10 ms·

A Dying Scientist and His Rogue Vaccine Trial

127 points by tchalla 9y ago

mkirklions 9y ago
>“If I can help people suffering from herpes, isn’t it my duty to do so?” Gosh I here that statement echoing in my head about the problems in my life... Also, this is exactly the kind of problem in healthcare that is completely government and establishment driven. Physicians keep propping their monopoly up with literally hundreds of millions of dollars in lobbying/bribery. Every profession in medical seems to be similar, dumping massive money into politicians: https://www.opensecrets.org/lobby/top.php?indexType=s https://www.opensecrets.org/lobby/top.php?indexType=s Then their 'scientific method' has completely let me down after reading what these 'experts' consider a study. Lots of hypothesis getting validated by any-means-necessary. Not to mention their understanding of statistics usually tosses in the word 'P-value' for extra points, despite their population sample and study being a terrible representation of outcomes. Medical is corrupt AF
- ThomPete 9y ago
  But what are you going to do about it?
- gvb 9y ago
  >“If I can help people suffering from herpes, isn’t it my duty to do so?” That is a question, not a statement "Since I can help...". The problem is that he did significant harm to people trying to answer that question. The results of his experimentation are not fully realized, but the story indicates his injections caused harm in some cases and do not appear to have achieved the promise cure in any(?) of the cases. The counterbalance question is "If my hypothesis is wrong and I harm people, isn't it my duty to do no harm?"
- techterrier 9y ago
  >“If I can help people suffering from herpes, isn’t it my duty to do so?” He missed out the 'first do no harm' bit. It's quite important.
  - Afforess 9y ago
    "First, do no harm" is not part of the hippocratic oath at all. [1] The actual line in the hippocratic oath is much more flexible: >I will follow that system of regimen which, according to my ability and judgment, I consider for the benefit of my patients, and abstain from whatever is deleterious and mischievous. Based on the reported specifics of the rogue vaccine trial, it would seem Halford did most of this. The article questions his judgement over the confusion between HSV-1 and HSV-2 strains, but that seems the most notable lapse. The picture painted is of a scientist trying to cure a disease in spite of obstacles - not disrupt the system or intentionally cause harm. [1] https://www.health.harvard.edu/blog/first-do-no-harm-201510138421 https://www.health.harvard.edu/blog/first-do-no-harm-2015101...
reasonattlm 9y ago
This captures the fundamental issues of incentives in this sort of thing. It takes a lot of money to run trials, and regardless of what is said about risk and what participants agree too, anyone suffering an adverse effect has a strong incentive to resort to the legal system. The FDA system is the only way to get therapies to large numbers of patients. But it isn't the only way to get therapies to patients period, and it has serious flaws. The FDA is risk averse to the point of suppressing progress. The costs have doubled in the last ten years for no good reason. There is a desperate need for a less heavy handed, more distributed, faster system that favors pace of progress - but all attempts to build it will run into this problem of incentives. The organizations running trials are targets, and people will respond poorly to being struck by risk no matter what they sign or are given to understand up front. Non-profits may work for low-cost treatments, such as repurposed cheap-to-manufacture compounds from the drug databases (e.g. senolytics), but some types of therapy genuinely do require an organization with tens of millions in the bank to sustain development. How do they proceed if not via the FDA?
drewg123 9y ago
It seems like the key to making medical progress is realizing that not all treatments are "one size fits all" and figuring out why treatments that are safe and effective for some people are unsafe for others. The vaccine from this story seemed to be safe and effective for some participants, but nearly killed another. How can we differentiate the people that it will help from the people that it could kill? This is a real problem in FDA approved medications. Just look at the side effects list for some of the "biologic" TNF blocking treatments for autoimmune diseases. Yet they are beneficial for most people.
- djsumdog 9y ago
  Human bodies are vastly different and one of the biggest difficulties is finding compounds that work the same 99% of the time, with minimal but known and treatable side effects. There's a reason this research takes so long. Things might have gotten to market sooner decades ago, but it all comes down to a trade-off with potential good vs safety. When political maneuvering gets in the way, you can get things like the Vioxx disaster. Even with Vioxx, FDA monitoring and procedures did do what they were suppose to in identifying the problem and pulling it off the market. The biggest problem really seems to be money, resources and funding the research. You might discover something promising, but your company will need to pay all those people, buy equipment and purchase animals to go forward. If you get to monkeys and lose a single one, you gotta go back to the beginning. You might find a side effect in 5% that's really bad/serious and your entire compound might need to be scrapped. Companies need to make money off of those investments so the compounds that do succeeded might become insanely expensive. The entire process is pretty backwards and I know people who are biochemists in this field who get paid really shitty despite their important work. A lot of money goes to equipment, but a lot also goes to management and cronies in the shops that can fund this stuff. It's a mess. There needs to be a better, not-for-profit model where a failed compound doesn't matter as much.
  - barry-cotter 9y ago
    > There's a reason this research takes so long. Things might have gotten to market sooner decades ago, but it all comes down to a trade-off with potential good vs safety. Agreed. We’re way past the sane point on the trade off. Aspirin would not pass FDA review under the current regime. Efficacy testing doesn’t appear to do much good but it clearly makes getting a drug to market slower and more costly. For more on this see http://www.fdareview.org/ http://www.fdareview.org/
JohnJamesRambo 9y ago
Reading programmers discuss medicine on HN is as painful as reading doctors discussing programming.
- gamw_mana_sou 9y ago
  ...while not being able to even grasp the concept of Excel macros. Opinions are like yada yada.
- Xc43 9y ago
