Statistical challenges of investigating a disease with a complex diagnosis, 2021, Nacul et al

View ORCID ProfileJoao Torrado Malato, View ORCID ProfileLuis Graca, View ORCID ProfileLuis Nacul, View ORCID ProfileEliana Mattos Lacerda, View ORCID ProfileNuno Sepulveda

Preprint
Abstract
Given the absence of a disease-specific biomarker, there are more than 20 symptoms-based case definitions of myalgic encephalomyelitis/chronic fatigue syndrome. As a consequence, the diagnosis for a given patient could vary from one case definition to another. In this context, we analyse data from a biobank dedicated to this disease in order to study the agreement between different case definitions, the similarity between symptom's profile among all participants including healthy controls and patients with multiple sclerosis. We also investigate the impact of patients' misclassification on a hypothetical association analysis using data simulation.

https://www.medrxiv.org/content/10.1101/2021.03.19.21253905v2

 

Malato et al said

"Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease whose patients manifest unexplained fatigue lasting for more than six months (Fukuda et al., 1994) or suffer from post-exertional malaise that is not alleviated by rest (Carruthers et al., 2003)."

Well that doesn't inspire confidence in me that they know what they are looking at.


"There were 269 (97.8%), 233 (84.7%), 229 (83.3%) and 213 (77.5%) out of 275 suspected cases whose symptoms agreed with CDC-1994, IOM-2005, CCC-2003, and ICC-2011, respectively (Table 1). This finding suggests that the general practitioners who referred the suspected cases to a possible integration in the biobank made their diagnosis based on the CDC-1994."

Or that, as is far more likely, they use the NICE criteria.


"There were also three individuals whose symptoms agreed with ICC-2011 only, IOM-2005 only, or both criteria. These individuals were considered to be fatigued but non-ME/CFS patients given that they did not agree with either the CDC-1994 or the CCC-2003 as recommended for ME/CFS research (Pheby et al., 2020)."

Hmm. This seems more than unlikely to me. And I definitely disagree with Fukuda being used for research.


"In summary, our analysis showed that suspected cases of ME/CFS from the UKMEB did not fully agree with four main case definitions of the disease. In addition, some of these suspected cases showed symptom’s severity profiles similar to healthy controls and patients with multiple sclerosis. These findings demonstrated the difficulty of diagnosing ME/CFS based on symptoms’ assessment alone."

Well, if you use NICE and Fukuda then yes, you will get people resembling healthy controls. And as to MS, mis-diagnosis and comorbidity is a thing.

 

We already knew that something like 46% of patients referred to specialist CFS clinics were misdiagnosed.

That doesn't include people with ME who were referred to other specialities because they were misdiagnosed with something else. To psychiatry for depression or neurology for suspected MS. Faced with disbelief or ridicule, or saddled with an unfalsifiable diagnosis such as depression many of these patients will simply get tired of being gaslit and abused and disappear from.the system.

Applying statistics to the problem when the validity of your data is so obviously cr@p is, as they say, like polishing the metaphorical t**d.

 

All in all, I found the percentages of patients who met each of the case definitions to be quite high. I suspected the problem would be much bigger!

 

I think the clinics use a pick and mix approach. One of the BACME guides said something like, 'We use NICE 2007 but also Fukuda'. So it makes sense that referrals would meet Fukuda criteria.

 

What would be the likelihood of a misdiagnosis in the early years of ‘supposedly ME’ compared to a long timer? It would make sense to me that there is a higher likelihood of a misdiagnosis early on, or people developing other illnesses, and basically giving the patient a ME ‘placeholder’ diagnosis.

(Note: i didn’t read the paper)

 

From my own personal experience I would say high.

I fit the criteria for ME and had the diagnosis confirmed by more than one specialist and yet, I have also been told I shouldn't have the diagnosis because i also suffer from a couple of rule out comorbidities.

I have met people who told me they had ME and were diagnosed by a doctor. However, as long as they took anti depressants, they were fine & could lead a normal life, teach aerobics etc.

Then there's the people who have a history of depression.who develop extra symptoms that's put down to primary depression but the new symptoms are suspiciously like ME.

It's a bit of a mess.

 

I was diagnosed by an ME doctor as 'atypical' ME. I was in a support group and he didn't give a dx of ME to around 80% of the group. He told them that he didn't know what was wrong and couldn't help them.

 

I am not sure that being diagnosed by a doctor means much for most of us with ME as very few doctors know enough about it and those who do are too ill to work!

 

IOM report was produced in 2015.

My GP diagnosed me in 2009. She did not know anything about ME. She didn’t know about the various symptoms other than the dreaded fatigue, nor she would know of any diagnostic criteria. However as clever as i am i did not want to rot under her care. I got my diagnosis confirmed by no less than 3 well known ME experts. The lack of specialist care for ME is a tragedy.

Edit to add: i am rotting under her care.