Protocol Serial Paediatrics Omics Tracking in [ME] (SPOT-ME): protocol paper for a multidisciplinary, observational study..., 2024, Armstrong+

[Hutan]

@MelbME, @Nightsong has posted copies of the BASC-3 PRS survey on the BASC-3 thread. It is pretty obvious that a child with ME/CFS would score very highly on the somatisation scale, as would any child with a debilitating chronic illness.

What has taken me aback a bit is that I recognise some of the questions. So, actually my son's and my experience with the neuropsychology of Royal Children's unfortunately seems to be very relevant.

My son took part in a study run by Sarah Knight (who I believe is heading up the neuropsych arm of your study) some years ago and he and I were given surveys to fill out. I think part of the survey I was given was the BASC PRS - I recall the question 'do they chew or smoke tobacco'. There were other odd questions that aren't in the BASC PRS including 'are they afraid of spiders?'. Presumably those questions were part of a survey to assess anxiety.

The reason that I am telling you this is that at no point were my son and I told that these questions were to assess psychopathology including somatisation. At the time, unaware of the purpose of the survey, I actually made a complaint to Sarah, saying that many of the questions were inappropriate and irrelevant. She said that it was all fine and that I could complain to the Royal Children's Ethics person about it if I wanted to. I did, but was told it was all fine, 'these are just standard surveys'. Still, no one told me that the researchers were assessing psychopathology. I can probably find the emails if I look.

Needless to say, even though the surveys were carefully completed, my son was not invited on to the rest of the study. I cannot recall any paper being published reporting the results of the survey from that study. I don't think we were sent a copy of any resulting paper. I have no idea if the results of the survey, with the scores from the BASC were sent on to my son's GP.

I think there is quite a bit that is of concern here, specifically about the neuropsychologists working with children with ME/CFS in Melbourne. I will be surprised if things have improved in the nearly ten years since this happened.

If I get some spare time, I will follow up with Sarah Knight again.

 

[Peter T]

It is a concern that such questionnaires have not been evaluated in relation to ill or disabled populations, and that their design means they do not reliably distinguish between psycho pathological responses in the physically well and rational or even positively adaptive responses in the ill or physically disabled. Certainly in relation to their use in relation to ME/CFS it is even more concerning that so many researchers seem unaware of their limitations when used with this population.

Historically their use with ME/CFS reflects an unevidenced belief that the condition results from or is sustained by false cognitions, and reflects researchers failing to recognise confirmation bias. So not only have they been of dubious scientific value in this context, but they have been misused to justify ineffective and potentially harmful interventions.

I don’t know the rationale for their use in this context, but any researchers wanting to use them needs a clear justification and to demonstrate how they plan to overcome their problematic nature when used with the ME/CFS population. Historically as others have said there have been problems with the issue of informed consent in this context.

Increasingly I feel at our current level of understanding whether any researchers wanting to involving children with ME/CFS is appropriate and certainly that we should not be engaging with pyschobehavioural investigations involving children with ME/CFS, until we can guarantee that the historical harms inflicted on this population will be avoided.

 

[rvallee]

I don't think that is true. There are still doctors trotting out 'stress' as a cause; I think that has been documented on the forum. There are still doctors pointing to psychosocial causes in multiple sclerosis. People generally love to say that people suffering misfortune have brought it on themselves due to their wrong behaviour and wrong personality, so that they can feel safer. Sometimes, these ideas might even have a grain of truth - perhaps surges of adrenalin do play some part in peptic ulcers, or the behaviour of smoking may increase the impact of the HP infection?

I'm sure there are physicians still clinging to their preferred version of reality, but I meant in the research. I haven't seen a single mention of peptic ulcers in the hundreds of papers and studies posted on the forum. Everything has instead moved towards 'functional' GI problems, which peptic ulcers 100% would be included in if it hadn't been for the work of a small team.

