Thanks for sharing, Jack. Not at all irrelevant to undrlying Knot issues. In a way, this is sort of a contrapositive example of LNT nonsense. Sorry you're having to deal with this and spend so much, but glad it's effective!
Very worth reading, Jack! I'm glad it's working for you, and I'm glad you & your oncologist did the experiment that the drug company neglected. I'd be glad to have my taxes used to keep you writing.
Note: If you have side effects from the drug, I'm sure the company has other drugs to treat them! ;-)
Yep. My wife has been on a BP med for well over a decade. She also had some side effects, among them that the prescribed dose would often make her BP rather low. She began monitoring it herself regularly and ended up cutting the dose (and each pill) in half. The result: 120/80 +/-10 and no more side effects.
I bet the optimal dose for any drug varies from one individual to the next.
For sure. One problem is doctors are scared to play around with the dose because of possible legal problems. And specialists tend to only worry about their specialty. If a cancer drug kills you by causing afib, that's the cardiologist's problem. A very mild form of NRC's dismissing all the health issues they create by making nuclear expensive.
Hell that's close to the bone - the past three years I've been dealing with the 'relatively uncommon' autoimmune condition myasthenia gravis, but Waldenstrom sounds like it runs away with the rarity Blue Ribbon. But a bunch of similar issues - small potential customer pool, expensive development and approvals process, and grossly misaligned incentives mean that while there a promising treatments available for MG - as of my neurologists put it "they're among some of the most expensive drugs on the planet" - and totally inaccessible to me here in Australia.
One of the more interesting pathways in Phase 2 at present is a modified CAR-T process that originates from the blood cancer field - essentially takes the bodies own T-cells, genetically modifies them, cultures up a population of them, reinfuses them to kill off the entire B-cell immunoglobulin population. After a few weeks the production of them resumes - but in a naive 'reset' population that no longer produces the bad antibody. So far the trials have looked very promising - but at U$500k a pop it's not happening for most patients. Yet oddly enough if this one treatment was the 'cure' the total cost to the health system would be way lower than the life time costs we incur at present.
Al large part of the problem is the way massive unaccountable bureaucracies align with private sector corporates to put their own interests ahead of the purpose they ostensibly serve. It's the same problem in the nuclear space - and one that's been slowly crippling Western nations for decades.
Philip, is it literally illegal for you to order and import your medication from out of country?
Or are the medical and/or health insurance agencies merely not endorsing it at all for public reimbursement as a legitimate medical cost? Certainly that cost level is prohibitive for most private persons, but a real denial of liberty if it is actually illegal.
I am often amazed at how much they seem to know about the cascade of biochemical interactions that end up supplying the end state desired biological result; and conversely provide information on possible blockage points to minimize or stop undesirable reactions.
Also interesting that so many of us can use Substack across the Anglophone world to inform or commiserate about the pluses and minuses of our respective governance and bureaucratic bodies.
In the first instance these drugs would need to be prescribed by specialists - they are simply not sold to individuals. Even so the cost would be prohibitive and the chances are they would be intercepted at the border and confiscated.
Essentially anything you import into Australia that is not TGA approved (the Aus equivalent of the FDA) is at risk when you import.
Could this be a hormesis dose-response? Seems like there is a parabolic response in the range of doses you’ve tried. Certainly not an LNT or other monotonic dose-response curve.
Sure. Drugs are substances that have a hormetic effect if we define hormesis broadly. And wherever there is a positive response, there will be an optimal dose for each individual. On either side of that optimum there will be too little and too much. In many cases, the optimum will be rather broad and flat. If the drug is expensive, we want to be near the low end of that flat regime.
But we need to be careful in identifying situations in which radiation is a drug. There are situations where it clearly is: for example, treating anaerobic infection (eg gangrene) where the flesh has lost the ability to supply oxygen to the tissue. We can artificially create ROS in that flesh with radiation and kill the bugs. But is a NPP release one of those situations?
No digression. I appreciate your frankness. I'm a little taken aback/appreciative in the clinical style in which you discuss this as you are the object of the treatment, It's a rarity to see.
To take a different a tack i suspect some aspect of single payer healthcare, with private care (as single payer isn't working at all in Canada) the beveridge model through taxation that is fully funded. A lot of demographics analysis has to go into it.
Most importantly the cost of drug discovery, start to finish has to be catalogued. I'm really hoping researchers using AI will develop more and more specific targeted systems, as drug discovery has often been luck and incredibly time consuming.
I wish you the best of health in the future. I've enjoyed reading your posts. Feel free to indulge anytime.
I second Binder's comment about the quality of your clinical style of reporting on such an otherwise personal issue.
I plan to forward your email to a subset of my contact list for their awareness and possible education.
