Malcolm Hooper PhD, B Pharm, MRIC, C Chem
Professor of Medicinal Chemistry,
University of Sunderland
THE PACE TRIAL – 3Ts OF CRITICISM
TRAVESTY OF SCIENCE
TRAGEDY FOR PATIENTS/CARERS
TANTAMOUNT TO FRAUD
A TRAVESTY OF SCIENCE
ALL IS NOT FINE WITH THE PACE TRIAL
SAME PRE-DETERMINED PRIMARY OUTCOME MEASURES BASED ON
PHYSICAL FUNCTIONING - SF-36 SUBSCALE
FATIGUE – Chalder Bimodal Fatigue Scale
PRIMARY OUTCOMES
SF-36 SCORE - 75% OR MORE - ENTRY 70% OR LESS
FATIGUE CHALDER SCALE 3 OR LESS - ENTRY 4 OR MORE
FINE CONCLUSIONS…..the effect is small and not statistically
significant at one year followup……..
CBT/GET, AS MEASURED BY THESE PARAMETERS IS NOT
EFFECTIVE IN TREATING OR MANAGING CFS/ME
PACE
SF-36 SCORE – ENTRY 60,65, 70
60 (11)
65*
70
SF-36 SCORES – OUTCOMES –NORMAL RANGE +/- 1 SD
60
65
70
75
80
85
- 5%
ALL A.A.
A. W.A.
90
CHALDER FATIGUE 11-PONT BIMODAL SCALE
ENTRY – 4 OR MORE LATER RAISED TO 6 POINTS TO AVOID
ONLY TRIVIAL DIFFERENCES – [3 OR LESS NORMAL
FATIGUE]
OUTCOMES- DATA COLLECTED USING CF BIMODAL SCALE
ANALYSIS NOT DONE –DATA EXPRESSED AS LIKERT
SCALE- A 33 POINT SCALE WHICH DOES NOT SIMPLY
RELATE TO CF SCALE BUT CLAIMED TO IDENTIFY SMALL
DIFFERENCES
FINE – data had been re-analysed by Likert found
clinically
modest but statistically significant effect on fatigue [but no
effect on physical functioning.]
REVISED OUTCOMES - INTERCONVERSION
CHALDER
LIKERT
4
8 – 19
5
10 -21
6
12 – 23
9
18 -29
18 ON LIKERT SCALE ALWAYS INDICATES ABNORMAL
FATIGUE; EQUATES TO CHALDER 4, 5, 6 … 9. ENTRY
LEVELS FOR FATIGUE IN ‘THE NORMAL RANGE’ MAY BE
HIGHER THAN LEVEL AT ENTRY INTO THE TRIAL.
SOME PEOPLE MAY HAVE DETERIORATED AT THE END OF
THE TRIAL – CONFUSION WORSE CONFOUNDED
WHAT IS NORMAL? –A KEY QUESTION THAT NEEDS TO BE
ADDRESSED.
THREE “NORMATIVE” DATA BASES USED
1. ALL ADULT SF- 36 VALUES PHYSICAL FUNCTION
2. ALL WORKING ADULT WORKING POPULATION SF-36
VALUES
3. ADULT ATTENDEES AT GENERAL PRACTICES IN UK
[MEASURED 1 YEAR PRIOR TO PACE TRIAL]
NO CONSIDERATION OF CONSEQUENCES OF KNOWN
HEAVILY SKEWED DATA FOR SF-36 DATA.
IF FATIGUE IS NORMALLY DISTRIBUTED IN THE
POPULATION IT IS THE ONLY HEALTH STATUS INDICATOR
THAT IS –NEEDS FURTHER COMMENT.
