Aripiprazole - Abilify

Milo said:
Chances are, these physicians do not have the relevant training and support to conduct clinical trials, for many reasons, including the fact that they never did it before, and they are not necessarily supported by academic institution.
Click to expand...

Correct. I tried to make this same point on a different thread. Plus they are too busy plus there is no incentive for them to conduct trials/publish results.
 
Milo said:
Chances are, these physicians do not have the relevant training and support to conduct clinical trials, for many reasons, including the fact that they never did it before, and they are not necessarily supported by academic institutions.
Click to expand...

So why do they claim to be world beating ME research experts, pray?

All medical students get the training. Beyond that all you need is common sense and being careful. I know because I never had any training beyond what I had at medical school. I set up trials using common sense and consulting with senior colleagues (which was free). Knowing how to do trials properly is also necessary part of keeping up with the literature on your field - so that you can assess the evidence. Anyone who cannot is not entitled to play around with off label drugs.

As long as patients accept this myth that doing trials is too difficult there will be no trials. What's the point in that?
 
Last edited:
Milo said:
we don’t have the money for that. No funding. Clinical trials are very complicated. It would take too long.
Click to expand...
But none of these are reasons for patients not to ask for proper trials to be done. Responsible clinicians who have the patients interest at heart should be open to the idea of proving that the treatments that they give to patients work. They should want to have either the reassurance that they are proved right by a clinical trial or the knowledge that they have been prescribing something that actually doesn't help the patients.
 
Jonathan Edwards said:
As long as patients accept this myth that doing trials is too difficult there will been trials. What's the point in that?
Click to expand...
I am not one who accept this, however i am being perceived as trouble maker by suggesting it is time we get clinical trials. Of course it will take time to set trials, and of course it will need funding. Bureaucracy and push back from the supplier of service (admin) will make this difficult. And i would suspect there is not going to be hard trials such as Abilify until it is well beyond phase 2- if at all.
 
Andy said:
But none of these are reasons for patients not to ask for proper trials to be done. Responsible clinicians who have the patients interest at heart should be open to the idea of proving that the treatments that they give to patients work
Click to expand...

it is difficult @Andy i am not sure i can give much detail here, but i agree with you. My response to Jonathan above explains a bit but it’s complicated.
 
Milo said:
Bureaucracy and push back from the supplier of service (admin) will make this difficult. And i would suspect there is not going to be hard trials such as Abilify until it is well beyond phase 2- if at all.
Click to expand...

I don't understand these points.

If physicians in a service are already using a drug liberally off label the presumably the admin don't really care about ethics and are not going to complain about doing a proper trial. The cost is already going through the system.

I thought that Abilify was licensed for other conditions. So the only phase 2 here is the phase 2 trials we want done. (Phase 1 safety has already been done.) How can the trials be after phase 2 if there are the phase 2?
 
@Jonathan Edwards has pointed out that the rituximab trial was well conducted.

I'd like to see a trial of aripiprazole-abilify in ME; however I wonder though would it only help a sub-group - I assume a well conducted trial would pick that up. The rituximab trial was expensive; however the cost of rituximab (cancer drug) may be much higher than aripiprazole-abilify. We've had one trial, so others are feasible, if someone can come up with the evidence to support a trial and the money to run it.
 
In many ways the best sort of trial is a dose response study. Dose response profiles are much more convincing evidence of efficacy than simple test-control differences. Moreover, dose response trials can be done without there being a group that seems to get no treatment. Bias problems are much less, even with an open study. Aripiprazole has a long half life and comes in at least four dose sizes so a dose response study would be easy to do.

And it would cost NOTHING AT ALL over and above off label usage.
 
Trish said:
Would a dose response study need to blind patients to which dose they were getting?
Click to expand...

Not if nobody knew what they thought was the best dose.
The clever thing about a dose response curve is that it emerges out of the results from lots of different people. Each individual result is clouded by the risk of bias but there is no reason for that bias to produce a predicted curve.
If the information sheet says that the investigators think that 5mg is best and that 2mg is not so good and 10mg will give side effects you will see that appearing as suggested. But if the information sheet says that nobody knows what the relation of effect to dose is or even if it works then you are fine.

Blinding is always bested it is relatively easy to do with pills. However, there tend to be costs associated with production of dummy pills and with random coding of bottles. If I was studying aripiprazole and had no grant funds I would probably do small dose response study open label (but definitely randomised). I would probably get a colleague to do the dispensing and instructions on dosing so that I could assess patients without knowing what they had received (so single blind - blind for assessor but open for patient).
 