  Except that a good percentage of programmers are not as subject to the know-it-all symptom that comes from prestige. Because, our field is not as set as medecine.
  - cpfohl 9y ago
    I call BS. I know I'm an insufferable know it all at times. Many of my coworkers past and present were/are as well. Furthermore software's image is skyrocketing.
    - Xc43 8y ago
      Ok. Agreed.
  - dsfyu404ed 9y ago
    Have you read the comments on non-programming issues in here? It's hilariously full of "well obviously the solution to X is Y" for things outside the author's area of expertise.
    - deleted 9y ago
      [deleted]
    - Xc43 8y ago
      I assumed wrongly. I guess I thought most programmers were as I am.
  - 9y ago
stickfigure 9y ago
Before rushing to judgement (which is easy to do given just one reporter's perspective), it's a good idea to read Scott Alexander's experience with institutional review boards: http://slatestarcodex.com/2017/08/29/my-irb-nightmare/ http://slatestarcodex.com/2017/08/29/my-irb-nightmare/
- tptacek 9y ago
  * The provenance of the vaccine couldn't be accounted for. * Neither could chain of custody from manufacture to application. * Subjects who experienced adverse effects were removed from the trial without further tracking. * People with HSV-1 were administered a vaccine based on live HSV-2. * Subjects were tracked with self-assessment questionnaires of poor design. * Subjects socialized with investigators and with at least one cheerleading investor. If this story was about a pharma company, we'd be calling for heads on spikes But there's a rooting interest for underdogs (especially those up against the US regulatory state).
- Fomite 9y ago
  This could very well be written by the head of the IRB as "My Scott Alexander Nightmare". These questions all have purposes, and are there for a reason. For example: "That was the first ten pages or so of the Application. The rest was increasingly bizarre questions such as “Will any organs be removed from participants during this study?” (Look, I promise, I’m not a Nazi)." There are a number of studies done by Not Nazis that still involve removing organs. "And: “Will prisoners be used in the study?” (COME ON, I ALREADY SAID I WASN’T A NAZI)." I'm not a Nazi, and for one of my studies, the answer was yes - prisoners get treated at the hospital I was using EHR records for, which meant they were in the data set. As prisoners have a very distorted capacity for informed consent, it's an important question to ask. "And: “What will you do if a participant dies during this research?” (If somebody dies while I’m asking them whether they sometimes feel happy and then sad, I really can’t even promise so much as “not freaking out”, let alone any sort of dignified research procedure)." This is a perfectly fair question to be asked during a study - especially as for many trials, determining whether or not the death was due to the study is an important question. As far as I can tell, this essay is "In which Scott Alexander didn't do his basic homework, but still wants to be able to do a biomedical study, and is upset the IRB didn't pre-emptively read his mind and tailor his form for his particular case." He actually made me feel sympathetic toward the IRB...which is an impressive feat in and of itself.
patrickg_zill 9y ago
There surely has to be a middle ground in some cases between the two cases of $100 million trials and essentially unregulated and unaccountable hotel room doctors. Could there be a series of exams that a would be patient would have to write, to demonstrate that they truly understand the risks, and what protocol is to be followed? In investment they have an "accredited investor" category to avoid higher risk investments from being offered to those who can't afford the risk. If you have a chronic disease and pass the exam then you become an "accredited trial patient".
- throwaway84742 9y ago
  Trump wanted to introduce “right to try”, which I think is a great idea. Got shut down in Congress. Don’t recall why.
  - tonysdg 9y ago
    IIRC, part of the argument against is that you're allowing biotech/pharma companies to test on vulnerable populations. Here's a story on NPR about the pros and cons: https://www.npr.org/sections/health-shots/2017/03/03/517796956/patients-demand-the-right-to-try-experimental-drugs-but-costs-can-be-steep https://www.npr.org/sections/health-shots/2017/03/03/5177969...
    - throwaway84742 9y ago
      Sure, that’s inextricably a part of the deal. Don’t sign on the dotted line if you’re uneasy about it. As long as nobody is forcing you to do it, I don’t have a problem. The situation where I can try things (at my discretion) is strictly better than the one where i unconditionally die.
      - lallysingh 9y ago
        The information asymmetry is a real problem.
        9y ago
anovikov 9y ago
Phase 1 trials - safety ones - are really cheap. I don't think they make much more than 1% of total cost of getting a drug into market (while in a total volume, they might be, because so many drugs fail them). There is no need to risk killing a lot of people by skipping Phase 1 trials. After that, i think it's fine to try an untested drug on consenting patient with a severe chronic, or an acute life-threatening condition. I understand why it isn't done. Market forces forcing companies to save money on trials or die, may quickly unwrap this situation to Dr. Mengele-style 'trials' if not kept in check.
bufferoverflow 9y ago
My friend just went through an experimental procedure that was supposed to help her with her MS. She had to travel to a foreign country, where it's not regulated. And it was quite expensive. Before she went I asked her - if that treatment has a 10% chance of killing you, would you do it? She said she would. And she did. She is better now, not fully cured, but can walk and drive. One of the younger girls who was with her in the treatment was completely disabled, bound to a wheelchair, couldn't talk, could barely see, and on day four after the treatment she got up, could walk and talk. A true freaking miracle of science. That girl now does mountain biking and mountain climbing, fully recovered.
- Roritharr 9y ago
  You can't provide such tales without going into more factual detail. What kind of treatment? What country? Where can I find more about this magical therapy?
  - bufferoverflow 9y ago
    Stem cell transplant (HSCT) with chemo. Russia. There are small trials in multiple countries, but very hard to get in. http://www.bbc.com/news/health-43435868 http://www.bbc.com/news/health-43435868
    - Roritharr 9y ago
      Thank you!
esaym 9y ago
> He told them that the vaccine carried risks, as all vaccines do Oh no, I thought it was taboo to say such a thing!
- hexane360 9y ago
  https://en.wikipedia.org/wiki/Straw_man https://en.wikipedia.org/wiki/Straw_man Vaccines carry risk, but the risk of disease is orders of magnitude higher.

