A look at what happened to the outcome measures that had been promised
Registering one's trial and outcome measures is very important now - some journals won't accept trials that haven't been registered.
The authors went one step further and published their protocols in a journal.
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.
http://www.biomedcentral.com/1471-2377/7/6
Here's a look at what happened to them
[Aside: The analyses they promised would need to be looked at separately (I'm not promising I'll do it)]
Measures
Primary outcome measures – Primary efficacy measures (you're really not supposed to touch these)
Since we are interested in changes in both symptoms and disability we have chosen to designate both the symptoms of fatigue and physical function as primary outcomes. This is because it is possible that a specific treatment may relieve symptoms without reducing disability, or vice versa. Both these measures will be self-rated.
The 11 item Chalder Fatigue Questionnaire measures the severity of symptomatic fatigue [27], and has been the most frequently used measure of fatigue in most previous trials of these interventions. We will use the 0,0,1,1 item scores to allow a possible score of between 0 and 11. A positive outcome will be a 50% reduction in fatigue score, or a score of 3 or less, this threshold having been previously shown to indicate normal fatigue [27].
Not given per protocol.
Likert scoring used (not necessarily a bad thing but a change)
Normal fatigue no longer given as a primary outcome measure
(when it is given later, not in the abstract, the 50% threshold is not used and a score of 18 is seen as acceptable which, most people would say, does not equate to 3 or less on bimodal scale (out of 11); a score of 18 is a minimum of 4 (out of 11) on the bimodal scoring and a maximum of 9).
The SF-36 physical function sub-scale [29] measures physical function, and has often been used as a primary outcome measure in trials of CBT and GET. We will count a score of 75 (out of a maximum of 100) or more, or a 50% increase from baseline in SF-36 sub-scale score as a positive outcome. A score of 70 is about one standard deviation below the mean score (about 85, depending on the study) for the UK adult population [51,52].
Not given per protocol.
Normal physical functioning no longer given as a primary outcome measure
(when it is given later, not in the abstract, the 50% increase is not used and a score of 60 or more is suddenly seen as acceptable despite the fact that a score of 65 or less lets one into the trial).
Those participants who improve in both primary outcome measures will be regarded as overall improvers.
Not given per protocol.
Data is given, but not as a primary outcome measure, but it uses these new, lower thresholds, mentioned above
Secondary outcome measures – Secondary efficacy measures
1. The Chalder Fatigue Questionnaire Likert scoring (0,1,2,3) will be used to compare responses to treatment [27].
Has become one of the primary outcome measures.
2. The self-rated Clinical Global Impression (CGI) change score (range 1 – 7) provides a self-rated global measure of change, and has been used in previous trials [45]. As in previous trials, we will consider scores of 1 or 2 as a positive outcome ("very much better" and "much better") and the rest as non-improvement [23].
Per protocol.
3. The CGI change scale will also be rated by the treating therapist at the end of session number 14, and by the SSMC doctor at the 52-week review.
Neither of these are given.
4. "Recovery" will be defined by meeting all four of the following criteria: (i) a Chalder Fatigue Questionnaire score of 3 or less [27], (ii) SF-36 physical Function score of 85 or above [47,48], (iii) a CGI score of 1 [45], and (iv) the participant no longer meets Oxford criteria for CFS [2], CDC criteria for CFS [1] or the London criteria for ME [40].
Not given.
The commentary by Knoop & Bleijenberg talks about the percentage in "recovery" but doesn't use anything close to this definition (just to clarify, they don't give extra data).
5. The Hospital Anxiety and Depression Scale scores in both anxiety and depression sub-scales [38].
Given (both)
6. The Work and Social Adjustment scale provides a more comprehensive measure of participation in occupational and domestic activities [33].
Given (both)
7. The EuroQOL (EQ-5D) provides a global measure of the quality of life [39].
Not given
8. The six-minute walking test will give an objective outcome measure of physical capacity [31].
Given
9. The self-paced step test of fitness [43].
Not given
10. The Borg Scale of perceived physical exertion [44], to measure effort with exercise and completed immediately after the step test.
Not given
11. The Client Service Receipt Inventory (CSRI), adapted for use in CFS/ME [31], will measure hours of employment/study, wages and benefits received, allowing another more objective measure of function.
Not given
12. An operationalised Likert scale of the nine CDC symptoms of CFS [1].
Not given per protocol.
We are just give a composite yes/no score for the 8 CDC symptoms combined and a percentage present/absent score for two of the symptoms.
Likert scoring is the opposite of yes/no (or present/abscent) scoring
What they actually asked that patients at different stages about each of the symptoms was the following:
not present at all
present a little
presence more often than not
present most of the time
present all of the time
but we don't get this data.
13. The Physical Symptoms (Physical Health Questionnaire 15 items(PHQ15)) [35].
Not given
14. A measurement of participant satisfaction with the trial will also be taken at 52 weeks [53].
Given
Adverse outcomes
Adverse outcomes (score of 5–7 of the self-rated CGI) will be monitored by examining the CGI at all follow-up assessment interviews [49]. An adverse outcome will be considered to have occurred if the physical function score of the SF-36 [28] has dropped by 20 points from the previous measurement. This deterioration score has been chosen since it represents approximately one standard deviation from the mean baseline scores (between 18 and 27) from previous trials using this measure [23,25]. Furthermore, the RN will enquire regarding specific adverse events at all follow-up assessment interviews.
Not given per protocol
A lot of people would miss this but they redefined it to be “any two consecutive assessment interviews” [Quote:
“Serious deterioration in health was defined as any of the following outcomes: a short form-36 physical function score decrease of 20 or more between baseline and any two consecutive assessment interviews”] Comment: it is already hard for a patient to drop 20 points on the SF-36.