Jonathan Edwards said:
If the information sheet says that the investigators think that 5mg is best and that 2mg is not so good and 10mg will give side effects you will see that appearing as suggested. But if the information sheet says that nobody knows what the relation of effect to dose is or even if it works then you are fine.
Click to expand...
I understand that, but in the real situation now, lots of patients are discussing in various places online which dose works best for them. If that patient discussion reaches some sort of consensus before the dose response trial, that could influence the results if the patients know which dose they are getting.
 
Jonathan Edwards said:
In many ways the best sort of trial is a dose response study. Dose response profiles are much more convincing evidence of efficacy than simple test-control differences. Moreover, dose response trials can be done without there being a group that seems to get no treatment. Bias problems are much less, even with an open study. Aripiprazole has a long half life and comes in at least four dose sizes so a dose response study would be easy to do.

And it would cost NOTHING AT ALL over and above off label usage.
Click to expand...

If e.g. there are particular problems/barriers in the US, then another option would be to do this in the EU, UK ----. In fact, Ron Tompkins (OMF Stanford), highlighted that they would be working with researchers in the UK to (among other things) get around issue of taking muscle biopsy's, from healthy people (controls) this is basically not possible in the US.
 
FMMM1 said:
If e.g. there are particular problems/barriers in the US, then another option would be to do this in the EU, UK ----. In fact, Ron Tompkins (OMF Stanford), highlighted that they would be working with researchers in the UK to (among other things) get around issue of taking muscle biopsy's, from healthy people (controls) this is basically not possible in the US.
Click to expand...

I don't actually think you should get muscle biopsies from healthy people. It is very painful and likely to leave scar if an adequate sample is taken. I alsodonot see why it is any different here from the US. Itmay beard total biopsies in a private clinic but then you have to ask why it is hard and why it should be any easier anywhere else. These things are usually easier where there is some sort of coercion going on - like getting junior members of staff to volunteer.
 
Jonathan Edwards said:
I don't actually think you should get muscle biopsies from healthy people. It is very painful and likely to leave scar if an adequate sample is taken. I alsodonot see why it is any different here from the US. Itmay beard total biopsies in a private clinic but then you have to ask why it is hard and why it should be any easier anywhere else. These things are usually easier where there is some sort of coercion going on - like getting junior members of staff to volunteer.
Click to expand...

I assume this is the OMF/UK muscle research link
Paul Greenhaff, PhD, Professor of Muscle Metabolism, University of Nottingham
https://www.s4me.info/threads/omf-m...esearch-center-at-harvard-funded-by-omf.6128/
 
Jonathan Edwards said:
Not if nobody knew what they thought was the best dose.
The clever thing about a dose response curve is that it emerges out of the results from lots of different people. Each individual result is clouded by the risk of bias but there is no reason for that bias to produce a predicted curve.
If the information sheet says that the investigators think that 5mg is best and that 2mg is not so good and 10mg will give side effects you will see that appearing as suggested. But if the information sheet says that nobody knows what the relation of effect to dose is or even if it works then you are fine.

Blinding is always bested it is relatively easy to do with pills. However, there tend to be costs associated with production of dummy pills and with random coding of bottles. If I was studying aripiprazole and had no grant funds I would probably do small dose response study open label (but definitely randomised). I would probably get a colleague to do the dispensing and instructions on dosing so that I could assess patients without knowing what they had received (so single blind - blind for assessor but open for patient).
Click to expand...

When you put it like that, it appears to be relatively easy. However, possibly the problem is getting a proposed study through an ethics committee - which potentially suggests lack of evidence of efficacy @Sid
 
Milo said:
Here’s the answer you’d get: “we don’t have the money for that. No funding. Clinical trials are very complicated. It would take too long.” Chances are, these physicians do not have the relevant training and support to conduct clinical trials, for many reasons, including the fact that they never did it before, and they are not necessarily supported by academic institutions. And that explains why so many drugs are offered off-label.
Click to expand...

Yes, I think doctors feel even less incentive to do a proper trial when the treatment in question is already generic (affordable) and they can easily prescribe off-label. Patients don’t push for proper trials in this case because they don’t have to wait many years and can do a trial of n=1. I, like many, have done that, like when I took Valcyte.
 
Last edited:
I remember thinking a while ago that if there’s a drug that gets Whitney better.. that’s the one I would try. I’m not keen on trying many new things but I am interested in looking into this more. Even though I feel scared about the side effects. Seeing the effect on people with Very Severe ME in particular (I’ve heard other stories too, not just Whitney), is what is making me wonder. I don’t want to get worse because of a drug. I know it’s not been tested and gone through any trials yet. I wish it had been. I would be so happy for something that would make me better, and even reduce my sensory sensitivities - that in itself would be like something out of a dream.
 
Last edited:
You must log in or register to reply here.
Back
Top Bottom