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Ethics and Clinical Trials

Forums General Melanoma Community Ethics and Clinical Trials

  • Post
    mrf
    Keymaster

      Many of you saw the NY Times article this past Sunday, describing cousins, both with Stage IV melanoma.  They both enrolled in a clinical trial of PLX4032–the BRAF inhibitor by Plexxikon/Roche.  One cousin received the BRAF inhibitor and is doing well.  The other, who received the control, has died.

      This raises a lot of questions about clinical trial design.  Our Scientific Advisory Committee has engaged in a very robust online discussion about this, involving about 150 emails!  I wonder what your opinions are on this.  Here are a few questions:

      Many of you saw the NY Times article this past Sunday, describing cousins, both with Stage IV melanoma.  They both enrolled in a clinical trial of PLX4032–the BRAF inhibitor by Plexxikon/Roche.  One cousin received the BRAF inhibitor and is doing well.  The other, who received the control, has died.

      This raises a lot of questions about clinical trial design.  Our Scientific Advisory Committee has engaged in a very robust online discussion about this, involving about 150 emails!  I wonder what your opinions are on this.  Here are a few questions:

      –Is it ethical for the control segment of a clinical trial to be a therapy that is approved, but is almost certain to be far less effective than the drug being tested?  (But, if you don't use a control, then how can you be sure the data are real and not because the patient or treatment team acted differently because they thought they were on a miracle drug?)

      –If a person on the control arm does not respond to the approved drug, should they be allowed to "crossover" and get on the drug being tested?  (But, if you allow crossover, then the data for overall survival benefit is compromised, possibly limiting the future approval of the drug.)

      –It seems clear that drugs in development right now are showing more promise that drugs that are currently approved.  If this is the case, is it ethical for a doctor to put a patient with metastatic melanoma on an approved treatment without first discussing the option of clinical trials?

      If this post results in some robust responses I will work to get this input to the FDA and to the researchers and industry people involved in these trials.

      Tim–MRF

    Viewing 24 reply threads
    • Replies
        Jocelyn
        Participant

          i don't see why they have to compare the Braf drugs to anything. They are different than anything we have seen  before. Just keep conducting trials in which all Braf positive people get the drug and see how long they live. It wouldn't be too hard to conclude that, even if the drug eventually stops working, the patients have more than likely outlived anyone who takes DTIC.

          I know this isn't how trials work. Phase III are the conclusive ones and always call for a comparison arm. Scientists would argue that, once Braf stops working, melanoma may come back with a vengeance, erasing any time gains against something like DTIC. But that seems unlikely–DTIC usually only extends life by 2 or 3 months, and so many Braf patients get an almost disease free 6-12 months, or or at least tumor reduction and extended stability. Some have tried to say that Braf patients just get a hunk of quality time, but it seems apparent that they also get MORE time. This is just a subjective impression, but it sure looks this way to me, from what I have read.

          And to answer your question, is it ethical to place patients in a control arm that we KNOW doesn't work as well as the Braf–of course it isn't ethical. It's almost the same as conducting a Phase 3 trial using a placebo. The types of drugs, and the way they work, is being revolutionized. This calls for a change in the way we conduct trials, especially phase 3. Perhaps it's a simple answer–insert some common sense into the trial process? Anyone with half a brain can see  that the Braf drugs work better than DTIC.

            Lauren S. Sutton
            Participant

              I really dont believe how accurate these trials are especially if they ask for scans every three months how healthy is that for the body. And if you are on a placebo all you are doing is getting radiation and killing the good cells and taking the risk of getting another cancer.

              Lauren S. Sutton
              Participant

                I really dont believe how accurate these trials are especially if they ask for scans every three months how healthy is that for the body. And if you are on a placebo all you are doing is getting radiation and killing the good cells and taking the risk of getting another cancer.

                Lauren S. Sutton
                Participant

                  I really dont believe how accurate these trials are especially if they ask for scans every three months how healthy is that for the body. And if you are on a placebo all you are doing is getting radiation and killing the good cells and taking the risk of getting another cancer.

                Jocelyn
                Participant

                  i don't see why they have to compare the Braf drugs to anything. They are different than anything we have seen  before. Just keep conducting trials in which all Braf positive people get the drug and see how long they live. It wouldn't be too hard to conclude that, even if the drug eventually stops working, the patients have more than likely outlived anyone who takes DTIC.

                  I know this isn't how trials work. Phase III are the conclusive ones and always call for a comparison arm. Scientists would argue that, once Braf stops working, melanoma may come back with a vengeance, erasing any time gains against something like DTIC. But that seems unlikely–DTIC usually only extends life by 2 or 3 months, and so many Braf patients get an almost disease free 6-12 months, or or at least tumor reduction and extended stability. Some have tried to say that Braf patients just get a hunk of quality time, but it seems apparent that they also get MORE time. This is just a subjective impression, but it sure looks this way to me, from what I have read.

