Saline infusions

[Milo]

Maybe run them all in at the same rate for the first minute then slow the smaller doses down invisibly with a programmed pump

Having worked in nursing for decades, the infusion pumps make noise that are noisier when they go faster. Also, a rate of 150 ml/ hr would be felt by the patient compared to a 20 ml per hour, in terms of pressure and feeling cold up the arm. 20 ml per hour is known as KVO (keep vein open). Moreover the pump usually displays the rate of infusion, and it is usually near the patient. There would need to be a screen between the pump, the IV bag and perhaps consider temperature of the IV solution. Cold liquid could cause vasoconstriction and in my case being a little cold always help my POTS and capacity to remain upright.

Just some thoughts. I am sure @MelbME has it all covered

Edit: I also have Raynauds

 

[MelbME]

Having worked in nursing for decades, the infusion pumps make noise that are noisier when they go faster. Also, a rate of 150 ml/ hr would be felt by the patient compared to a 20 ml per hour, in terms of pressure and feeling cold up the arm. 20 ml per hour is known as KVO (keep vein open). Moreover the pump usually displays the rate of infusion, and it is usually near the patient. There would need to be a screen between the pump, the IV bag and perhaps consider temperature of the IV solution. Cold liquid could cause vasoconstriction and in my case being a little cold always help my POTS and capacity to remain upright.

Just some thoughts. I am sure @MelbME has it all covered

Always appreciate input like this. Thank you

 

[Jonathan Edwards]

What do you think happened with the Rituximab trial? Went from 67% responding in Fukuda patients to 26% responding in CCC patients. Was it just the definition difference? Why do you think placebo (35%) was better than Rituximab in the phase 3?

Oystein Fluge let me go through the detailed kinetics of all the data from extended phase II. I forget the details now but everything I saw in all those trials was consistent with nobody responding to drug as such - just a combination of expectation effects and chance.

The initial phase II study showed no significant effect at the primary endpoint. The reason for going to phase III was that the six month endpoint data would have been significant if chosen as primary endpoint. I had pointed out in PLOS One comments that six months should have been chosen for primary endpoint because that is when the effect of rituximab is maximal in autoimmune diseases. That meant that it was worth checking that the six month data are not a fluke. As it turned out they must have been a fluke. My confidence in getting a positive result went down a lot when looking at the detailed kinetics because there was no interpretable pattern in the blinded data. For diseases where rituximab works the kinetics are elegantly consistent, even if with some variation in parameters.

The most striking message from the rituximab studies is that people with ME/CFS who get recruited to trials of this sort quite often show major improvement. Moreover, when the treatment is open it looks like a true placebo response from expectation. I don't think you can relate it to a physiological effect of saline. The kinetics indicate an expectation bias. So blinding is crucial.

 

[Jonathan Edwards]

Having worked in nursing for decades, the infusion pumps make noise that are noisier when they go faster.

My very recent experience is of a pump hidden in a box that is completely silent, but they may be pricy!

I think the main problem with blinding is that those receiving 500ml will be desperate for a pee within half an hour.

 

[FMMM1]

"I think the main problem with blinding is that those receiving 500ml will be desperate for a pee within half an hour." --- laughing!

 

[Kitty]

If any of them are ladies my age, showing them a glass of water is enough to make them desperate for a pee!

But seriously, are there problems with giving participants some information, e.g. that the trial includes exploring what the optimum dose (most effective, least uncomfortable) might be? To an experienced eye there might be obvious problems with that, but I genuinely don't know.

 

[Jonathan Edwards]

But seriously, are there problems with giving participants some information, e.g. that the trial includes exploring what the optimum dose (most effective, least uncomfortable) might be?

Dose ranging studies are very standard in the pharmaceutical area. At some stage they are required, to optimise dose. I am not sure what legal requirements are but as an ethics committee member my memory is that as long as patients/subjects are given reasonably sufficient information to make an informed choice about being in a trial the precise details are not always necessary.

Subjects should be told that the trial included dummy treatments and a range of doses. Mentioning a range of doses may have the advantage that subjects do not try too hard to guess whether they had the treatment or not. It would be impossible to try to work out which dose one had.

 

[Kitty]

Mentioning a range of doses may have the advantage that subjects do not try too hard to guess whether they had the treatment or not.

Thanks, that was what I was thinking. If people are told this, any who have enough experience to be aware they'd only received a smallish dose might be less inclined to question it or base expectations on it. Similarly, any who spent the next two hours wearing out the carpet leading to the bathroom might assume it was connected to a comfort/acceptability aspect.