Aa
Outcome predicted with accuracy using genetic test
Here is another study describing a different prognostic test. As I stated in another thread there are quite a few of them out there. In this particular one the authors said, "we could predict the outcome of therapy with greater than 95% coverage and 100% accuracy, raising the possibility of a prognostic test to reduce therapeutic failures"
These are exciting developments for HCV patients. Focusing tx on those it can help while allowing those who would ultimately fail tx to avoid the toxic drugs is a win/win scenario. In the other study I posted the approach was different. It determined who was at the most risk of developing cirrhosis allowing that group to treat early with more chance of success, while allowing the low risk group to wait for better tx modalities. This study below also shows how subtypes and quasi-species reside in relation to a major genotype and explains what genetic distance refers to in this setting. ---ML
"Genome-wide hepatitis C virus amino acid covariance networks can predict response to antiviral therapy in humans"
http://www.jci.org/articles/view/37085
These are exciting developments for HCV patients. Focusing tx on those it can help while allowing those who would ultimately fail tx to avoid the toxic drugs is a win/win scenario. In the other study I posted the approach was different. It determined who was at the most risk of developing cirrhosis allowing that group to treat early with more chance of success, while allowing the low risk group to wait for better tx modalities. This study below also shows how subtypes and quasi-species reside in relation to a major genotype and explains what genetic distance refers to in this setting. ---ML
"Genome-wide hepatitis C virus amino acid covariance networks can predict response to antiviral therapy in humans"
http://www.jci.org/articles/view/37085
,"....the insurance companies would love to exclude some based on their genetics...and sure, you are right, it would be cheaper....but where does that lead us?"
I understand your concern, but guarding private data has always been a problem. There are many laws, both state and federal which address the issue of privacy and security regarding genetic data. Its been a concern ever since the discovery of DNA and it still is for everyone. It's 1984 and more. All you can do is have heavy penalties and build as much security into the system as technology allows.
I started IFN before there was such a thing as a 12 week cutoff for those with <2 log drop. In fact,for a G1 the first test wasn't until six months into tx. Now everybody accepts the 12 weeks cutoff as the standard but the fact is there is still about 2%-3% who WOULD still have gone on to SVR even though they did not meet the 'required' 2 log drop at 12 weeks and tx was discontinued. Many insurance companies base their decisions to extend or discontinue tx on this 12 week standard.
How did they get the number of 12 weeks as the best cutoff ? Its based on tx SVR data and cost/benefit analysis by the INS CO's. To hit the 100% mark of SVR inclusivity would require longer treatment until a cutoff date and the question then becomes do you expose a larger number of people to needless tx in order to capture that 2-3% extra in SVR patients ? The answer appears to be no, and this seems to be accepted by the medical profession as the right answer for now .
willy-
The addition of PI with current SOC does increase SVR substantially for G1 . PI monotherapy on the other hand has had little success. This points to the synergistic effect the combination has. Since IFN/Riba will be used these viral genetic markers being discussed could indicate if someone would have the odds asscociated with PI monotherapy or not, something which could alter tx strategy. This , in turn could lead to new tx algorithms to optimize success and minimize exposure.-ML
dsrt--It is referring to the viral genetic makeup. As you know we already use viral genetics (genotype, subtype, QS diversity) as predictors of response. This is a more refined and detailed look at what viral genetic features exist in all tx failures. And in 100% of the cases it was the same 7 markers, the same ones found in other studies that I will post in the future. - ML
I understand your concern, but guarding private data has always been a problem. There are many laws, both state and federal which address the issue of privacy and security regarding genetic data. Its been a concern ever since the discovery of DNA and it still is for everyone. It's 1984 and more. All you can do is have heavy penalties and build as much security into the system as technology allows.