                  And to answer your question, is it ethical to place patients in a control arm that we KNOW doesn't work as well as the Braf–of course it isn't ethical. It's almost the same as conducting a Phase 3 trial using a placebo. The types of drugs, and the way they work, is being revolutionized. This calls for a change in the way we conduct trials, especially phase 3. Perhaps it's a simple answer–insert some common sense into the trial process? Anyone with half a brain can see  that the Braf drugs work better than DTIC.

                  jag
                  Participant

                    I think if you were coming up with a treatment for chronic diseases like diabetes, the FDA system might be a little more realistic.  In the meantime, when average overall survival for diseases like melanoma hasn't increased in oh say 20 years, that is a pretty good sign that a change is needed.    

                      jag
                      Participant

                        the other thing to consider might be to approve more stage IV treatments for lower stage diseases.  Interleukin 2 for example.  I imagine it is about as bad as interferon, yet it isn't approved for stage II or stage III patients.  People get presented with a whole bunch of options that they have to think about when they may only have months to live.  Breast Cancer patients for example, sometimes get complete mastectomies if there is a familial predilection for breast cancer.  Are they definitely going to get it? no.  Yet they are offered the option before they ever do.  Preventative care like that may be something to consider. 

                        jag
                        Participant

                          the other thing to consider might be to approve more stage IV treatments for lower stage diseases.  Interleukin 2 for example.  I imagine it is about as bad as interferon, yet it isn't approved for stage II or stage III patients.  People get presented with a whole bunch of options that they have to think about when they may only have months to live.  Breast Cancer patients for example, sometimes get complete mastectomies if there is a familial predilection for breast cancer.  Are they definitely going to get it? no.  Yet they are offered the option before they ever do.  Preventative care like that may be something to consider. 

                        jag
                        Participant

                          I think if you were coming up with a treatment for chronic diseases like diabetes, the FDA system might be a little more realistic.  In the meantime, when average overall survival for diseases like melanoma hasn't increased in oh say 20 years, that is a pretty good sign that a change is needed.    

                          Jim in Denver
                          Participant

                            Tim:

                            To ask about ethics involoved in trial design becomes a discussion about morality.  So the question becomes one regarding morality.  It is not moral for one person or group to deprive another person or group of potentially life saving treatment when other options offer comparatively small benefit, in my opinion.  There are scientific reasons for current trial design criteria, but those need to be reevaluated. particularly when there appear to be great differences in efficacy between approved "standard" treatments and new treatments under development. 

                            The current model takes as a premise that there will be only incremental differences in efficacy between old and new treatments. There is good reason to require long studies to demonstrate significant differences in human sample groups, using accepted statistical methods, when there are only minor differences in the effectiveness between old and new drugs.  Given the large financial rewards involved in a new drug becoming the "standard of care" when there may be minimal improvements for patients, there is good reason to require rigorous, detailed, and lengthy studies that are currently required.

                            However, when there are clear and significant differences between old and new treatments, a different methodology  for trials would be appropriate.  When a quantum leap appears possible or likely, a different set of criteria for testing and approval should be used.  We are witnessing just such a situation in melanoma treatment currently with the development of targeted genetic treatments and systemic treatments, from a fair reading of available data. 

                            Different situations require different methodologies, for ethical and moral reasons.  It is not acceptable on ethical  grounds to withhold a promising treatment that has shown clear and significant improvement in quality of life and/or survival.  If a new drug's safety profile is no worse than the current standard of care and it appears to be significantly more effective during Phase I and II Trials, a different path to (conditional?) approval should exist.  The NY Times article illustrates the moral dilemma all too well.  The moral choice is clear.

                            Thanks,

                            Jim

                             

                             

                            Jim in Denver
                            Participant

                              Tim:

                              To ask about ethics involoved in trial design becomes a discussion about morality.  So the question becomes one regarding morality.  It is not moral for one person or group to deprive another person or group of potentially life saving treatment when other options offer comparatively small benefit, in my opinion.  There are scientific reasons for current trial design criteria, but those need to be reevaluated. particularly when there appear to be great differences in efficacy between approved "standard" treatments and new treatments under development. 

                              The current model takes as a premise that there will be only incremental differences in efficacy between old and new treatments. There is good reason to require long studies to demonstrate significant differences in human sample groups, using accepted statistical methods, when there are only minor differences in the effectiveness between old and new drugs.  Given the large financial rewards involved in a new drug becoming the "standard of care" when there may be minimal improvements for patients, there is good reason to require rigorous, detailed, and lengthy studies that are currently required.

                              However, when there are clear and significant differences between old and new treatments, a different methodology  for trials would be appropriate.  When a quantum leap appears possible or likely, a different set of criteria for testing and approval should be used.  We are witnessing just such a situation in melanoma treatment currently with the development of targeted genetic treatments and systemic treatments, from a fair reading of available data. 