Although of course there is the whole 'functional overlay' nonsense where anything can be included, but that's just because they made the set of their things so large that literally everything fits in them by default, and only remains in there until 'innocence can be proven'.

 

[Amw66]

@MelbME, did you have any comments on the lack of evidence for cortisol being a problem in ME/CFS?

I think the plain language summary rather glosses over the significant use of surveys to gather information about the psychological status of the young people in this project. We've said it before, psychological information seems so often to be the tax that has to be paid in order to get decent biological studies. This study is no exception.

These are some of the the surveys that the protocol says will be applied.




Re HADS and it having been recommended as a mood screening tool in ME/CFS: Reference 42 is
Deale A, Husain K, Chalder T, et al. 2001, Long-term outcome of cognitive behavior therapy versus relaxation therapy for chronic fatigue syndrome: a 5-year follow-up study.
That's hardly a reliable recommendation. It's easy to think that these surveys are a lot more scientific than they actually are. MelbME, if you haven't already, please do the surveys yourself, imagining that you are a young person with ME/CFS.

Have a look at this thread on HADS
The Hospital Anxiety and Depression Scale (HADS) - a discussion
Towards the end of that thread, there are links to a number of papers that found that HADS is not suitable in chronic disease and specifically not in ME/CFS.

I don't think we have discussion threads on the other two surveys yet.

The results from flawed surveys have the potential to do a lot of harm. They have been used to cause harm. I really hope that your patient advisory panel are monitoring issues related to the use of these surveys closely and that they will be given the chance to scrutinise anything planned to be published about the results.

HADS isn't appropriate for chronic illness full stop .

 

[Utsikt]

@MelbME

Have you read all of the questions in BASC-3 as a part of the preparations for this study?

 

[Trish]

@MelbME

Have you read all of the questions in BASC-3 as a part of the preparations for this study?

I think it's unlikely a biochemist would normally be expected to study and comment on the details of the part of a joint study that is so far outside their field. Though this can be a learning experience about which sort of team to work with in future, and what questions to ask and seek advice about.

 

[Utsikt]

I think it's unlikely a biochemist would normally be expected to study and comment on the details of the part of a joint study that is so far outside their field.

I don’t view the questions as details - they are at the core of that part of the research.

Not wanting to over rule the «experts» sounds like an excuse to not check on the work or to not speak up. I know it comes at a personal cost to intervene, but we can’t just accept bad research practices because they are common. And we’re dealing with children - which ups the responsibilities.

I have no doubt in the sincere intention to help push ME/CFS research forward, and I’m gratefull for that. But it’s still a very unfortunate situation.

 

[Utsikt]

Using scales is important in this line of work, any time we moved from standard scales we were pulled up by ethics. They are very rigorous and careful with what you present to children in question form, so they stick to standards.

I don’t follow the logic of ethics here. Standard does not automatically equal safe, appropriate or ethical. The ethics should be assessed on a case-by-case basis.

I can understand that one would argue that non-standard is not ethical because it hasn’t been tested, but that does not make the standard ethical. IMHO, the only ethical thing in this case is to disallow any questionaire due to the issues outlined in this thread.

We should not allow bad neuropsych research just because they don’t have better alternatives. The best bad option is still bad.

 

[Trish]

People with ME/CFS have been plagued by so called ethical use of completely inappropriate questionnaires for decades. It seems all it takes to 'validate' a questionnaire is to dream up some questions, get some people to fill them in, run the data through some stats packages and publish them. No matter what harmful conclusions get drawn from applying them to sick people.
I think our argument here is with the neuropsych people not with @MelbME.

 

[bobbler]

People with ME/CFS have been plagued by so called ethical use of completely inappropriate questionnaires for decades. It seems all it takes to 'validate' a questionnaire is to dream up some questions, get some people to fill them in, run the data through some stats packages and publish them. No matter what harmful conclusions get drawn from applying them to sick people.
I think our argument here is with the neuropsych people not with @MelbME.

