A wait list control is pretty poor. I read this paper really only interested in their actimeter results, but not much info was given on them. I think that they may have messed up their supplementary files. They also mentioned doing a range of analyses, but I couldn't see the results for a lot of them. It is past my bed-time though, so I may have just missed them in my rush.
I pulled out some bits that I thought were of interest, but this was only a quick read through:
I feel like they should have explained that this related to depression and anxiety, not CFS.
Guided variants of internet treatment are more effective than unguided variants,8
8 Spek V, Cuijpers P, Nyklicek I, Riper H, Keyzer J, Pop V. Internet-based cognitive
behaviour therapy for symptoms of depression and anxiety: a meta-analysis.
Psychol Med 2007; 37: 319–28
This was part of their entry criteria:
(c) being severely disabled, operationalised
as a score of 700 or higher on the Sickness Impact Profile 8
(SIP8);
The average SF36-PF score for all three groups was 62 at baseline. ie the average participant fulfilled the PACE trials SF36-PF recovery criteria (although this is also under the PACE trial's entry criteria for severe and disabling fatigue, which required and SF36-PF of 65 or under). Presumably many of the participants had scores significantly higher than this too.
I've not looked at the reference for this, but it's from 1988 and it doesn't mention CFS in the preview page that was available:
The SF-36 is a reliable and valid instrument to assess
self-reported health status in patients with CFS.19
19
Stewart A, Hays R, Ware J. The MOS short-form general health survey. Reliability
and validity in a patient population.
Med Care 1988; 26: 724–35.
Interesting that they gave no justification for this cut off:
Fatigue scores in the normal range were defined as a score of <35
on the CIS fatigue severity subscale at second assessment, together
with a reliable change index (RCI) >1.96.
They mentioned these changes from their protocol (protocol is here, I've not read it:
https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-015-0392-3 ):
After trial registration but before the start of the study, we added
the Chalder Fatigue Questionnaire (CFQ)24 and Work and Social
Adjustment Scale (WSAS)25 to the assessment battery as both
instruments are often used in CFS intervention studies. Adding
them aids comparison of treatment effects between studies (see
also Worm-Smeitink et al)26 Another deviation of the original
study protocol was the decision not to determine quality-adjusted
life-years; because of limited resources we were unable to perform
a cost-effectiveness study. The quality of life questionnaire (the
EQ-6D)27 was, however, still part of the assessment battery.
I thought it was a bit fun that they took such care with this, but then had a wait-list control:
Patients were not informed about the existence of the two iCBT
treatments to avoid contamination between the two treatment arms.
I wonder why this was?
Six patients were included with less than four CDC symptoms
(one being randomised to the waiting list and five to the ondemand
treatment).
Maybe this is where the 40% recovery claim came from? I wonder if there was a press release for this paper:
Significantly more patients had
fatigue scores in the normal range following protocol-driven iCBT
than controls (protocol-driven 29/80 (36%) v. waiting list 12/80
(15%): χ2(1,n = 160) = 9.5, P = 0.0021; number needed to treat
(NNT) = 4.7) (supplementary Fig. 1).
Significantly more patients
had fatigue scores in the normal range following treatment than
the controls (on demand 34/80 (43%) v. waiting list 12/80 (15%):
χ2(1,n = 160) = 14.8, P = 0.0001; NNT = 3.6) (supplementary Fig. 1).
Yeah - this was from later on:
Comparing iCBT outcomes with
those of patients allocated to the waiting list, we found a significantly
larger reduction of fatigue severity, overall impairment and
psychological distress in the treatment groups, with approximately
40% of completers reporting fatigue scores within the normal range.
They said:
Patients who received iCBT were asked if they had experienced
negative side-effects of the therapy.
This is mentioned here, but I can't see supplementary Table 2 in the supplementary files.
No serious adverse events were reported. Some patients indicated
adverse events: 4 of 38 (11%) patients in the protocol-driven
condition, 7 of 39 (18%) in the on-demand condition, and 12 of
46 (26%) in the control condition (see supplementary Table 2 for
details and the patients’ perception of iCBT side-effects). The chisquared
analysis revealed no significant differences for the three
conditions in the proportion of patients reporting an exacerbation
of symptoms and/or functional impairments.
I don't really understand what was happening with their actigraphy, why they were not planning to assess results, and why they then did. The mentions it gets:
We conducted post
hoc ANCOVAs for the CFQ, the WSAS and the assessment of physical
activity using actigraphy to determine the effects of the intervention.
