Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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Phillips was answered
- Neville W Goodman (11 November 2005)
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Autism and MMR - no fiasco.
- Michael D Innis (11 November 2005)
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Why should the Daily Mail eat humble pie?
- John Stone (11 November 2005)
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On the limitations of RCTs and meta-analyses.
- Richard G Fiddian-Green (12 November 2005)
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Re: On the limitations of RCTs and meta-analyses.
- Andrew D Hutchinson (12 November 2005)
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Do RCTs overlook confounding?
- David Pitches (13 November 2005)
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Medical profession record on autism?
- Jenny L Robertson (14 November 2005)
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What's woeful
- Malcolm E Kendrick (14 November 2005)
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Eight years on
- John Stone (14 November 2005)
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What has to be done to lay this issue to rest?
- Onisillos Sekkides (14 November 2005)
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Re: This is What Has to Be Done to Lay This Issue to Rest
- Clifford G Miller (15 November 2005)
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Re: What has to be done to lay this issue to rest?
- John Stone (15 November 2005)
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Humble Pie Not on Menu
- Clifford G. Miller (15 November 2005)
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Re: Re: What has to be done to lay this issue to rest?
- Onisillos Sekkides (17 November 2005)
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Re:Re: What has to be done to lay this issue to rest?
- Joseph R. Herr (18 November 2005)
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Brain abnormalities at birth in autism
- Ellen C G Grant (18 November 2005)
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Humble pie?
- John P Heptonstall (19 November 2005)
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Re: What has to be done to lay this issue to rest?
- Charles R Whiting (19 November 2005)
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A question for Michael Fitzpatrick from an anxious member of the middle-classes
- John Stone (19 November 2005)
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Re: What has to be done to lay this issue to rest?
- Lisa C Blakemore-Brown (19 November 2005)
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Why we are in this position in the first place.
- Hilary Butler (20 November 2005)
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Cochrane, research bias and Dr Wakefield
- John Stone (22 November 2005)
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"The Next MMR" - but what about the present one?
- John Stone (25 November 2005)
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BBC: MMR not impacting on measles?
- John Stone (15 February 2008)
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mmr the choices
- Ian Fleming (26 April 2009)
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Re: mmr the choices
- Peter J Flegg (1 May 2009)
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Neville W Goodman, Consultant Anaesthetist Southmead Hospital, Bristol, BS10 5NB
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At least the Guardian (Nov 9) published some excellent letters in answer to Phillips' article, all of which were rightly highly critical of her. Competing interests: None declared |
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Michael D Innis, Not relevant Home
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Editor, Dr Fitzpatrick says, “the price of this self indulgence (Phillips is one of Britain's best paid journalists) is borne by the real victims of the MMR-autism fiasco. These are parents anxiously facing decisions about immunisation and parents of children with autism who carry an unwarranted burden of guilt over having had their children immunised.” The anxiety of these parents would be greatly relieved, I am sure, if Tony Blair announced he had his son immunized with MMR and if Dr Fitzpatrick could assure the anxious parents his own son, seen on Television, did not develop Autism within 28 days of being vaccinated with MMR. . “They have provided a voice for middle class anxieties” – middle class? middle class? Please explain Dr Fitzpatrick Michael Innis Competing interests: I believe Autism, as described by Wakefield et al; is an Immunecomplex disorder |
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John Stone, none London N22
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The conclusion of the Cochrane Review contrasts remarkably with - even contradicts - the headline: “We were disappointed by our inability to identify effectiveness studies with population or clinical outcomes. Given the existence of documented elimination of targeted diseases in large population by means of mass imunisation campaigns, however, we have no reason to doubt the effectiveness of MMR. “The safety record of MMR is possibly best attested by its almost universal use; its evaluation cannot be divorced from its effectiveness and the importance of the targeted diseases. As such MMR remains an important preventative global intervention.” This lack of conclusiveness about the matter is in fact astounding all these years after the controversy first blew up. It is also very interesting how in the end the endorsement of safety such as it is seems to be based on sentiment. What is "The safety record of MMR is best attested by its almost universal use" supposed to mean, and what are parents supposed to make of the statement "its evaluation cannot be divorced from its effectiveness and the importance of the targeted diseases"? This is scarcely reassuring, except to people of the faith like Michael Fitzpatrick. Competing interests: Autistic son |
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Richard G Fiddian-Green, None None
