Dying of cancer
July 22, 2023 9:12 AM Subscribe
Once you pass a certain threshold - when your expected time remaining on this planet is measurable in an easily stated number of weeks, say - there are a lot of rules that really shouldn't apply to you. Being allowed to try an experimental or off-label drug that might prolong your life or improve the quality of what time remains is definitely on that list.
posted by potrzebie at 9:29 AM on July 22, 2023 [38 favorites]
posted by potrzebie at 9:29 AM on July 22, 2023 [38 favorites]
wow, that is so brutal. based on the photo he is still pretty damn young. its terrible that he cannot access experimental drugs due to bureaucracy bullshit. even if nothing worked for him, it could help advance medicine for the next person, which I'm pretty sure would at least give him some solace.
posted by supermedusa at 9:33 AM on July 22, 2023 [10 favorites]
posted by supermedusa at 9:33 AM on July 22, 2023 [10 favorites]
FDA: Expanded Access (aka "compassionate use")
posted by neuron at 10:04 AM on July 22, 2023 [4 favorites]
posted by neuron at 10:04 AM on July 22, 2023 [4 favorites]
I do think some nuance is called for here. Think of the suffering of women who underwent high-dose chemotherapy for breast cancer in the 90s--the availability of which was aggressively demanded by advocates--for no benefit.
Also note that compassionate use can authorize the administration of non-approved drugs.
posted by praemunire at 10:22 AM on July 22, 2023 [19 favorites]
Also note that compassionate use can authorize the administration of non-approved drugs.
posted by praemunire at 10:22 AM on July 22, 2023 [19 favorites]
There's a big difference between terminal patients being able to try whatever they want, with informed consent for the heightened possibility that it might degrade quality of remaining life, and payors being required to pay for speculative therapies, sometimes at thousands or tens of thousands of dollars a dose. Lots of people are dying every day, and paying to thrown things at the wall for them is not a sound policy.
posted by MattD at 10:33 AM on July 22, 2023 [14 favorites]
posted by MattD at 10:33 AM on July 22, 2023 [14 favorites]
There should absolutely be allowances for terminal patients to access experimental therapies via compassionate use. The bureaucracy is not needless though. The FDA is important, not just to find the most effective therapies, but to try to preserve the trust that the public has in medical system in general. If they approve people and doctors to try whatever they want, it undermines public trust that medicine works. You have to weigh the people helped by access to experimental therapies against the people hurt when trust in vaccines/medicine goes down a few percent.
posted by being_quiet at 10:45 AM on July 22, 2023 [7 favorites]
posted by being_quiet at 10:45 AM on July 22, 2023 [7 favorites]
There’s also now a “right to try” law, which creates a parallel pathway that pretty much skips the FDA. I think that originates in response to these kinds of deregulation arguments, which have been around for a while (as the date on the MR post will show).
I don’t really object to people having these options, but I’m not particularly convinced that it’s going to accelerate research all that much, at least without also deregulating other parts of the pipeline that have bigger tradeoffs. Somebody has to pay for you to get the drug. Insurance isn’t going to want to do that if it’s unclear that it does anything. The drug developer is only going to want to do that if they think it’s going to help them get a drug approved. People who want to get into clinical trials are sometimes frustrated to find out that they are either too sick, or not sick enough, to be considered as subjects. I think Derek Lowe of the “In the Pipeline” pharma blog had similar thoughts on “Right to Try” when laws were being passed at the state level - actually I think he was even more cynical. Anything that shifts the framing of experimental treatments towards “ray of hope” instead of “opportunity to participate in research” is largely giving people the wrong idea.
posted by atoxyl at 10:49 AM on July 22, 2023 [8 favorites]
I don’t really object to people having these options, but I’m not particularly convinced that it’s going to accelerate research all that much, at least without also deregulating other parts of the pipeline that have bigger tradeoffs. Somebody has to pay for you to get the drug. Insurance isn’t going to want to do that if it’s unclear that it does anything. The drug developer is only going to want to do that if they think it’s going to help them get a drug approved. People who want to get into clinical trials are sometimes frustrated to find out that they are either too sick, or not sick enough, to be considered as subjects. I think Derek Lowe of the “In the Pipeline” pharma blog had similar thoughts on “Right to Try” when laws were being passed at the state level - actually I think he was even more cynical. Anything that shifts the framing of experimental treatments towards “ray of hope” instead of “opportunity to participate in research” is largely giving people the wrong idea.
posted by atoxyl at 10:49 AM on July 22, 2023 [8 favorites]
one of my oldest friends is currently suffering through a brutal cancer "adventure". He's not officially terminal but neither is there a clear path to remission ... so they're trying lots of stuff. Or as he likes to put it, tongue painfully in cheek. "They obviously can't guarantee me eternal life, but there's definitely hope that the miracles of modern medicine can prolong my suffering for as much as ten years."