Finally, the post
hoc analyses revealed that CFQ scores and social impairment
(WSAS) were significantly reduced and objectively assessed activity
was significantly increased following the iCBT conditions compared
with the waiting list (supplementary Table 1).
I can't see supplementary Table 1 either. I've got table three, but it looks like they may not have uploaded the final file:
I think that this is as close as they come to addressing criticisms (ref 32 is PACE recovery, 34 is PACE Lancet):
There is an
ongoing debate in the literature and among patient advocacy groups
that challenge the efficacy and safety of CBT for CFS. [No references for
that... wouldn't want readers to be aware of the details of the debate!] First, in line
with previous studies this study has shown that a subgroup of patients
with CFS were able to reduce their fatigue severity to healthy proportions
and reduce their overall impairment and improve psychological
well-being.18,32 Second, this study has shown, in line with previous
research, that CBT is a safe intervention.33,34 Unfortunately, only
half of the patients in our trial were asked to report on the occurrence
of adverse events as this evaluation was not added until a portal update
halfway through the study. Still, the available data did not show more
patientswith adverse events in the iCBT conditions comparedwith the
waiting-list condition and none of the adverse events reported were
serious. Furthermore, we found no evidence of a higher prevalence
of clinically significant exacerbation in fatigue and other outcomes
in the treatment conditions.
One could argue that the use of a waiting-list control does not
control for non-specific therapy factors and limits the external validity.
However, a meta-analysis that studied active placebo conditions for
CFS did show low responses,35 as was also true for standardised specialistmedical
care.34
This is what they say on physical functioning:
Impact of iCBT on physical functioning
One iCBT condition did not result in a significant increase in physical
functioning. This seems remarkable as previous studies did find positive
effects of face-to-face CBT on physical functioning (for example
White et al).34 Previous studies, however, often used compromised
physical functioning as an inclusion criterion, excluding patients
who score within the ‘normal range’ on physical functioning. In
our study these patients could be included if they reported severe
impairments in other domains of functioning, like work or social
functioning, as assessed with the SIP8. The fact that our study did
not select on the level of physical functioning will make it more difficult
to find an effect of iCBT on physical functioning. It would be
interesting to directly compare iCBT and face-to-face CBT in a
sample of patients with CFS with a compromised physical functioning
scoring below a cut-off on the SF-36 to determine if the interventions
differ in their effect on physical functioning. A post hoc analysis
showed that objectively assessed physical activity significantly
increased after iCBT. However, this might be an accidental finding,
taking the amount ofmissing data into account and previous research
that did not find an increase in physical activity following CBT.36
Limitations
The effects of iCBT were only assessed 6 months post-randomisation
as the medical ethical committee considered it unethical to
let patients wait longer than the regular waiting period for start of
treatment in usual care. Moreover, step two of our (stepped care)
study consisted of face-to-face therapy if patients were still fatigued
at the second assessment, therefore ruling out a controlled followup.
More men participated in this study as compared with other
CBT for CFS trials. This can be explained by the inclusion criteria
How do we even know that the patients received some or all of the treatment? We know that they started 'treatment modules', but there is no proof that they completed them. What if they felt an obligation to say they completed modules because they wanted to please or look like they tried?
I let Unrest run on Netflix while I was doing something else, just to indicate an interest. It's hard to check on some of this stuff. They gave some more details on this here:
Our integrity check showed that 90.3% of the interventions were
delivered according to protocol with an interrater reliability
(Cohen’s Kappa) of 0.96. A total of, 4 of 80 (5%) patients in the
protocol-driven condition and 6 of 80 (8%) in the on-demand condition
did not start the intervention. Without taking the relapse
module into account, 39 (49%) patients in the protocol-driven condition
were adherent to following our criteria of emailing fortnightly
and having opened all modules. Of the patients in the on-demand
condition, 74 (93%) were adherent to following our criterion of
having opened all modules. When the relapse module was taken
into account, this percentage dropped considerably to 16 and
19%, respectively (see supplementary Table 3). Finally, the post
hoc analyses revealed that CFQ scores and social impairment
(WSAS) were significantly reduced and objectively assessed activity
was significantly increased following the iCBT conditions compared
with the waiting list (supplementary Table 1).
I'd be interested to hear more from just the technology side.
