ME/CFS Alert: Episode 77 - Dr. Derek Enlander

[alex3619]

I think J Edwards means that none of these types of studies are interpretable because they are open-label and use self-report measures, so they can't provide reliable evidence.

With this type of implementation any double blinding would be impossible, but objective outcome measures are very likely. I would be surprised if objective measures were not in the study.

We don't know the severity of problems that patients were experiencing other. They may not have been sufficiently intense or dangerous to warrant the study stopping. I would be suprised, if the information from Enlander is correct, if this were not under regular review.

Stopping a study midway because the outcomes were very undesirable would be almost as good as having a study that showed GET did not work from the point of view of challenging the PACE trial.

 

[Kati]

In the UK or at least my local BMT unit they insist that their patients are no more than a 40 min (perhaps an hour) drive away from the unit (or an outpost unit). They have flats for patients to stay in where this is difficult. They also do a lot of monitoring even as out patients.

One of the things that worried me about some people getting Rituxumab is where people were traveling long distances to get an infusion.

Bone marrow transplant is a different beast, which involves much higher risks, multiple high dose chemo agents and yes, these patients would be required to stay within a certain radius of the center.

Aa for rituximab as a single agent, there are little risks to get discharged home once the infusion is done, with instructions ( what to do in case of fever, chills, itching, etc)

 

[Kati]

I was initially commenting on Kati's comments about chemo therapy being done in a day hospital where they are but with a great deal of care.

But It has got me wondering about what the follow ups that would happen when giving someone with Rituximab. I assume they would still go to regular clinics and see a doctor and have various blood tests at regular intervals? Also access to the clinic via phone if there are new/unusual symptoms? I'm guessing this is important if say the NHS were to roll out Rituximab for ME what would be required in terms of general follow up?

There is very little blood test required after Rituximab. Perhaps a cbc monthly to rule out the very remote risk of becoming neutropenic (it sounds like it happened to a patient or 2 in Norway).

There is a likelihood of getting chills, fever and possibly itching the day or 2 of Rituxan, so patients are recommended to have tylenol and benadryl on hand in case thIs happens at night. In general it is very well tolerated and patients do not have major issues once they return home.

 

[jimells]

There is a likelihood of getting chills, fever and possibly itching the day or 2 of Rituxan,

When I have a day with only symptoms as mild as these, I consider it to be a very good day indeed.

 

[Jonathan Edwards]

I think J Edwards means that none of these types of studies are interpretable because they are open-label and use self-report measures, so they can't provide reliable evidence.

But if Dr Enlander is using some objective measures (e.g. actigraphy or biological tests) then that may be very be helpful evidence. Also, whatever we think of these studies, agencies like IOM, CDC, Cochrane and NICE seem to love them, so the study may be very helpful to present as evidence to any such agency.

I hope the exercise study has a robust methodology, as far as is possible for this type of study, and replicates PACE by using incremental exposure to exercise.

I agree that it would be nice to think that there are objective outcome measures.

What worries me is that this study may 'replicate the PACE trial' in terms of putting out information about results from an arm of treatment, with a value judgment, in the middle of the trial. To indicate that patients in one arm had adverse outcomes before any statistical analysis has been possible is strange. If the finding is thought to be significant then the trial should clearly be halted.

 

[BurnA]

What worries me is that this study may 'replicate the PACE trial' in terms of putting out information about results from an arm of treatment, with a value judgment, in the middle of the trial. To indicate that patients in one arm had adverse outcomes before any statistical analysis has been possible is strange

Do we know at what stage the trial is ? 65% seemed like a precise no. to be throwing out - not the sort of figure you would mention if guessing or going by judgement. Earlier posts suggested this trial may be ongoing for quite a while, if so I would like to think maybe it's nearing or at completion.
If not, then it's very strange.
Also, if he was trying to prove if exercise is beneficial or not you would like to think he was rigourous in the methodology.
There have been so many exercise related trials before that have been 'uninterpretable', to steal a phrase, why would he assume his is going to be conclusive unless absolutely rigourous.

 

[justinreilly]

While the results, if as described above, will be immensely beneficial for the patient community, it seems awful that patients have to be harmed to prove something we already know. I hope they haven't been harmed too much.

If this was a pharmocological trial and 65% of patients were harmed you could imagine the outcry.

Noone should worry about this study hurting patients.

I was in this simple study. I would be surprised if the exercise/activity caused any real harm. It was just two minutes on an exercise bike (some or most of the other patients did the same thing just with their arms instead of their legs- dont know what you'd can that exercise/machine). There was very minimal resistance- I would have laughed at it and said it wasn't a real study bc it wasnt real exercise IF I didn't have ME and know better. The instruction he gave was something along the lines of 'just go at a pace you're comfortable with' (dont remember exactly). It did 'tire me out' at the time and I did have PEM. But getting to his office and waiting there is more tiring/PEM-causing than the actual exercise/activity itself.

I did experience some moderate detriment, but was happy to be in the study.

He has also completed a second, more formal exercise/activity study at Mt. Sinai with blood work, etc., but it has not been written up yet.

 

[justinreilly]

Dr Enlander says @ 20.30 that 65% of participants have been "hindered, if not hurt" after exercise. (He doesn't say 65% were "harmed", unless he discusses it elsewhere in the video and uses different wording.)

This doesn't necessarily mean that 65% deteriorate or report adverse effects when exposed to exercise, but it may mean that any improvements are not as great as the control group. We don't know what it means until published.

@Dolphin, just bringing your attention to this, in case you wanted to know: your opening post says that 65% have been "harmed".

He just means their Karnofsky score went down (to a significant degree, Im assuming). It was just Karnofsky score pre-exertion; one day after and two days after. I assume he would use two control groups- one who came to the office and did not do the exercise/activity and one that did not come to office and also did not do the exercise/activity. Im going to ask them about this last part and try to get back you guys here.

 

[Kati]

He just means their Karnofsky score went down (to a significant degree, Im assuming). It was just Karnofsky score pre-exertion; one day after and two days after. I assume he would use two control groups- one who came to the office and did not do the exercise/activity and one that did not come to office and also did not do the exercise/activity. Im going to ask them about this last part and try to get back you guys here.

It is very difficult to drop Karnowsky one point (technically, 10 points, say from 60 to 50, where one would suddenly requiring assistance for activity of daily living. i have done a few 2 consecutive days CPET and while getting help with meals would be lovely, it did not make me think I needed to hire someone to help me to the toilet. ( I hope I will not go anywhere near that )

Karnowsky still remains in my views a meaningless measure of health status, when other measures like an activity meter can be much more precise in measuring activity. One can drop from 1000 steps a day down to 200 steps a day and still be at 60 on Karnowsky.