The CDC hosted a conference call for ME/CFS patients and advocates today. The highlight of the call was a presentation from Dr. Ian Lipkin about his pathogen and immunology work in ME/CFS. But we received an important update on the CDC multisite study, and it remains to be seen whether advocates will accept what we were given.
You may recall that at the May 2013 CFSAC meeting, advocates were aghast at Dr. Unger’s statement that the CDC multisite study would not use two-day cardiopulmonary exercise testing (CPET) despite the research showing that this protocol produces evidence of post-exertional malaise, metabolic dysfunction, and is a potential diagnostic marker for ME/CFS. When questioned, Dr. Unger said she had not discussed the protocol with Dr. Chris Snell or Staci Stevens (who created it). This seemed like yet another example of CDC having an opportunity to do good science and intentionally choosing not to do so.
On July 22, 2013, eleven groups and thirty-one individuals sent a letter to CDC requesting, among other things, that the multisite study use the two-day protocol. Here’s what they said:
The two-day CPET regimen known as the Stevens Protocol provides gas exchange and other objective and measurable results “which can’t be faked.” With properly trained personnel in place, this test can be done using technology which has been used in hospitals and other facilities for decades. Having CPET testing performed by trained personnel on subjects involved in the multi-site clinical assessment should be considered a TOP PRIORITY in order to maximize standardized data and take advantage of the opportunity provided by this important CDC-initiated study.
We cannot over-emphasize the importance of measuring and understanding post-exertional malaise (PEM) in this study. PEM is most often the largest obstacle to activities of daily living, gainful employment, exercise, and more. A combination of data from the two-day CPET test and the on-line cognitive test that is already planned will provide the data needed for effective analysis of this debilitating symptom.
Dr. Unger responded in writing on August 30th, but for unknown reasons the advocates did not receive her response until today. Both the letter and Dr. Unger’s comments on the call today explain why CDC has chosen to do one day of maximal effort testing, followed by 48 hours of cognitive testing and symptom measurements. Especially important (and highlighted in the excerpt below) is Dr. Unger’s representation of Dr. Snell’s opinion on the protocol:
To address concerns regarding the cardio-pulmonary exercise testing (CPET) in the second stage of the study, I would like to share additional details, and the rationale that we used to select the one-day maximal exercise test. Our primary objective is to measure the exercise capacity in as many of the enrolled patients as possible using a standardized protocol, and to monitor the post-exertional response for 48 hours with online cognitive testing and visual analogue scales of fatigue, pain, and symptoms. Maximal CPET with one day of testing and 48-hour follow-up of cognition was developed in consultation with Dr. Gudrun Lang (cognition) and Dr. Dane Cook and Connie Sol (exercise). The exercise protocol was discussed also with Dr. Chris Snell. Dr. Snell favors the two-day test because it gives more information, however he believes the one-day maximal CPET will provide useful information. We chose the one-day test so that more patients could be tested. The two-day test would require an additional overnight stay for those patients who travel long distances to attend clinic and excludes those who are most severely affected because of the heavy physical toll. In developing the protocol, we strived to find a balance between testing that would yield meaningful data in the broadest representation without placing an unnecessary burden on the patients.
I immediately asked Dr. Snell if this was an accurate representation of his comments, and he said it was. He commented:
As you know, we believe that the 2 day test provides important metabolic data as well as potential to objectively document fatigue following physical exertion. I do believe, for most patients, a single max test will elicit PEM which should affect the post-test cognitive scores and fatigue scale scores. The CPET data however may not be a true reflection of physiological function post exertion for all patients.
On balance, I am happy that the CDC chose to use a validated protocol for functional assessment that does incorporate objective measures of effort. This is infinitely preferable to dubious “sub-maximal” tests. I did indicate that the study was still worthwhile even absent the second test. On what may be a selfish note, I am disappointed that the study does nothing to validate the diagnostic value of repeated CPET testing for ME/CFS. It was briefly mentioned that this might be part of subsequent studies.
So is this CDC protocol a reasonable compromise? I’m sure it was influenced by budget, to some degree. CPET testing is expensive (as I can personally attest), and creates a serious burden of recovery. CDC is choosing to compromise by using a single maximal test and then measuring the effect on patients. Will a one day test be sufficient to demonstrate PEM, including the cognitive and physical symptoms of a crash? Will advocates be satisfied, especially in light of Dr. Snell’s support of CDC’s protocol for this study?
I think CDC will capture good data this way, but it won’t be a complete demonstration of PEM and the metabolic dysfunction that characterizes ME/CFS. The second day of testing captures the significant drop in VO2max, oxygen consumption at the anaerobic threshold, peak workload, and workload at the anaerobic threshold. The second day results differentiate ME/CFS patients from other illness groups. It is possible that the CDC multisite results will not do so without that second day of testing. In my opinion, that is a huge missed opportunity.