In some cases it can take more than 6 months to get approved with a DMT. Would running a short (3 - 6 months) study against placebo with the safeguards you suggest jeopardise patient health and outcomes that much?
Sure for phase 3 and longer term studies it's a different matter but for short term studies? As you say, a blanket ban on placebo studies will force drug development to grind to a halt.
As a PWMS who is currently assessing my options for restarting a DMT after a recent relapse, I am seriously considering joining the Vidofludimus phase 3 trial despite having to travel from Wales to Sheffield. I think that, in this case, the drug sounds so interesting and promising that it may be worth taking the risk on the placebo phase. (I haven't been on a DMT for the last 5 years anyway.) After the placebo period I presume I would be entitled to the actual drug for the 8 year open label extension period, and before it is available generally.
However, I am still waiting to hear back whether this will actually be possible, and the details of the agreement I'd be entering into. I'd have thought it would be ethical to give me the choice of doing this? (Although the idea of switching straight to the actual drug in the case of a relapse would clearly be preferable.)
Personally, I think this is exciting, and no, I don’t think it is unethical. If a patient enters a trial (and I do not believe a limited 6 month trial is breathtakingly dangerous) with full knowledge, understanding and consent, this could benefit myriad pwMS. If it benefits the smouldering, that would be amazing. With protections built in should critical issues arise, I just do not see such trials as unethical. The potential benefits outweigh the risks, particularly if, again, the study is structured to monitor any crises that should arise in placebo arm. Just my two cents.
1st point is that drugs on trial are usually pitted against older low efficacy drugs. Is that non more unethical than using a placebo arm.
2ndly, using placebos is arguably not even generally a cross the board unhelpful/ineffective given. A not-insignificant number defy the odds and do well off dmts altogether (even if this is a minority it's still worth considering.
3rdly, concerning the use of steroids in infusions is a possible confounder in that it is a performance enhancer which I think would be banned in pro sports due to equanimity...
Lastly I am not sure asking us pwMS is east to argue as either the right or wrong choice. Perspectives vary and vary for various reasons! Also, I believe it is NOT
Unethical to change our ethics OVER TIME and as years of research advance.
Children learn quicker for many biogical reasons, but also because they far less afraid of being wrong!
"How should help decide on whether or not a placebo-controlled phase 2 MS trial is unethical?" I think the "How" in this survey question should say "Who"?
That nitpicking apart, I feel the PwMS should decide whether or not they want to participate in a trial. 3-6 months of possibly not being on a DMT doesn't seem like a big deal to me. I live in Canada and have access to all the things, however time being the variable that slows that down. I've waited up to a year to get a neuro appt, MRI, start/switch to a new DMT, so 3-6 months seems like nothing to me. I would participate in trial, but I'm too old now (57) to be considered for one, even if I wanted to participate.
The best trials are head to head. You either get a dominant treatment, an ICER or really good evidence that the new treatment is not as good as the existing treatment. The difficulty is convincing pharma to allow you to potentially prove that a new treatment dominates the drug that they have spent money on developing. This is why older off patent (less effective) meds are usually used in head to head research.
Typically how many people take part in a phase 2 trial?
Of these how many will be on placebo?
You said people who partake in trials do better longer term. Does this apply to phase 2 trials or only to phase 3? ( if phase 2, wow! Really makes the point time in brain and even 6 months of intensive monitoring can make a difference. This then raises so many other ethical questions about standards of treatment in MS)
Is this drug available for other diseases already or is it a novel drug?
I think this is an incredibly difficult question. At least for me, really. For the old timers perhaps dealing with smoldering, it is much different than a newly diagnosed. The latter, most of them, are incapable of making significantly fine distinctions in their decisions at first. Too soon and not enough experience, you can’t really expect otherwise. Part of the disease is uncertainty and confusion, unlike most other illnesses. It is a major component.
In my humble opinion, at the Selfie, we are in the top 25% of rational informed decision makers about our own illness. The next 50% can be seen, for example, on Reddit, who follow peer pressure, gossip, miracle cures, unsubstantiated rumor and the like, although it seems a majority are being treated there. The lower 25% can’t effectively deal with MS themselves and wait until too late and never really know what to make of it. Those are the people who need to be protected. The available pool of subjects for the study of this disease is skewed by the misinformed and un-motivated. I don’t think we are aware of just how much this is true and what kind of difference this can make. My opinion.
In some cases it can take more than 6 months to get approved with a DMT. Would running a short (3 - 6 months) study against placebo with the safeguards you suggest jeopardise patient health and outcomes that much?
Sure for phase 3 and longer term studies it's a different matter but for short term studies? As you say, a blanket ban on placebo studies will force drug development to grind to a halt.