                              Different situations require different methodologies, for ethical and moral reasons.  It is not acceptable on ethical  grounds to withhold a promising treatment that has shown clear and significant improvement in quality of life and/or survival.  If a new drug's safety profile is no worse than the current standard of care and it appears to be significantly more effective during Phase I and II Trials, a different path to (conditional?) approval should exist.  The NY Times article illustrates the moral dilemma all too well.  The moral choice is clear.

                              Thanks,

                              Jim

                               

                               

                              Jim M.
                              Participant

                                Hi Tim,

                                 I'll respond to your third question. I believe doctors need to present all the options to patients, not only approved treatments. The purpose is for the patient to make an informed decision. Granted at some hospitals there may be fewer options but doctors need to be informed on what's working, where these treatments are provided and explain this to the patient. If doctors are uncertain where certain treatments/ trials are offered at least they should provide useful website(s) to each patient . My doctor did explain interferon, a clinical trial with Ipilimumab or watch and wait. He was very thorough and spent much time with my wife and I. That is something I will never forget and it made all the difference in my treatment decisions. Thank you for your email.

                                 Jim M.

                                 

                                Jim M.
                                Participant

                                  Hi Tim,

                                   I'll respond to your third question. I believe doctors need to present all the options to patients, not only approved treatments. The purpose is for the patient to make an informed decision. Granted at some hospitals there may be fewer options but doctors need to be informed on what's working, where these treatments are provided and explain this to the patient. If doctors are uncertain where certain treatments/ trials are offered at least they should provide useful website(s) to each patient . My doctor did explain interferon, a clinical trial with Ipilimumab or watch and wait. He was very thorough and spent much time with my wife and I. That is something I will never forget and it made all the difference in my treatment decisions. Thank you for your email.

                                   Jim M.

                                   

                                  TAC
                                  Participant

                                    I have believed for quite some time that the clinical trial models maybe great in a hypothettical situation when in reality, they are dealing with live, human beings. The end point of some trials is to wait until an arbitrary number, IMHO,of enrolled patients have died…like say 300. So let me see, I couldn't conclude after 200 or 250 0r 275 have died that the drug didn't work..good grief. A child of two could come to that conclusion much sooner…..but let's not violate the clinical trial protocol and the statstics…sarcasm off. I'm concerned that the researchers are so ingrossed in the methodology that they forget that they are treating patients. "Nope, we can't declare that the drug is a failure because only 299 patients have died when our goal is 300"….. Meanwhile the trial goes on and other patients continue to receive this worthless drug. This is not only unethical, it is criminal. So ask a researcher, would you enroll you father or mother in this trial knowing that there is a placebo arm or in a trial that has used an old drug with minimal success and they are likely to get that arm?

                                    In my opinion, there should never be a placebo for any arm of any trial. At least compare the drug that is new against something that has worked reasonably well in the past. I thought the goal was to move the success measure forward. At least the patients are getting something that "may" work. Well you say, "we'll let them crossover to the new drug when it becomes evident that it is working"….again, good grief…by that time the tumor load may be so great that these crossover patients have little to no chance….but the methodology still is intact!!!

                                    The clinical trial models are outdated, antiquated and don't serve the patients well. Why not include a patient advocate on every clinical trial team. At least someone has been charged with looking out for the patients.

                                     

                                    My name is Al Cato…..Stage III melanoma, Stage I Renal cell carcinoma; Stage I adenocarcinoma.

                                    TAC
                                    Participant

                                      I have believed for quite some time that the clinical trial models maybe great in a hypothettical situation when in reality, they are dealing with live, human beings. The end point of some trials is to wait until an arbitrary number, IMHO,of enrolled patients have died…like say 300. So let me see, I couldn't conclude after 200 or 250 0r 275 have died that the drug didn't work..good grief. A child of two could come to that conclusion much sooner…..but let's not violate the clinical trial protocol and the statstics…sarcasm off. I'm concerned that the researchers are so ingrossed in the methodology that they forget that they are treating patients. "Nope, we can't declare that the drug is a failure because only 299 patients have died when our goal is 300"….. Meanwhile the trial goes on and other patients continue to receive this worthless drug. This is not only unethical, it is criminal. So ask a researcher, would you enroll you father or mother in this trial knowing that there is a placebo arm or in a trial that has used an old drug with minimal success and they are likely to get that arm?

                                      In my opinion, there should never be a placebo for any arm of any trial. At least compare the drug that is new against something that has worked reasonably well in the past. I thought the goal was to move the success measure forward. At least the patients are getting something that "may" work. Well you say, "we'll let them crossover to the new drug when it becomes evident that it is working"….again, good grief…by that time the tumor load may be so great that these crossover patients have little to no chance….but the methodology still is intact!!!

                                      The clinical trial models are outdated, antiquated and don't serve the patients well. Why not include a patient advocate on every clinical trial team. At least someone has been charged with looking out for the patients.

                                       

                                      My name is Al Cato…..Stage III melanoma, Stage I Renal cell carcinoma; Stage I adenocarcinoma.

                                      KatyWI
                                      Participant

                                        Tim,

                                        I'm glad you're starting this conversation.