127 points by tchalla 9y ago

>“If I can help people suffering from herpes, isn’t it my duty to do so?” Gosh I here that statement echoing in my head about the problems in my life... Also, this is exactly the kind of problem in healthcare that is completely government and establishment driven. Physicians keep propping their monopoly up with literally hundreds of millions of dollars in lobbying/bribery. Every profession in medical seems to be similar, dumping massive money into politicians: https://www.opensecrets.org/lobby/top.php?indexType=s https://www.opensecrets.org/lobby/top.php?indexType=s Then their 'scientific method' has completely let me down after reading what these 'experts' consider a study. Lots of hypothesis getting validated by any-means-necessary. Not to mention their understanding of statistics usually tosses in the word 'P-value' for extra points, despite their population sample and study being a terrible representation of outcomes. Medical is corrupt AF

ThomPete 9y ago
But what are you going to do about it?
gvb 9y ago
>“If I can help people suffering from herpes, isn’t it my duty to do so?” That is a question, not a statement "Since I can help...". The problem is that he did significant harm to people trying to answer that question. The results of his experimentation are not fully realized, but the story indicates his injections caused harm in some cases and do not appear to have achieved the promise cure in any(?) of the cases. The counterbalance question is "If my hypothesis is wrong and I harm people, isn't it my duty to do no harm?"
techterrier 9y ago
>“If I can help people suffering from herpes, isn’t it my duty to do so?” He missed out the 'first do no harm' bit. It's quite important.
- Afforess 9y ago
  "First, do no harm" is not part of the hippocratic oath at all. [1] The actual line in the hippocratic oath is much more flexible: >I will follow that system of regimen which, according to my ability and judgment, I consider for the benefit of my patients, and abstain from whatever is deleterious and mischievous. Based on the reported specifics of the rogue vaccine trial, it would seem Halford did most of this. The article questions his judgement over the confusion between HSV-1 and HSV-2 strains, but that seems the most notable lapse. The picture painted is of a scientist trying to cure a disease in spite of obstacles - not disrupt the system or intentionally cause harm. [1] https://www.health.harvard.edu/blog/first-do-no-harm-201510138421 https://www.health.harvard.edu/blog/first-do-no-harm-2015101...

