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JerryfromFauq.
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- February 12, 2014 at 10:02 am
Cobourg patient drew the 'short straw' in cancer drug trial | Toronto …
4 days ago – Adrienne Lotton has Stage 4 melanoma; a drug still in testing could … FREE SATURDAY STAR with a DIGITAL ACCESS SUBSCRIPTION Find out more …. In Canada, the Special Access Program allows a doctor to apply to …
Adrienne Lotton, 34, seen here in a photo taken last year, has Stage 4 melanoma and is in rapid decline. Her mother, Marilyn Lotton, is desperately trying to get access to nivolumab, a promising drug that's currently in Phase 3 trials. But its manufacturer, Bristol-Myers Squibb, won't release the drug.
Adrienne Lotton is 34 years old, a newly minted veterinarian who organizes food drives and goes to the gym.
Or, she used to. Now, she’s stricken with a deadly illness. And she’s running out of time.
And her hopes of avoiding death or buying more time are tangled in the web of medicine and moral quandary that surrounds access to developmental drugs. It’s a wrestling match between the interests of one patient and many; between scientific rigour and desperate hope; between benefit and risk; ultimately, between the chance to live and certain death.
Lotton was diagnosed with Stage 4 melanoma in the spring of 2012, not long after she had moved to Regina, Sask., to work at an animal clinic.
Melanoma accounts for 5 per cent of skin cancers but 77 per cent of deaths. The five-year survival for metastatic melanoma is 15 per cent.
Lotton came home for treatment at Princess Margaret Hospital in Toronto. After radiation, chemotherapy and a new drug, ipilimumab, Lotton went back to work in Regina, back to the gym, back to her life.
“She was so excited, we were all so happy,” says Lotton’s mother, Marilyn. “But it was short-lived.”
Three months later, Lotton’s checkup at Princess Margaret showed lesions in her abdomen. She came home for good.
“It’s just been downhill ever since,” says Marilyn.
But there is a new drug, nivolumab, that’s showing promising results in treating advanced melanoma in clinical trials.
Lotton made it into a Phase 3 trial last fall. But she landed in the control group that would receive currently proven treatments that, for her, aren’t working. She couldn’t get the drug.
“She pulled the short straw,” says Marilyn. Lotton withdrew from the trial and her oncologist asked the pharmaceutical company, Bristol-Myers Squibb, to release nivolumab on compassionate grounds. The company refused.
Bristol-Myers Squibb hasn’t released nivolumab outside of clinical trials. Darcy Doherty, a 48-year-old father of three, died of melanoma in July 2012 after waging a highly public campaign for access to it.
The company says there isn’t enough information yet to use it outside a trial.
“We empathize with patients who have limited treatment options and will continue to assess available data on nivolumab to determine if the established benefit/risk profile allows for expanded access use outside a well-controlled clinical trial in the future,” says a statement emailed by spokesperson Sarah Koenig.
Clinical trials are done in phases. The first and second phases determine a treatment’s safety and effectiveness. Phase 3 involves a large group to confirm earlier results and compare it to other treatments. That usually means part of the group receives the new treatment and part does not.
For those, like Lotton, whose lives potentially hinge on a random selection of who gets what, it’s excruciating.
Dr. Janet Dancey, who leads the High Impact Clinical Trials program at the Ontario Institute for Cancer Research, says it’s a balance, between the care of an individual and research that improves treatment for all patients.
“The desire to do the best you can for a patient and for a patient to get the treatment that you think could help them, versus the need to be certain that treatments really work and that there’s a real benefit and it’s worth whatever risk, that’s always going to be a tension,” says Dancey, who is also director of clinical translational research at NCIC Clinical Trials Group. “There are no easy answers to this. There’s no one-size-fits-all.”
Researchers are obligated to prove a drug or treatment is safe and effective, says Dancey. And Phase 3 trials are the most rigorous testing that can be done. Treatments that showed great promise in early phases of testing have tanked in Phase 3.
“We’re all aware of those examples, where we thought from early results that we had a winner and in fact, what we ended up with was something that was no better and in a few cases at least, was actually worse,” she says.
In Canada, the Special Access Program allows a doctor to apply to Health Canada to authorize a company to dispense a drug that’s in development. But no one can make the company do it.
