Be kind and good to your loved ones. Life is short and no one knows how much time we have left. While the FDA’s antiquated bureaucracy does no good, the true enemy is the disease itself. I believe in science and I hope that someday no one else will needlessly suffer as my brother has.
This is the real reminder for young people. Every single one of us is one tiny cellular mishap away from an untreatable, agonizing demise. Be KIND to one another, because when it is your turn to die, you will have wanted to have had a positive impact on the world and those around you.
Stabbing backs to maybe get a pay raise will mean nothing to you or your family. It's just one more person who won't honor your temporary existence.
I was a student of your brother's at the University of Arizona for a semester. It was over a decade ago at this point, but I think it was English 109. It's hard to explain how humbling it felt to chat with him one-on-one. He struck me as a genuine, intelligent, and friendly guy who was worth listening to.
This is such terrible news and I wish Jake and yourself the best.
"We need to have a much stronger “right to try” presumption"
Quite.
I'm now four years older than my mother was when she passed away after two really exciting years. I can't remember the exact description of the killer but "squamous" was involved. Radio, chemo, surgery bordering on butchery etc. Bout one seemed to be in remission and all clear sounded only to be rescinded a few months later, second run was a negative outcome. Faith healer for a laugh "but you never know" - mum wasn't daft but when you are out of reasonable options, you might as well invent a few more!
However, there is still hope whilst breathe still flows and there is absolutely nothing wrong with hoping for a miracle. They do sometimes happen. Keep fighting and kicking and being a pain and only give up when it is obviously hopeless.
Lost my brother to a carcinoma, a disease that most likely will be successfully treated, cured and even prevented in my lifetime. I feel for your brother but also for you.
While I can't comment on this particular case, I sincerely recommend Americans to explore treatment options for treatable diseases in other countries - like India, South Korea, Cuba (?) etc. - that have excellent doctors and decent healthcare infrastructure. They may charge foreigners a bit more than the locals, but you will get better service that is unlikely to bankrupt you.
(Not sure about Cuba's current healthcare infrastructure).
I would hate to ask the author this, as it seems cruel, but is the FDA denying him access? As he points out, Moderna has two drug trials going. The FDA "right to try" page[0] clearly spells out that Moderna could give him unproven medicine currently in a clinical trial under the right to try laws. So Moderna could let him into one of the two studies, or give him the medicine under the right to try laws if it rejects him.
Likely, Moderna doesn't want him to take the drugs because they will probably be ineffective this late in the cancer stage. It doesn't want its treatment to be associated with his death.
Actually the Moderna trials are recruiting metastatic and treatment resistant disease. From his description he has not met inclusion/exclusion criteria for the studies due to treatments received and not received rather than being too advanced in stage.
It's highly highly highly unusual to be offering an experimental therapy on compassionate grounds when conventional options that have potential to actually work well haven't been tried yet. In this post he only describes locoregional therapy and it appears he has not tried anything systemic yet.
The closest I've seen is we at least try a very short attempt of something in clinical use and then say patient refused/intolerable side-effects/treatment failure and move on. I can't imagine a circumstance where medical ethics would allow to skip a trial of validated therapy for something without even phase I data. It's not like this mRNA by Moderna is known to actually work.
Are there conventional therapies that he has not tried that could be effective? It seems he has never had chemotherapy, but he implies at this point that's a long, almost impossible, shot.
I think the issue is that Moderna just doesn’t have much incentive to do it and it’s more a distraction than anything. But yeah it could also just be too late. My dad was recently in a similar position, but by the time he theoretically could get his hands on the drug, he was too weak too handle them.
I feel somewhat closer to this person because I was once in his position as a child fighting a neuroblastoma in 1981 and some how my mother found a way to get me on an experimental list which saved my life. Half of the kids that took the drug died by the time they were teens due to heart failure, obviously I wasn't one of them, but am thankful for the chance to live a full life.
When the odds are against survival, there shouldn't be any rules limiting treatment, if it means even a slightly higher chance of winning. That's something our government has forgotten about or doesn't care about. If I was in this persons shoes, I would make it as personal as possible against those in control of the FDA. Show up at their houses, work, kids soccer practice, get in their face and let them see what their inaction is doing in person.
> When the odds are against survival, there shouldn't be any rules limiting treatment, if it means even a slightly higher chance of winning.
I agree with you. But the FDA would ask you to rigorously define "slightly higher chance of winning" -- and prove it. In the event you cannot do this, they believe that letting you try an experimental drug would be more unethical than letting you die of neglect.
So I'd rephrase that statement of yours: "When the odds are against survival, there shouldn't be any rules limiting treatment, regardless of type of treatment or odds of efficacy." ("When the odds are against survival" can be quantified, e.g. a 90% chance of dying within a year.)