And if there is a gate keeping issue going on

 

[Utsikt]

I think our argument here is with the neuropsych people not with @MelbME.

For the most part, yes. But its unfortunate if his(?) project enables harmfull research from others.

 

[dave30th]

It is often understood in medicine to mean that psychological factors are contributing to the disease.

This might vary from country to country? I'm not aware in the U.S. that "complex" in this context often means "psychological factors" or something parallel to "biopsychosocial" (in UK--biopsychosocial is used differently by clinicians I know in US and not in the limited UK BPS manner).
Who is using "complex" to mean psychological factors?

 

[MelbME]

Hi @MelbME. Thank you for your continuing engagement here and your willingness to listen to criticism and suggestions. All too rare among researchers, we find.

Have I got this right? As a non clinician, the only way you could access a cohort of child patients for your omics study was through a group of clinicians who diagnose and treat children with ME/CFS. In order for them to agree to be involved in the study and recruit patients for you, they decided they would do some research of their own using questionnaires.

You are therefore stuck with your cohort of participants being concurrently researched on omics and on psychobehavioural factors.

My question is, do you, in order to fulfil your ethically approved protocol, have to include analysis of the psychobehavioural questionnaires alongside the omics data? Or can you simply ignore the questionnaire data and publish an omics paper?

To me it seems infinitely preferable that you publish the omics data without contaminating it with doubtless spurious associations with psychobehavioural stuff.

Yes that's about right.

The plan is that omics work will be published independently. There is potential to combine for a later paper if someone has the interest/time. The project recruitment itself was delayed considerably by COVID lockdowns, timeline is blown out.

 

[MelbME]

Are the scales calibrated or verified with regards to the unique characteristics of PEM? There’s a reason FUNCAP was created - PEM does not fit with most models of how disease and the body works.



This is not very encouraging. The research standards for both the neuro and psych fields are rather poor, and I can’t imagine that it gets any better if you combine them.

Are the scales «good enough» for proper research, or are they just «what people use». The latter does not guarantee the former. Neither does an ethics clearance. You have an independent responsibility to ensure that any measurement tool in your study is good enough, that can’t be outsourced.



Data can have bias that was introduced during the measuring phase. The tools that collect the data can also have bias. Data isn’t some infallible our neutral thing - it’s quite the opposite.

FUNCAP was not published at the time we began recruiting for this study unfortunately. Would have liked that to be part of this, it's in all our more recently started projects.

We typically look for best available scales. At the time the best for ME specifically was the DSQ.

 

[Utsikt]

Thank you for taking the time!

We typically look for best available scales. At the time the best for ME specifically was the DSQ.

Great to see that FUNCAP is becoming more if a standard. Can’t expect you to use it before it came out.

This is where I end up asking if the DSQ is actually good enough, despite being the best option? The question is probably more like: did you need a scale or could you have done the study without it?

The plan is that omics work will be published independently.

Very good!

 

[MelbME]

The bigger problem is that they can't be reliably identified, so we can never know what is actually happening. There are no tests or markers for either, they are at the very best a guess. When the standard description of anxiety is worrying about outcomes, but then it's been turned into having symptoms of sympathetic arousal resembling stress, or whatever, and people routinely get labeled with either or both after infectious diseases or other causes where the whole process isn't understood. They are generically valid concepts, but for individual cases they are far less accurate and valid than even a chronic fatigue description. The state of knowledge is comparable to medicine's knowledge of autoimmune diseases in the 17th century. At least I haven't seen anything better than this.

Definitely. None of this relates to my experience in any way, and the confusion I described above, along with the decades of miserable failure, means I want absolutely no research dealing with this stuff. Ever. It's simply not useful and never will be, because no one knows what these things are or can differentiate them.