                                        In theory, in a Phase III trial the investigators are still supposed to be truly unsure whether the new treatment is any better than current treatments.  IF that were true, then the presence of a standard control arm, like dacarbazine, would be ethical.  But we have phase II trials to give us an idea whether the new treatment has any benefit.  By the time a drug reaches stage III, almost no one has genuine uncertainty about the new treatment (even if they turn out to be wrong, as may or may not have been the case for adjuvant GM-CSF).  I think it is hard for a physician in this situation to enroll patients in a control arm and still adhere to his/her Hippocratic oath.  Perhaps the control arm "does no harm," but it probably does not do as much help as the experimental arm.

                                        Actually, as much as than the BRAF trial and its dacarbazine control raise concerns, I am more bothered by the Oncovex trial (NCT00769704).  The control on the Oncovex trial is subcutaneously injected GM-CSF.  GM-CSF monotherapy has been studied as an adjuvant for fully resected stage III and IV disease, but nowhere can my doctor or I find published results of any research indicating efficacy of subcutaneous GM-CSF alone against the active stage III and IV disease at which the trial is targeted.  It is as if a Phaes II study is being conducted under the guise of a Phase III control arm.  It's a logical, scientific control – after all, Oncovex expresses GM-CSF – but in the absence of any proof of efficacy, I can't see how it is an ethical control for human trials. 

                                        I think that a crossover design reduces the ethical concerns in Phase III trials.  A crossover design certainly encourages patients to enroll because it reduces the (real or perceived) risk associated with the control arm.  Yes, a crossover design screws up your statistics if overall survival is the primary endpoint.  Sorry if I fail to contain my sarcasm as I say, "Waa."  The rest of us have no wish to REACH that "endpoint."  The E1690 trial carried out after the approval of Interferon was a crossover design (the control arm was "watch & wait"), and some believe this is why Interferon did not show a survival benefit in this testing.  Perhaps this is also why the initial promise of INF – to "reduce the risk of recurrence" – has subsequently been edited to "extend the time to recurrence".

                                        Statistics such as reduction in overall tumor load, or percentage reaching NED on a treatment, or duration of response, all can be measured before crossover occurs.  Perhaps overall survival has outlived its usefulness in the context of a controlled trial.  We have plenty of data on historical overall survival, and OS is a very useful comparison in Phase II trials with matched historical controls, or even as an overall average comparison.  But if we continue to rely on Phase III trials with appropriate controls for ultimate drug approval, perhaps it is time to eliminate OS as a primary endpoint and embrace the crossover design as a more ethical way to conduct human research. 

                                        The question about needing to fail conventional treatment before becoming eligible for trials is one that my doctor and I wrestled with as well.  I would have preferred to go straight into an available Phase II study when I became stage IV last year, and the trial protocol seemed to have an "out" – it required one to have failed or refused IL-2 therapy.  Nonetheless, my doctor encouraged me to try IL-2 first, even though he disagreed with the requirement to fail conventional therapy first, becuase it was what he is expected to do.  The only rational reason he could offer for trying IL-2 first is that becaues no one has tried the experimental treatment without trying IL-2 first, we don't know if IL-2 somehow primes the body to succeed on the experimental treatment.  All the same, if I'd insisted and gone straight into the trial, would I be sitting here with brain mets, just four months out of apparently successful IL-2 + surgery?

                                        In some ways, the presence of a control arm in phase III trials seems redundant with the requirement to fail conventional therapy before entering a trial.  After all, we already know that at least one conventional treatment doesn't work for the individuals entering the trial!

                                        Again, thank you for inviting us into this conversation.  With sincere regards,

                                        KatyWI

                                        If you bundle together our responses in communication with the FDA, I am willing to provide my full name if requested.

                                         

                                        KatyWI
                                        Participant

                                          Tim,

                                          I'm glad you're starting this conversation.

                                          In theory, in a Phase III trial the investigators are still supposed to be truly unsure whether the new treatment is any better than current treatments.  IF that were true, then the presence of a standard control arm, like dacarbazine, would be ethical.  But we have phase II trials to give us an idea whether the new treatment has any benefit.  By the time a drug reaches stage III, almost no one has genuine uncertainty about the new treatment (even if they turn out to be wrong, as may or may not have been the case for adjuvant GM-CSF).  I think it is hard for a physician in this situation to enroll patients in a control arm and still adhere to his/her Hippocratic oath.  Perhaps the control arm "does no harm," but it probably does not do as much help as the experimental arm.

                                          Actually, as much as than the BRAF trial and its dacarbazine control raise concerns, I am more bothered by the Oncovex trial (NCT00769704).  The control on the Oncovex trial is subcutaneously injected GM-CSF.  GM-CSF monotherapy has been studied as an adjuvant for fully resected stage III and IV disease, but nowhere can my doctor or I find published results of any research indicating efficacy of subcutaneous GM-CSF alone against the active stage III and IV disease at which the trial is targeted.  It is as if a Phaes II study is being conducted under the guise of a Phase III control arm.  It's a logical, scientific control – after all, Oncovex expresses GM-CSF – but in the absence of any proof of efficacy, I can't see how it is an ethical control for human trials. 