The push for access to trial-phase drugs has its roots in the 1980s, in the early days of the AIDS epidemic, says Udo Schuklenk, Ontario Research Chair in Bioethics at Queen’s University. People were dying, desperate to get into clinical trials that might offer them a new lease on life and not satisfied that only half those participating would actually get treatment.
“The idea that you could force people, in a liberal democracy, that are fighting for their lives . . . into clinical trials because you just prevent them from accessing potentially life-preserving medication by other means is just ludicrous,” says Schuklenk.
Francoise Baylis, a health-care ethics expert at Dalhousie University, says those entering clinical trials need to understand what research is.
“The purpose of participating in a trial is not to access treatment,” says Baylis. “The purpose of participating in a trial is to contribute to knowledge production.”
It’s not known, at trial phase, whether a new treatment will work better than the current best practice. If it was, it wouldn’t be a trial — it would be treatment, she says.
“The very treatment you have today is because somebody else participated in a trial,” says Baylis. “Along the way, some people will benefit, some people will be harmed. But it’s a bigger picture, a different goal, that’s looking at a population of people and saying to the individual: Can you help us achieve this goal for other people like you?”
But that doesn’t make it hurt less for those who feel the means to saving their life or the life of someone they love is just out of reach.
Frank Burroughs founded the Abigail Alliance for Better Access to Developmental Drugs in Virginia after his 21-year-old daughter died of cancer. The family had lobbied hard for access to what’s now marketed as Erbitux, then a promising drug in trials.
“It’s like your child has fallen off a boat, and there’s a life raft there with a rope on it and somebody is telling you that you can’t get that to them,” says Burroughs. “At least try to get it to them. It might not work, but at least let me have the life raft so I can throw it over the side and maybe reach this person.”
Professor Arthur Schafer, director of the University of Manitoba’s Centre for Professional and Applied Ethics, says patients should have the choice to access experimental drugs. But he cautioned that, usually, drugs aren’t the miracle people hope for. They may only add a few weeks or months, and side effects can render that time “wretched.”
“Many patients and their families think, and many people in society think, that if you’re dying and your prognosis is very bleak, then you have nothing to lose. I don’t agree,” says Schafer. “If you’re taking aggressive therapy . . . your last days, weeks or months of life are not spent quietly and in a dignified way, talking to your family, saying goodbye, putting your affairs in order. What you lose is an opportunity to die well.”
Lotton is at her mother’s home in Cobourg. She’s trying to get into another trial. She’s been upbeat through her illness, keeping a blog that documents her battle wryly, wittily, encouraging friends to donate blood to replace what she’s using through transfusions.
They are still hopeful, that the next trial will go well, that something will come out. That BMS will give them the drug that could save her.
“I’m a mother and it’s really hard to see your child suffering,” says Marilyn. “I have to do something.”
She will do anything, go anywhere, to save her daughter. But the best chance depends on a pharmaceutical company.
- Replies
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- February 12, 2014 at 1:31 pm
This is my biggest fear about getting involved in a clininal trial… being assigned to the control arm. At some point though, many of us may need to roll the dice and take our chances on that randomization.
Kevin
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- February 12, 2014 at 1:31 pm
This is my biggest fear about getting involved in a clininal trial… being assigned to the control arm. At some point though, many of us may need to roll the dice and take our chances on that randomization.
Kevin
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- February 12, 2014 at 1:31 pm
This is my biggest fear about getting involved in a clininal trial… being assigned to the control arm. At some point though, many of us may need to roll the dice and take our chances on that randomization.
Kevin
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- February 12, 2014 at 1:53 pm
I HAVE ASSKED FOR MORE INFO ON THEIR TRIAL. We need to push hard for there to be a setup such that if one's tumor load continues advancing beyond a certain poin, that somewhere down the line one will be swapped to the actual drug, not just left to die, while many in the other arm gets to live. More and more trials are going this way now than used to do so.
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- February 12, 2014 at 1:53 pm
I HAVE ASSKED FOR MORE INFO ON THEIR TRIAL. We need to push hard for there to be a setup such that if one's tumor load continues advancing beyond a certain poin, that somewhere down the line one will be swapped to the actual drug, not just left to die, while many in the other arm gets to live. More and more trials are going this way now than used to do so.