NO DISCUSSION OF PRE-DETERMINED ‘PRIMARY IN
RELATIONSHIP TO EFFICACY MEASURES’ TO THE
OUTCOME DATA IN LANCET PAPER
AN INDEPENDENT STATISTICAL ANALYSIS OF ALL THE
RAW DATA GENERATED IN THE TRIAL IS ESSENTIAL TO
ADDRESS THESE AND MANY OTHER FUNDAMENTAL
CRITICISMS
Other major comments
COMPARISON BETWEEN THE 4
GROUPS
CBT ALONE –
30% (14)
GET ALONE -
28% (12)
ADAPTIVE PACING -
16%
SSMC
15%
-
AT BEST THIS CAN
ONLY BE
REGARDED AS A
MODEST GAIN
FROM CBT AND
GET
THERE WAS NO CONTROL GROUP – AGE/SEX MATCHED
THE TRIAL WAS NOT A RANDOMISED CONTROLLED TRIAL
AS PROPOSED.
THERE WAS NO OBJECTIVE DATA – MAKING THE TRIAL
DATA ANECDOTAL!!
THE WALKING TEST AT END OF TRIAL REPLACED THE
ONLY OBJECTIVE MEASURE- ACTIGRAPHY – AND WAS SO
BADLY PERFORMED THAT IT WAS USELESS.
THE DISTANCE WALKED BY ALL GROUPS < THAN PEOPLE
WHO ARE ILL WITH COPD, TBI, THE ELDERLY.
CBT GROUP < SMC
AN OBJECTIVE TEST WAS AVAILABLE FROM PDW’S OWN
WORK ON TNF-ALPHA. THIS ALSO INDICATED THE
DELAYED EFFECTS OF POST-EXERTIONAL MALAISE.
White et al JCFS 2004;12:57-66.
POST-EXERTIONAL MALAISE – THE CARDINAL SIGN OF
M.E. WAS NOT A NECESSARY CRITERION FOR CFS/ME
OXFORD CRITERIA DESCRIBES ONLY IDIOPATHIC FATIGUE
– WHATEVER ITS ORIGIN.
THE LONDON CRITERIA – NEVER VALIDATED- WERE USED
TO CREATE A NEW VERSION THAT WAS SUITED TO THE
AIMS OF THE STUDY.
ADAPTIVE PACING IS NOT PACING AS COMMONLY USED
AND FOUND HELPFUL BY THE M.E. COMMUNITY.
IT INVOLVES STRUCTURED EXERCISE (GET?) AND ITS
FAILURE MAY REFLECT THAT.
“The PACE trial paper refers to chronic fatigue syndrome
(CFS) which is operationally defined;
it does not purport to be studying CFS/ME”.
PDW – letter to Editor of Lancet
FACTUALLY INCORRECT – WHO ICD-10 MAKES CFS AND
ME EQUIVALENT TERMS IN G.93.3; NEUROLOGICAL
CONDITIONS
FACTUALLY INCORRECT – VIRTUALLY ALL, THE 2000
PAGES, OF TRIAL DOCUMENTATION REFER TO CFS/ME
This gives the game away – the whole trial was designed
to justify the labelling of ME (a neurological condition) as
CFS (a mental and behavioural, somatoform disorder).
OVER ALL THE TRIAL, DATA AND ANALYSIS ARE
CONFUSED, CONVOLUTED, CONTRADICTORY,
MISREPRESENTATIVE.
MANIPULATION OF BENCHMARKS LEADS TO AN ABSURD
SITUATION WHERE THE SAME OR LOWER ENTRY SCORE IS
DEEMED TO REPRESENT A SUCCESSFUL OUTCOME.
THE SERIOUSLY FLAWED TRIAL ATTEMPTS TO JUSTIFY
THE PSYCHIATRIC VIEW OF CFS/ME
ONLY A ‘ROOT & BRANCH’ INDEPENDENT ANALYSIS OF
ALL THE RAW DATA WILL CLARIFY THESE ISSUES. IT IS
URGENTLY NEEDED.
