questionnaire: 0-100 scoring (0 is worst score, 100 best) and
norm-based scoring, with a population norm of 50 and SD of 10 (again,
lower is worse).
The 0-100 scoring method has been more common in ME/CFS papers up till now.
Anyway, in the Fluge et al. (2011) study on Rituximab, they didn't
make it clear which method they used. Many people, being more used to
the 0-100 scoring method, probably presumed that was the scoring
method.
However, I suspected it was norm-based scoring so asked the question
of the authors. They replied it was norm-based scoring.
The correspondence is copied below. As one see (e.g. last few posts),
the results are more impressive once one sees norm-based scoring was
used. (It may be easier to read the correspondence on the site).
At the end, I've also posted some other calculations a poster on a forum ma=
de.
Tom
http://bit.ly/tYGrp6 =A0i.e.
http://www.plosone.org/annotation/listThread.action?inReplyTo=3Dinfo%3Adoi%=
2F10.1371%2Fannotation%2Ff31cc17f-d930-4bb5-828b-cfadc2fc37c9&root=3Dinfo%3=
Adoi%2F10.1371%2Fannotation%2Ff31cc17f-d930-4bb5-828b-cfadc2fc37c9
Thread: Could the authors give the raw (non-normalized) SF-36 subscale scor=
es
Original Article
Benefit from B-Lymphocyte Depletion Using the Anti-CD20 Antibody
Rituximab in Chronic Fatigue Syndrome. A Double-Blind and
Placebo-Controlled Study
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Could the authors give the raw (non-normalized) SF-36 subscale scores
Posted by tkindlon on 05 Nov 2011 at 14:49 GMT
The eight SF-36 subscale scores in the Myalgic
Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) field have
generally been given in the past as raw scores (the PCS and MCS are
given as normalised scores). The figures in Table 4 look to me like
the eight subscales have been normalised. This makes comparisons with
most of the studies in the ME/CFS field difficult especially when
different population norms exist for different countries. Also, it
means many may interpret them as raw scores when as I say they appear
to me to be normalised scores.
Assuming I am correct and these are normalised scores, could the
authors give the eight subscale scores as raw (i.e. unadjusted
scores). Alternatively, could the authors give the data on which
population norms were used e.g. was it a Norwegian sample or a US
sample (for example).
The figures look much more impressive if the figures in Table 4 are
normalised scores e.g. if one looks at the physical function subscale,
with a baseline mean of 34 and a mean max change of 39%. A mean max
change of 39% is 47.26 (although this may not be exactly correct as
there is rounding). This is very close to 50 i.e. the population norm
so looks much more impressive than if it was 47 as a raw score.
Thank you.
Competing interests declared: I am the information officer of the
Irish ME/CFS Association. All my work for the Association is voluntary
(i.e. unpaid).
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RE: Could the authors give the raw (non-normalized) SF-36 subscale scores
Fluge replied to tkindlon on 07 Nov 2011 at 15:03 GMT
We thank dr. Kindlon for his remark to Table 4 in our article
describing SF-36 scores, and for the opportunity to clarify aspects of
the analyses to help the readers interpret the data.
The patients recorded the SF-36 short form scheme (Norwegian
translation) at baseline (pre-treatment) and every month until 10
months follow-up.
The analyses of SF-36 short forms, with physical health summary score,
mental health summary score, and scores for the eight SF-36
subdimensions, were generated from a SPSS syntax file.
Dr. Kindlon is correct that the values for the SF-36 subdimentions are
norm-based, and the population norm from US 1998 was used.
The table presents data on SF-36 scores for physical health summary
score, mental health summary score, and scores for the eight SF-36
subdimensions, and shows baseline levels (mean with SD) for both the
Rituximab and Placebo groups. Because the time-frame for responses
vary among patients, we chose also to present the mean values of
maximum changes in SF-scores during follow-up, as compared to
baseline.
We think the SF-36 data supports the main findings of the study,
showing a significant difference in maximum changes as compared to
baseline, in favour of the Rituximab group, for physical health
summary score, and the subdimentions physical function and bodily
pain. We should take caution in comparing these data to other CFS/ME
studies, and we think the most important aspect is the comparison
between the two intervention groups in our study.
Competing interests declared: Haukeland University Hospital has
patents and pending patent applications on the issue of B-cell
depletion therapy for chronic fatigue syndrome. Family members of
WO2009083602 A1 are pending, as well as granted US 12/348024. The two
authors =D8F and OM are named as inventors in these applications.
