Presentation on theme: "University of Sunderland"— Presentation transcript:
1University of Sunderland Malcolm Hooper PhD, B Pharm, MRIC, C ChemProfessor of Medicinal Chemistry,University of SunderlandTHE PACE TRIAL – 3Ts OF CRITICISMTRAVESTY OF SCIENCETRAGEDY FOR PATIENTS/CARERSTANTAMOUNT TO FRAUD
3ALL IS NOT FINE WITH THE PACE TRIAL SAME PRE-DETERMINED PRIMARY OUTCOME MEASURES BASED ONPHYSICAL FUNCTIONING - SF-36 SUBSCALEFATIGUE – Chalder Bimodal Fatigue Scale
4FINE CONCLUSIONS- PRIMARY OUTCOMES SF-36 SCORE - 75% OR MORE - ENTRY 70% OR LESSFATIGUE CHALDER SCALE 3 OR LESS - ENTRY 4 OR MOREFINE 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
6CHALDER 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 SCALEANALYSIS NOT DONE –DATA EXPRESSED AS LIKERT SCALE- A 33 POINT SCALE WHICH DOES NOT SIMPLY RELATE TO CF SCALE BUT CLAIMED TO IDENTIFY SMALL DIFFERENCESFINE – data had been re-analysed by Likert found clinically modest but statistically significant effect on fatigue [but no effect on physical functioning.]
7REVISED OUTCOMES - INTERCONVERSION CHALDER LIKERT– 19– 2318 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
8WHAT IS NORMAL? –A KEY QUESTION THAT NEEDS TO BE ADDRESSED. THREE “NORMATIVE” DATA BASES USEDALL ADULT SF- 36 VALUES PHYSICAL FUNCTIONALL WORKING ADULT WORKING POPULATION SF-36 VALUESADULT 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.
9NO DISCUSSION OF PRE-DETERMINED ‘PRIMARY IN RELATIONSHIP TO EFFICACY MEASURES’ TO THE OUTCOME DATA IN LANCET PAPERAN INDEPENDENT STATISTICAL ANALYSIS OF ALL THE RAW DATA GENERATED IN THE TRIAL IS ESSENTIAL TO ADDRESS THESE AND MANY OTHER FUNDAMENTAL CRITICISMS
10COMPARISON BETWEEN THE 4 GROUPS CBT ALONE – 30% (14) Other major commentsCOMPARISON BETWEEN THE 4 GROUPSCBT ALONE – 30% (14)GET ALONE - 28% (12)ADAPTIVE PACING - 16%SSMC %AT BEST THIS CAN ONLY BE REGARDED AS A MODEST GAIN FROM CBT AND GETTHERE WAS NO CONTROL GROUP – AGE/SEX MATCHEDTHE TRIAL WAS NOT A RANDOMISED CONTROLLED TRIAL AS PROPOSED.
11THERE 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 < SMCAN 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.
12POST-EXERTIONAL MALAISE – THE CARDINAL SIGN OF M. E POST-EXERTIONAL MALAISE – THE CARDINAL SIGN OF M.E. WAS NOT A NECESSARY CRITERION FOR CFS/MEOXFORD 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.
13it does not purport to be studying CFS/ME”. “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 LancetFACTUALLY INCORRECT – WHO ICD-10 MAKES CFS AND ME EQUIVALENT TERMS IN G.93.3; NEUROLOGICAL CONDITIONSFACTUALLY INCORRECT – VIRTUALLY ALL, THE 2000 PAGES, OF TRIAL DOCUMENTATION REFER TO CFS/METhis 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).
14OVER 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/MEONLY 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.
15A TRAGEDY FOR PATIENTS DENIED APPROPRIATE MEDICAL CARE (25% Group) REGARDED AS DELUDED (FALSE ILLNESS BELIEF)SPOILT CHILDRENLAZY (S Wessely)MANY FALSE AND MISSED DIAGNOSESSUBJECT TO THE MANTRADO NOT LISTEN TO YOUR OWN BODY’S SIGNALSDO NOT TRUST YOUR OWN FEELINGSDO NOT TRUST YOUR OWN THOUGHTS (Wilhelmsen 2005)BENEFITS WILL BE CHALLENGED, REMOVED OR SIGNIFICANTLY REDUCEDSECTIONING UNDER MENTAL HEALTH ACT (ADULTS/CHILDREN, MSBP)
16MYALGIC 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 201116
17NICE 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
18IT DOES NOT DO WHAT IT SAYS ON THE TIN TANTAMOUNT TO FRAUDIT DOES NOT DO WHAT IT SAYS ON THE TIN
19NO OBJECTIVE DATA – ONLY SUBJECTIVE REPORTING. NOT A RANDOMISED CONTROLLED TRIALNO 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, 1998FINE 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!
