MED: (Part g) Tom Kindlon's submission on the CDC's draft 5-year plan for CFS
Tom Kindlon
team have �operationalized� the Fukuda definition with the �empiric
definition� (Reeves, 2005).
I have previously mentioned virtually all the points I would like to make on
the topic as comments on papers that involved the definition. They are
appended below in green (as they were included in my last submission).
Frustrated with both the lack of feedback and the CDC�s continued use of the
definition, I set up a petition on the issue (see Appendix 1). Despite the
petition�s text not being very �catchy�, there are 1440 signatures.
I am appending the signatures below along with comments they made (more
people me they made comments but for some reason some comments never showed
up � given these are people signing a petition against the definition, these
would not have been positive comments).
As I said in my (written) testimony to the May 2009 CFSAC meeting: �If one
has a heterogeneous group of patients, it can mean that in intervention
trials, if �true� CFS patients only make up a tiny fraction of the cohort,
useful interventions could come up as showing no effect (or even being
detrimental); alternatively, interventions may come up as being useful for
CFS when in fact if one had only looked at those with �true� CFS, the
intervention may have made no difference or may even have been detrimental.�
Given that the CDC is now moving towards intervention studies, this is a
particularly important issue.
The CDC�s response to this criticism might be that using subsets can deal
with this issue. However the definition has been broadened so much by the
empiric definition that it is far from clear that this is enough. The
prevalence rates from CDC CFS studies went up from 0.235% to 2.54%. That
means that on average, patients satisfying the Fukuda definition as the CDC
was previously using it would only make up 9.25% of the patients covered by
the �empiric definition�. And of course due to the nature of probabilities,
the actual figures could well be lower. And even if 9.25% were inducted
into a study, on average in a trial which had at least two �arms�, one of
the arms would have a cohort with less than 9.25% of the individuals
satisfying the Fukuda definition as the CDC was previously defining it. And
of course, even at the earlier stage, it was recognized that even the Fukuda
definition captured a heterogeneous population.
Of course, this point is true in general with the �empiric� definition � the
definition has become so broad that it may now be impossible to find the
subsets that make up CFS.
One other point: as far as I can see, the only virus group specifically
referred to in the CDC�s long 5-year Strategic Plan is HHV6.
It would be good if some of the CDC's (not inconsiderable) CFS research
budget could be used to investigate enteroviruses in CFS. In 2007 a study
involving enteroviruses[4] resulted in much excitement in the media on the
subject. It found, in a sample of CFS patients who had gastrointestinal
symptoms, that 135/165 (82%) biopsies stained positive for VP1 within
parietal cells, whereas 7/34 (20%) of the controls stained positive
(p=<0.001). Earlier studies have demonstrated circulating antigen of
enterovirus, raised antibody titres and viral RNA in the blood and muscle
biopsy specimens of patients with CFS[4-8]. John Chia does recognize that
other infections could be playing a part in some CFS cases but enteroviruses
are by far the most common infection he is finding in his clinic in
California[9].
References
[1] Gelman JH, Unger ER, Mawle AC, Nisenbaum R, Reeves WC: Chronic fatigue
syndrome is not associated with expression of endogenous retroviral p15E.
Molec Diagnosis 2000, 5:155-156.
[2] Vernon SD, Shukla S, Reeves WC: Absence of Mycoplasma species DNA in
chronic fatigue syndrome. J Med Microbiol 2003, 52:1027-1028.
[3] Jones JF, Kulkarni PS, Butera ST, Reeves WC: GB virus-C--a virus without
a disease: we cannot give it chronic fatigue syndrome. Jones JF, Kulkarni
PS, Butera ST, Reeves WC. BMC Infect Dis 2005, 5:78
[4] Yousef GE, Mann GF, Smith DF, et al: Chronic enterovirus infection in
patients with postviral fatigue syndrome. Lancet 1988;1:146-7.
[5] Cunningham L, Bowles NE, Lane RJM, et al: Persistence of enteroviral RNA
in chronic fatigue syndrome is associated with abnormal production of equal
amounts of positive and negative strands of enteroviral RNA. J Gen Virol
1990;71:1399-402.
[6] Galbraith DN, Nairn C, Clements GB: Phylogenetic analysis of short
enteroviral sequences from patients with chronic fatigue syndrome. J Gen
Virol 1995;76:1701-7.
[7] Lane RJ, Soteriou BA, Zhang H, et al: Enterovirus related metabolic
myopathy: a postviral fatigue syndrome. J Neurol Neurosurg Psychiatry
2003;74:1382-6.
[8] Douche-Aourik F, Berlier W, Fe�asson L, et al: Detection of enterovirus
to human skeletal muscle from patients with chronic inflammatory muscle
disease or fibromyalgia and healthy subjects. J Med Virol 2003;71:540-7.
[9] Chia JK, Chia A: Diverse etiologies for the chronic fatigue syndrome.
Clin Infect Dis 2003;36:671-2.
----------------------
Other viruses and microbes are also worthy and studies that involve the gut
may provide more information than studies that just use blood samples.