MEANWHILE ALL CONCLUSIONS DRAWN FROM THE TRIAL
MUST BE PUBLICLY RESCINDED IN THE SCIENTIFIC
LITERATURE, POPULAR MEDIA, DWP, MRC, NICE,
GOVERNMENT & BENEFITS/INSURANCE INDUSTRY.
A TRAGEDY FOR PATIENTS
DENIED APPROPRIATE MEDICAL CARE (25% Group)
REGARDED AS DELUDED (FALSE ILLNESS BELIEF)
SPOILT CHILDREN
LAZY (S Wessely)
MANY FALSE AND MISSED DIAGNOSES
SUBJECT TO THE MANTRA
DO NOT LISTEN TO YOUR OWN BODY’S SIGNALS
DO NOT TRUST YOUR OWN FEELINGS
DO NOT TRUST YOUR OWN THOUGHTS (Wilhelmsen 2005)
BENEFITS WILL BE CHALLENGED, REMOVED OR SIGNIFICANTLY REDUCED
SECTIONING UNDER MENTAL HEALTH ACT (ADULTS/CHILDREN, MSBP)
MYALGIC ENCEPHALOMYELITIS
“NEVER IN THE FIELD
OF MODERN MEDICINE
HAS SO MUCH HARM
BEEN DONE TO SO
MANY BY SO FEW”.
Dr Irving Spurr Liverpool ME Seminar 2011
NICE GUIDELINE – “UNFIT FOR PURPOSE” – WILL CONTINUE UNCHALLENGED
AND DESTRUCTIVE ADVICE WILL BE SENT OUT TO PATIENTS & DOCTORS
….interventions recommended in the original guideline, such
as CBT and GET, were described as the interventions for
which there is the clearest evidence-base of benefit.
This is supported by the recently published PACE trial….The
results of the study are in line with current NICE guideline
recommendations on the management of CFS/ME….There are
no factors…which would invalidate or change the direction of
the current guideline recommendations. The CFS/ME
guideline should not be updated at this time”.
“The PACE findings can be generalised to patients who
also meet alternative diagnostic criteria for chronic fatigue
syndrome and myalgic encephalomyelitis but only if
fatigue is their main symptom”. Lancet 2011
TANTAMOUNT TO FRAUD
IT DOES NOT DO WHAT
IT SAYS ON THE TIN
NOT A RANDOMISED
CONTROLLED TRIAL
NO ENGAGEMENT WITH PRE-DETERMINED PRIMARY
EFFICACY MEASURES. ONLY SECONDARY MEASURES.
NO OBJECTIVE DATA – ONLY SUBJECTIVE REPORTING.
Failed to provide “high quality evidence” promised
”The world cannot be divided into ‘the ill’ and the ‘well’ on the
basis of the degree of Fatigue.” S.Wessely, 1998
FINE and PACE STUDIES are predicated on this possibility.
If this was acknowledged in 1998 then why were the FINE and
PACE studies funded at >£6million along with the Fatigue
Clinics – this is not value for money!
Science, Medicine, people and money have been sacrificed
in an ideological attempt to impose a false understanding of
the illness.
To witness so many in a once respected occupation so easily
being made to look foolish by psychiatric creationism
suggests strongly that perhaps one wouldn't even need to be
able to think for oneself in order to practice medicine in the
UK - a rather frightening situation for us all. Dr from Australia
The media, popular, scientific and medical have been
prostituted by the grandiose presentation of the trial
“results”, media spin, and attempts to disallow any criticism
of the Trial.
Reminiscent of totalitarian regimes which Britain claims to
abhor.
SOMATISATION PAR EXCELLENCE [Hysteria]
“CAUSATION
FORGET IT!!!!”
WHAT DO YOU THINK OF PACE TRIAL,NHS
TREATMENT AND NICE GUIDELINES?
Courtesy of Dr Irving Spurr, 2011
ME – A CHRONIC, PROGRESSIVE, COMPLEX, MULTI-SYSTEM ILLNESS
EV
HERPES
OTHER
VIRUSES
CHEMICALS
VACCINES
INTRACELLULAR ORGANISMS.
