PACE Trial Normal Range Fatigue – Another Untenable Construct

Fatigue as measured on the Chalder Fatigue Scale was a Primary Outcome Measure in the PACE Trial.  The chart below is adapted from the published Lancet data:

lancet-fatigue-big7

Van Kessel et al was  ‘A Randomized Controlled Trial of Cognitive Behavior Therapy for Multiple Sclerosis Fatigue’, 2008.[1]  Jerjes et al measured ‘Urinary Cortisol and Cortisol Metabolite Excretion in Chronic Fatigue Syndrome’, 2006, and included healthy controls.[2]

Of note is that Trudie Chalder of the Chalder Fatigue Scale was a Principal Investigator of the PACE Trial.  She was also an author of Van Kessel et al, 2008.

 The Primary Outcome Measures of ‘Recovery’ and ‘Improved’ were discarded by the PACE investigators after the Trial, and replaced with ‘Normal Range’.  As with the SF36PF criteria, the ‘Normal Range’ threshold for Fatigue, fell in the precise spot to create the appearance of a treatment effect.  However, compared to Healthy Controls, Normal Range appears to be clinically meaningless, especially considering that according to the theories of the PACE Trial investigators, they were only treating ‘deconditioning’ and activity phobia.  Treatment should have been straightforward if the theories were correct.  Yet participants ‘improvement’ left them as badly fatigued as untreated Multiple Sclerosis patients.

 The SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials states:[3] “…major discrepancies in the primary outcomes designated in protocols/registries/regulatory submissions versus final trial publications are common; favour the reporting of statistically significant primary outcomes over non-significant ones; and are often not acknowledged in final publications. 172-176 Such bias can only be identified and deterred if trial outcomes are clearly defined beforehand in the protocol and if protocol information is made public. 177

And: “Results for the primary outcome can be substantially affected by the choice of analysis methods. When investigators apply more than one analysis strategy for a specific primary outcome, there is potential for inappropriate selective reporting of the most interesting result. 6 The protocol should prespecify the main (“primary”) analysis of the primary outcome (Item 12), including the analysis methods to be used for statistical comparisons”

 

[1] Van Kessel et al. 2008. ‘A Randomized Controlled Trial of Cognitive Behavior Therapy for Multiple Sclerosis Fatigue’. Psychosomatic Medicine February/March 2008 vol. 70 no. 2 205-213.

[2] doi: 10.1097/01.psy.0000222358.01096.54 Psychosomatic Medicine July 1, 2006 vol. 68 no. 4 578-582.

[3] Online: http://www.bmj.com/highwire/filestream/623874/field_highwire_article_pdf/0/bmj.e7586

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s