                                          I think that a crossover design reduces the ethical concerns in Phase III trials.  A crossover design certainly encourages patients to enroll because it reduces the (real or perceived) risk associated with the control arm.  Yes, a crossover design screws up your statistics if overall survival is the primary endpoint.  Sorry if I fail to contain my sarcasm as I say, "Waa."  The rest of us have no wish to REACH that "endpoint."  The E1690 trial carried out after the approval of Interferon was a crossover design (the control arm was "watch & wait"), and some believe this is why Interferon did not show a survival benefit in this testing.  Perhaps this is also why the initial promise of INF – to "reduce the risk of recurrence" – has subsequently been edited to "extend the time to recurrence".

                                          Statistics such as reduction in overall tumor load, or percentage reaching NED on a treatment, or duration of response, all can be measured before crossover occurs.  Perhaps overall survival has outlived its usefulness in the context of a controlled trial.  We have plenty of data on historical overall survival, and OS is a very useful comparison in Phase II trials with matched historical controls, or even as an overall average comparison.  But if we continue to rely on Phase III trials with appropriate controls for ultimate drug approval, perhaps it is time to eliminate OS as a primary endpoint and embrace the crossover design as a more ethical way to conduct human research. 

                                          The question about needing to fail conventional treatment before becoming eligible for trials is one that my doctor and I wrestled with as well.  I would have preferred to go straight into an available Phase II study when I became stage IV last year, and the trial protocol seemed to have an "out" – it required one to have failed or refused IL-2 therapy.  Nonetheless, my doctor encouraged me to try IL-2 first, even though he disagreed with the requirement to fail conventional therapy first, becuase it was what he is expected to do.  The only rational reason he could offer for trying IL-2 first is that becaues no one has tried the experimental treatment without trying IL-2 first, we don't know if IL-2 somehow primes the body to succeed on the experimental treatment.  All the same, if I'd insisted and gone straight into the trial, would I be sitting here with brain mets, just four months out of apparently successful IL-2 + surgery?

                                          In some ways, the presence of a control arm in phase III trials seems redundant with the requirement to fail conventional therapy before entering a trial.  After all, we already know that at least one conventional treatment doesn't work for the individuals entering the trial!

                                          Again, thank you for inviting us into this conversation.  With sincere regards,

                                          KatyWI

                                          If you bundle together our responses in communication with the FDA, I am willing to provide my full name if requested.

                                           

                                          washoegal
                                          Participant

                                            I fully understand the need for a control group and for blind studies.  But to avoid the problem faced as with the cousins, I believe researchers should take a more aggressive approach to monitoring patients well being.  When the patient does not respond, I believe the patient should be offered another alternative immediately.  Maybe even a "free-pass" into another study where they are guaranteed the drug or compassionate use of the drugin which  they were in the study group.   These alternatives and more agressive monitoring must be set up prior to the establishment of the study.  I realize that this will raise the drug cost even more, and require the drug companies to work togeather in some cases but it must be done to humanely test drugs and still bring safe drugs to market.

                                             

                                            Mary Kranz

                                            Stage 3

                                            washoegal
                                            Participant

                                              I fully understand the need for a control group and for blind studies.  But to avoid the problem faced as with the cousins, I believe researchers should take a more aggressive approach to monitoring patients well being.  When the patient does not respond, I believe the patient should be offered another alternative immediately.  Maybe even a "free-pass" into another study where they are guaranteed the drug or compassionate use of the drugin which  they were in the study group.   These alternatives and more agressive monitoring must be set up prior to the establishment of the study.  I realize that this will raise the drug cost even more, and require the drug companies to work togeather in some cases but it must be done to humanely test drugs and still bring safe drugs to market.

                                               

                                              Mary Kranz

                                              Stage 3

                                              paul
                                              Participant

                                                Hi Tim,

                                                Great that youʻre encouraging this conversation! 

                                                Iʻm not sure itʻs really a question about "ethics" in the classic sense, so much as a tactical question of how to incrementally reform the current medical industrial complex, to encourage collaboration and combination-therapy flexibility, and to make the newer treatments more readily available. Philosophically, double-blind studies seem ethical at the collective level where there is genuinely insufficient scientific means of knowing the relative efficacy of a drug. Then one could make an "ethics" case that harming some (giving them a potentially harmful or inferior course of treatment) will be of benefit to others in the long run. It doesnʻt seem like anyone is really making such a science-based argument in this case, which would be required for a genuine argument about medical "ethics." Instead, there seems to hover behind the whole conversation a set of economic considerations; as several recent articles on the cost and difficulty of developing new drugs (in THE NEW YORKER and elsewhere) make clear, itʻs trickier than a leftist stage IV patient like myself would have it. 

                                                Good luck, and thanks . . . . 

                                                Paul   

                                                paul
                                                Participant

                                                  Hi Tim,

                                                  Great that youʻre encouraging this conversation! 