Thank you for taking the time to read this.
Tom Kindlon
====================
Appendix 1: Petition
http://www.ipetitions.com/petition/empirical_defn_and_CFS_research/index.htm
l
CDC CFS research should not involve the empirical definition (2005)
The petition
We call on the Centers for Disease Control and Prevention (CDC) to stop
using the "empirical" definition[1] (also known as the Reeves 2005
definition) to define Chronic Fatigue Syndrome (CFS) patients in CFS
research.
The CDC claim it is simply a way of operationalizing the Fukuda (1994)
definition[2]. However the prevalence rates suggest otherwise: the
"empirical" definition gives a prevalence rate of 2.54% of the adult
population[3] compared to 0.235% (95% confidence interval, 0.142%-0.327%)
and 0.422% (95% confidence interval, 0.29%-0.56%) when the Fukuda definition
was used in previous population studies in the US[4,5].
The definition lacks specificity. For example, one research study[6] found
that 38% of those with a diagnosis of a Major Depressive Disorder were
misclassified as having CFS using the empirical/Reeves definition.
References
[1] Reeves WC, Wagner D, Nisenbaum R, Jones JF, Gurbaxani B, Solomon L,
Papanicolaou DA, Unger ER, Vernon SD, Heim C. Chronic fatigue syndrome--a
clinically empirical approach to its definition and study. BMC Med. 2005 Dec
15;3:19.
Link: http://www.biomedcentral.com/1...
[2] Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The
chronic fatigue syndrome; a comprehensive approach to its definition and
study. Ann Int Med 1994, 121:953-959.
[3] Reeves WC, Jones JF, Maloney E, Heim C, Hoaglin DC, Boneva RS, Morrissey
M, Devlin R. Prevalence of chronic fatigue syndrome in metropolitan, urban,
and rural Georgia. Popul Health Metr. 2007 Jun 8;5:5.
[4] Reyes M, Nisenbaum R, Hoaglin DC, Unger ER, Emmons C, Randall B, Stewart
JA, Abbey S, Jones JF, Gantz N, Minden S, Reeves WC: Prevalence and
incidence of chronic fatigue syndrome in Wichita, Kansas. Arch Int Med 2003,
163:1530-1536.
[5] Jason LA, Richman JA, Rademaker AW, Jordan KM, Plioplys AV, Taylor RR,
McCready W, Huang CF, Plioplys S. A community-based study of chronic fatigue
syndrome. Arch Intern Med. 1999 Oct 11;159(18):2129-37.
[6] Jason, LA, Najar N, Porter N, Reh C. Evaluating the Centers for Disease
Control's empirical chronic fatigue syndrome case definition. Journal of
Disability Policy Studies 2008, doi:10.1177/1044207308325995.
Further reading:
Problems with the New CDC CFS Prevalence Estimates
Leonard Jason, Ph.D., DePaul University
tinyurl.com/2qdgu4 i.e.
http://www.iacfsme.org/Issuesw...
Brief comment from Tom Kindlon: I have Chronic Fatigue Syndrome (CFS) for
over 20 years.
I want a lot of research progress in my lifetime and believe the empirical
definition (2005) (also known as the Reeves definition (2005)) decreases the
chances that this will occur: abnormalities that would show up using a more
strictly defined definition won't show up using the empirical/Reeves
definition; and abnormalities that might show up in the broad group covered
by the empirical/Reeves definition are not necessarily representative of CFS
patients.
Similarly treatments that might work on a more strictly defined group of
patients might not show up using the very broad empirical/Reeves definition
and treatments that might appear to work overall on the group defined using
the empirical/Reeves definition might not be suitable for people who satisfy
a stricter definition. This messes up the CFS literature even further.
--
Technical note: I am not sure why some people have grey boxes in the
comments section. Some people have told me they have sent comments that
never went up. I have not idea why this is happening.
Petition sponsor
Tom Kindlon, a patient with Chronic Fatigue Syndrome (CFS) for over 20
years. I have done a lot of voluntary work in the area for over a decade.
Recently I had two letters on CFS published in medical journals.
Links
The paper defining the empirical/Reeves definition can be read at:
http://www.biomedcentral.com/1741-7015/3/19
Some comments on the paper have been posted at:
http://www.biomedcentral.com/1741-7015/3/19/comments
An article by Leonard Jason PhD on the issue can be read at:
tinyurl.com/2qdgu4 i.e.
http://www.iacfsme.org/IssueswithCDCEmpiricalCaseDefinitionandPrev/tabid/105
/Default.aspx
http://me-cfs.se/dok/081205-cfs-no-longer-cfs.pdf
By Kasper Ezelius M.Sc. This includes some links to other definitions,
Kasper's take on the issues and a list of some papers that have involved
using the empirical definition (this list is not up-to-date; virtually all
the papers from the CDC 2-day Wichita study and also from the Georgia cohort
have used the empirical definition to define CFS)
http://www.ipetitions.com/petition/empirical_defn_and_CFS_research/signature
s-1.html
(Included the 1440 signatures and comments)
(I also included the text of my previous submission below this in green)