Most likely most cases have a physical cause that can be identified with more advanced technology, but that's about as useful as sending a radio signal to someone who knows nothing about electromagnetic radiation, antennas or anything related to electrical circuits, and definitely doesn't have a radio or anything more complex than using a coconut as a cup. It will be decades before medicine does something useful here, and mostly likely it will be AI that does it. This stuff is just too complex to deal with for now, human nature just gets in the way and no good can come out of it for us.

It would be useful to understand this, but psychosocial questionnaires ain't the way. It just categorically isn't. Most of them are plain weird and reflect deeply disturbing beliefs held by people who clearly struggle to relate to lived experience different than their own.

@MelbME, it would be helpful to know if you have overall responsibility for the combined project, and for ensuring the participants and their families are not harmed by the project. If there are in fact two separate projects, who has responsibility for the neuropsych project?


It would also be very helpful if the patient information sheet (and any other document that prospective participants were given to explain what the project involved) could be posted here.

It seems possible that either the young people or the parents or both did not understand that the parent would be assessing their child using tools for identifying psychopathology, and providing that information to the researchers. And that information would then be passed on to the young person's GP (with or without the parent and the young person being aware of the findings - I'm not clear on that yet). It seems possible to me because I can't imagine signing my child up for the study under those conditions, and I'd be surprised if many parents, especially after having dealt with the stigma of ME/CFS from medical professionals, would do that.

If that is indeed what happened, that participants were not completely informed, I think it would be good if they are told retrospectively, and told that they can participate in the project without participating in the neuropsych evaluation, and were reminded that they can withdraw data.

We as a team are responsible for overseeing the project that it's sticks to the ethically approved protocol, the neuropsychs are responsible for the patients they speak to as part of the study.

I'm not sure if we can share the documents without ethical clearance but can look into it. I will bring up with the team about reminding people they are free to withdraw from trial or specifically withdraw their data from a specific section.

The section I think you had concerns with was filled by the parents and guardians. The children only do cognitive tasks. The report is given to the parent/guardian.

 

[MelbME]

But, we don't know that ME/CFS is complicated, it may be simple, it's just that we don't understand it yet. What specifically is complicated? Wouldn't 'poorly understood' be more accurate if that is what you mean?

What multiple factors are involved in ME/CFS? Do you mean factors relating to onset? What factors are those? I don't think we know those specifically yet. If you mean that there is an interplay between host factors (some of them produced by genetics) and a pathogen trigger, isn't that true of every infectious disease? I don't think we label the common cold 'complex' just because that is true.

Heterogenous - do you mean the presentation is varied? That is certainly true, but even the common cold is expressed differently by different people, but, as I said, I don't think we typically describe the common cold as 'complex'. Or do you mean that among the people diagnosed with ME/CFS there may be subsets of two or more different diseases? That might be true, but we don't know that yet. In any case, 'complex' does not sound like a very useful term to get that across in the meantime. Why not just use 'with a heterogenous presentation'?

'Complex' is a vague word, liable to misinterpretation. It is often understood in medicine to mean that psychological factors are contributing to the disease. Given all that, and the presence of other words that I believe could convey your meaning better, isn't it best that that word is avoided when describing ME/CFS?

Well the ME/CFS cohort is wildly variable. Different triggers, different symptoms, different severities, different co- morbidities, different order of symptom severities. It's defined by broad symptoms and by exclusion of other diseases that explain those symptoms.

I have heard from clinicians about a lot of patients that were diagnosed by ME/CFS but ended up being later diagnosed with a genetic disorder or MS or some other condition. These patients are in our cohorts we study because the diagnosis that defines the disease let's them in. So that's a big part why it's complex.

It could be a simple mechanism but it's unlikely to be because of how it's defined, it's far more likely that it's a complex multi-factor mechanism or multiple different mechanisms with a shared phenotype.

I'm not used to using complex as it pertains to psychology, I'll tone down my use of the word.