reasonattlm 9y ago

This captures the fundamental issues of incentives in this sort of thing. It takes a lot of money to run trials, and regardless of what is said about risk and what participants agree too, anyone suffering an adverse effect has a strong incentive to resort to the legal system. The FDA system is the only way to get therapies to large numbers of patients. But it isn't the only way to get therapies to patients period, and it has serious flaws. The FDA is risk averse to the point of suppressing progress. The costs have doubled in the last ten years for no good reason. There is a desperate need for a less heavy handed, more distributed, faster system that favors pace of progress - but all attempts to build it will run into this problem of incentives. The organizations running trials are targets, and people will respond poorly to being struck by risk no matter what they sign or are given to understand up front. Non-profits may work for low-cost treatments, such as repurposed cheap-to-manufacture compounds from the drug databases (e.g. senolytics), but some types of therapy genuinely do require an organization with tens of millions in the bank to sustain development. How do they proceed if not via the FDA?

drewg123 9y ago

It seems like the key to making medical progress is realizing that not all treatments are "one size fits all" and figuring out why treatments that are safe and effective for some people are unsafe for others. The vaccine from this story seemed to be safe and effective for some participants, but nearly killed another. How can we differentiate the people that it will help from the people that it could kill? This is a real problem in FDA approved medications. Just look at the side effects list for some of the "biologic" TNF blocking treatments for autoimmune diseases. Yet they are beneficial for most people.

djsumdog 9y ago
Human bodies are vastly different and one of the biggest difficulties is finding compounds that work the same 99% of the time, with minimal but known and treatable side effects. There's a reason this research takes so long. Things might have gotten to market sooner decades ago, but it all comes down to a trade-off with potential good vs safety. When political maneuvering gets in the way, you can get things like the Vioxx disaster. Even with Vioxx, FDA monitoring and procedures did do what they were suppose to in identifying the problem and pulling it off the market. The biggest problem really seems to be money, resources and funding the research. You might discover something promising, but your company will need to pay all those people, buy equipment and purchase animals to go forward. If you get to monkeys and lose a single one, you gotta go back to the beginning. You might find a side effect in 5% that's really bad/serious and your entire compound might need to be scrapped. Companies need to make money off of those investments so the compounds that do succeeded might become insanely expensive. The entire process is pretty backwards and I know people who are biochemists in this field who get paid really shitty despite their important work. A lot of money goes to equipment, but a lot also goes to management and cronies in the shops that can fund this stuff. It's a mess. There needs to be a better, not-for-profit model where a failed compound doesn't matter as much.
- barry-cotter 9y ago
  > There's a reason this research takes so long. Things might have gotten to market sooner decades ago, but it all comes down to a trade-off with potential good vs safety. Agreed. We’re way past the sane point on the trade off. Aspirin would not pass FDA review under the current regime. Efficacy testing doesn’t appear to do much good but it clearly makes getting a drug to market slower and more costly. For more on this see http://www.fdareview.org/ http://www.fdareview.org/

JohnJamesRambo 9y ago

Reading programmers discuss medicine on HN is as painful as reading doctors discussing programming.

gamw_mana_sou 9y ago
...while not being able to even grasp the concept of Excel macros. Opinions are like yada yada.
Xc43 9y ago
Except that a good percentage of programmers are not as subject to the know-it-all symptom that comes from prestige. Because, our field is not as set as medecine.
- cpfohl 9y ago
  I call BS. I know I'm an insufferable know it all at times. Many of my coworkers past and present were/are as well. Furthermore software's image is skyrocketing.
  - Xc43 8y ago
    Ok. Agreed.
- dsfyu404ed 9y ago
  Have you read the comments on non-programming issues in here? It's hilariously full of "well obviously the solution to X is Y" for things outside the author's area of expertise.
  - deleted 9y ago
    [deleted]
  - Xc43 8y ago
    I assumed wrongly. I guess I thought most programmers were as I am.
- 9y ago

stickfigure 9y ago

Before rushing to judgement (which is easy to do given just one reporter's perspective), it's a good idea to read Scott Alexander's experience with institutional review boards: http://slatestarcodex.com/2017/08/29/my-irb-nightmare/ http://slatestarcodex.com/2017/08/29/my-irb-nightmare/