                                                  Iʻm not sure itʻs really a question about "ethics" in the classic sense, so much as a tactical question of how to incrementally reform the current medical industrial complex, to encourage collaboration and combination-therapy flexibility, and to make the newer treatments more readily available. Philosophically, double-blind studies seem ethical at the collective level where there is genuinely insufficient scientific means of knowing the relative efficacy of a drug. Then one could make an "ethics" case that harming some (giving them a potentially harmful or inferior course of treatment) will be of benefit to others in the long run. It doesnʻt seem like anyone is really making such a science-based argument in this case, which would be required for a genuine argument about medical "ethics." Instead, there seems to hover behind the whole conversation a set of economic considerations; as several recent articles on the cost and difficulty of developing new drugs (in THE NEW YORKER and elsewhere) make clear, itʻs trickier than a leftist stage IV patient like myself would have it. 

                                                  Good luck, and thanks . . . . 

                                                  Paul   

                                                  Jocelyn
                                                  Participant

                                                    Just curious if the same ethical concerns came up, for example, when ipi was being tested against GP-100. Probably not as much, because ipi effect is not so dramatic or fast as the effect of the Braf. The major reason that the ethical issue has become so big now is because of the astonishing INITIAL response to targeted therapy. It stares doctors and patients in the face and screams loudly for immediate approval, at least as compassionate use. No other drug has made people want so much to bypass or alter the traditional trial methodology.

                                                    I also wonder if all this hoopla and growing demand might make Roche all the more stubborn in its refusal to make its drug available on a compassionate basis.

                                                    Jocelyn
                                                    Participant

                                                      Just curious if the same ethical concerns came up, for example, when ipi was being tested against GP-100. Probably not as much, because ipi effect is not so dramatic or fast as the effect of the Braf. The major reason that the ethical issue has become so big now is because of the astonishing INITIAL response to targeted therapy. It stares doctors and patients in the face and screams loudly for immediate approval, at least as compassionate use. No other drug has made people want so much to bypass or alter the traditional trial methodology.

                                                      I also wonder if all this hoopla and growing demand might make Roche all the more stubborn in its refusal to make its drug available on a compassionate basis.

                                                      amybusby
                                                      Participant

                                                        I definitely think the procedures for FDA approval are out dated and the new targeted therapies are such a breakthrough that they need to determine more efficient methods for proving effictiveness and / or survival benefit.  And obviously I think the standard for terminally ill patients should be dramatically different than that for drugs designed to be "life enhancing" or to manage chronic illness.

                                                        Treatments for terminally ill patients should be mined for data through Lazarus Effect studies – how long did this drug keep a person at death's door alive and in what condition.

                                                        A 10 month life extension during which you're suffereing, often hoispitalized, losing cognitive function ,or physical abilities is not more valuable than a drug that gives an 8 month extension but that time is spent mostly at home and in great physical condition.

                                                        That summarizes MY basic delimma right now.  I want to fight for targeted therapy but I don't want to wait too long and have it be too far gone.  And what if I wait for nothing?  Chances of getting it from somewhere are slim.  Or do I try to get on a compassionate use program for ipi – travel alot, much higher side effects, longer wait to know if I am a "responder".

                                                        People want to point fingers at the "evil pharma. companies" but often, as in my case, both my dr. and the drug company support me getting back in a trial but regulations prevent it.  Trying to get a new cohort to fit me is alot of back & forth bs.

                                                        My position like most patients I would think, is that I think I should have access to anything that seems to be a step up from the horrifyingly low success rates of the "approved" treatments.  If that means developing new ways to asses the date and make conclusions about the new drugs then I would think that should be something the scientists can design based on their drug and trial design.

                                                        I don't think it's right to compare the kinds of treatments developing now to "standard" treatments is ethical in a case like melanoma where there are no effective treatments (yes, I'm lookin at you IL2 and your measly 15%).  Not only is it apples and oranges but it's no medical accomplishment to simply "do better" than the last straggler coming around the bend  to cross the finish line.  That's like someone saying "Hey!  I'm taller than Amy!  woo hoo!" and everyone else saying "Big Deal."

                                                        The design of clinical trials penalizes the warriors that stay alive the longest.  To stay alive we're obviously tried everything under the sun so by the time the new trial drug appears it excludes us all except for the newly diagnosed.  Because if you've done XYZ in the past you're ineligible for XYZ 2.0.  But if you had not done XYZ then you wouldn't even be alive to see the development of XYZ 2.0

                                                        See what I mean?  Instead of being rewarded for my success over the last 8 years and mining my obviously miraculous (haha) body for relevent medical data that could help others, I get the door closed in my face since I am no longer a blank slate.  Ethical?  Hardly.  Medically sound as far as the data?  I think not.  I am sure much could be learned from my CNS mets – when / why / how they developed?  how can the targeted therapies be more CNS effective?  Have their been chances in the cells or tumors or non-metastesized tissues due to the targeted therapy?  etc. etc. etc.

