Cunningham Panel Reliability: Corrigendum and Flawed Study Methodology"
A published corrigendum to the 2017 Hesselmark and Bejerot study raises important considerations when evaluating the reliability of the Cunningham Panel™. In the corrigendum, “Corrigendum to Biomarkers for Diagnosis of Pediatric Acute Neuropsychiatric Syndrome (PANS)—Sensitivity and Specificity of the Cunningham Panel 1,” the authors reported using invalid serum collection tubes different from the Red Top glass tubes recommended by Moleculera Labs for specimen collection.
The corrigendum applies to the 2017 Hesselmark and Bejerot study, “Biomarkers for Diagnosis of Pediatric Acute Neuropsychiatric Syndrome (PANS)—Sensitivity and Specificity of the Cunningham Panel2,” which evaluated the sensitivity and specificity of the Cunningham Panel™ in patients with PANS. The authors acknowledged that use of a different blood collection tube “could be viewed as a limitation” because the autoantibodies tested with the Cunningham Panel™ had not, to their knowledge, been tested using both collection-tube types.
INVALID COLLECTION TUBES IMPACT TEST RELIABILITY
“We have been informed that Moleculera Labs recommend Red Top glass tubes when collecting blood for the Cunningham Panel™. In our study, we have used serum sampling tubes (BD Vacutainer® SST™ II Advance tubes, Gold Top) but erroneously reported sampling in serum sampling tube (BD Vacutainer, yellow top).”
“The use of another blood collection tube than the one recommended by Moleculera could be viewed as a limitation in our study.”
In fact, the autoantibodies tested with the Cunningham Panel™ “have to our knowledge not been tested using the two different types of tubes.”
Using the wrong collection tubes can greatly impact the reliability of the Cunningham Panel™ test results. “Invalid blood collection methods alone would render the results questionable at best, but potential assay interfering substances which could alter the results would render the study void,” explains Richard Frye, MD, in his correspondence entitled “Reliability of the Cunningham Panel3.”
Control-group selection also affects the reliability of the Cunningham Panel™ test results. In his correspondence, Frye questioned whether the Hesselmark and Bejerot study included a sufficiently representative healthy-control population.
This study lacked a reliable “healthy control” population. And while it is not mentioned in the corrigendum, this is a significant flaw in the study, Frye states.
He noted that many participants classified as healthy controls demonstrated an elevation in the antibody-mediated cell signaling calcium/calmodulin-dependent protein kinase II (CaMKII) activation assay.
“The clinical value of a medical test is highly dependent on applying it to an appropriate symptomatic disease population,” Frye states. This study lacked a reliable “healthy control” population.
For instance, when selecting “healthy controls” the study:
- Included both adults and children in its control population.
- Did not exclude participants with a family history of psychiatric, autoimmune, or movement disorders.
- Included participants who were treated for a psychiatric disorder for longer than one year prior to enrollment.
- Did not screen for, or exclude, participants with recent or active infections.
Taken together, the specimen-collection and healthy-control selection issues identified in the study limit the extent to which its findings can be used to assess the sensitivity and specificity and reliability of the Cunningham Panel™.
REVIEW THE PUBLISHED RECORD
Review the original study, its corrigendum, and the related scientific correspondence when evaluating claims about the Panel’s reliability. The correction and methodological concerns are necessary for an informed interpretation of the study’s findings.
References
- Hesselmark E, Bejerot S. Biomarkers for diagnosis of Pediatric Acute Neuropsychiatric Syndrome (PANS)—Sensitivity and specificity of the Cunningham Panel. Journal of Neuroimmunology. 2017;312:31–37. https://doi.org/10.1016/j.jneuroim.2017.09.002
- Hesselmark E, Bejerot S. Corrigendum to Biomarkers for diagnosis of Pediatric Acute Neuropsychiatric Syndrome (PANS)—Sensitivity and specificity of the Cunningham Panel. Journal of Neuroimmunology. 2017;313:116–117. https://doi.org/10.1016/j.jneuroim.2017.11.001
- Frye, R.E., Shimasaki, C. Reliability of the Cunningham Panel. Transl Psychiatry 9, 129 (2019). https://doi.org/10.1038/s41398-019-0462-1