20Reminiscent of totalitarian regimes which Britain claims to abhor. 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 AustraliaThe 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.
21SOMATISATION PAR EXCELLENCE [Hysteria] “TB” “ME”“CAUSATIONFORGET IT!!!!”CFS PATHWAY PANEL- courtesy of Dr Spurr21
22WHAT DO YOU THINK OF PACE TRIAL,NHS TREATMENT AND NICE GUIDELINES? RUBBISH!!Courtesy of Dr Irving Spurr, 201122
23ME – A CHRONIC, PROGRESSIVE, COMPLEX, MULTI-SYSTEM ILLNESS EVHERPESOTHER VIRUSESCHEMICALSVACCINESINTRACELLULAR ORGANISMS. LYME, Q-FEVER, MYCOPLASMAS, CHLAMYDIATBIME-LIKE SYMPTOMSMIXTURE OF SUB-GROUPSMULTIPLE SYMPTOMS CV, CNS, ANS, IMMUNE, ENDOCRINE
24ME MANY SYMPTOMS SUMMARY SLIDE – ITS MAKES SENSE! Cancer (Prostate) Thyroid, NHL HydeCOMPLEXI LLNESSMANY INSULTSTInflammation Cardiovascular Disease Vance Spence et alME MANY SYMPTOMSGenetics – Kerr et al, Gow et al Proteomics –Schutzer, KogelnikRNaseL Immune Dysregulation Autoimmunity De Meirleir et alVirus Susceptibility Enteroviruses Coxsacchie B Herpes EBV etc Richardson, Chia, Lerner
25CFS/ME Hypothesis Initial processes Insults BCDEFGHIJKFinal common pathway(s)CFS/MEInsultsInitial processesCourtesy of Jonathan Kerr JID 2008This is my hypothesis of the cumulative factors which underlie the development of CFS. There are various insults (virus infection, emotional stress, vaccination, etc) which give rise to various initial processes. But, it is the final common pathways that we are particularly interested in, which are involved in perpetuation of the phenotype of CFS. This is what we are aiming to study with our gene expression studies.
26PROTEOMICS Separation of proteins in CSF in Neurologic post treatment Lyme Disease and ME-CSF patients Schutzer et al 2011
27EARLY DIAGNOSIS. Hospital or Home MINIMAL ACTIVITY. Rest sick cells TREATMENT. [ACUTE/CHRONIC PHASE] How do I achieve and maintain*Improvement*EARLY DIAGNOSIS. Hospital or HomeMINIMAL ACTIVITY. Rest sick cellsSTRESS REDUCTION. Home tuition. Flexi-hours. Benefit payments.IMMUNE REGULATION with IGGDefer Pregnancy.“Grandma’s Organic Cooking”CHOLINE/VITC27
28WHICH OF THESE TWO CAN HAVE A ROUTINE TEST FOR VP1 – ENTEROVIRUS MARKER
29TREATMENTS 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) - LIMITEDLAURICIDINOLIVE LEAF EXTRACTOXYMATRINE- CHINESE HERBAL EXTRACT- (CHIA)ANTIRETROVIRALS RALTEGRAVIR/AZT OTHERS ?
30OTHER ORGANISMS-CHLAMYDOPHILA, RICKETTSIA, BORRELIA, MYCOPLASMASDOXYCYCLINE, CLARITHROMYCIN, MINOCYCLINE, AZITHROMYCIN, QUINOLONES(CIPROFLOXACIN etc), CHLORAMPHENICOL. Prolonged – 6 weeks-and 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-BIOTICSVITAMINS/MINERAL SUPPLEMENTSGUT ENZYMESGLUTAMINENicolson CFIDS Chronicle September/October 1999.
31COMPASSION- THOUGHT – CARE ARE NEEDED EFFECTIVE TREATMENTS ARE AVAILABLE NOW?MORE RESEARCH BIOMEDICAL IS DEFINITELY NEEDED MUCH MORE FUNDING IS NEEDEDPATIENTS AND CARERS NEED SUPPORT AND HELPWHY ARE WE DOING NOTHING AND PREVENTING PROVEN TREATMENTS?Thank you