread deserves consideration. They made a ton of money for a few years and that is now drying up, since competition came in and the prevalent patient population has shrunk as the drug is a cure. Down the road there will be large savings to the healthcare system, as the costs of a patient leading up to, through and after a liver transplant is insanely large, and the frequency of those will dramatically be reduced because of the HepC drugs. Sharing the cost savings to the overall healthcare system with the innovator drug company incentivizes drug companies to effectivley address expensive diseases. The timing of the economic benefits (reduced advanced liver disesase) and costs (HepC drug price) uncoupled to the casual viewer so Gilead looks to be just a money-grubbing corporation.
I’m also uneasy about federal officials appointing a panel that has final say on drug prices. It’s a hypothetical, and details would matter. Done wrong it could crash industry investment. To those that claim that there will always be investment- How much of your IRA/401K is in small/mid-cap biotech? -there are huge risks and expenses getting drugs to market, and looking at the profitable companies assumes huge survivorship bias on the companies that "made it".
Look at the state of antibiotics drug development (this terrifies me), or look at the availably of a standard, approved bladder cancer drug (Bacillus Calmette-Guerin or BCG) or a handful of other drugs (please internet search for BCG / chemotherapy shortage). These real-time problems illustrate the fragility of the economics of development and manufacture of drugs. Its not just a turn-the-crank widget. Should drug companies be spending on superbowls ads, no. Should Skrelli reprice proven drugs by 500x, Nope. Anything like Valeant or Purdue pharma, just nope. Should a pharma CEO be making $50MM /year, probably not. There are many problems to fix, but hitting the industry with a wrecking ball in order to set drug prices is short sighted will have consequences. Transparency on pricing is a good step. Get the PBMs, the Payors, and Pharma all to disclose where the money is flowing and what the true costs are. That will allow for some informed discussion. I’m not a pharma shill. They need to be held accountable, but accusations such as ditching cancer or Alzheimer disease cures isn’t valid or constructive. It doesn’t even make sense.
Thank you for the thought provoking comments. Hope my rant is coherent and useful to you.
So the FDA should be more lax on requirements for approval?
Should they reduce the Preclicnal PharmTox requirements? How long should a cancer trial take if it has 500 brain cancer patents to enroll and it measures improvements in survival that takes over a year? Should Pharma just one study or should they do a coulple of serially run clinical studies to understand the toxicities and how the drug works best? I'd love for development timelines to be quicker, but I need a Gantt chart to better understand where the time savings would come from without compromising the safety and data supporting efficacy. Help me understand.
Also.
Most substantial patents are filed way before the approval of the drug. Rarely if ever has a drug had, for example, a composition of matter patent for 20 years after approval-- even with the extensions for regulatory delay that the USPTO allows. Not to say that Pharma don't extensively engage in product life-cycle management, sometimes very questionably extending exclusivity of products, and that is something that should be addressed.
Isn't FDA a factor in delay rather than throughput?
> If investment costs/risk aren't limiting abundant new drugs, what is?
If we had lots of new drugs available for testing in the first place, they would still require the 6y minimum of trials, then a few years for approval. So FDA doesn't really sound like a good reason to single out.
Such a good example! It only costs ~$84,000 to take a full coarse of sofosbuvir in the United States......................................................................... ... .....
Counterpoint: Sovaldi was basically a miracle drug for a widespread, expensive disease and even priced at $84K, that represented huge savings for the US healthcare system.
At the time it came out, the destiny for a Hep C patient was a $1M liver transplant. And that's not even including all of the other costs and misery Hep C patients incur as their liver fails. Now those people are treated quickly, saving tons of money and time, as well as improving their lives.
Also, because of the high price, it inspired competition and innovation. Within a couple years of Sovaldi and Harvoni, several other improved and cheaper drugs appeared on the market. The cost dropped to a quarter of the price of Harvoni and with half of the treatment cycle and better cure rates (Mavyret).
"improving our lifestyles and environments would be more realistic in the short term"
Unfortunately not realistic but it would be very desirable. For some reason it's accepted that people live very unhealthy lives and have big medical expenses but it's not accepted to change things like exercise and eating habits which would be very cheap and simple.
From the aspect of what would happen first, this would be more realistic than getting more companies on board for curing and preventing vs maintaining.
Having a regional or even global movement for healthier lifestyles would be easier done than convincing shareholders to make less money. Sad, but true.
I'm not saying I agree with this, I'm saying this is how pharama business works. I've worked for some of the biggest players globally, and I can tell you they are not in the business for cures.
I'm also familiar with the industry. At what level are the cure being limited? Are Pharma scientists not looking for curative potentially approaches? or maybe ditching promising candidates precinically? are Pharma ClinDev folks designing studies for cures to intentionally fail maintaining demain for their chronic drugs? Did GIlead miss the opportunity to break cure they spent all that cash on? the I'm having a hard time understanding the specifics of how this strategy is executed.
There is MUCH wrong with the pharma industry.The noise of conspiracy theories can dilute legitimate criticisms that could lead to corrective pressures.
The impression the original article gave was that the company ignored compelling evidence because they couldn't make any money off of it. But the "compelling evidence" actually comes across more like the sort of thing you'd find here: https://www.tylervigen.com/spurious-correlations . As Derek Lowe puts it, "One of the biggest objections to the idea inside the company was that this finding was unlikely to be real because Enbrel doesn’t really penetrate into the brain."
A final coda: the actual data may not have been public, but the potential correlative results were published in 2010: https://www.ncbi.nlm.nih.gov/pubmed/20478733/. So much for being buried?