I am not yet done thinking on this area, so my thoughts here are incomplete, but thay said:
Would this not also open the door for any snakeoil salesman to prey on what might be medically "hopeless" cases?
If I am ever diagnosed with something currently uncurable, but there are experimental stuff in the works, of course I'd like a shot at those experimental drugs, but I hope that me/my family would also not squander whatever assets we have on snakeoil, in which case I'd rather my surviving family was not impoverished in the fight.
I assume that, at least partially, this is why regulations in this area were put in place to begin with.
Before anyone shows up at FDA decision makers' kids soccer practice please consider things from the point of view of an FDA decision maker. They have to make a choice which they know will lead to both type 1 and type 2 errors. For life saving medicine, when the decision isn't clear, both type 1 and type 2 errors are awful. It's likely they already feel the burden of responsibility.
Category A - approved by the FDA, basically what we have right now
Category B - approved by some other established regulatory body (EU). Comes with all the warnings, doctors can write it off-label, insurance companies may not cover it but doctors can ask for a variance
Category C - approved by some non-OECD body. Insurance companies under no obligation to cover
Category D - experimental, this is stuff maybe still only in animal models, but pharmacies can still order and dispense it
Category E - experimental and basically limited run from pharmaceutical companies. These essentially need to be tailor-made or produced by a GMP kilo lab. There are plenty of drugs in this category - I worked on them - and the intended recipients are entirely animals, QA, and regulatory agencies. But maybe if some crazy S.R. Hadden type (billionaire in Contact) wants to guinea pig themselves, let em.
The latter category also opens the door for custom therapies (gene/mRNA) that you basically can't test the active pharmaceutical ingredient for efficacy on.
> Category B - approved by some other established regulatory body (EU). Comes with all the warnings, doctors can write it off-label, insurance companies may not cover it but doctors can ask for a variance
We can already prescribe off-label if the FDA has approved it for at least 1 indication, and it mostly gets reimbursed.
> Category C - approved by some non-OECD body. Insurance companies under no obligation to cover
There's very little that's approved by a non-US body and approved by the EU or non-OECD body that warrants clinical use, and if it is it gets reviewed quickly. The US is the largest market for manufacturers so they almost always start here.
> Category D - experimental, this is stuff maybe still only in animal models, but pharmacies can still order and dispense it
Pharmacists and physicians are ethically bound to prescribe to the best of their ability and avoid harm, by prescribing something only validated in animal models it means we are not prescribing/dispensing something validated in humans and therefore not meeting or exceeding the standard of care.
This sounds like a recipe for killing people.
> The latter category also opens the door for custom therapies (gene/mRNA) that you basically can't test the active pharmaceutical ingredient for efficacy on.
Huh? There are many ongoing gene-directed and mRNA studies being tested.
Do you know what else sounds like a recipe for killing people? Not allowing people to access therapeutics that might save their life because it hasn't yet gone through regulatory approval yet for whatever reason (delays, too expensive to submit), etc.
> There's very little that's approved by a non-US body and approved by the EU or non-OECD body that warrants clinical use, and if it is it gets reviewed quickly
LOL. What are you talking about. There are so many examples.
One of the most tragic is amisulpride. Amisulpride is an antipsychotic medication used to treat schizophrenia and other psychiatric conditions. Some key notes about its regulatory status:
- Amisulpride was first approved in France in the 1980s and is widely used in Europe.
- It was never approved by the FDA for use in the United States, and at this point there's not organization that can afford to go through the approval process because there's no patent.
- The reason often cited is that the manufacturer did not apply for approval with the FDA. It was likely not considered commercially viable for the US market at the time.
- Amisulpride is believed to have comparable efficacy to other second-generation antipsychotics like olanzapine and risperidone, but with a lower side effect burden according to some studies.
- In Europe, amisulpride is considered a first-line treatment option for schizophrenia, but American psychiatrists do not have access to it. According to some sources, it is literally recommended as the best antipsychotic in other countries.
There are "right to try" laws both Federally and in 40+ states. It's unfortunate the author doesn't address those, I'm curious how they interact with his case.
I was an early investor about 20 years ago (nothing to write home about) for a company in this space. Small molecule therapy though, not MRNA.
Very slow going, as is all speculative biotech stuff but it made it to approvals on the vetinary side (dogs and horses) and is sold in the US for those purposes. However, I believe the human trials are somewhere around P2 currently for H&N and other indications are even further back.
Only mentioning it because I still follow the annual reports, and I know that despite having no approvals they've treated a few patients via the various avenues that are available in Australia to people who have exhausted all other options.