LYME, Q-FEVER, MYCOPLASMAS,
CHLAMYDIA
TBI
ME-LIKE
SYMPTOMS
MIXTURE
OF SUBGROUPS
MULTIPLE SYMPTOMS CV, CNS, ANS, IMMUNE, ENDOCRINE
SUMMARY SLIDE – ITS MAKES SENSE!
C
O
M
P
L
E
X
I
L
L
N
E
S
S
Cancer (Prostate)
Thyroid, NHL Hyde
Inflammation
Cardiovascular Disease
Vance Spence et al
ME
MANY
SYMP
Genetics – Kerr et al, Gow et al
Proteomics –Schutzer, Kogelnik
TOMS
RNaseL Immune Dysregulation
Autoimmunity De Meirleir et al
Virus Susceptibility
Enteroviruses Coxsacchie B
Herpes EBV etc Richardson,
Chia, Lerner
M
A
N
Y
I
N
S
U
L
T
S
T
Hypothesis
Insults
A
B
C
D
E
F
G
H
I
J
K
Initial processes
Final common
pathway(s)
CFS/ME
Courtesy of Jonathan
Kerr JID 2008
PROTEOMICS Separation of proteins in CSF in Neurologic post treatment Lyme
Disease and ME-CSF patients Schutzer et al 2011
TREATMENT. [ACUTE/CHRONIC PHASE].
How do I achieve and maintain*Improvement*
• EARLY DIAGNOSIS. Hospital or Home
• MINIMAL ACTIVITY. Rest sick cells
• STRESS REDUCTION. Home tuition.
Flexi-hours. Benefit payments.
• IMMUNE REGULATION with IGG
• Defer Pregnancy.
• “Grandma’s Organic Cooking”
• CHOLINE/VITC
WHICH OF THESE TWO CAN HAVE A ROUTINE
TEST FOR VP1 – ENTEROVIRUS MARKER
TREATMENTS VIRUSES – ANTIVIRAL AGENTS
POOLED Human IgG (IM,IV)- ADOLESCENTS (RICHARDSON et al,
Ben Nathan)
ANTIVIRALS –VALGANCiCLOVIR et al (HERPES FAMILY), Lerner,
Montoya et al RCT in submitted for subset .
PLECONARIL - picornaviruses, enteroviruses, rhinoviruses etc ?
INTERFERONS ( b- KERR),
AMPLIGEN etc (DER MEIRLEIR) - LIMITED
LAURICIDIN
OLIVE LEAF EXTRACT
OXYMATRINE- CHINESE HERBAL EXTRACT- (CHIA)
ANTIRETROVIRALS RALTEGRAVIR/AZT OTHERS ?
OTHER ORGANISMSCHLAMYDOPHILA, RICKETTSIA, BORRELIA, MYCOPLASMAS
DOXYCYCLINE, CLARITHROMYCIN, MINOCYCLINE, AZITHROMYCIN,
QUINOLONES(CIPROFLOXACIN etc), CHLORAMPHENICOL. Prolonged – 6 weeksand repeat cycles (2-6) with spacing to check on evidence of infection.
ESSENTIAL TO SUPPORT GENERAL HEALTH AND ESPECIALLY TO
PROTECT THE GUT-
PRO- & PRE-BIOTICS
VITAMINS/MINERAL SUPPLEMENTS
GUT ENZYMES
GLUTAMINE
Nicolson CFIDS Chronicle September/October 1999.
COMPASSION- THOUGHT – CARE ARE NEEDED
EFFECTIVE TREATMENTS ARE AVAILABLE NOW?
MORE RESEARCH BIOMEDICAL IS DEFINITELY
NEEDED MUCH MORE FUNDING IS NEEDED
PATIENTS AND CARERS NEED SUPPORT AND
HELP
WHY ARE WE DOING NOTHING AND PREVENTING
PROVEN TREATMENTS?
Thank you