The PACE Trial Alternative Cost Analysis Introduction The PACE Trial (Lancet 2011; 377: 82336) cost

5 million. A lot of that was taxpayers money but who will benefit and how? A cost effectiveness analysis of the treatments on test (McCrone et al 2012) was published by PLOSone (http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0040808). The following informal analysis will examine wider issues and costs. PACE Trial participants received either Cognitive Behaviour Therapy (CBT); Graded Exercise Therapy (GET); Adaptive Pacing Therapy (APT) or Specialist Medical Care (SMC the Control Group). Theories CBT was intended to treat fear avoidance by rationalizing painful symptoms and anxiety about activity. This would enable the participant to work through the pain and anxiety preventing recovery to normal functioning. GET was intended to overcome deconditioning theorised to be preventing recovery due to a lack of fitness and unpleasant symptoms caused by long illness. These rehabillitiation therapies were derived from wessely-school theories which also assume that there is no physical illness or injury to prevent return to normal life. Results The trial results for improved show that GET had an effect for 16% and CBT for 14% compared to the SMC control group. The results for normal ranges show that GET had an effect for 13% and CBT for 15%. Thus around 15% of patients improved or reached normal ranges with GET or CBT. This produced a number needed to treat (NNT) figure of 7. For every 7 patients treated with one of these therapies, one will improve. APT a Secondary Control Group? The researchers concluded that APT is not an effective treatment: APT was no better than was SMC alone. Therefore APT data from the PACE Trial represents a valid Secondary Control Group. It matched all research conditions and provided participants with an effectively blinded placebo-like treatment, yet being ineffective it represents an excellent secondary control group highly suitable for comparison.
The data shows that GET and CBT resulted in Positive Change in only 10% more

participants compared to APT. CBT is 10 (ten).

The resulting Number Needed to Treat to achieve positive change with GET or
(GET EER=0.417; CBT EER=0.415; APT EER=0.307; GET NNT=10 (9.43) CBT NNT=10 (9.26).)

The FINE Trial, published a year earlier, established that rehabilitation therapies do not benefit severely ill patients (BMJ 2010:340:c1777). If the PACE Trial had included 25% of severely ill patients to reflect the general patient population it is reasonable to project that Positive Change resulting from GET or CBT would have occurred in 8%. 1

Due to Research conditions and other factors Clinical Trial results are rarely matched in practice. It is reasonable to deduct a very modest 1% to allow for this; making Positive Change likely in 7%, producing a more realistic NNT of 15. Treatment targets Physical Function Measures The researchers decided that an SF36 score of 60 was normal range. This is 24 points below the UK mean (average) of 84 in the working age population. The difference in physical function between GET or CBT and the Control Group was 9.1 and 7.4 respectively on a scale of 100. Just 2 changes in the way the participant completed the SF-36 questionnaire could account for this level of difference. Here is a sample Physical Function form showing 2 changes:

By changing just 2 ratings from limited a little to not limited at all the SF36 Physical Function improves by 10 points. This is MORE than the difference between GET or CBT and the Control Group. (http://www.sf-36.org/demos/SF-36.html) A Physical Function score of 60 meets the PACE Trial benchmark for Normal Ranges. However, any score of 65 or lower was considered bad enough to ENTER the PACE Trial. (The Lancet Vol 377 March 5, 2011 p.826)

Fatigue Measures The difference in Fatigue between GET or CBT and the Control Group was 3.2 and 3.4 respectively on a scale of 33 (where 33 is the worst score). Here is an illustration of this difference: 2

(for information about anomalies with the Chalder Fatigue Scale in the PACE Trial please see: http://evaluatingpace.phoenixrising.me/aps3chalder.html#a)

Chalder Fatigue Questionnaire (PACE Trial Full Protocol p.162)

SCORE: Do you have problems with tiredness? Do you need to rest more? Do you feel sleepy or drowsy? Do you have problems starting things? Do you lack energy? Do you have less strength in your muscles? Do you feel weak? Do you have difficulty concentrating? Do you make slips of the tongue when speaking? Do you find it more difficult to find the correct word?
Better than usual 0 Less than usual 1 No more than usual 2 More than usual 3 Much more than usual

X X X X X X X X X X

X X X
No worse than usual

Worse than usual

Much worse than usual

How is your memory?