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"The recent publication of a Cochrane systematic review [concluded]..that there is "no credible evidence" of a link between the measles, mumps, and rubella (MMR) vaccine and either inflammatory bowel disease or autism"(1). It also concluded that, "The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate"(2). An importance issue in this context is the dose response to the cytokines presumably released by the vaccines. Might, for example, the combination of the three attenuated viruses in the MMR induce a far greater release of cytokines than each of the attentuated viruses on its own? The release of cytokines could in theory compromise tissue energetics either focally, regionally of systemicallly [and induce dysfunction, apoptopsis or even necrosis] especially if other pathology, such as another viral or bacterial infection, coexisted. The limitations of a RCT and a meta-analysis are that they overlook confounding variables in individuals unless screened for and specifically excluded propter hoc. At the end of the day is not pathophysiological logic a far more sensitive and arguably better form of proof of a risk of harm than the results of any RCT or even meta-analysis. 1. Michael Fitzpatrick. Why can't the Daily Mail eat humble pie over MMR? BMJ 2005;331:1148 (12 November), doi:10.1136/bmj.331.7525.1148 2. Demicheli V, Jefferson T, Rivetti A, Price D, Demicheli V. Vaccines for measles, mumps and rubella in children. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD004407. Competing interests: None declared |
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Andrew D Hutchinson, Head of Medicines Management South Leeds PCT
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Dr Fiddian-Green asked "At the end of the day is not pathophysiological logic a far more sensitive and arguably better form of proof of a risk of harm than the results of any RCT or even meta- analysis?" The answer is no. HRT preventing heart disease and ibuprofen inhibiting the antithrombotic effects of aspirin are just two examples which spring to mind, of pathophysiological logic which has not been borne out in actual clinical practice (see, for example, MHRA/EMEA evaluations of both). Disease oriented outcomes (DOOs) can be useful hypothesis generators and are much better than nothing at all, but they can throw us off the scent. We need to look for the POOs (patient oriented outcomes), tested in well conducted RCTs or large epidemiological studies. Competing interests: None declared |
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David Pitches, Specialist Registrar in Public Health Sandwell, B70 9LD
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Richard G Fiddian-Green writes "The limitations of a RCT and a meta- analysis are that they overlook confounding variables in individuals unless screened for and specifically excluded". But by definition a randomised controlled trial, so long as it is properly randomised, excludes the possibility of confounding variables accounting for observed results. This is because the very point of randomisation is not to exclude subjects with confouding variables but to ensure that they are randomly, and therefore equally, distributed across all arms of the trial. In which case each arm has by chance an equal proportion of confounding variables which therefore cease to be a potential explanation for different results in different arms of the trial. In the case of a systematic review and meta-analysis, individual trials should be assessed for methodological quality to ensure, amongst other things, that those with inadequate randomisation are excluded from the meta-analysis or at the very least subjected to a sensitivity analysis. Dr. David Pitches Specialist Registrar in Public Health Competing interests: None declared |
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Jenny L Robertson, Writer London
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Michael Fitpatrick's review is delightfully revealing. In a pompous tone he dismisses "middle class anxieties" and accuses Phillips of emotional journalism while engaging in some pretty emotive writing himself. The real clincher is the solemn announcement that journalists have a poor record on autism, written without an ounce of irony. What about the record of the medical profession? Surely that is far more relevant. What progress is being made by the medical profession in understanding, treating and supporting the thousands of children and families now afflicted? An obsession with "discrediting" certain people is sadly not going to help autistic children. The real scandal is the failure of the medical profession to get to grips with an even basic understanding of this growing problem and how it can best be managed, leaving autistic children and their families to research and develop their own strategies as best they can. Perhaps that is why "middle class" parents are so frustrated with established sources of authority on science and medicine, Mr Fitzpatrick? Competing interests: None declared |
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Malcolm E Kendrick, Salaried GP Benchill Medical Centre
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'Phillips's defiant article stands as a symbol of the woeful role of the media in the course of the MMR controversy.' Having spent a lot of time trying to find out more about the MMR 'controversy.' (Although I would prefer the term, scientific debate), I have concluded that there may be a (relatively weak) association between the MMR vaccine and regressive autism. Or, to be more accurate, I feel that there may be a connection between the increase in the number of childhood vaccines and the rise in the incidence and prevalence autism - factor(s) unidentified. However, I do not think that the evidence is strong enough to alter the current vaccination policy. I accept the possibility that my conclusion(s) may be flawed. What I find hard to accept is that any of the recent epidemiological studies have proven, or disproven, the case one way or another. What I find woeful, however, is the sure and certain knowledge that anyone who dares to suggest even the slightest possibility that there may be a link between vaccintaion and autism will be subjected to personal and professional attack. In this debate people are being cowed into silence by vitriolic attacks from the 'experts.' Here are just a few of the emotive words culled from Dr Fitzpatrick's article. ‘Woeful, flawed, captivated, crusader, martyrdom, best-paid, victimhood, humble-pie, self-indulgance, fiasco, anxieties, distrust.’ Is this how a scientific debate should be carried out? Competing interests: None declared |
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John Stone, none London N22
