The PACE Trial Recovery Rates

The PACE Trial Protocol states that: "Recovery" will be defined by meeting all four of the following criteria: a Chalder Fatigue Questionnaire score of 3 or less [27], SF-36 physical Function score of 85 or above [47,48], a CGI score of 1 [45], and the participant no longer meets Oxford criteria for CFS or the London criteria for ME [40].
1. 2. 3. 4.

[2],

CDC criteria for CFS

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This could not be more straightforward. All the data for the above must be readily available. Yet the Lancet article reporting the PACE Trial results makes only one reference to recovery and that is in a description of the rationale for Adaptive Pacing Therapy (APT). For those frustrated by the omission this article will attempt to provide some figures and analysis working from the restricted data that was published; though it cannot explain why the researchers went to the trouble to define and publish Recovery criteria in the Protocol then completely omitted this data in the results. The PACE Protocol states: The trial will be conducted in compliance with the Declaration of Helsinki. The Declaration of Helsinki is a set of ethical guidelines for medical research which states:
27. Both authors and publishers have ethical obligations. In publication of the results of research, the investigators are obliged to preserve the accuracy of the results. Negative as well as positive results should be published or otherwise publicly available.

Until we see the official recovery data and an explanation for the omission from the Lancet article it will not be possible to evaluate why this information was withheld. In the interim some of the figures that were published in the Lancet can be used to estimate the number of recovered participants.

Recovery Condition 1. A Chalder Fatigue Questionnaire score of 3 or less

The first recovery criteria in the Protocol is a Chalder Fatigue Questionnaire score of 3 or less. The researchers published data from the questionnaire with a different scoring method to the Protocol (though using the raw data reconverting to the original method would be a simple matter). With the method used in the Lancet a maximum of 9 on a scale of 0 to 33 (0 very good, 33 very bad) is required to meet the criteria for recovery. Here is a chart from the Lancet showing the results:

This looks rather good. However, a score of 9 is not even visible on this chart. Here is exactly the same data adjusted to show the full scale of the Fatigue Questionnaire ranging from 0 to 33:

This does not look so impressive. The difference between treatment and control is small. It is certainly not a difference that one would associate with an effective treatment. Compared to the PACE Trials own criteria for recovery, or to van Kessel et al, the PACE Trial results are very poor. (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).

Recovery Condition 2. An SF-36 Physical Function score of 85 or above

Here is another graph from the Lancet showing Physical Function. This also does not show the recovery score, which is 85:

And here is the same data again expanded to show the full range of 0 to 100 (100=best, 0=worst). Seen in this context the difference between groups is minor:

The difference between treatment and no-treatment is smaller than the improvement seen in untreated participants. This does not accord with participants receiving an effective treatment. The cohorts are not remotely close to recovery.

Recovery Condition 3. A CGI score of 1

The third Recovery criteria in the PACE Protocol is the Clinical Global Impression of change in overall health (CGI). With no reason given, this 7 point scale was condensed into 3 grades in the Lancet: Positive change was defined as very much better or much better. Minimum change was defined as a little better, no change, or a little worse. Negative change was defined as much worse or very much worse. Therefore scores of 2 or 1 are undifferentiated, concealing how many actually met the recovery criteria. This chart shows the CGI results by percentage.

The grey columns show minimum change and indicate the percentage for whom treatment had a negligible effect. This is clearly the majority in every group. The red columns show negative change. Although few, these include any that may have suffered serious deterioration and must be weighed against any advantages of treatment. The green columns show the percentage getting positive change. GET and CBT had only around 10% more than APT which was not considered a viable treatment and 15% more than SMC - the Control Group.

These poor results show that the treatments are not treatments at all. Furthermore, those recording very much better (score=1, meeting recovery criteria) with this measure, could have been the severely ill participants who improved enough to say that they were very much better, yet still remained significantly impaired. Such participants would obviously not meet the other 3 criteria for recovery.

Recovery Condition 4. No Longer Meets Diagnostic Criteria for CFS

The fourth criteria for recovery requires that the participant no longer meets Oxford criteria for CFS, CDC criteria for CFS or the London criteria for ME. The Lancet provided no data for participants meeting this measure. However, the Lancet results include the mean (average) CFS Symptom Count. Here is this data put in a chart:

As with the CGI data, the data for the Symptom Count is not correlated in the research report with other measures, so it is only a guide. This shows the mean number of symptoms, i.e., the number of symptoms an average participant had. It is just possible that a few participants may have had one or zero symptoms at outcome. If a participant had one symptom and that was fatigue then the participant could still meet the Oxford criteria for CFS and would not be recovered. Participants with zero symptoms would almost certainly meet the other criteria for recovery; but then why has the correlation not been established and the figures for recovery duly published? The vast majority of participants obviously still had multiple symptoms and once more, these poor results suggest that the treatments on trial are not effective treatments for M.E. or CFS.

Conclusion
Given the very poor results of the PACE Trial which prove that GET and CBT are not in fact, treatments for M.E. or CFS; and the failure of the therapies to get the PACE Trial cohorts remotely close to the recovery criteria, it seems safe to estimate: The recovery rate of the target illnesses with the therapies on trial was 0%.

If authoritative contradictory data becomes available it will be my pleasure to publish a correction. Peter Kemp December 2012