X FATIGUE = 24 : FATIGUE = 20

This is MORE than the difference between GET/CBT and the Control Group

The PACE Trial determined that a participant score of 18 or less on the Chalder Fatigue Scale meant that fatigue was normal range. Here is an example of what a normal range might look like:
Less than usual No more than usual More than usual Much more than usual

Do you have problems with tiredness? Do you need to rest more? Do you feel sleepy or drowsy? Do you have problems starting things? Do you lack energy? Do you have less strength in your muscles? Do you feel weak? Do you have difficulty concentrating? Do you make slips of the tongue when speaking? Do you find it more difficult to find the correct word?
Better than usual

X X X X X X X X X X
No worse than usual Worse than usual Much worse than usual

How is your memory?

This chart would score 18 and is what the PACE Trial decided was normal. This level of fatigue was also considered severe enough to ENTER the Trial Yet even with such inexplicably low targets for Physical Function and Fatigue (which GET and CBT were supposed to treat): 3

 111 of 154 (72%) in the GET group DID NOT reach normal ranges 104 of 148 (70%) in the CBT group DID NOT reach normal ranges

Small Effects Van Kessel et al employed the Fatigue Scale in A Randomized Controlled Trial of Cognitive Behavior Therapy for Multiple Sclerosis Fatigue.
(Psychosomatic Medicine February/March 2008 vol. 70 no. 2 205-213)

The average fatigue score of their 72 healthy control subjects was 12.5 At 6 months follow-up, fatigue in participants with MS receiving CBT had changed from 20.94 to 10.37. The baseline fatigue in Multiple Sclerosis participants, which was considered severe enough to be worth treating, was virtually the same as the outcome from GET and CBT in the PACE Trial.

FATIGUE SCALE: 33=worst 0=best 12=healthy score Research has found that Exercise Therapy and Cognitive Behaviour Therapy can be useful adjuncts to regular treatment of diverse physical conditions such as MS, Parkinsons, arthritis, heart disease, etc; improving fatigue, physical function and other factors. Therefore GET and CBT are expected to produce improvements even when not affecting the underlying condition. The modest effect with these therapies in PACE Trial correlates with their effect in other diseases. As with other diseases, failure to cure or restore participants to normal functioning strongly suggests that there is underlying pathology in participants not ameliorable with GET or CBT. With small effects and only 10% reaching criteria for a Positive Outcome, the only rational conclusion is that GET and CBT are not treatments for M.E. and CFS. If the theories that suggested these treatments were correct then the majority should have improved enough to resume a normal active life and many should have made a full recovery.

Human Costs and Monetary Costs Due to the way that the results of the trial were published and publicised in the media, it seems that some doctors and patients believe that GET and CBT are effective treatments for M.E. and CFS. Therefore a cost analysis of the PACE Trial cannot be based only on what the research discovered. It must consider what people believe it discovered and discrepancies between beliefs and reality.

A predictable result of ill-informed doctors sending their patients for GET or CBT will be disappointment in over 90% of cases. Instead of only NOT benefiting from the research, as many as 14 out of 15 patients and their doctors may have the added burden of wasted time, energy, money and disappointment. The doctor/patient relationship and quality of care provided may suffer as a result. Referred patients would be seeing either GET or CBT therapists. Dedicated therapists who mistakenly believe that GET or CBT effectively treat M.E. and CFS may well be disappointed (not to say confused) when most hardly benefit at all and may in fact be made worse. Therapists may question the commitment of their client and the client may question the competence of the therapist. The therapeutic relationship could decline into an abusive one, adding to the suffering of the patient and leading to accusations and complaints. As well as damaging a patients medical support; misperceptions about what the PACE Trial actually showed may lead to widespread scepticism and criticism of patients for not improving with GET or CBT. Family, partners and friends; employers, teachers etc., may withdraw support and blame the patient for not improving. Patients in receipt of Sickness Benefits will encounter doctors and staff from the DWP, ATOS, their employers and insurance companies who may mistakenly believe that the PACE Trial proved that M.E. and CFS can be treated with GET and CBT. They may believe that this means the illnesses are simply lack of fitness and oversensitivity to pain. As a result many could be refused state and other financial support for sickness and may be forced to claim Unemployment Benefits and actively seek and accept employment even though they are too ill to work; or depend on support from others or simply be left to starve and die.