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It is now more than eight years since Andrew Wakefield first voiced his concern about MMR, autism and bowel disease. If epidemiology was being used to discount the possibility it has failed at two levels. 1) It could not disprove on a population basis that the effect does not occur at an individual level. 2) It has failed to demonstrate conclusively that there has been no measurable effect at a population level. Cochrane, with all its contradictions and lacunae shows just how completely the project has come unstuck. Competing interests: Autistic son |
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Onisillos Sekkides, Medical Editor London, NW1
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It chills me to the bone to hear people still pushing the anti-MMR agenda, when despite the drawbacks of the studies it still seems clear that MMR is not linked to autism. And if, as some researchers propose, autism is a developmental disorder that begins prior to birth then the act of immunisation can have no influence. I don't wish to sound like I disagree with open debate, but it is this issue (portrayed by the media as debate with equal weight on either side) that has potentially exposed more children to the risk of measles (which is still among the top 10 global killer diseases). Competing interests: None declared |
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Clifford G Miller, Lawyer, graduate physicist, former university examining lecturer in law BR3 3LA
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Dear Sir, The answer Onisillos Sekkides, Medical Editor, London, NW1 needs is below. The full text is published by parents organisation JABS [1] and also by www.redflagsweekly.com. The author is Dr F. E. Yazbak, a US Board Certified paediatrician of long standing. Dr Yazbak is an autism expert with numerous peer reviewed publications which have revealed the flaws in numerous studies, including those cited in the recently published Cochrane review. Here is his answer:- "MMR and Autism
The evidence supporting an MMR-autism link was carefully collected and duplicated and is rock solid. It is certainly not “biased opinion, speculation or suspicion.” In hundreds of children with post-MMR regressive autism, a specific type of enterocolitis has been identified by many investigators in several countries. Some of the affected children have evidence of measles virus genomic RNA in the cerebrospinal fluid, some in the gut wall and some in both sites. In many, the sequences obtained were consistent with being vaccine strains and, in these children, there was no history of exposure to wild measles. Many affected children have specific patterns of urinary polypeptides, high serum measles and MMR antibody titers and elevated myelin basic protein auto-antibody levels. In fact, it will be safe to say that it is impossible to find one normal child who has evidence of both MMR antibody and myelin basic protein auto-antibodies in his serum or his cerebrospinal fluid or one child, who regressed after MMR vaccination, who does not have at least one of the following: the typical enterocolitis of autism, a suggestive pattern of urinary polypeptides, evidence of measles virus genomic RNA, elevated serum measles virus antibody, MMR antibody or myelin basic protein auto-antibodies. These are not suspicions. These are facts — rock-solid facts. In many children, two regressions have been clearly documented by health-care providers, photographs and videos. The first regression occurred shortly after the first MMR vaccination and the second, much more severe, after the MMR booster at age 4 or 5, following a period of relative improvement. This biphasic course, or challenge-dechallenge-rechallenge, has been accepted as evidence of causation by the courts and by a special committee of the Institute of Medicine. In a May 2005 presentation to the American Gastroenterological Association of a study titled “Autistic enterocolitis: confirmation of a new inflammatory bowel disease in an Italian cohort of patients,” Frederico Balzola, MD, of Turin, Italy, and associates described in detail the many gastrointestinal (GI) findings in nine consecutive patients with autism who had long-standing and serious GI symptomatology including abdominal pain, bloating, constipation and/or diarrhea. The authors concluded, “These preliminary data are strongly consistent with previous descriptions of autistic enterocolitis and supported a not-coincidental occurrence. Moreover, they showed for the first time a small intestinal involvement, suggesting a panenteric localization of this new IBD. The treatment to gain clinical remission has still to be tried and it will be extremely important to ameliorate the quality of life of such patients who are likely to be overlooked because of their long-life problems in the communication of symptoms.” Now this is the kind of study that Demicheli and his colleagues should have looked at ......" [1] Alive and Well: The MMR-Autism Connection, F. Edward Yazbak, MD, FAAP - http://www.jabs.org.uk/frontpage/frontpage.htm Contact Clifford Miller via http://www.cliffordmiller.com Competing interests: None declared |
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John Stone, none London N22
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I do not understand the basis of Onisillos Sekkides's rancour. He does not even claim any special knowledge and yet he wants to deny those that may have knowledge the right to disagree with him. The studies have "drawbacks", yet "it still seems clear", but why? He does not tell us. A sentence like: "And if, as some researchers propose, autism is a developmental disorder that begins prior to birth then the act of immunisation can have no influence." demonstrates he is completely out of his depth. He cites conjecture and logical fallacy. It should be pointed out that MMR is not the only form of measles vaccine, and that the reason why measles is a major killer in the developing world is because of poor nutrition and sanitation. Sekkides has a strong view of how things ought to be, but where is the hard science? Perhaps he has been let down. Perhaps we all have. Competing interests: Autistic Son |
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Clifford G. Miller, Lawyer, graduate physicist, former university examining lecturer in law BR3 3LA
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Dear Sir,
HUMBLE PIE NOT ON MENU For this final
"Final Word" on
MMR, the only relevant conclusion is missing. It is just
not there. Nowhere in this Cochrane
review does it say:-
"Conclusive evidence was found that there is no causal connection between MMR
and autism"
Instead, what is claimed to the world as a 'conclusion' is not:- "No credible evidence of an involvement of
MMR with either autism or Crohn's disease was found."