I started IFN before there was such a thing as a 12 week cutoff for those with <2 log drop. In fact,for a G1 the first test wasn't until six months into tx. Now everybody accepts the 12 weeks cutoff as the standard but the fact is there is still about 2%-3% who WOULD still have gone on to SVR even though they did not meet the 'required' 2 log drop at 12 weeks and tx was discontinued. Many insurance companies base their decisions to extend or discontinue tx on this 12 week standard.
How did they get the number of 12 weeks as the best cutoff ? Its based on tx SVR data and cost/benefit analysis by the INS CO's. To hit the 100% mark of SVR inclusivity would require longer treatment until a cutoff date and the question then becomes do you expose a larger number of people to needless tx in order to capture that 2-3% extra in SVR patients ? The answer appears to be no, and this seems to be accepted by the medical profession as the right answer for now .
willy-
The addition of PI with current SOC does increase SVR substantially for G1 . PI monotherapy on the other hand has had little success. This points to the synergistic effect the combination has. Since IFN/Riba will be used these viral genetic markers being discussed could indicate if someone would have the odds asscociated with PI monotherapy or not, something which could alter tx strategy. This , in turn could lead to new tx algorithms to optimize success and minimize exposure.-ML
dsrt--It is referring to the viral genetic makeup. As you know we already use viral genetics (genotype, subtype, QS diversity) as predictors of response. This is a more refined and detailed look at what viral genetic features exist in all tx failures. And in 100% of the cases it was the same 7 markers, the same ones found in other studies that I will post in the future. - ML
Like a gun or a car, it isn't the object, but rather how it gets used.
I think that if a test were a 95% (hey, 90% ain't hay, neither!) predictor. If people want to act on it, or their doctor, it's purely their call.
I think that whereas I agree that you make a point it could prevent some people from treating, it would also serve to keep people, many more people from treating unnecessarily. ; )
I think that more information is always good.
My question remains, doesn't this test pertain to SOC? Once triple therapy is approved (what, in 12-18 months?) they may need a slightly different algorithm to predict response. I would also think that there are several other predictors, (IR, viral kinetics after starting) that would/could/should be used on patients. One could tack these all together and have a nice "no-brainer" plan for us all. So much of it now is the nearly one size fits all SOC and the skill and experience of the doctors (which can vary just a little bit). ; )
Thanks for your input.
Willy
I think that if a test were a 95% (hey, 90% ain't hay, neither!) predictor. If people want to act on it, or their doctor, it's purely their call.
I think that whereas I agree that you make a point it could prevent some people from treating, it would also serve to keep people, many more people from treating unnecessarily. ; )
I think that more information is always good.
My question remains, doesn't this test pertain to SOC? Once triple therapy is approved (what, in 12-18 months?) they may need a slightly different algorithm to predict response. I would also think that there are several other predictors, (IR, viral kinetics after starting) that would/could/should be used on patients. One could tack these all together and have a nice "no-brainer" plan for us all. So much of it now is the nearly one size fits all SOC and the skill and experience of the doctors (which can vary just a little bit). ; )
Thanks for your input.
Willy
Not sure I'm understanding this. Are they saying they can predict tx outcome based solely on the virus' genetic makeup? Not taking the patients' genes into consideration at all?
I think you missed my point, which I didn't make clear...
there is a 25 to 30% disparity between those treating with current SOC and those treating with new PI's. Even among former relapers the rate of SVR is 20- 25% higher on newer PI's. (50% SOC vs 75-80% with PI's &SOC)
If we say to those with good predictors you don't need the PI's, we are reducing their odds none the less and likewise since even tough cases are getting much better results, how can they assume the predictors will work in every case? they won't, they will condemn many to illness who may have succeeded!
What they need to focus on is viral penetration...I mean look what Inovio has done with electropolation....99% virus gone in a couple of days....yet where the push to get the right drugs and techniques to achieve this worldwide?? I agree, current tx is expensive...another reason to focus elsewhere...reducing VL in hours not weeks or months..that would be a start!!!!!