posted by philip-random at 11:09 AM on July 22, 2023 [14 favorites]
posted by philip-random at 11:09 AM on July 22, 2023 [14 favorites]
paying to thrown things at the wall for them is not a sound policy
On the other hand, the FDA has approved new drugs which either have little effect, or in some notable cases, have killed people for marginal clinical benefit. The cozy relationship between regulators and regulatees is probably not going away any time soon — there's just too much money — and it could be made to work for those who are terminal and who consent to experimental treatments.
posted by They sucked his brains out! at 11:25 AM on July 22, 2023 [6 favorites]
On the other hand, the FDA has approved new drugs which either have little effect, or in some notable cases, have killed people for marginal clinical benefit. The cozy relationship between regulators and regulatees is probably not going away any time soon — there's just too much money — and it could be made to work for those who are terminal and who consent to experimental treatments.
posted by They sucked his brains out! at 11:25 AM on July 22, 2023 [6 favorites]
This was very powerful in it's directness. How tragic, what powerlessness.
Stepping back, I am 100% in agreement with right to try policies for people with terminal illness. Having said that, I do not think this is the biggest problem for the FDA when you consider the impact, and I agree with the above statements that the FDA likely OVER approves drugs that have no value except profit making for already rich companies.
The agency seems to need a huge overhaul but is also symptomatic of huge problems in political power relations in the US, to say nothing of our cruel and dysfunctional healthcare system.
posted by latkes at 12:00 PM on July 22, 2023 [5 favorites]
Stepping back, I am 100% in agreement with right to try policies for people with terminal illness. Having said that, I do not think this is the biggest problem for the FDA when you consider the impact, and I agree with the above statements that the FDA likely OVER approves drugs that have no value except profit making for already rich companies.
The agency seems to need a huge overhaul but is also symptomatic of huge problems in political power relations in the US, to say nothing of our cruel and dysfunctional healthcare system.
posted by latkes at 12:00 PM on July 22, 2023 [5 favorites]
I agree with the above statements that the FDA likely OVER approves drugs that have no value except profit making for already rich companies
One argument on the other side here is that treatments of marginal value can still lead towards better treatments in the future. To me the problem with the idea that more people may be harmed by slow progress in drug development than availability of bad drugs is less that it’s obviously wrong - it’s that how the hell do you even know? And in the areas in which it’s most likely to be right, is regulation really the main barrier?
I suppose an underlying point here is that it’s easy to come up with dramatic examples of treatments that never should have seen widespread use, as well as treatments that were unnecessarily delayed, but both are probably secondary compared to the big problems in health care, if you really want to think in utilitarian terms.
posted by atoxyl at 12:56 PM on July 22, 2023 [3 favorites]
One argument on the other side here is that treatments of marginal value can still lead towards better treatments in the future. To me the problem with the idea that more people may be harmed by slow progress in drug development than availability of bad drugs is less that it’s obviously wrong - it’s that how the hell do you even know? And in the areas in which it’s most likely to be right, is regulation really the main barrier?
I suppose an underlying point here is that it’s easy to come up with dramatic examples of treatments that never should have seen widespread use, as well as treatments that were unnecessarily delayed, but both are probably secondary compared to the big problems in health care, if you really want to think in utilitarian terms.
posted by atoxyl at 12:56 PM on July 22, 2023 [3 favorites]
Oncologist and cancer drug developer here (as in, I run R&D for a biotech company, cancer drug developer). This is, without a doubt, a very sad and tragic story of a young person with an aggressive cancer and few therapeutic options. I feel compelled to provide my perspective on this topic.
First, it's important to remember (IMHO) that compassionate use or early access to experimental therapeutics is a very complex issue, but underlying it is the stone-cold fact that experimental therapeutics are, by their very nature, not proven to work. There's a well-known concept in human subjects research called "the therapeutic misconception" and it's something we have to bear in mind, and that's that experiments are not therapy. Therapy is something proven to modify/improve the disease.
Second, the mRNA cancer vaccines that were referenced in the article, are still experimental. We don't know if they'll help. In fact, for the majority of cancer drugs that are approved, none work in 100% of patients tried. In many instances, in relapsed cancers, you'll see response rates between 30-60%. The mRNA vaccines are even more problematic in that they are given in combination with immune-stimulating therapeutics such as immune checkpoint inhibitors like the PD-1 inhibitor pembrolizumab. We know that for patients who have tumors that are initially treated with a checkpoint inhibitor and who respond then have disease progression, some of those patients re-respond when you wait and retreat them with the same drug. Because the mRNA cancer vaccines are tested in combination with a checkpoint inhibitor, in patients who typically have already progressed on a checkpoint inhibitor, it's hard to know without a longer, randomized study, whether the responses that we're seeing are due to the vaccine, or if it's a re-treatment effect from the checkpoint inhibitor. As a result, these trials can take longer to prove that it's the vaccine causing the effect. These trials oftentimes are larger and more complex, and therefore the path to FDA approval is longer. Nobody slow-rolls a trial - it costs millions of dollars a month to just keep the clinical trial machinery running for a single trial. Time, in drug development, is a lot of money.