This sentence is not based on the contents of the review. That is odd. It does not appear in the body of the text, the authors' conclusions or in the discussion. There is more to be said later about this sentence and other aspects. Further, as no clinical nor dechallenge rechallenge evidence was considered then a statement in a review of statistical studies that evidence was not found is not much of a surprise. What is a surprise is that not only does the word 'credible' only appear once in the body of the paper, when it does appear, it is not used in the context of autism or Crohn's disease. For autism outcomes, and after looking at and discounting most of 5000 papers - this review claiming safety in the current use of MMR in 90 countries around the world is based on four papers for autism and one for PDD:- DeStefano 2004 Madsen 2002 Makela 2002 Smeeth 2004 Taylor 1999 A sixth paper is completely discounted (Fombonne 2001) Interestingly, the only paper to look at PDD (Smeeth 2004) stated "We were not able to separately identify the subgroup of cases with regressive symptoms to investigate the hypothesis that only some children are vulnerable to MMR-induced disease and that this is always regressive." These seem to be the very category of children Wakefield's original paper was concerned with that lead to this furore. Being unable to comment of this point, the Smeeth paper then referred to the Fombonne [1] and Taylor [2] papers for support on this point. However, Cochrane discounts Fombonne as noted above as being impossible to interpret and states regarding Taylor "The absence of unvaccinated controls limits the inductive statements that can be made from this study". Additionally, the Taylor paper was criticised in testimony to the US Congress by Professor Walter Spitzer an Emeritus Professor of Epidemiology from McGill University [3]:- "..... the use of the case series strategy of analysis is unconventional, not accepted by mainstream scientists and leaves the paper at best as a hypothesis-generating study ....." Others complained about the data not being made available. This means peer review was impossible and therefore also were key elements of scientific method: repeatability and reproducibility. Looks like full circle then? As for your correspondent's comment in the main article: "If children die from measles, the MMR scandal may indeed get worse." If children were to die (and that is unlikely for the reasons stated below) that can be laid at the door of our government for taking away choice of a proven alternative. MMR is not the only vaccine. There is no need for children to die. The BMJ is engaging in irresponsible scaremongering and should instead be calling for choice. Choice is the official policy of the Conservative Party. What is more, death is an unlikely outcome. In 1987, the year prior to the introduction of MMR and when monovalent measles vaccine was in use with incomplete and lower coverage, according to statistics from the Office for National Statistics, out of 8,535 deaths from all causes in the age range of children up to 14, one child died of measles, one from encephalitis and two from pneumonia post measles. In 1989, the year following MMR's introduction, out of a corresponding 8,061 deaths in this age range, there was one death from encephalitis and one from otitis, post measles. So how many cases of autism do we balance against this, Dr Fitzpatrick? [1] Fombonne E, Chakrabarti S. No evidence for a new variant of measles-mumps-rubella-induced autism. Pediatrics 2001;108(4):E58 [2] Smeeth L, Cook C, Fombonne E, Heavey L, Rodrigues LC, Smith PG, et al. MMR vaccination and pervasive developmental disorders: a case-control study. Lancet 2004;364(9438):963 [3] 106th Congress House Hearings, Autism: Present Challenges, Future Needs--why the Increased Rates? Hearing Before the Committee on Government Reform, House of Representatives, One Hundred Sixth Congress, Second Session, April 6, 2000, Serial No. 106-180 http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=106_house_hearings&docid=f:69622.wais Contact Clifford Miller via http://www.cliffordmiller.com Competing interests: None declared |
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Onisillos Sekkides, Medical Editor London, NW1
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I was remiss in not providing a reference to my statement, "as some researchers propose, autism is a developmental disorder that begins prior to birth". An appropriate reference is: Redcay E, Courchesne E. When is the brain enlarged in autism? A meta- analysis of all brain size reports. Biol Psychiatry. 2005 Jul 1;58(1):1-9 Competing interests: None declared |