Estimated Numbers Estimates put the number of M.E. and CFS patients in the UK at around 150,000. At 2,000 per treatment with GET or CBT plus SMC the cost of treating all patients would be 300 million. With a number needed to treat figure of 15; 140,000 patients would experience little or no benefit. 300 million to help 10,000 patients might not be excessive if those patients were cured or at least restored to a normal, active life. Unfortunately, the vast majority of this 10,000 would continue to have significant illness and impairment requiring medical, social and financial support. 5

There is substantial and convincing evidence that shows that CBT and GET can worsen the condition of patients with M.E. and CFS, e.g.: the ME Association survey of 4,217 patients and carers in 2010 found that with GET (n=906) 33.1% were made much worse and with CBT (n=997) 7.9% were made much worse.
(http://www.meassociation.org.uk/wp-content/uploads/2010/09/2010-survey-report-lo-res10.pdf)

The deterioration of some patients receiving these therapies can be severe and longlasting. This could increase their dependency upon all forms of support and damage their long-term prospects for improvement. Not only has the PACE Trial failed to give adequate warnings about this, it may actually increase the risk because of false reports about what GET and CBT can realistically achieve. The added costs incurred in the forms of extra support, prolonged illness and suffering should be considered. Research for Researchers The data shows that the theories espoused by the wessely-school over many years are wrong. The researchers are supporters of these theories. This raises questions about the knowledge, skill and motives of this group. Yet far from being required to address concerns about the research their lucrative status as experts on M.E. and CFS appears to be protected. As well as publishing the results of the PACE Trial, The Lancet also published a favourable editorial and hosted interviews with researchers. Richard Horton, the editor of The Lancet, has appeared on a radio show, praising the research and the researchers, whilst seemingly unfamiliar with the actual findings of the research that his journal published; and apparently, little understanding of the reason why Conflicts of Interest have been significant to publishers and readers of journals for many, many years. (http://www.abc.net.au/radionational/programs/healthreport/comparison-oftreatments-for-chronic-fatigue/2993296)

The Science Media Centre (SMC) which hosted the press conference for the publication of the PACE Trial in The Lancet declare: The overall goal of the Centre is to help renew public trust in science by working to promote more balanced, accurate and rational coverage of the controversial science stories that now regularly hit the headlines. (http://www.sciencemediacentre.org/uploadDir/536adminconsultation_report.pdf) The SMC expert for press inquiries about M.E. and CFS is Professor Simon Wessely who happened to be a Centre Leader in the PACE Trial. Following the SMC press conference for The Lancet publication these headlines appeared in the press:
(for more detail see: http://www.scribd.com/doc/112487732/Media-Coverage-of-the-PACE-Trial) The Daily Mail: Got ME? Fatigued patients who go out and exercise have best hope of recovery, finds study The Independent: Got ME? Just get out and exercise, say scientists The Guardian: Study finds therapy and exercise best for ME The Telegraph: Exercise and therapy can help ME sufferers, study claims The Daily Express: TRIAL OFFERS HOPE FOR ME SUFFERERS The Daily Record: Exercise and therapy can reverse effects of ME The Daily Star: TRIAL OFFERS HOPE FOR ME SUFFERERS Reuters: Pushing limits can help chronic fatigue patients

From the above it would appear that if the actual findings of the PACE Trial were widely publicized, it may cause embarrassment not only to the wessely-school but also to The Lancet and the Science Media Centre; as well as those members of the national Press who prefer to publish reliable information but mistakenly reported the PACE Trial as though it had discovered effective treatments for M.E. and CFS. UK tax-payers have already paid 5 million for a Clinical Trial that showed that GET and CBT do not treat M.E. or CFS. Yet they may end-up getting another bill of 300 million to provide these disproved therapies to patients. Financing research to identify and address the organic pathology of M.E. and CFS might lead to real treatments that can help patients with these diseases. Tax-payers might consider this a more rational investment of their money. Conclusion The PACE Trial appears to be a medical and scientific mirage that could end-up costing UK tax-payers 300 million for treatments that do not work. Science has been relegated to spin. Medicine has been relegated to pride and vested interests. This is bad for society, science, medicine, research, publishing, patients, physicians, therapists and tax-payers. Peter Kemp November 2012

Reference McCrone P, Sharpe M, Chalder T, Knapp M, Johnson AL, et al. (2012) Adaptive Pacing, Cognitive Behaviour Therapy, Graded Exercise, and Specialist Medical Care for Chronic Fatigue Syndrome: A Cost-Effectiveness Analysis. PLoS ONE 7(8): e40808. doi:10.1371/journal.pone.0040808. Online. Available at: http://www.plosone.org/article/citationList.action?articleURI=info%3Adoi %2F10.1371%2Fjournal.pone.0040808

Further information: http://www.scribd.com/doc/110421439/The-PACE-Trial-Psychiatrists-Spinning-Out-ofControl-4 http://www.meactionuk.org.uk/COMPLAINT-to-Lancet-re-PACE.htm http://www.investinme.org/Article400%20Magical%20Medicine.htm