The drug is tigilanol tiglate. It's had some success to date, with some immune responses in distal tumors after the initial application.
There is plenty of published research available, so please don't anyone take this comment as any kind of recommendation or advice.
One aspect of the problem here is the difficulty in running a clinical trial, particularly at the recruitment stage. The covid-19 trials all had a surfeit of participants because of a pandemic, but with modern cancer treatment trials the qualification requirements significantly cut down on the eligible population.
This, in itself, isn't a huge obstacle. The problem is the state of healthcare data systems. It's next to impossible to perform high-quality search (even by individuals approved to do so by the IRB). The state of the art in most places is regex searching in SQL.
This is something we have the power to contribute to. Bringing modern search capabilities to important datasets like health (while maintaining HIPAA-conpliance) is a much better use of engineering time than mining spyware data for creepy insights...
[Disclosure: I contributed heavily to one of the major medical search products on the market. We dealt with organisations that expended tens of thousands of dollars and many months per candidate for recruitment. Using some very straightforward IR tech we literally found all their candidates in a few minutes, plus many more. But there is so much more to do!]
Yes, very true. Beyond just access to clinical data there are often major differences between how the same conditions are recorded between different provider organizations based on EHR data models and local practices. Researchers who want to use data from multiple organizations typically have to put a huge amount of work into their data pipelines for cleansing and normalization. Some standards development organizations such as HL7 (including their various FHIR accelerators) are now writing more detailed and specific implementation guides to improve data quality and consistency so I would encourage technologists to contribute to those projects.
Readit News
Anyone who has suffered through this disease or has a loved one that experienced it knows the feeling of helplessness.
More on Jake’s story below, and a link to the fundraiser to support him and his wife: https://www.gofundme.com/f/help-the-fight-against-cancer-wit...
Be kind and good to your loved ones. Life is short and no one knows how much time we have left. While the FDA’s antiquated bureaucracy does no good, the true enemy is the disease itself. I believe in science and I hope that someday no one else will needlessly suffer as my brother has.
You be good. I love you.
Stabbing backs to maybe get a pay raise will mean nothing to you or your family. It's just one more person who won't honor your temporary existence.
Be KIND.
I’m sorry for the very difficult times your brother is going through. I hope and pray that his situation improves.
1: https://news.ycombinator.com/user?id=jseliger
This is such terrible news and I wish Jake and yourself the best.
>We get wise too late
>and old too soon.
>—Danish proverb
Quite.
I'm now four years older than my mother was when she passed away after two really exciting years. I can't remember the exact description of the killer but "squamous" was involved. Radio, chemo, surgery bordering on butchery etc. Bout one seemed to be in remission and all clear sounded only to be rescinded a few months later, second run was a negative outcome. Faith healer for a laugh "but you never know" - mum wasn't daft but when you are out of reasonable options, you might as well invent a few more!
However, there is still hope whilst breathe still flows and there is absolutely nothing wrong with hoping for a miracle. They do sometimes happen. Keep fighting and kicking and being a pain and only give up when it is obviously hopeless.
Love you too. Take care.
(Not sure about Cuba's current healthcare infrastructure).
Likely, Moderna doesn't want him to take the drugs because they will probably be ineffective this late in the cancer stage. It doesn't want its treatment to be associated with his death.
[0]https://www.fda.gov/patients/learn-about-expanded-access-and...
It's highly highly highly unusual to be offering an experimental therapy on compassionate grounds when conventional options that have potential to actually work well haven't been tried yet. In this post he only describes locoregional therapy and it appears he has not tried anything systemic yet.
The closest I've seen is we at least try a very short attempt of something in clinical use and then say patient refused/intolerable side-effects/treatment failure and move on. I can't imagine a circumstance where medical ethics would allow to skip a trial of validated therapy for something without even phase I data. It's not like this mRNA by Moderna is known to actually work.
Dead Comment
When the odds are against survival, there shouldn't be any rules limiting treatment, if it means even a slightly higher chance of winning. That's something our government has forgotten about or doesn't care about. If I was in this persons shoes, I would make it as personal as possible against those in control of the FDA. Show up at their houses, work, kids soccer practice, get in their face and let them see what their inaction is doing in person.
I agree with you. But the FDA would ask you to rigorously define "slightly higher chance of winning" -- and prove it. In the event you cannot do this, they believe that letting you try an experimental drug would be more unethical than letting you die of neglect.
So I'd rephrase that statement of yours: "When the odds are against survival, there shouldn't be any rules limiting treatment, regardless of type of treatment or odds of efficacy." ("When the odds are against survival" can be quantified, e.g. a 90% chance of dying within a year.)