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RE: RE: Could the authors give the raw (non-normalized) SF-36 subscale scor=
es
SMcGrath replied to Fluge on 30 Nov 2011 at 10:00 GMT
Thank you for clarifying that Table 4 uses SF-36 norm-based scores.
Could the authors also confirm if the maximum change percentages are
per cent changes to the norm-scores or to the raw (0-100) scores?
Ideally, could the authors also provide mean "maximum" SF-36 scores (I
don't think they can be calculated from the data given in Table 4) for
both Rituximab and placebo groups? This aditional information would
give readers the fullest picture of the size of the effect from
Rituximab.
No competing interests declared.
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RE: RE: RE: Could the authors give the raw (non-normalized) SF-36
subscale scores
Fluge replied to SMcGrath on 01 Dec 2011 at 17:15 GMT
The analyses of the SF-36 short forms were generated from a SPSS
syntax file, with values norm-based using the population norm from US
1998.
For all dimensions (physical health summary score, mental health
summary score, and the eight subdimensions), the baseline values
(before intervention) and values generated from SF-36 recorded every
month until 10 months after intervention, were calculated the same way
using the same syntax file.
Due to different time frames for clinical responses, we chose to
calculate in each patient the maximum changes during follow-up (for
each dimension), as compared to the baseline level for the actual
dimension.
In addition to the baseline levels for each dimension presented as
mean with standard deviation in each group, we also the present the
maximum changes during follow-up as compared to baseline (in percent),
and demonstrated as mean with standard deviation for each group
(Rituximab and Placebo). These maximum changes during follow-up
therefore are not representative for the complete follow-up period,
but reflect the status at the time the patients are feeling at the
best (or worst) i.e. with maximum difference from baseline.
As an answer to the question, the maximum changes presented are
percent changes from the baseline scores, which were norm-based.
Two examples:
For patient ID4 in the Rituximab group, the scores for mental health
summary score during the study were: baseline: 52.9, month 1: 52.9,
month 2: 54.0, month 3: 56.9, month 4: 57.5, month 5: 56.9, month 6:
52.4, month 7: 53.4, month 8: 52.9, month 9: 52.9, month 10: 51.2.
Thus in this patient the maximum change in mental health summary score
during follow-up was 9%. (Score 57.5 (at 8 months) =96 score 52.9
(baseline)/ score 52.9 (baseline)=3D0.09).
In Table 4, the mean values for mental health summary score at
baseline were 46 in the rituximab group, and 46 in the placebo group.
When calculating the maximum difference from baseline during follow-up
for all patients, for mental health summary score, the mean values
were 9% (SD 54) in the rituximab group, and 5% (SD 32) in the placebo
group, which was not a significant difference between the two groups.
For patient ID19 in the rituximab group, the scores for the
subdimension bodily pain during follow-up were: baseline: 28.7, month
1: 28.7, month 2: 36.6, month 3:36.6, month 4: 50.3, month 5: 50.3,
month 6: 36.6, month 7: 36.6, month 8: 40.7, month 9: 32.8, month 10:
28.7.
Thus in this patient the maximum change in bodily pain score during
follow-up was 75%. (Score 50.3 (at 8 months) =96 score 28.7 (baseline)/
score 28.7 (baseline)=3D0.75)
In Table 4, the mean values for bodily pain score at baseline were 32
in the rituximab group, and 34 in the placebo group.
When calculating the maximum difference from baseline during follow-up
for all patients, for bodily pain, the mean values (for maximum
difference) were 40% (SD 31) in the rituximab group, and 8% (SD 24) in
the placebo group, which was a significant difference between the two
groups.
Competing interests declared: Haukeland University Hospital has
patents and pending patent applications on the issue of B-cell
depletion therapy for chronic fatigue syndrome. Family members of
WO2009083602 A1 are pending, as well as granted US 12/348024. The two
authors =D8F and OM are named as inventors in these applications.
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SMcGrath replied to Fluge on 16 Dec 2011 at 20:05 GMT
Thank you for the comprehensive explanation of how maximum change
percentages were calculated from the norm-scores for individual
patients.
For those not familiar with norm-based scoring, it's worth pointing
out that the percentage increase in the underlying raw (0-100) scores
will be much bigger than the increase for norm-scores.
