Most of the evidence relating to biomarkers would have been excluded according to the rules of evidence. I don't think many appreciate the issues with evidence based medicine, or why I considered the IOM report premature by some years. In the video Nancy Klimas said the evidence at the time would not have changed their conclusions. She also said that current evidence might have.
Evidence based approaches are good when excessive bias is minimized, and when a field of research is mature. CFS research is not mature - lack of funding, lack of replication studies, widespread denial of grants, these prevent the research published from reaching "evidence based" standards. Yet that is in itself a denial of the principles of evidence based medicine. Evidence based medicine is about use the best available evidence. Its not about using a truncated set of evidence, though ranking of evidence occurs. If the best evidence that exists is just a few case studies, that is what you have.
This idea that "RCTs good, everthing else bad" distorts how the information is being processed. Even RCTs are often wrong, and the error rate may be much higher than most expect. Similarly meta-studies risk amalgamating poor studies into larger analyses, reinforcing systematic bias. On the other hand even case series studies have good value if the effect sizes and outcomes are very clear.
There is a well established principle that good studies with large effect sizes can have their evidence ranking upgraded. Similarly a study can have its evidence ranking downgraded, and this may mean that particular RCTs are considered to be far less then the gold standard. Sadly in typical reviews and metastudies this adjustment of ranking does not occur. Nobody has the time or the resources.
To be clear, for clinical trials (and not other types of studies) an RCT is not gold standard either. To be ideal it must be both double blinded and placebo controlled, not merely having a comparison group. It should have other sources of bias minimized, the effect sizes should be large, and the primary data should be on objective observations.
For the record, the RCTs used in psychogenic theorizing about CFS, that is the use of CBT/GET, are not double blinded. They are not placebo controlled. They are from an insular group that ignores other data. The effect sizes are tiny. The primary outcome measure are subjective. When you look at studies that try to become more rigorous from using objective measures then typically the results are much worse, and can even look like CBT/GET is detrimental to patients. It is NOT gold standard. As I described in one of my blogs, the best label might be "lead standard", and then they pretend to turn lead into gold. Modern day alchemy.
In five or ten years a report like that done for the IOM might be appropriate if research continues to make the gains we are seeing, or even bigger gains. I think this is why the panel put such an emphasis on revisiting the topic in not more than five years.
A diagnostic biomarker panel, cytokine or otherwise, will change the research done in CFS and ME forever. Its a huge next step.