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- February 12, 2014 at 1:53 pm
I HAVE ASSKED FOR MORE INFO ON THEIR TRIAL. We need to push hard for there to be a setup such that if one's tumor load continues advancing beyond a certain poin, that somewhere down the line one will be swapped to the actual drug, not just left to die, while many in the other arm gets to live. More and more trials are going this way now than used to do so.
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- February 12, 2014 at 6:06 pm
There would have to be prettty stringent guidelines for crossover – otherwise having a control arm is useless. Like the article says, this is research first and foremost. Having been on the other end of a clinical trial and trying to compile and use data to get FDA approval gives me a feel for both ends of the spectrum. It's extremely HARD to get FDA approval and any deviations from their established protocol may result in jeopardizing the whole trial. Very expensive and if the trial doesn't succeed, no one gets the drug. The clinical trial process is always going to have eithical repercussions but the ultimate goal is still to get a product approved so ANYONE has access.
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- February 12, 2014 at 6:06 pm
There would have to be prettty stringent guidelines for crossover – otherwise having a control arm is useless. Like the article says, this is research first and foremost. Having been on the other end of a clinical trial and trying to compile and use data to get FDA approval gives me a feel for both ends of the spectrum. It's extremely HARD to get FDA approval and any deviations from their established protocol may result in jeopardizing the whole trial. Very expensive and if the trial doesn't succeed, no one gets the drug. The clinical trial process is always going to have eithical repercussions but the ultimate goal is still to get a product approved so ANYONE has access.
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- February 12, 2014 at 6:06 pm
There would have to be prettty stringent guidelines for crossover – otherwise having a control arm is useless. Like the article says, this is research first and foremost. Having been on the other end of a clinical trial and trying to compile and use data to get FDA approval gives me a feel for both ends of the spectrum. It's extremely HARD to get FDA approval and any deviations from their established protocol may result in jeopardizing the whole trial. Very expensive and if the trial doesn't succeed, no one gets the drug. The clinical trial process is always going to have eithical repercussions but the ultimate goal is still to get a product approved so ANYONE has access.
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- February 12, 2014 at 7:40 pm
Janner, thank you for explaining what things look like from the other side of the clinical trial desk. You are correct, heartbreaking as some of these situations are, it is very important for new treatments to get FDA approved so everybody can get them.
The only consolation I can offer is that as better melanoma treatments get approved, those become the new "standard of care" and can be used as the control arm for new clinical trials. Two years ago, control arms were mostly good old-fashioned DTIC or interferon; now control arms are more likely to be BRAF or Yervoy which is a definite improvement.
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- February 12, 2014 at 7:40 pm
Janner, thank you for explaining what things look like from the other side of the clinical trial desk. You are correct, heartbreaking as some of these situations are, it is very important for new treatments to get FDA approved so everybody can get them.
The only consolation I can offer is that as better melanoma treatments get approved, those become the new "standard of care" and can be used as the control arm for new clinical trials. Two years ago, control arms were mostly good old-fashioned DTIC or interferon; now control arms are more likely to be BRAF or Yervoy which is a definite improvement.
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- February 12, 2014 at 7:40 pm
Janner, thank you for explaining what things look like from the other side of the clinical trial desk. You are correct, heartbreaking as some of these situations are, it is very important for new treatments to get FDA approved so everybody can get them.
The only consolation I can offer is that as better melanoma treatments get approved, those become the new "standard of care" and can be used as the control arm for new clinical trials. Two years ago, control arms were mostly good old-fashioned DTIC or interferon; now control arms are more likely to be BRAF or Yervoy which is a definite improvement.
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- February 12, 2014 at 8:12 pm
Very good point, Janner. Trials are merely a way to test a drug (on ratties like myself), see what happens, test a few more to see if it sticks, and if it does…test some more and up against a "control" or "med of the moment" to see if the new thing is better….all with the goal of finding better treatments for the masses.