tptacek 9y ago
* The provenance of the vaccine couldn't be accounted for. * Neither could chain of custody from manufacture to application. * Subjects who experienced adverse effects were removed from the trial without further tracking. * People with HSV-1 were administered a vaccine based on live HSV-2. * Subjects were tracked with self-assessment questionnaires of poor design. * Subjects socialized with investigators and with at least one cheerleading investor. If this story was about a pharma company, we'd be calling for heads on spikes But there's a rooting interest for underdogs (especially those up against the US regulatory state).
Fomite 9y ago
This could very well be written by the head of the IRB as "My Scott Alexander Nightmare". These questions all have purposes, and are there for a reason. For example: "That was the first ten pages or so of the Application. The rest was increasingly bizarre questions such as “Will any organs be removed from participants during this study?” (Look, I promise, I’m not a Nazi)." There are a number of studies done by Not Nazis that still involve removing organs. "And: “Will prisoners be used in the study?” (COME ON, I ALREADY SAID I WASN’T A NAZI)." I'm not a Nazi, and for one of my studies, the answer was yes - prisoners get treated at the hospital I was using EHR records for, which meant they were in the data set. As prisoners have a very distorted capacity for informed consent, it's an important question to ask. "And: “What will you do if a participant dies during this research?” (If somebody dies while I’m asking them whether they sometimes feel happy and then sad, I really can’t even promise so much as “not freaking out”, let alone any sort of dignified research procedure)." This is a perfectly fair question to be asked during a study - especially as for many trials, determining whether or not the death was due to the study is an important question. As far as I can tell, this essay is "In which Scott Alexander didn't do his basic homework, but still wants to be able to do a biomedical study, and is upset the IRB didn't pre-emptively read his mind and tailor his form for his particular case." He actually made me feel sympathetic toward the IRB...which is an impressive feat in and of itself.

patrickg_zill 9y ago

There surely has to be a middle ground in some cases between the two cases of $100 million trials and essentially unregulated and unaccountable hotel room doctors. Could there be a series of exams that a would be patient would have to write, to demonstrate that they truly understand the risks, and what protocol is to be followed? In investment they have an "accredited investor" category to avoid higher risk investments from being offered to those who can't afford the risk. If you have a chronic disease and pass the exam then you become an "accredited trial patient".

throwaway84742 9y ago
Trump wanted to introduce “right to try”, which I think is a great idea. Got shut down in Congress. Don’t recall why.
- tonysdg 9y ago
  IIRC, part of the argument against is that you're allowing biotech/pharma companies to test on vulnerable populations. Here's a story on NPR about the pros and cons: https://www.npr.org/sections/health-shots/2017/03/03/517796956/patients-demand-the-right-to-try-experimental-drugs-but-costs-can-be-steep https://www.npr.org/sections/health-shots/2017/03/03/5177969...
  - throwaway84742 9y ago
    Sure, that’s inextricably a part of the deal. Don’t sign on the dotted line if you’re uneasy about it. As long as nobody is forcing you to do it, I don’t have a problem. The situation where I can try things (at my discretion) is strictly better than the one where i unconditionally die.
    - lallysingh 9y ago
      The information asymmetry is a real problem.
      - 9y ago

anovikov 9y ago

Phase 1 trials - safety ones - are really cheap. I don't think they make much more than 1% of total cost of getting a drug into market (while in a total volume, they might be, because so many drugs fail them). There is no need to risk killing a lot of people by skipping Phase 1 trials. After that, i think it's fine to try an untested drug on consenting patient with a severe chronic, or an acute life-threatening condition. I understand why it isn't done. Market forces forcing companies to save money on trials or die, may quickly unwrap this situation to Dr. Mengele-style 'trials' if not kept in check.

bufferoverflow 9y ago

My friend just went through an experimental procedure that was supposed to help her with her MS. She had to travel to a foreign country, where it's not regulated. And it was quite expensive. Before she went I asked her - if that treatment has a 10% chance of killing you, would you do it? She said she would. And she did. She is better now, not fully cured, but can walk and drive. One of the younger girls who was with her in the treatment was completely disabled, bound to a wheelchair, couldn't talk, could barely see, and on day four after the treatment she got up, could walk and talk. A true freaking miracle of science. That girl now does mountain biking and mountain climbing, fully recovered.

Roritharr 9y ago
You can't provide such tales without going into more factual detail. What kind of treatment? What country? Where can I find more about this magical therapy?
- bufferoverflow 9y ago
  Stem cell transplant (HSCT) with chemo. Russia. There are small trials in multiple countries, but very hard to get in. http://www.bbc.com/news/health-43435868 http://www.bbc.com/news/health-43435868
  - Roritharr 9y ago
    Thank you!

esaym 9y ago

> He told them that the vaccine carried risks, as all vaccines do Oh no, I thought it was taboo to say such a thing!

hexane360 9y ago
https://en.wikipedia.org/wiki/Straw_man https://en.wikipedia.org/wiki/Straw_man Vaccines carry risk, but the risk of disease is orders of magnitude higher.