Finally, many (but not all) companies will offer some form of compassionate use, but this remains at the discretion of the company. Some companies have the resources (or drug supply) to support compassionate use. Some don't. And while there is a federal "right to try" law on the books, there's no mandate for companies to provide supply. So it's a toothless law. As of today, in the US, you can't force a private company to provide drug. From the point of view of the company, compassionate use programs cost a great deal to set up and maintain, in terms of drug supply, safety monitoring, and internal human effort - and those resources often times are being fully utilized to move the clinical trials and development efforts forward - in biotech, we rarely have spare capacity. Fortunately, for relapsed patients there are often many Phase 1 trials, and many compassionate use programs, so it's rare for there to be truly zero options for access to something to try.
posted by scblackman at 1:01 PM on July 22, 2023 [73 favorites]
First, it's important to remember (IMHO) that compassionate use or early access to experimental therapeutics is a very complex issue, but underlying it is the stone-cold fact that experimental therapeutics are, by their very nature, not proven to work. There's a well-known concept in human subjects research called "the therapeutic misconception" and it's something we have to bear in mind, and that's that experiments are not therapy. Therapy is something proven to modify/improve the disease.
Second, the mRNA cancer vaccines that were referenced in the article, are still experimental. We don't know if they'll help. In fact, for the majority of cancer drugs that are approved, none work in 100% of patients tried. In many instances, in relapsed cancers, you'll see response rates between 30-60%. The mRNA vaccines are even more problematic in that they are given in combination with immune-stimulating therapeutics such as immune checkpoint inhibitors like the PD-1 inhibitor pembrolizumab. We know that for patients who have tumors that are initially treated with a checkpoint inhibitor and who respond then have disease progression, some of those patients re-respond when you wait and retreat them with the same drug. Because the mRNA cancer vaccines are tested in combination with a checkpoint inhibitor, in patients who typically have already progressed on a checkpoint inhibitor, it's hard to know without a longer, randomized study, whether the responses that we're seeing are due to the vaccine, or if it's a re-treatment effect from the checkpoint inhibitor. As a result, these trials can take longer to prove that it's the vaccine causing the effect. These trials oftentimes are larger and more complex, and therefore the path to FDA approval is longer. Nobody slow-rolls a trial - it costs millions of dollars a month to just keep the clinical trial machinery running for a single trial. Time, in drug development, is a lot of money.
Finally, many (but not all) companies will offer some form of compassionate use, but this remains at the discretion of the company. Some companies have the resources (or drug supply) to support compassionate use. Some don't. And while there is a federal "right to try" law on the books, there's no mandate for companies to provide supply. So it's a toothless law. As of today, in the US, you can't force a private company to provide drug. From the point of view of the company, compassionate use programs cost a great deal to set up and maintain, in terms of drug supply, safety monitoring, and internal human effort - and those resources often times are being fully utilized to move the clinical trials and development efforts forward - in biotech, we rarely have spare capacity. Fortunately, for relapsed patients there are often many Phase 1 trials, and many compassionate use programs, so it's rare for there to be truly zero options for access to something to try.
posted by scblackman at 1:01 PM on July 22, 2023 [73 favorites]
My dad died of this exact cancer ten years ago. It's utterly demoralizing that we appear to have made no progress.
posted by petiteviolette at 1:01 PM on July 22, 2023 [5 favorites]
posted by petiteviolette at 1:01 PM on July 22, 2023 [5 favorites]
My dad died of this exact cancer ten years ago. It's utterly demoralizing that we appear to have made no progress.
Relapsed/metastatic head and neck squamous cell carcinoma (HNSCC) is a terrible cancer, and the most recent generation of approved therapies for relapsed disease shows overall survivals of only about 12-16 months.
I'm so sorry about your dad.
posted by scblackman at 1:06 PM on July 22, 2023 [9 favorites]
Relapsed/metastatic head and neck squamous cell carcinoma (HNSCC) is a terrible cancer, and the most recent generation of approved therapies for relapsed disease shows overall survivals of only about 12-16 months.
I'm so sorry about your dad.
posted by scblackman at 1:06 PM on July 22, 2023 [9 favorites]
I’ve lost 3 family members to progressive, incurable terminal illnesses in the last 5 years. Part of the dying process is patient, friends and family googling the clinical trials and suggesting there is a miracle out there that will save the patient from their fate. This is a false hope.
posted by interogative mood at 1:15 PM on July 22, 2023 [12 favorites]
posted by interogative mood at 1:15 PM on July 22, 2023 [12 favorites]
in some notable cases, have killed people for marginal clinical benefit [referencing Vioxx]
This would be a good place to say that despite my username I am not an expert in pharmacology but it’s interesting to me how much this is still a go-to example of an FDA failure because my impression of developments since is that we have kind of realized that COX inhibitors (NSAIDs) in general, including those long available OTC, have cardiovascular risks - perhaps to varying degrees but it’s not obvious that the COX-2 selective ones are categorically worse, nor even that Vioxx was a huge outlier among them.