BUT…it does all boil down to access, doesn't it? That's the problem with so much in medicine. Simple, old, and inexpensive inhaled corticosteriods to control asthma are much less prescribed for and used by minority children. Ipi, now on the market, isn't as readily available to the masses as it should be! I posted a discussion by Ribas and Weber (Blog Nov 18, 2013) on this very topic with Ribas noting that in his own county hospital "it is hard to find a patient who has been on [ipi] because it has not been approved for administration [in that hospital] even though it is an FDA-approved drug." And then there's Ralph Steinman (see the Scientific American article: The Patient Scientist, Jan 2012) who was an incredibly brilliant man, whose work with dendritic cells will probably prove even more important than we realize, and allowed to select from "several new immunotherapies that were being evaluated in clinical trials he could enter as a special single patient, rather than enrolling according to the experimenters' original designs" once he was diagnosed with pancreatic cancer. Even taking ipi in 2010 when so many of us were dreaming/wishing/begging that WE could!
So, I guess my point is….When there's a will – there's a way!!!!!!!! Providers can do better to make sure marginalized patient populations get the care and medications they deserve. Patients and advocacy groups can push healthcare facilities to actually administer newly FDA approved meds like ipi. And, clearly, when researchers want to make adjustments to trials and rules…they can. But, not even going as far as the case of Mr. Steinman….many MORE trials can be written and evaluated such that cross over IS allowed without jeopardizing the results or chance of FDA approval for use in the greater population. My own trial of Nivolumab was amended many, many times. At first, no prior ipi use and specific HLA typing due to a vaccine component were requirements. (Many folks lost out on the opportunity to be in those first arms due to that HLA typing rule! Boot2aboot was seriously pissed and I don't blame her. Bless her…miss her still.) Later, arms and amendments were added to allow prior ipi failures specifically. Even later groups without the HLA typing were added since the vaccine component was dropped. And…to me…that's all for the better. Yes, I'm sure Weber, et al have had to work very hard to get all that past the Moffitt IRB and FDA requirements. Still…when researchers do that, not only the ratties currently enrolled, but all of us waiting in the wings….come out ahead.
Yours, Celeste
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- February 12, 2014 at 8:12 pm
Very good point, Janner. Trials are merely a way to test a drug (on ratties like myself), see what happens, test a few more to see if it sticks, and if it does…test some more and up against a "control" or "med of the moment" to see if the new thing is better….all with the goal of finding better treatments for the masses.
BUT…it does all boil down to access, doesn't it? That's the problem with so much in medicine. Simple, old, and inexpensive inhaled corticosteriods to control asthma are much less prescribed for and used by minority children. Ipi, now on the market, isn't as readily available to the masses as it should be! I posted a discussion by Ribas and Weber (Blog Nov 18, 2013) on this very topic with Ribas noting that in his own county hospital "it is hard to find a patient who has been on [ipi] because it has not been approved for administration [in that hospital] even though it is an FDA-approved drug." And then there's Ralph Steinman (see the Scientific American article: The Patient Scientist, Jan 2012) who was an incredibly brilliant man, whose work with dendritic cells will probably prove even more important than we realize, and allowed to select from "several new immunotherapies that were being evaluated in clinical trials he could enter as a special single patient, rather than enrolling according to the experimenters' original designs" once he was diagnosed with pancreatic cancer. Even taking ipi in 2010 when so many of us were dreaming/wishing/begging that WE could!
So, I guess my point is….When there's a will – there's a way!!!!!!!! Providers can do better to make sure marginalized patient populations get the care and medications they deserve. Patients and advocacy groups can push healthcare facilities to actually administer newly FDA approved meds like ipi. And, clearly, when researchers want to make adjustments to trials and rules…they can. But, not even going as far as the case of Mr. Steinman….many MORE trials can be written and evaluated such that cross over IS allowed without jeopardizing the results or chance of FDA approval for use in the greater population. My own trial of Nivolumab was amended many, many times. At first, no prior ipi use and specific HLA typing due to a vaccine component were requirements. (Many folks lost out on the opportunity to be in those first arms due to that HLA typing rule! Boot2aboot was seriously pissed and I don't blame her. Bless her…miss her still.) Later, arms and amendments were added to allow prior ipi failures specifically. Even later groups without the HLA typing were added since the vaccine component was dropped. And…to me…that's all for the better. Yes, I'm sure Weber, et al have had to work very hard to get all that past the Moffitt IRB and FDA requirements. Still…when researchers do that, not only the ratties currently enrolled, but all of us waiting in the wings….come out ahead.