There are thousands of cancer patients walking around who were given a 2% chance of survival...they took their chances and won. If the genetics become the standard then all bets are off. It will become selective genocide...your odds are bad...so you can't try....someone else had good odds and they can, they may fail, but they can try.
The trouble is, genes aside, people beat the odds everyday, while some that should succeed won't and that is a fact of life, and genetics aside, no one knows yet why one immune system will rally and put on a stallar defense with the help of chemo, while another will not...so it's not all cut and dry.
If it were all about the cost, then we should deny care to everyone not likely to succeed...or cure...maybe we should exclude all virus's, why maintain costly diseases like HIV at all if cost is the issue?? BY that logic, we shouldn't try to maintain or cure a whole lot of things.n mean, Why cure those who can't contribute...maybe it's unreaonable to maintain diebetics etc etc etc.!!??
I'm joking of course. But this is the same circular thinking that came out of every draconian and facist culture eventually...the idea that our health should be decided by the state, and that a patient and doctor cannot together make a decision, odds aside, government interferance aside,....the insurance companies would love to exclude some based on their genetics...and sure, you are right, it would be cheaper....but where does that lead us?
what happens to those that do beat the odds then?
example: Cocksparrow just reached SVR.
why, because despite his predictors, and several failed attempts, he was able to add certain herbs, a new PI' drug, and control his Insulin resistance, and the combo of all this has led to his SVR.
But if the genetics become used to deny those whose cells show an unlikely outcome, then he would have been denied even the opportunity to try and regain his health.
I hope now what I am saying is more clear.
I'm not against telling folks their odds are low...and if they want to forego treatment then, well so be it.
What I am against is making the test the final arbitrator of who gets treatment.
That is what is abhorrent here.
remember also that the best lab tests out there are only accurate 95% of the time..and .many lab tests only have a 60-80% accuracy level.
I don't think anyone should be denied treatment based on sciences known to be less than 100% reliable.
mb
there is a 25 to 30% disparity between those treating with current SOC and those treating with new PI's. Even among former relapers the rate of SVR is 20- 25% higher on newer PI's. (50% SOC vs 75-80% with PI's &SOC)
If we say to those with good predictors you don't need the PI's, we are reducing their odds none the less and likewise since even tough cases are getting much better results, how can they assume the predictors will work in every case? they won't, they will condemn many to illness who may have succeeded!
What they need to focus on is viral penetration...I mean look what Inovio has done with electropolation....99% virus gone in a couple of days....yet where the push to get the right drugs and techniques to achieve this worldwide?? I agree, current tx is expensive...another reason to focus elsewhere...reducing VL in hours not weeks or months..that would be a start!!!!!
There are thousands of cancer patients walking around who were given a 2% chance of survival...they took their chances and won. If the genetics become the standard then all bets are off. It will become selective genocide...your odds are bad...so you can't try....someone else had good odds and they can, they may fail, but they can try.
The trouble is, genes aside, people beat the odds everyday, while some that should succeed won't and that is a fact of life, and genetics aside, no one knows yet why one immune system will rally and put on a stallar defense with the help of chemo, while another will not...so it's not all cut and dry.
If it were all about the cost, then we should deny care to everyone not likely to succeed...or cure...maybe we should exclude all virus's, why maintain costly diseases like HIV at all if cost is the issue?? BY that logic, we shouldn't try to maintain or cure a whole lot of things.n mean, Why cure those who can't contribute...maybe it's unreaonable to maintain diebetics etc etc etc.!!??
I'm joking of course. But this is the same circular thinking that came out of every draconian and facist culture eventually...the idea that our health should be decided by the state, and that a patient and doctor cannot together make a decision, odds aside, government interferance aside,....the insurance companies would love to exclude some based on their genetics...and sure, you are right, it would be cheaper....but where does that lead us?
what happens to those that do beat the odds then?
example: Cocksparrow just reached SVR.
why, because despite his predictors, and several failed attempts, he was able to add certain herbs, a new PI' drug, and control his Insulin resistance, and the combo of all this has led to his SVR.
