Re: PACE trial authors’ reply to letter by Kindlon
Following publication of the PACE Trial results in 2011[1], White et al wrote to The Lancet's editor Richard Horton stating that: "The normal range analysis was plainly stated as post hoc, given in response to a reviewer's request."[2]
From this it is clear that the normal range analysis was performed after trial data were examined. This is important because it shows that the decision to replace the protocol's strict definition of recovery[3] with far less demanding criteria was made after the trial's results were known, as the revised criteria were taken directly from the same normal range analysis.[4]
Sean Lynch argues that "protocol changes are not that unusual in large trials"[5] and this may be so. However, it is clearly unsatisfactory to allow investigators to analyse trial data first before choosing how to define something as important as recovery.
Published protocols exist to protect patients. We ignore them at our peril.
REFERENCES
[1] White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare JC, Baber HL, Burgess M, Clark LV, Cox DL, Bavinton J, Angus BJ, Murphy G, Murphy M, O'Dowd H, Wilks D, McCrone P, Chalder T, Sharpe M; [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 Mar 5;377(9768):823-36. Epub 2011 Feb 18. PMID: 21334061. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065633
[3] White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R; [PACE trial group]. Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BMC Neurol. 2007 Mar 8;7:6. PMID 17397525. http://www.biomedcentral.com/1471-2377/7/6
[4] White PD, Johnson AL, Goldsmith K, Chalder T, Sharpe MC. Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychol Med 2013;1-9, published online 31 Jan. doi:10.1017/S0033291713000020.
Rapid Response:
Re: PACE trial authors’ reply to letter by Kindlon
Following publication of the PACE Trial results in 2011[1], White et al wrote to The Lancet's editor Richard Horton stating that: "The normal range analysis was plainly stated as post hoc, given in response to a reviewer's request."[2]
From this it is clear that the normal range analysis was performed after trial data were examined. This is important because it shows that the decision to replace the protocol's strict definition of recovery[3] with far less demanding criteria was made after the trial's results were known, as the revised criteria were taken directly from the same normal range analysis.[4]
Sean Lynch argues that "protocol changes are not that unusual in large trials"[5] and this may be so. However, it is clearly unsatisfactory to allow investigators to analyse trial data first before choosing how to define something as important as recovery.
Published protocols exist to protect patients. We ignore them at our peril.
REFERENCES
[1] White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare JC, Baber HL, Burgess M, Clark LV, Cox DL, Bavinton J, Angus BJ, Murphy G, Murphy M, O'Dowd H, Wilks D, McCrone P, Chalder T, Sharpe M; [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 Mar 5;377(9768):823-36. Epub 2011 Feb 18. PMID: 21334061. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065633
[2] http://www.meactionuk.org.uk/whitereply.htm (Accessed 02/12/13)
[3] White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R; [PACE trial group]. Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BMC Neurol. 2007 Mar 8;7:6. PMID 17397525. http://www.biomedcentral.com/1471-2377/7/6
[4] White PD, Johnson AL, Goldsmith K, Chalder T, Sharpe MC. Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychol Med 2013;1-9, published online 31 Jan. doi:10.1017/S0033291713000020.
[5] Lynch S (2013). Re: PACE trial authors’ reply to letter by Kindlon. BMJ Rapid Response. http://www.bmj.com/content/347/bmj.f5963/rr/671597
Competing interests: No competing interests