It’s a positive outcome when scrutiny on new drugs leads to learning more about the tradeoffs around old drugs, of course, but it feels like a story that illustrates some of the biases in which risks we notice as a result of which risks we bother to look for.
posted by atoxyl at 1:23 PM on July 22, 2023
This would be a good place to say that despite my username I am not an expert in pharmacology but it’s interesting to me how much this is still a go-to example of an FDA failure because my impression of developments since is that we have kind of realized that COX inhibitors (NSAIDs) in general, including those long available OTC, have cardiovascular risks - perhaps to varying degrees but it’s not obvious that the COX-2 selective ones are categorically worse, nor even that Vioxx was a huge outlier among them.
It’s a positive outcome when scrutiny on new drugs leads to learning more about the tradeoffs around old drugs, of course, but it feels like a story that illustrates some of the biases in which risks we notice as a result of which risks we bother to look for.
posted by atoxyl at 1:23 PM on July 22, 2023
Fuck cancer, and fuck needless suffering. (The rest of it is complicated, and people are working on it.)
posted by k3ninho at 3:31 PM on July 22, 2023 [2 favorites]
posted by k3ninho at 3:31 PM on July 22, 2023 [2 favorites]
You'd think after all the battles that were fought during the AIDS crisis in the 80s and 90s, with dying people demanding to have access to experimental drugs because they were dying and it wouldn't matter...
You'd think we've have learned these lessons already.
I don't know if we can get a new ACT-UP kind of action going on for these kind of patients, but we certainly should be talking about it.
posted by hippybear at 3:53 PM on July 22, 2023 [1 favorite]
You'd think we've have learned these lessons already.
I don't know if we can get a new ACT-UP kind of action going on for these kind of patients, but we certainly should be talking about it.
posted by hippybear at 3:53 PM on July 22, 2023 [1 favorite]
The OP really hit.
The author is young, knows he is going to die, and really doesn't want to die. I get it. I am also fighting cancer, I am relatively young, and I really don't want to die. But I have to no ire for the FDA and only appreciation and respect for the countless scientists and medical professionals working furiously to extend my life.
I have been fighting ovarian cancer for eight years.
If I had gotten this disease 30 years ago, they would have sent me home to die upon diagnosis. As it was, I got surgery, chemo and great follow-up care, because of amazing recent advancements in medicine. Still, I was only given a 20% chance of making it another five years.
I have recurred multiple times, and each time, there's a new drug rolled out of clinical trials and approved by the FDA for me to take and enjoy a few more months of delicious, deliriously joyful life.
I know this ride will end for me eventually, as it does for us all. But a weird gift of cancer is I now appreciate and enjoy the fuck out of every damn day.
Just another perspective for y'all.
posted by birdsongster at 4:17 PM on July 22, 2023 [68 favorites]
The author is young, knows he is going to die, and really doesn't want to die. I get it. I am also fighting cancer, I am relatively young, and I really don't want to die. But I have to no ire for the FDA and only appreciation and respect for the countless scientists and medical professionals working furiously to extend my life.
I have been fighting ovarian cancer for eight years.
If I had gotten this disease 30 years ago, they would have sent me home to die upon diagnosis. As it was, I got surgery, chemo and great follow-up care, because of amazing recent advancements in medicine. Still, I was only given a 20% chance of making it another five years.
I have recurred multiple times, and each time, there's a new drug rolled out of clinical trials and approved by the FDA for me to take and enjoy a few more months of delicious, deliriously joyful life.
I know this ride will end for me eventually, as it does for us all. But a weird gift of cancer is I now appreciate and enjoy the fuck out of every damn day.
Just another perspective for y'all.
posted by birdsongster at 4:17 PM on July 22, 2023 [68 favorites]
You'd think after all the battles that were fought during the AIDS crisis in the 80s and 90s, with dying people demanding to have access to experimental drugs because they were dying and it wouldn't matter...
This is a delicate thing to talk about for obvious reasons but I will try because it’s a good illustration of some of the major themes discussed in this thread. Looking at the history of HIV treatment in retrospect it’s pretty clear that most of the experimental stuff didn’t work, and that the “establishment” approach to antiviral treatment - which took a lot of flak in the early days when it meant big doses of things like AZT with nasty side effects - really did work, eventually, once there were enough antivirals with different mechanisms of action that could be combined. And the much-maligned AZT ended up being a totally legit drug once its proper dosage and place in a treatment regimen was figured out.
So on one hand it shows the importance of patient engagement and advocacy in pushing forward medical progress, in general, and it’s another case from which one can argue that people in such a desperate position have a fundamental right to try experimental treatment. And on the other it shows that many experimental treatments are false hopes, and that the experts do, sometimes, have the right idea.
posted by atoxyl at 4:38 PM on July 22, 2023 [13 favorites]
This is a delicate thing to talk about for obvious reasons but I will try because it’s a good illustration of some of the major themes discussed in this thread. Looking at the history of HIV treatment in retrospect it’s pretty clear that most of the experimental stuff didn’t work, and that the “establishment” approach to antiviral treatment - which took a lot of flak in the early days when it meant big doses of things like AZT with nasty side effects - really did work, eventually, once there were enough antivirals with different mechanisms of action that could be combined. And the much-maligned AZT ended up being a totally legit drug once its proper dosage and place in a treatment regimen was figured out.