With the ongoing corruption of medical schools with DEI type programs, it also has to be a concern that the quality of physicians and specialists will decline, both as to their medical knowledge and their bravery in experimenting with a given patient's situation.
Conversely, the importance of personal health to so many may be the impetus to reverse DEI in med schools before most other institutions.
Thank you for being here and there and eventually everywhere, archived!
Often, personal stories are the “truth” hiding amongst the daily fiction. Respect, courageous and intellect are words that come mind when thinking of Jack Devanney.
As others have commented, this certainly hits close to home and most certainly agree this topic fits with the general tenor of GKN. I admire your openness and wish you well Jack.
Glad to hear of your clinical success on this- many have not had the chance to be so lucky in the past! Unfortunately, this is an incorrect analysis of the drug development and dose finding process performed in clinical trials.
Phase 1 trials are all about safety in healthy volunteers. You slowly increase the dose carefully looking for problems along the way (after you do it in animals first) and this sets your upper limits of what can be studied later.
Phase 2 is generally where the trials start trying to treat the actual disease in a small number of clinical subjects and there is certainly a dose finding exercise there- it is absolutely NOT a "blast 'em with everything we got" type of approach as that would dramatically risk finding toxicology issues that were not seen in the Phase 1 trial with lower numbers of patients. There is typically a second part of a Phase 2 trial that attempts to show efficacy with optimized dosing conditions prior to spending money on the really big and expensive Phase 3 trials- essentially trying to maximize the benefit and minimizing the harm (very much unlike radiation dose studies!).
In between each stage there are multiple meetings with regulatory bodies around the world (FDA, EMA Rapporteurs, etc.) which evaluate the data and approve moving to the next step prior to starting the trial. It certainly isn't a perfect process and is definitely subject to undue influence sometimes, but it has worked pretty well historically.
So while it may have been possible in your case that the BTK inhibitor ended up having the most efficacy studied at the highest dose, that was almost certainly not how it was studied. The caveat is that it would cost infinite money to get infinite data, so there are chances where doses can be too high or low, but that is generally corrected with time and real world use (post marketing surveillance or Phase 4 trials). So for your values, it likely made sense to titrate the dose down, but this is probably not the best place to start for treatment naive patients and your case might just be additional valuable data for others!
Thanks for sharing, Jack. Not at all irrelevant to undrlying Knot issues. In a way, this is sort of a contrapositive example of LNT nonsense. Sorry you're having to deal with this and spend so much, but glad it's effective!
Very worth reading, Jack! I'm glad it's working for you, and I'm glad you & your oncologist did the experiment that the drug company neglected. I'd be glad to have my taxes used to keep you writing.
Note: If you have side effects from the drug, I'm sure the company has other drugs to treat them! ;-)
Yep. My wife has been on a BP med for well over a decade. She also had some side effects, among them that the prescribed dose would often make her BP rather low. She began monitoring it herself regularly and ended up cutting the dose (and each pill) in half. The result: 120/80 +/-10 and no more side effects.
I bet the optimal dose for any drug varies from one individual to the next.
For sure. One problem is doctors are scared to play around with the dose because of possible legal problems. And specialists tend to only worry about their specialty. If a cancer drug kills you by causing afib, that's the cardiologist's problem. A very mild form of NRC's dismissing all the health issues they create by making nuclear expensive.
Jack, thank you for sharing this.
George is also deciding about an experimental drug.
As David Butz said, I am sorry you have to deal with this, but glad the drug is effective!
Warmest wishes,
Meredith
Hope you feel better Jack
Hell that's close to the bone - the past three years I've been dealing with the 'relatively uncommon' autoimmune condition myasthenia gravis, but Waldenstrom sounds like it runs away with the rarity Blue Ribbon. But a bunch of similar issues - small potential customer pool, expensive development and approvals process, and grossly misaligned incentives mean that while there a promising treatments available for MG - as of my neurologists put it "they're among some of the most expensive drugs on the planet" - and totally inaccessible to me here in Australia.
One of the more interesting pathways in Phase 2 at present is a modified CAR-T process that originates from the blood cancer field - essentially takes the bodies own T-cells, genetically modifies them, cultures up a population of them, reinfuses them to kill off the entire B-cell immunoglobulin population. After a few weeks the production of them resumes - but in a naive 'reset' population that no longer produces the bad antibody. So far the trials have looked very promising - but at U$500k a pop it's not happening for most patients. Yet oddly enough if this one treatment was the 'cure' the total cost to the health system would be way lower than the life time costs we incur at present.
Al large part of the problem is the way massive unaccountable bureaucracies align with private sector corporates to put their own interests ahead of the purpose they ostensibly serve. It's the same problem in the nuclear space - and one that's been slowly crippling Western nations for decades.