Take the SF-36 Physical Function (PF) results as an example. The
norm-score Rituximab group baseline was 34 with a mean maximum
increase of 39%, giving an estimated mean maximum norm-score of 47.3.
However, the equivalent raw scores for these figures are: baseline
44.9 , maximum 76.5 - an increase in the raw score of 70% or 31.6
points (i.e. much higher than the 39% increase in norm-scores).
The 31.6 points raw score gain for the Rituximab group in this example
compares with a gain of 9.2 points (19%) in the Placebo group on the
same basis. This represents an exceptional relative peak gain in
physical function for the Rituximab group.
SF-36 Physical Function scores are of particular interest as
substantial impairment is a defining feature of CFS. Although in this
study SF-36 PF scores were one of a number of secondary outcomes,
other studies - including the two largest clinical trials to date
(1,2) - have used them as a primary outcome, albeit using endpoint
rather than peak scores.
References:
1. Wearden AJ, Dowrick C, Chew-Graham C, et al on behalf of the PACE
trial management group Fatigue Intervention by Nurses Evaluation
(FINE) trial writing group and the FINE trial group. Nurse led, home
based self help treatment for patients in primary care with chronic
fatigue syndrome: randomised controlled trial. BMJ. 2010;340:c1777.
2. White PD, Goldsmith KA, Johnson AL, et al on behalf of the PACE
trial management group. Comparison of adaptive pacing therapy,
cognitive behaviour therapy, graded exercise therapy, and specialist
medical care for chronic fatigue syndrome (PACE): a randomised trial.
Lancet. 2011;377(9768):823-36.
No competing interests declared.
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Subject: SF-36 PF estimate if non-responders only scored the same as
the placebo group
tkindlon replied to SMcGrath on 16 Dec 2011 at 20:38 GMT
Thanks to SMcGrath for posting that information.
Note that 76.5 would be a lower bound* for the SF-36 PF scores for the
responders.
We only have SF-36 PF scores for 13 of the CFS patients on Rituximab,
9 of whom were responders.
If the non-responders only increased at peak by the same amount as the
placebo group i.e. 9.2, then the 9 responders would have reached, on
average, a very impressive 86.5** on the SF-36 PF.
*Approximately as these calculations depend on average percentage
increases - what a particular percentage increase translates to
depends on the initial value. But we don't have added information to
make any assumptions other than the individual differences would
balance out when the mean was obtained.
**Calculation (using SMcGrath's figures): Total increase among the 13
on Rituximab: 31.6*13=3D410.8 points. Amount of this obtained by the
four non-responders, if the response the same as the placebo group:
9.2*4=3D36.8.
Therefore, improvement in responders compared to baseline: (410.8-36.8)/9=
=3D41.6.
Or mean score at peak =3D baseline score + improvement =3D 44.9+41.6=3D86.5
Competing interests declared: Information Officer (voluntary
position), Irish ME/CFS Association
Report a Concern Respond to this Posting
SF-36 USA 1998 population norms (raw figures)
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tkindlon replied to Fluge on 16 Dec 2011 at 21:15 GMT
It took me a little while but I have now found a place giving the
population norms in raw figures:
http://www.sf-36.org/nbscalc/index.shtml. (and type in a figure).
There are probably other places but this does the job:
Non normalised USA 1998 population means (SDs):
PF: 83.0 (23.8)
RP: 77.9 (35.3)
BP: 70.2 (23.4)
GH: 70.1 (21.4)
VT: 57.0 (21.1)
SF: 83.6 (23.0)
RE: 83.1 (31.6)
MH: 75.2 (17.6)
Competing interests declared: Information Officer (voluntary
position), Irish ME/CFS Association
-----------
Some data from a forum:
http://forums.phoenixrising.me/showthread.php?14297-Astounding-Norwegian-re=
search-breakthrough-with-Rituximab-can-solve-CFS-mystery!!!&p=3D223444&view=
full=3D1#post223444
If anyone is curious about back calculation of the raw SF-36 scores
using the calculator:
http://www.sf-36.org/nbscalc/index.shtml
Baseline (raw) for Rituxumab group:
PF 44.8
RP 0
BP 28.2
GH 21
VT 25.4
SF 16.8
PCS 24
Max Change (raw):
PF 76.5
RP 27
BP 58
GH 41.7
VT 40.5
SF 64.2
PCS 39.1
Note, the max change PCS from the paper was 37, suggesting that not
all symptoms had the "Max change" improvement at the same time.
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