So on one hand it shows the importance of patient engagement and advocacy in pushing forward medical progress, in general, and it’s another case from which one can argue that people in such a desperate position have a fundamental right to try experimental treatment. And on the other it shows that many experimental treatments are false hopes, and that the experts do, sometimes, have the right idea.
posted by atoxyl at 4:38 PM on July 22, 2023 [13 favorites]
I’ve lost 3 family members to progressive, incurable terminal illnesses in the last 5 years. Part of the dying process is patient, friends and family googling the clinical trials and suggesting there is a miracle out there that will save the patient from their fate. This is a false hope.
Which those of us in this COVID era understand very well, as many of us have friends or family convinced that Big Pharma hid hydroxychloroquine, ivermectin, zinc, high-dose vitamins, red soap, direct sunlight, vodka, betel leaves, industral methanol, hot saunas, coilloidal silver, Indian cow urine, oleandrin, this chair, this paddle-ball game and/or this stapler from the public as reliable COVID preventatives/treatments because they (insert your least favorite uncle's profane rant here).
posted by delfin at 5:29 PM on July 22, 2023 [3 favorites]
Which those of us in this COVID era understand very well, as many of us have friends or family convinced that Big Pharma hid hydroxychloroquine, ivermectin, zinc, high-dose vitamins, red soap, direct sunlight, vodka, betel leaves, industral methanol, hot saunas, coilloidal silver, Indian cow urine, oleandrin, this chair, this paddle-ball game and/or this stapler from the public as reliable COVID preventatives/treatments because they (insert your least favorite uncle's profane rant here).
posted by delfin at 5:29 PM on July 22, 2023 [3 favorites]
And on the other it shows that many experimental treatments are false hopes, and that the experts do, sometimes, have the right idea.
Many of the patients volunteering for false hope drugs were signing up to be data points proving those drugs to be dead ends. They knew what they were doing, and even in their deaths they were offering hope of life, or at least crossing false hope of life off the list, for others.
I was following a lot of this quite closely at the time.
posted by hippybear at 6:02 PM on July 22, 2023 [20 favorites]
Many of the patients volunteering for false hope drugs were signing up to be data points proving those drugs to be dead ends. They knew what they were doing, and even in their deaths they were offering hope of life, or at least crossing false hope of life off the list, for others.
I was following a lot of this quite closely at the time.
posted by hippybear at 6:02 PM on July 22, 2023 [20 favorites]
My dad died of this exact cancer ten years ago.
My dad died of this exact cancer twenty-eight years ago. He tried Taxol which I think was experimental at the time. About five months before he died he got pneumonia and the doctors suggested that they could treat it or we could let him go - we said, “What? Of course treat it.” We would have tried anything.
posted by bendy at 6:17 PM on July 22, 2023 [2 favorites]
My dad died of this exact cancer twenty-eight years ago. He tried Taxol which I think was experimental at the time. About five months before he died he got pneumonia and the doctors suggested that they could treat it or we could let him go - we said, “What? Of course treat it.” We would have tried anything.
posted by bendy at 6:17 PM on July 22, 2023 [2 favorites]
I also work in cancer research, in a support role. I was in a meeting with a bunch of doctors once, and one mentioned going before the IRB with a drug that had a projected mortality rate of 30%. (Yes, that's from the drug itself. Still better than existing treatments.) I also had the following conversation with my boss;
"We need to change the dose schedule on <trial?"
"Why?"
"Too many children are dying."
Research drugs can do bad stuff.
posted by Spike Glee at 6:19 PM on July 22, 2023 [5 favorites]
"We need to change the dose schedule on <trial?"
"Why?"
"Too many children are dying."
Research drugs can do bad stuff.
posted by Spike Glee at 6:19 PM on July 22, 2023 [5 favorites]
Lots of people are dying every day, and paying to thrown things at the wall for them is not a sound policy.
Compared to what?
posted by Ray Walston, Luck Dragon at 6:54 PM on July 22, 2023
Compared to what?
posted by Ray Walston, Luck Dragon at 6:54 PM on July 22, 2023
speculative therapies, sometimes at thousands or tens of thousands of dollars a dose.
WHY they are tens of thousands of dollars a dose bears some examination, as it is not a single actor or factor causing that.
posted by delfin at 8:18 PM on July 22, 2023 [2 favorites]
WHY they are tens of thousands of dollars a dose bears some examination, as it is not a single actor or factor causing that.
posted by delfin at 8:18 PM on July 22, 2023 [2 favorites]
When you are talking biologics or chemo the “why is it tens of thousands of dollars” is actually pretty straightforward, especially when each dose is being hand crafted in a trial. There are many many drugs that are needlessly expensive. Experimental drugs are really not on that list. Making extraordinarily pure substances is hard, it’s harder if you don’t have a manufacturing line dedicated to it, it’s expensive to produce the components of biologics, it’s difficult to work with dangerous substances, etc etc. This is one of those times where actually yeah it costs that much and not entirely because of profit motive.
posted by Bottlecap at 8:51 PM on July 22, 2023 [13 favorites]
posted by Bottlecap at 8:51 PM on July 22, 2023 [13 favorites]
its terrible that he cannot access experimental drugs due to bureaucracy bullshit. even if nothing worked for him, it could help advance medicine for the next person, which I'm pretty sure would at least give him some solace.