                                                        I could go on and on even more than I have but it's frustrating to know your contributions to advancing melanoma treatment are not being utilized to their best advantage in a way that could help others and maybe even me.

                                                        I have to go take a nap. 

                                                        Amy
                                                         

                                                          Sherron
                                                          Participant

                                                            Sweet dreams, Sweet Amy….go rest…You are one of the warriors I have ever seen….Hugs to you.

                                                            Take Care,

                                                            Sherron, wife to Jim

                                                            Sherron
                                                            Participant

                                                              Sweet dreams, Sweet Amy….go rest…You are one of the warriors I have ever seen….Hugs to you.

                                                              Take Care,

                                                              Sherron, wife to Jim

                                                              jag
                                                              Participant

                                                                Well said Amy, obviously the disease in your cranium has not affected your mind.

                                                                Hang in there-praying for a solution that works for you. 

                                                                John 

                                                                jag
                                                                Participant

                                                                  Well said Amy, obviously the disease in your cranium has not affected your mind.

                                                                  Hang in there-praying for a solution that works for you. 

                                                                  John 

                                                                  Jocelyn
                                                                  Participant

                                                                    Alert: Forward Amy's post to the FDA and all the pharmas and trial centers dealing with inhibitors!

                                                                    You will get it somehow, somewhere Amy; I just know you will. I know you are pulling out every stop to do so. I don't think anything about access to this drug is carved in stone, and there must be several loopholes. You are a great warrior but also a pioneer in this new area for which the rules simply–and so obviously– have to change.

                                                                    Jocelyn
                                                                    Participant

                                                                      Alert: Forward Amy's post to the FDA and all the pharmas and trial centers dealing with inhibitors!

                                                                      You will get it somehow, somewhere Amy; I just know you will. I know you are pulling out every stop to do so. I don't think anything about access to this drug is carved in stone, and there must be several loopholes. You are a great warrior but also a pioneer in this new area for which the rules simply–and so obviously– have to change.

                                                                    amybusby
                                                                    Participant

                                                                      I definitely think the procedures for FDA approval are out dated and the new targeted therapies are such a breakthrough that they need to determine more efficient methods for proving effictiveness and / or survival benefit.  And obviously I think the standard for terminally ill patients should be dramatically different than that for drugs designed to be "life enhancing" or to manage chronic illness.

                                                                      Treatments for terminally ill patients should be mined for data through Lazarus Effect studies – how long did this drug keep a person at death's door alive and in what condition.

                                                                      A 10 month life extension during which you're suffereing, often hoispitalized, losing cognitive function ,or physical abilities is not more valuable than a drug that gives an 8 month extension but that time is spent mostly at home and in great physical condition.

                                                                      That summarizes MY basic delimma right now.  I want to fight for targeted therapy but I don't want to wait too long and have it be too far gone.  And what if I wait for nothing?  Chances of getting it from somewhere are slim.  Or do I try to get on a compassionate use program for ipi – travel alot, much higher side effects, longer wait to know if I am a "responder".

                                                                      People want to point fingers at the "evil pharma. companies" but often, as in my case, both my dr. and the drug company support me getting back in a trial but regulations prevent it.  Trying to get a new cohort to fit me is alot of back & forth bs.

                                                                      My position like most patients I would think, is that I think I should have access to anything that seems to be a step up from the horrifyingly low success rates of the "approved" treatments.  If that means developing new ways to asses the date and make conclusions about the new drugs then I would think that should be something the scientists can design based on their drug and trial design.

                                                                      I don't think it's right to compare the kinds of treatments developing now to "standard" treatments is ethical in a case like melanoma where there are no effective treatments (yes, I'm lookin at you IL2 and your measly 15%).  Not only is it apples and oranges but it's no medical accomplishment to simply "do better" than the last straggler coming around the bend  to cross the finish line.  That's like someone saying "Hey!  I'm taller than Amy!  woo hoo!" and everyone else saying "Big Deal."

                                                                      The design of clinical trials penalizes the warriors that stay alive the longest.  To stay alive we're obviously tried everything under the sun so by the time the new trial drug appears it excludes us all except for the newly diagnosed.  Because if you've done XYZ in the past you're ineligible for XYZ 2.0.  But if you had not done XYZ then you wouldn't even be alive to see the development of XYZ 2.0

                                                                      See what I mean?  Instead of being rewarded for my success over the last 8 years and mining my obviously miraculous (haha) body for relevent medical data that could help others, I get the door closed in my face since I am no longer a blank slate.  Ethical?  Hardly.  Medically sound as far as the data?  I think not.  I am sure much could be learned from my CNS mets – when / why / how they developed?  how can the targeted therapies be more CNS effective?  Have their been chances in the cells or tumors or non-metastesized tissues due to the targeted therapy?  etc. etc. etc.

                                                                      I could go on and on even more than I have but it's frustrating to know your contributions to advancing melanoma treatment are not being utilized to their best advantage in a way that could help others and maybe even me.