As a PWMS who is currently assessing my options for restarting a DMT after a recent relapse, I am seriously considering joining the Vidofludimus phase 3 trial despite having to travel from Wales to Sheffield. I think that, in this case, the drug sounds so interesting and promising that it may be worth taking the risk on the placebo phase. (I haven't been on a DMT for the last 5 years anyway.) After the placebo period I presume I would be entitled to the actual drug for the 8 year open label extension period, and before it is available generally.
However, I am still waiting to hear back whether this will actually be possible, and the details of the agreement I'd be entering into. I'd have thought it would be ethical to give me the choice of doing this? (Although the idea of switching straight to the actual drug in the case of a relapse would clearly be preferable.)
As with all things MS, information and education is absolutely critical to enable pwms to make their own informed decisions.
The ethicality should be determined by pwms as much if not more so than HCP's.
I'm a tad tired of governments, and by association areas of public services, telling us what is good for us without ever asking.
HCP's in general do a fantastic job but give me the information and I'll tell you what's best for me, not the other way around!!
Personally, I think this is exciting, and no, I don’t think it is unethical. If a patient enters a trial (and I do not believe a limited 6 month trial is breathtakingly dangerous) with full knowledge, understanding and consent, this could benefit myriad pwMS. If it benefits the smouldering, that would be amazing. With protections built in should critical issues arise, I just do not see such trials as unethical. The potential benefits outweigh the risks, particularly if, again, the study is structured to monitor any crises that should arise in placebo arm. Just my two cents.
1st point is that drugs on trial are usually pitted against older low efficacy drugs. Is that non more unethical than using a placebo arm.
2ndly, using placebos is arguably not even generally a cross the board unhelpful/ineffective given. A not-insignificant number defy the odds and do well off dmts altogether (even if this is a minority it's still worth considering.
3rdly, concerning the use of steroids in infusions is a possible confounder in that it is a performance enhancer which I think would be banned in pro sports due to equanimity...
Lastly I am not sure asking us pwMS is east to argue as either the right or wrong choice. Perspectives vary and vary for various reasons! Also, I believe it is NOT
Unethical to change our ethics OVER TIME and as years of research advance.
Children learn quicker for many biogical reasons, but also because they far less afraid of being wrong!
"How should help decide on whether or not a placebo-controlled phase 2 MS trial is unethical?" I think the "How" in this survey question should say "Who"?
That nitpicking apart, I feel the PwMS should decide whether or not they want to participate in a trial. 3-6 months of possibly not being on a DMT doesn't seem like a big deal to me. I live in Canada and have access to all the things, however time being the variable that slows that down. I've waited up to a year to get a neuro appt, MRI, start/switch to a new DMT, so 3-6 months seems like nothing to me. I would participate in trial, but I'm too old now (57) to be considered for one, even if I wanted to participate.
The best trials are head to head. You either get a dominant treatment, an ICER or really good evidence that the new treatment is not as good as the existing treatment. The difficulty is convincing pharma to allow you to potentially prove that a new treatment dominates the drug that they have spent money on developing. This is why older off patent (less effective) meds are usually used in head to head research.
Typically how many people take part in a phase 2 trial?
Of these how many will be on placebo?
You said people who partake in trials do better longer term. Does this apply to phase 2 trials or only to phase 3? ( if phase 2, wow! Really makes the point time in brain and even 6 months of intensive monitoring can make a difference. This then raises so many other ethical questions about standards of treatment in MS)
Is this drug available for other diseases already or is it a novel drug?
The ethics of placebo-controlled trials aside, I wonder if this would be useful for people who have done IRT, but then have a relapse.
Somewhat related: does vidofludimus or teriflunomide have any effect on the TLR4/MyD88 pathway? Have TLR4 inhibitors ever been considered in MS?
I think this is an incredibly difficult question. At least for me, really. For the old timers perhaps dealing with smoldering, it is much different than a newly diagnosed. The latter, most of them, are incapable of making significantly fine distinctions in their decisions at first. Too soon and not enough experience, you can’t really expect otherwise. Part of the disease is uncertainty and confusion, unlike most other illnesses. It is a major component.
In my humble opinion, at the Selfie, we are in the top 25% of rational informed decision makers about our own illness. The next 50% can be seen, for example, on Reddit, who follow peer pressure, gossip, miracle cures, unsubstantiated rumor and the like, although it seems a majority are being treated there. The lower 25% can’t effectively deal with MS themselves and wait until too late and never really know what to make of it. Those are the people who need to be protected. The available pool of subjects for the study of this disease is skewed by the misinformed and un-motivated. I don’t think we are aware of just how much this is true and what kind of difference this can make. My opinion.
What about people who on diagnosis do not meet the criteria for a DMT? Could they not be given a chance to participate in trails?