I work in oncology clinical trial data management. I’ve worked on Phase II-III trials, and have also seen patients go on Expanded Access protocols. Clinical trials are designed to collect the data needed to determine whether drugs are effective and (tolerably) safe. Expanded access protocols are available to get patients access to drugs that aren’t yet approved. Any data collected is typically much more limited, and largely related to safety events associated with the drug. The level of data collection isn’t designed to support making conclusions about drug efficacy; rather, it’s adding to safety information about the drug, which may inform future clinical trials. It’s not nothing, but getting access to the drug via a Phase I trial would contribute much more to the science.
That isn’t to say patients shouldn’t be able to try experimental drugs, particularly those with such limited life expectancy. However, scblackman’s point about therapeutic misconception is important. We do trials specifically because we don’t know if a drug is effective or not. There are lots of promising drugs that turn out to be ineffective once they make it to trials. Trials need informed consent, along with lots of other reasons, because sick and terminal patients are a vulnerable population. They want to believe that this thing they’re signing up for will save them, or give them more time. But we really don’t know.
WHY they are tens of thousands of dollars a dose bears some examination, as it is not a single actor or factor causing that.
I’m very familiar with the structural, economic bullshit that makes the medical industry so fucked, especially in the US. I’m also a socialist, and do not support the profit motive involved with private companies being the ones tasked with creating drugs for the good of humankind. But a large part of the reason these drugs are so expensive is that they’re expensive to develop. The number of people involved in a single clinical trial, for a single indication of a drug (each type of cancer has to be tested before it can be approved for that indication) is amazing. And this is just in the testing portion of development. I have no idea what it takes to actually develop, and then manufacture for testing, new drugs, but I’m certain there are a lot of people doing a lot of work to make it happen. And that costs money.
posted by bluloo at 9:01 PM on July 22, 2023 [18 favorites]
I work in oncology clinical trial data management. I’ve worked on Phase II-III trials, and have also seen patients go on Expanded Access protocols. Clinical trials are designed to collect the data needed to determine whether drugs are effective and (tolerably) safe. Expanded access protocols are available to get patients access to drugs that aren’t yet approved. Any data collected is typically much more limited, and largely related to safety events associated with the drug. The level of data collection isn’t designed to support making conclusions about drug efficacy; rather, it’s adding to safety information about the drug, which may inform future clinical trials. It’s not nothing, but getting access to the drug via a Phase I trial would contribute much more to the science.
That isn’t to say patients shouldn’t be able to try experimental drugs, particularly those with such limited life expectancy. However, scblackman’s point about therapeutic misconception is important. We do trials specifically because we don’t know if a drug is effective or not. There are lots of promising drugs that turn out to be ineffective once they make it to trials. Trials need informed consent, along with lots of other reasons, because sick and terminal patients are a vulnerable population. They want to believe that this thing they’re signing up for will save them, or give them more time. But we really don’t know.
WHY they are tens of thousands of dollars a dose bears some examination, as it is not a single actor or factor causing that.
I’m very familiar with the structural, economic bullshit that makes the medical industry so fucked, especially in the US. I’m also a socialist, and do not support the profit motive involved with private companies being the ones tasked with creating drugs for the good of humankind. But a large part of the reason these drugs are so expensive is that they’re expensive to develop. The number of people involved in a single clinical trial, for a single indication of a drug (each type of cancer has to be tested before it can be approved for that indication) is amazing. And this is just in the testing portion of development. I have no idea what it takes to actually develop, and then manufacture for testing, new drugs, but I’m certain there are a lot of people doing a lot of work to make it happen. And that costs money.
posted by bluloo at 9:01 PM on July 22, 2023 [18 favorites]
Some of these medicines also cost tens of thousands of dollars a dose because thankfully there are not that many people who need them, so the cost of everything is much higher as there are no economies of scale.
posted by interogative mood at 9:46 PM on July 22, 2023 [3 favorites]
posted by interogative mood at 9:46 PM on July 22, 2023 [3 favorites]
> I think Derek Lowe of the “In the Pipeline” pharma blog had similar thoughts on “Right to Try”
Yeah, he does. Some 2014 thoughts on a CO bill; 2013 reflections on the challenges of compassionate access (including the potential problematic downstream effects on early-stage clinical trials); a 2014 look at stem cells (then one of the types of very experimental therapies patients frequently sought out); thoughts about the 2018 federal bill.
See also 2013 comments from Gorski at Science-Based Medicine (which mentions some of the AIDS analogies in a more cautionary vein), as well as discussion of the federal bill at its passing and a year later.