Yours, Celeste
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- February 12, 2014 at 8:12 pm
Very good point, Janner. Trials are merely a way to test a drug (on ratties like myself), see what happens, test a few more to see if it sticks, and if it does…test some more and up against a "control" or "med of the moment" to see if the new thing is better….all with the goal of finding better treatments for the masses.
BUT…it does all boil down to access, doesn't it? That's the problem with so much in medicine. Simple, old, and inexpensive inhaled corticosteriods to control asthma are much less prescribed for and used by minority children. Ipi, now on the market, isn't as readily available to the masses as it should be! I posted a discussion by Ribas and Weber (Blog Nov 18, 2013) on this very topic with Ribas noting that in his own county hospital "it is hard to find a patient who has been on [ipi] because it has not been approved for administration [in that hospital] even though it is an FDA-approved drug." And then there's Ralph Steinman (see the Scientific American article: The Patient Scientist, Jan 2012) who was an incredibly brilliant man, whose work with dendritic cells will probably prove even more important than we realize, and allowed to select from "several new immunotherapies that were being evaluated in clinical trials he could enter as a special single patient, rather than enrolling according to the experimenters' original designs" once he was diagnosed with pancreatic cancer. Even taking ipi in 2010 when so many of us were dreaming/wishing/begging that WE could!
So, I guess my point is….When there's a will – there's a way!!!!!!!! Providers can do better to make sure marginalized patient populations get the care and medications they deserve. Patients and advocacy groups can push healthcare facilities to actually administer newly FDA approved meds like ipi. And, clearly, when researchers want to make adjustments to trials and rules…they can. But, not even going as far as the case of Mr. Steinman….many MORE trials can be written and evaluated such that cross over IS allowed without jeopardizing the results or chance of FDA approval for use in the greater population. My own trial of Nivolumab was amended many, many times. At first, no prior ipi use and specific HLA typing due to a vaccine component were requirements. (Many folks lost out on the opportunity to be in those first arms due to that HLA typing rule! Boot2aboot was seriously pissed and I don't blame her. Bless her…miss her still.) Later, arms and amendments were added to allow prior ipi failures specifically. Even later groups without the HLA typing were added since the vaccine component was dropped. And…to me…that's all for the better. Yes, I'm sure Weber, et al have had to work very hard to get all that past the Moffitt IRB and FDA requirements. Still…when researchers do that, not only the ratties currently enrolled, but all of us waiting in the wings….come out ahead.
Yours, Celeste
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- February 12, 2014 at 11:13 pm
She went long with the trial until it became very obvious that she was not receiving any benefit from the treatment in the arm she was in and would die as a result.
This Lady is in Canada. These people followed the Canadian rules for getting the actual drug, The approving authority was not the one preventing the lady from geting the treatment, The pharmcutical company is who refused to allow her access to the treatment.
It would appear to me to be a plus for the pharmacuticaal company, for someone whose disease prgressed on the standard, if they were to then have the disease stabilize or regress on the drug being tried.
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- February 12, 2014 at 11:13 pm
She went long with the trial until it became very obvious that she was not receiving any benefit from the treatment in the arm she was in and would die as a result.
This Lady is in Canada. These people followed the Canadian rules for getting the actual drug, The approving authority was not the one preventing the lady from geting the treatment, The pharmcutical company is who refused to allow her access to the treatment.
It would appear to me to be a plus for the pharmacuticaal company, for someone whose disease prgressed on the standard, if they were to then have the disease stabilize or regress on the drug being tried.
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- February 12, 2014 at 11:13 pm
She went long with the trial until it became very obvious that she was not receiving any benefit from the treatment in the arm she was in and would die as a result.
This Lady is in Canada. These people followed the Canadian rules for getting the actual drug, The approving authority was not the one preventing the lady from geting the treatment, The pharmcutical company is who refused to allow her access to the treatment.
It would appear to me to be a plus for the pharmacuticaal company, for someone whose disease prgressed on the standard, if they were to then have the disease stabilize or regress on the drug being tried.
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