Would this not also open the door for any snakeoil salesman to prey on what might be medically "hopeless" cases?
If I am ever diagnosed with something currently uncurable, but there are experimental stuff in the works, of course I'd like a shot at those experimental drugs, but I hope that me/my family would also not squander whatever assets we have on snakeoil, in which case I'd rather my surviving family was not impoverished in the fight.
I assume that, at least partially, this is why regulations in this area were put in place to begin with.
Category A - approved by the FDA, basically what we have right now
Category B - approved by some other established regulatory body (EU). Comes with all the warnings, doctors can write it off-label, insurance companies may not cover it but doctors can ask for a variance
Category C - approved by some non-OECD body. Insurance companies under no obligation to cover
Category D - experimental, this is stuff maybe still only in animal models, but pharmacies can still order and dispense it
Category E - experimental and basically limited run from pharmaceutical companies. These essentially need to be tailor-made or produced by a GMP kilo lab. There are plenty of drugs in this category - I worked on them - and the intended recipients are entirely animals, QA, and regulatory agencies. But maybe if some crazy S.R. Hadden type (billionaire in Contact) wants to guinea pig themselves, let em.
The latter category also opens the door for custom therapies (gene/mRNA) that you basically can't test the active pharmaceutical ingredient for efficacy on.
We can already prescribe off-label if the FDA has approved it for at least 1 indication, and it mostly gets reimbursed.
> Category C - approved by some non-OECD body. Insurance companies under no obligation to cover
There's very little that's approved by a non-US body and approved by the EU or non-OECD body that warrants clinical use, and if it is it gets reviewed quickly. The US is the largest market for manufacturers so they almost always start here.
> Category D - experimental, this is stuff maybe still only in animal models, but pharmacies can still order and dispense it
Pharmacists and physicians are ethically bound to prescribe to the best of their ability and avoid harm, by prescribing something only validated in animal models it means we are not prescribing/dispensing something validated in humans and therefore not meeting or exceeding the standard of care.
This sounds like a recipe for killing people.
> The latter category also opens the door for custom therapies (gene/mRNA) that you basically can't test the active pharmaceutical ingredient for efficacy on.
Huh? There are many ongoing gene-directed and mRNA studies being tested.
Do you know what else sounds like a recipe for killing people? Not allowing people to access therapeutics that might save their life because it hasn't yet gone through regulatory approval yet for whatever reason (delays, too expensive to submit), etc.
> There's very little that's approved by a non-US body and approved by the EU or non-OECD body that warrants clinical use, and if it is it gets reviewed quickly
LOL. What are you talking about. There are so many examples.
One of the most tragic is amisulpride. Amisulpride is an antipsychotic medication used to treat schizophrenia and other psychiatric conditions. Some key notes about its regulatory status:
- Amisulpride was first approved in France in the 1980s and is widely used in Europe.
- It was never approved by the FDA for use in the United States, and at this point there's not organization that can afford to go through the approval process because there's no patent.
- The reason often cited is that the manufacturer did not apply for approval with the FDA. It was likely not considered commercially viable for the US market at the time.
- Amisulpride is believed to have comparable efficacy to other second-generation antipsychotics like olanzapine and risperidone, but with a lower side effect burden according to some studies.
- In Europe, amisulpride is considered a first-line treatment option for schizophrenia, but American psychiatrists do not have access to it. According to some sources, it is literally recommended as the best antipsychotic in other countries.
Very slow going, as is all speculative biotech stuff but it made it to approvals on the vetinary side (dogs and horses) and is sold in the US for those purposes. However, I believe the human trials are somewhere around P2 currently for H&N and other indications are even further back.
Only mentioning it because I still follow the annual reports, and I know that despite having no approvals they've treated a few patients via the various avenues that are available in Australia to people who have exhausted all other options.
The drug is tigilanol tiglate. It's had some success to date, with some immune responses in distal tumors after the initial application.
There is plenty of published research available, so please don't anyone take this comment as any kind of recommendation or advice.
This, in itself, isn't a huge obstacle. The problem is the state of healthcare data systems. It's next to impossible to perform high-quality search (even by individuals approved to do so by the IRB). The state of the art in most places is regex searching in SQL.
This is something we have the power to contribute to. Bringing modern search capabilities to important datasets like health (while maintaining HIPAA-conpliance) is a much better use of engineering time than mining spyware data for creepy insights...
[Disclosure: I contributed heavily to one of the major medical search products on the market. We dealt with organisations that expended tens of thousands of dollars and many months per candidate for recruitment. Using some very straightforward IR tech we literally found all their candidates in a few minutes, plus many more. But there is so much more to do!]
Thank you for giving us all some of your time on this earth.