Despite the heartbreak of people running out of available treatments, it's hard not to end up with the same fears that Lowe and Gorski express: that trying to further open up access to very early-stage drug candidates will actually help few people (most post-Phase I drug candidates don't work, and many have significant side effects and risks), but it will open up space for grifters to prey on desperate people and it may unfortunately make actual early stage drug research harder and less reliable (clinical trials are complicated and carefully regulated for a reason; ad hoc reporting on meds dispensed for compassionate use cannot really provide the same level of information at all). This absolutely isn't to say that compassionate access is never appropriate, but the very fact that people are looking at drug candidates very early in the clinical trial process (long before clinical efficacy is known) and thinking of them as "treatments that might save [them]" is precisely why this is such a hard problem, such a hard thing to get right - it's an illustration of exactly why patients in this situation and their families are a vulnerable population.
posted by ASF Tod und Schwerkraft at 10:10 PM on July 22, 2023 [11 favorites]
Yeah, he does. Some 2014 thoughts on a CO bill; 2013 reflections on the challenges of compassionate access (including the potential problematic downstream effects on early-stage clinical trials); a 2014 look at stem cells (then one of the types of very experimental therapies patients frequently sought out); thoughts about the 2018 federal bill.
See also 2013 comments from Gorski at Science-Based Medicine (which mentions some of the AIDS analogies in a more cautionary vein), as well as discussion of the federal bill at its passing and a year later.
Despite the heartbreak of people running out of available treatments, it's hard not to end up with the same fears that Lowe and Gorski express: that trying to further open up access to very early-stage drug candidates will actually help few people (most post-Phase I drug candidates don't work, and many have significant side effects and risks), but it will open up space for grifters to prey on desperate people and it may unfortunately make actual early stage drug research harder and less reliable (clinical trials are complicated and carefully regulated for a reason; ad hoc reporting on meds dispensed for compassionate use cannot really provide the same level of information at all). This absolutely isn't to say that compassionate access is never appropriate, but the very fact that people are looking at drug candidates very early in the clinical trial process (long before clinical efficacy is known) and thinking of them as "treatments that might save [them]" is precisely why this is such a hard problem, such a hard thing to get right - it's an illustration of exactly why patients in this situation and their families are a vulnerable population.
posted by ASF Tod und Schwerkraft at 10:10 PM on July 22, 2023 [11 favorites]
> But a large part of the reason these drugs are so expensive is that they’re expensive to develop. [...] I have no idea what it takes to actually develop, and then manufacture for testing, new drugs, but I’m certain there are a lot of people doing a lot of work to make it happen. And that costs money.
Yeah, I'm in a bit of academic research that overlaps with a lot of early drug discovery efforts (as in, I do the sort of basic science involved in characterizing potentially relevant proteins or biologically produced chemicals). And so I do get to see talks from industry folks involved in optimizing and scaling up drug production. And even if we're just talking about developing and producing the chemical itself, it's actually a huge challenge! When people first start synthesizing a drug candidate, they're initially just concerned with whether they can make the thing they want to make at all. A range of techniques that are too expensive or dangerous for scale-up may be employed at this stage, as well as the use of initial chemicals that are expensive or otherwise problematic. And when you're just scaling up to the point where you're killing cancer cells in a dish, you still don't need to make that much - yeah it may take a few weeks of full-time work from PhD-level chemists, but eh, at this stage, that's fine.
But as you move to trying to kill tumors in mice and to starting clinical trials in humans, you need more and more of the compound, and things get harder. Problem steps you over looked earlier on need to be addressed, because they're decreasing your yield, or leaving a trace amount of a chemical that's a problem, or because it's environmentally dangerous, or because it's clear the supplier for some precursor chemical won't be able to keep pace. So you start working with specialist "process chemists" (more PhD-credentialed folks) who'll start trying to redesign your synthetic approach, with an eye towards making it as cheap, green, and high-yield as possible. And they're proud of every cent per milligram they can shave off! (Seriously, they get so excited about this.)
And new problems show up: when killing cancer cells in a dish, things like "how bioavailable is it in a large tumor mass" and "what on earth will liver enzymes do to it" aren't a problem. But formulating things for use in the human body can have lots of nasty surprises that require tweaking - sometimes minor things about how the drug is dosed or delivered, sometimes more major chemical re-designs. (This is of course part of why we have Phase I trials!) All of these may, of course, force researchers back through the process just described.
For biologically derived treatments - like Pembrolizumab, mentioned above, part of a class of antibody treatments - things get worse. It's expensive to produce things like this: the antibody is produced in CHO cells, which means it can get certain kinds of chemical modifications that would be harder to correctly install when working in simpler systems like yeast or E. coli. But keeping cells like these alive and happy requires a carefully controlled (and otherwise sterile) environment, expensive medium, and (when it comes time to purify the antibody) a bunch of complicated techniques to gently isolate the antibody from a soup of chemically relatively-similar proteins. And by a chemist's standards, antibody production is horrifically wasteful, because the cells are spending so much of the input (in terms of material and energy) keeping themselves alive, rather than making new antibody! Naturally, making this sort of stuff also requires a fair amount of time and effort from well-trained staff, and the earlier stages of development require a lot of evaluation by PhD biologists.