                                                                      I have to go take a nap. 

                                                                      Amy
                                                                       

                                                                      jim Breitfeller
                                                                      Participant

                                                                        Who Gets to Play God?

                                                                        This really happened:

                                                                         

                                                                        health day

                                                                        TUESDAY, Sept. 21 (HealthDay News) — Continuous treatment with imatinib (Gleevec) is recommended for patients with advanced gastrointestinal cancer, a new study suggests.

                                                                        The study included 50 patients with advanced gastrointestinal stromal tumors (GIST) who'd been receiving Gleevec for three years and had no disease progression. The patients were randomly selected to either continue or stop treatment.

                                                                        The patients were assessed every three months with CT scans. The median time to disease progression was nine months among patients whose treatment was interruptedand was not reached in the group who continued treatment, the investigators found.

                                                                         

                                                                         

                                                                        Source: http://www.cancercompass.com/cancer-news/article/34280.htm?c=NL20100922

                                                                         

                                                                         

                                                                        This NEEDS TO STOP!!!!!!!

                                                                        jim Breitfeller
                                                                        Participant

                                                                          Who Gets to Play God?

                                                                          This really happened:

                                                                           

                                                                          health day

                                                                          TUESDAY, Sept. 21 (HealthDay News) — Continuous treatment with imatinib (Gleevec) is recommended for patients with advanced gastrointestinal cancer, a new study suggests.

                                                                          The study included 50 patients with advanced gastrointestinal stromal tumors (GIST) who'd been receiving Gleevec for three years and had no disease progression. The patients were randomly selected to either continue or stop treatment.

                                                                          The patients were assessed every three months with CT scans. The median time to disease progression was nine months among patients whose treatment was interruptedand was not reached in the group who continued treatment, the investigators found.

                                                                           

                                                                           

                                                                          Source: http://www.cancercompass.com/cancer-news/article/34280.htm?c=NL20100922

                                                                           

                                                                           

                                                                          This NEEDS TO STOP!!!!!!!

                                                                            paul
                                                                            Participant

                                                                              Wow. Call in the Harry Lime School of Applied Ethics.

                                                                              paul
                                                                              Participant

                                                                                Wow. Call in the Harry Lime School of Applied Ethics.

                                                                                paul
                                                                                Participant

                                                                                  Wow. Call in the Harry Lime School of Applied Ethics.

                                                                                  paul
                                                                                  Participant

                                                                                    Wow. Call in the Harry Lime School of Applied Ethics.

                                                                                  JerryfromFauq
                                                                                  Participant

                                                                                    Tim,

                                                                                    As you know I was "unavailable" when this was being asked.  I just ran across it. 
                                                                                       I think the subsequent death of our Dear Amy Busby, after getting clear of her Brain and spinal mets for the required two months, and still being denied any chance of returning to the GSK BRAF treatment that had almost eliminated her Melanoma tumors before the brain and spinal column became involved.  They neither allowed her to continue the anti-BRAF treatment while eliminating the brain/spinal problems nor, inspite of their promise,  would allow her to restart the anti-BRAF treatment after the 2 months of clear brain/spinal clear brain/spinal checks.

                                                                                     I believe that her case alone illustrates the need for revision of the federal setup of drug approval /usage that is currently mandated to be sure that no possible "harm" comes to a dying patient.

                                                                                    JerryfromFauq
                                                                                    Participant

                                                                                      Tim,

                                                                                      As you know I was "unavailable" when this was being asked.  I just ran across it. 
                                                                                         I think the subsequent death of our Dear Amy Busby, after getting clear of her Brain and spinal mets for the required two months, and still being denied any chance of returning to the GSK BRAF treatment that had almost eliminated her Melanoma tumors before the brain and spinal column became involved.  They neither allowed her to continue the anti-BRAF treatment while eliminating the brain/spinal problems nor, inspite of their promise,  would allow her to restart the anti-BRAF treatment after the 2 months of clear brain/spinal clear brain/spinal checks.

                                                                                       I believe that her case alone illustrates the need for revision of the federal setup of drug approval /usage that is currently mandated to be sure that no possible "harm" comes to a dying patient.

                                                                                      JerryfromFauq
                                                                                      Participant

                                                                                        Tim,

                                                                                        As you know I was "unavailable" when this was being asked.  I just ran across it. 
                                                                                           I think the subsequent death of our Dear Amy Busby, after getting clear of her Brain and spinal mets for the required two months, and still being denied any chance of returning to the GSK BRAF treatment that had almost eliminated her Melanoma tumors before the brain and spinal column became involved.  They neither allowed her to continue the anti-BRAF treatment while eliminating the brain/spinal problems nor, inspite of their promise,  would allow her to restart the anti-BRAF treatment after the 2 months of clear brain/spinal clear brain/spinal checks.

                                                                                         I believe that her case alone illustrates the need for revision of the federal setup of drug approval /usage that is currently mandated to be sure that no possible "harm" comes to a dying patient.

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