Philip, is it literally illegal for you to order and import your medication from out of country?
Or are the medical and/or health insurance agencies merely not endorsing it at all for public reimbursement as a legitimate medical cost? Certainly that cost level is prohibitive for most private persons, but a real denial of liberty if it is actually illegal.
I am often amazed at how much they seem to know about the cascade of biochemical interactions that end up supplying the end state desired biological result; and conversely provide information on possible blockage points to minimize or stop undesirable reactions.
Also interesting that so many of us can use Substack across the Anglophone world to inform or commiserate about the pluses and minuses of our respective governance and bureaucratic bodies.
In the first instance these drugs would need to be prescribed by specialists - they are simply not sold to individuals. Even so the cost would be prohibitive and the chances are they would be intercepted at the border and confiscated.
Essentially anything you import into Australia that is not TGA approved (the Aus equivalent of the FDA) is at risk when you import.
Could this be a hormesis dose-response? Seems like there is a parabolic response in the range of doses you’ve tried. Certainly not an LNT or other monotonic dose-response curve.
Tom,
Sure. Drugs are substances that have a hormetic effect if we define hormesis broadly. And wherever there is a positive response, there will be an optimal dose for each individual. On either side of that optimum there will be too little and too much. In many cases, the optimum will be rather broad and flat. If the drug is expensive, we want to be near the low end of that flat regime.
But we need to be careful in identifying situations in which radiation is a drug. There are situations where it clearly is: for example, treating anaerobic infection (eg gangrene) where the flesh has lost the ability to supply oxygen to the tissue. We can artificially create ROS in that flesh with radiation and kill the bugs. But is a NPP release one of those situations?
No digression. I appreciate your frankness. I'm a little taken aback/appreciative in the clinical style in which you discuss this as you are the object of the treatment, It's a rarity to see.
To take a different a tack i suspect some aspect of single payer healthcare, with private care (as single payer isn't working at all in Canada) the beveridge model through taxation that is fully funded. A lot of demographics analysis has to go into it.
Most importantly the cost of drug discovery, start to finish has to be catalogued. I'm really hoping researchers using AI will develop more and more specific targeted systems, as drug discovery has often been luck and incredibly time consuming.
I wish you the best of health in the future. I've enjoyed reading your posts. Feel free to indulge anytime.
I second Binder's comment about the quality of your clinical style of reporting on such an otherwise personal issue.
I plan to forward your email to a subset of my contact list for their awareness and possible education.
With the ongoing corruption of medical schools with DEI type programs, it also has to be a concern that the quality of physicians and specialists will decline, both as to their medical knowledge and their bravery in experimenting with a given patient's situation.
Conversely, the importance of personal health to so many may be the impetus to reverse DEI in med schools before most other institutions.
Thank you for being here and there and eventually everywhere, archived!
Often, personal stories are the “truth” hiding amongst the daily fiction. Respect, courageous and intellect are words that come mind when thinking of Jack Devanney.
As others have commented, this certainly hits close to home and most certainly agree this topic fits with the general tenor of GKN. I admire your openness and wish you well Jack.
Glad to hear of your clinical success on this- many have not had the chance to be so lucky in the past! Unfortunately, this is an incorrect analysis of the drug development and dose finding process performed in clinical trials.
Phase 1 trials are all about safety in healthy volunteers. You slowly increase the dose carefully looking for problems along the way (after you do it in animals first) and this sets your upper limits of what can be studied later.
Phase 2 is generally where the trials start trying to treat the actual disease in a small number of clinical subjects and there is certainly a dose finding exercise there- it is absolutely NOT a "blast 'em with everything we got" type of approach as that would dramatically risk finding toxicology issues that were not seen in the Phase 1 trial with lower numbers of patients. There is typically a second part of a Phase 2 trial that attempts to show efficacy with optimized dosing conditions prior to spending money on the really big and expensive Phase 3 trials- essentially trying to maximize the benefit and minimizing the harm (very much unlike radiation dose studies!).
In between each stage there are multiple meetings with regulatory bodies around the world (FDA, EMA Rapporteurs, etc.) which evaluate the data and approve moving to the next step prior to starting the trial. It certainly isn't a perfect process and is definitely subject to undue influence sometimes, but it has worked pretty well historically.
So while it may have been possible in your case that the BTK inhibitor ended up having the most efficacy studied at the highest dose, that was almost certainly not how it was studied. The caveat is that it would cost infinite money to get infinite data, so there are chances where doses can be too high or low, but that is generally corrected with time and real world use (post marketing surveillance or Phase 4 trials). So for your values, it likely made sense to titrate the dose down, but this is probably not the best place to start for treatment naive patients and your case might just be additional valuable data for others!