But if the genetics become used to deny those whose cells show an unlikely outcome, then he would have been denied even the opportunity to try and regain his health.
I hope now what I am saying is more clear.
I'm not against telling folks their odds are low...and if they want to forego treatment then, well so be it.
What I am against is making the test the final arbitrator of who gets treatment.
That is what is abhorrent here.
remember also that the best lab tests out there are only accurate 95% of the time..and .many lab tests only have a 60-80% accuracy level.
I don't think anyone should be denied treatment based on sciences known to be less than 100% reliable.
mb
hi merrybe-
I think these findings along with similar ones in other studies could result in new targets for new small molecule treatments. In the meantime as the study indicated standardized tests to identify those who will fail or succeed at tx would cost $100 v. $30K in tx costs that may have been unnecessary.--ML
hello newleaf--
I know of no other treatment regimens that can be as challenging as IFN/Riba is for so many with HCV as proven by its dropout rate (10%-20%). Reducing the potential harm of tx through pre-tx genetic tests not only saves the patient but also the burden on the healthcare system in terms of costs associated with tx that wasn't indicated. It would aslo help to identify those who would benefit from a longer tx course thereby eliminating many needless relapses.--ML
hi jelise- These med studies can certainly test your ability to read dry, boring, and in many cases undecipherable lexicon. Online dictionaries are a wonderful creation is all I can say. Unfortunately, it seems the studies with good methodology also have some of the hardest to understand papers. -- ML
I think these findings along with similar ones in other studies could result in new targets for new small molecule treatments. In the meantime as the study indicated standardized tests to identify those who will fail or succeed at tx would cost $100 v. $30K in tx costs that may have been unnecessary.--ML
hello newleaf--
I know of no other treatment regimens that can be as challenging as IFN/Riba is for so many with HCV as proven by its dropout rate (10%-20%). Reducing the potential harm of tx through pre-tx genetic tests not only saves the patient but also the burden on the healthcare system in terms of costs associated with tx that wasn't indicated. It would aslo help to identify those who would benefit from a longer tx course thereby eliminating many needless relapses.--ML
hi jelise- These med studies can certainly test your ability to read dry, boring, and in many cases undecipherable lexicon. Online dictionaries are a wonderful creation is all I can say. Unfortunately, it seems the studies with good methodology also have some of the hardest to understand papers. -- ML
Ouch - that really hurt my brain!
Thank you for the information though :) I hope these kinds of theories and studies help us understand all kinds of viruses.
Viruses are so interesting to read about...and so miserable to have.
Thank you for the information though :) I hope these kinds of theories and studies help us understand all kinds of viruses.
Viruses are so interesting to read about...and so miserable to have.
I started TX in Nov. 09 and many concepts changed during that 7 mos. TX period. 10 months later, it's like it's all turned over again. If these tests go into practice, certain TX failure will not have to be suffered through and those who treat will receive the minimally harmful TX that could be successful for them, or the max necessary. Less patients over-treated and less under-treated, hopefully. We don't need to kill the virus twice. Just plain dead is good enough. Such exciting times for HCV treatment and it just keeps coming. Thanks for posting, Mr.
yes , thanks for reminding us, when this research first surfaced last year we had some discussion....my concern was based on the chatter at ASSLD that soon some would be turned down, or at least a selection process would ensue so that only the worst predictors got the PI's....(meaning those on the fringe won't get the better newer drugs and those with the worst predictors...well...
that's what I find alarming...not that anyone should do a treatment that doesn't work...
but shouldn't the focus here rather be on solving for the discovery..
.i.e. how to stimulate hydrophobic amino acid pairs??
surely this has to have occured to someone.
mb
that's what I find alarming...not that anyone should do a treatment that doesn't work...
but shouldn't the focus here rather be on solving for the discovery..
.i.e. how to stimulate hydrophobic amino acid pairs??
surely this has to have occured to someone.
mb
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