 

[MelbME]

On that child's medical notes for life: potentially influencing every subsequent diagnosis and treatment (or lack of it), they ever receive. Without the knowledge of the parents or the child going into adulthood. I find this truly shocking, if I'm understanding that correctly.

No I I think I misrepresented that. A report is made from neurocognitive testing that includes the BASC, the report goes to the parent. The parent then has the option to provide this to their GP.

So it's not a direct transfer to the GP, I realize I miswrote that in a reply to @Hutan who was concerned regarding which clinicians would have access, I was meaning to say that it wouldn't be refereed on to a different clinician.

I have only now caught up with this thread, which raises a whole lot of issues. I guess that the psychobehavioural studies may just reflect the practice of the people looking after the children any way but I do see a very major danger in combining these with omics and ending up with papers that appear to validate concepts like somatisation.

Non-clinical researchers need to be aware just how dumb and interfering clinicians can be in this area. Maybe this will just be a lesson learned. But I would advise against trying to collaborate with anyone who believes in a concept of 'somatisation'. This is the incompetent psychology that has been so damaging for people with ME/CFS.

We won't be validating that concept of somatization but I understand the concerns of simply asking the questions. We will be careful with how we present this work.

 

[MelbME]

@MelbME, @Nightsong has posted copies of the BASC-3 PRS survey on the BASC-3 thread. It is pretty obvious that a child with ME/CFS would score very highly on the somatisation scale, as would any child with a debilitating chronic illness.

What has taken me aback a bit is that I recognise some of the questions. So, actually my son's and my experience with the neuropsychology of Royal Children's unfortunately seems to be very relevant.

My son took part in a study run by Sarah Knight (who I believe is heading up the neuropsych arm of your study) some years ago and he and I were given surveys to fill out. I think part of the survey I was given was the BASC PRS - I recall the question 'do they chew or smoke tobacco'. There were other odd questions that aren't in the BASC PRS including 'are they afraid of spiders?'. Presumably those questions were part of a survey to assess anxiety.

The reason that I am telling you this is that at no point were my son and I told that these questions were to assess psychopathology including somatisation. At the time, unaware of the purpose of the survey, I actually made a complaint to Sarah, saying that many of the questions were inappropriate and irrelevant. She said that it was all fine and that I could complain to the Royal Children's Ethics person about it if I wanted to. I did, but was told it was all fine, 'these are just standard surveys'. Still, no one told me that the researchers were assessing psychopathology. I can probably find the emails if I look.

Needless to say, even though the surveys were carefully completed, my son was not invited on to the rest of the study. I cannot recall any paper being published reporting the results of the survey from that study. I don't think we were sent a copy of any resulting paper. I have no idea if the results of the survey, with the scores from the BASC were sent on to my son's GP.

I think there is quite a bit that is of concern here, specifically about the neuropsychologists working with children with ME/CFS in Melbourne. I will be surprised if things have improved in the nearly ten years since this happened.

If I get some spare time, I will follow up with Sarah Knight again.

Yes we work with Sarah Knight and they are experienced with using these surveys. They publish on MRI work and not on these surveys, my impression is that they don't think the disease is somatization, they think it's to do with neural structures, at least that's their main interest.

The somatisation questions go to the parent/guardian. The patients fill cognitive questionnaires. I don't know if the data go to the GP or if that includes the somatisation questions, the report does have results of the cognitive questions. The parent is the one that gets report and decides if they want to pass it to their GP. That's all I know for sure. But I can clarify.

 

[MelbME]

@MelbME

Have you read all of the questions in BASC-3 as a part of the preparations for this study?

Yes, at least a version of it. It seemed like a typical broad set of questions you see on scales looking to assess mood and behavior. I think the interpretation for any of these answers to mean something serious is a problem though.

It's a tool that can do damage in the wrong hands but can be useful in the right hands. Haven't seen anything of our collaborators to suggest they are the wrong hands.

They are answered by the parent/guardian, not the child.