In the end, clinical trials are by far the biggest expense in drug development. But in early stages, producing enough pure and correctly formulated product can be a real expense and a bottleneck, and for some kinds of treatments, it is actually really hard to get the costs down even in the final product, for reasons that do legitimately go beyond pharma company greed. (Or, you know, what Bottlecap said, but at greater length.)
posted by ASF Tod und Schwerkraft at 10:58 PM on July 22, 2023 [21 favorites]
Yeah, I'm in a bit of academic research that overlaps with a lot of early drug discovery efforts (as in, I do the sort of basic science involved in characterizing potentially relevant proteins or biologically produced chemicals). And so I do get to see talks from industry folks involved in optimizing and scaling up drug production. And even if we're just talking about developing and producing the chemical itself, it's actually a huge challenge! When people first start synthesizing a drug candidate, they're initially just concerned with whether they can make the thing they want to make at all. A range of techniques that are too expensive or dangerous for scale-up may be employed at this stage, as well as the use of initial chemicals that are expensive or otherwise problematic. And when you're just scaling up to the point where you're killing cancer cells in a dish, you still don't need to make that much - yeah it may take a few weeks of full-time work from PhD-level chemists, but eh, at this stage, that's fine.
But as you move to trying to kill tumors in mice and to starting clinical trials in humans, you need more and more of the compound, and things get harder. Problem steps you over looked earlier on need to be addressed, because they're decreasing your yield, or leaving a trace amount of a chemical that's a problem, or because it's environmentally dangerous, or because it's clear the supplier for some precursor chemical won't be able to keep pace. So you start working with specialist "process chemists" (more PhD-credentialed folks) who'll start trying to redesign your synthetic approach, with an eye towards making it as cheap, green, and high-yield as possible. And they're proud of every cent per milligram they can shave off! (Seriously, they get so excited about this.)
And new problems show up: when killing cancer cells in a dish, things like "how bioavailable is it in a large tumor mass" and "what on earth will liver enzymes do to it" aren't a problem. But formulating things for use in the human body can have lots of nasty surprises that require tweaking - sometimes minor things about how the drug is dosed or delivered, sometimes more major chemical re-designs. (This is of course part of why we have Phase I trials!) All of these may, of course, force researchers back through the process just described.
For biologically derived treatments - like Pembrolizumab, mentioned above, part of a class of antibody treatments - things get worse. It's expensive to produce things like this: the antibody is produced in CHO cells, which means it can get certain kinds of chemical modifications that would be harder to correctly install when working in simpler systems like yeast or E. coli. But keeping cells like these alive and happy requires a carefully controlled (and otherwise sterile) environment, expensive medium, and (when it comes time to purify the antibody) a bunch of complicated techniques to gently isolate the antibody from a soup of chemically relatively-similar proteins. And by a chemist's standards, antibody production is horrifically wasteful, because the cells are spending so much of the input (in terms of material and energy) keeping themselves alive, rather than making new antibody! Naturally, making this sort of stuff also requires a fair amount of time and effort from well-trained staff, and the earlier stages of development require a lot of evaluation by PhD biologists.
In the end, clinical trials are by far the biggest expense in drug development. But in early stages, producing enough pure and correctly formulated product can be a real expense and a bottleneck, and for some kinds of treatments, it is actually really hard to get the costs down even in the final product, for reasons that do legitimately go beyond pharma company greed. (Or, you know, what Bottlecap said, but at greater length.)
posted by ASF Tod und Schwerkraft at 10:58 PM on July 22, 2023 [21 favorites]
But in early stages, producing enough pure and correctly formulated product can be a real expense and a bottleneck
Pharma greed is very much a thing. But I briefly paid the bills working as an admin assistant to one of the basic scientists who developed a particular cancer drug, the first of a class that dramatically affected treatment in a subtype of cancers, and it took seven years to go from Phase I to FDA approval. That's a lot of time to be putting money into a project with no return.
posted by praemunire at 11:17 PM on July 22, 2023 [1 favorite]
Pharma greed is very much a thing. But I briefly paid the bills working as an admin assistant to one of the basic scientists who developed a particular cancer drug, the first of a class that dramatically affected treatment in a subtype of cancers, and it took seven years to go from Phase I to FDA approval. That's a lot of time to be putting money into a project with no return.
posted by praemunire at 11:17 PM on July 22, 2023 [1 favorite]
as long as lawsuits in america are so prevalent, i really don't think anything will change. sure, clinical trial participants sign waivers and whatnot, but that won't really stop an angry family member when that person dies. or maybe it will, i dunno. the fda is slow and persnickety and hard to deal with and big pharma will say they have the patients in mind, but it's really their stock price that matters.
posted by misanthropicsarah at 1:31 PM on July 24, 2023
posted by misanthropicsarah at 1:31 PM on July 24, 2023
Amazingly large mammals like whales have a striking resistance to cancer, and other age related diseases, but we'll likely drive them all extinct before we understand why. At that point it'll be our own consumption that ends maybe our best hopes for discovering real cures for cancer, etc.
posted by jeffburdges at 3:51 PM on July 24, 2023
posted by jeffburdges at 3:51 PM on July 24, 2023
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This. Fuck cancer.
posted by chavenet at 9:21 AM on July 22, 2023 [11 favorites]