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Joseph R. Herr, Retired computer programmer 94507-1602
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One way to put the MMR issue to rest is to identify the cause of autism. There seems to be at least two variants of autism, one which is evident at birth and another in which the child develops normally and then regresses. In my opinion, oxygen deprivation underlies the brain injury which results in birth autism or regressive autism depending on time of deprivation. A paper on autism in twins suggested that an environmental factor underlying autism could be brain injury caused by 6 minutes or more of perinatal apnea (apnoea). [1] For a child to develop normally and to regress due to sleep apnea requires an event which triggers apnea. Sleep apnea can be triggered or exacerbated by nasal congestion. [2] Continuing, nasal congestion can be caused by, among various clinical syndromes, upper respiratory viral infections. [2] Instead of putting the issue to rest, measles as an upper respiratory viral infection puts measles vaccination, whether singly or in combination with mumps and rubella, on the ‘front burner’. “… early weaning may contribute to the etiology of infantile autism.” [3] suggests bottle feeding is somehow involved in sleep apnea. The forces used by the infant in bottle feeding are different from those involved in breast feeding and it is this difference in forces which results in a highly arched palate in those who were bottle fed. The highly arched palate predisposes bottle fed infants to obstructive sleep apnea. [4] A highly arched palate is found in sleep apnea patients. [5] The above information implies that prolonged breast feeding and avoiding measles vaccinations, singly or in combination with mumps and rubella, will reduce regressive autism. References 1. Folstein S, Rutter M. Genetic influences and infantile autism. Nature. 1977 Feb 24;265(5596):726-8. [full text] 2, Corey JP, Houser SM, Ng BA. Nasal congestion: a review of its etiology, evaluation, and treatment. Ear Nose Throat J. 2000 Sep;79(9):690 -3, 696, 698 passim. [full text] 3. Tanoue Y, Oda S. Weaning time of children with infantile autism. J Autism Dev Disord. 1989 Sep;19(3):425-34. [fulltext] 4. Palmer B. Breastfeeding: Reducing the Risk for Obstructive Sleep Apnea Breastfeeding Abstracts. 1999 feb;18(3):19-20. [full text] 5. Kushida CA, Efron B, Guilleminault C. A predictive morphometric model for the obstructive sleep apnea syndrome. Ann Intern Med. 1997 Oct 15;127(8 Pt 1):581-7. [full text] Competing interests: None declared |
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Ellen C G Grant, physician and medical gynaecologist Kingston-upon-Thames, KT2 7JU, UK
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Medical Editor Onisillos Sekkides believes that the findings of brain abnormalities at birth and in the first year of life in autism exclude later adverse reactions to MMR. In reality, the opposite may be the case if the diverse micro-structural brain abnormalities discovered in autistic children impair normal responses to environmental challenges.1 Maternal zinc deficiency in pregnancy can cause learning impairment in animals and brain abnormalities have also been found in dyslexia. However, dyslexic children are also significantly more likely to be zinc deficient when compared with healthy, age and sex matched controls living in similar environments.2 Zinc deficiency causes immune system impairments. 1 Courchesne E, Redcay E, Morgan JT, Kennedy DP. Autism at the beginning: Microstructural and growth abnormalities underlying the cognitive and behavioral phenotype of autism. Dev Psycopathol 2005;17: 577 -97. 2 Grant ECG, Howard JM, Davies S, Chasty H, Hornsby B, Galbraith J. Zinc deficiency in children with dyslexia: concentrations of zinc and other minerals in sweat and hair. BMJ 1989; 296: 607-9. Competing interests: None declared |
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John P Heptonstall, Director of the Morley Acupuncture Clinic Leeds LS27 8EG
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Sir/Madam I am grateful to Michael Fitzpatrick for alerting us to the Cochrane review of Demicheli, Jefferson et al into MMR and autism in his BMJ article “Why can't the Daily Mail eat humble pie over MMR?”; I say that tongue in cheek as I note that Dr. Fitzpatrick uses the Cochrane review to attack Melanie Phillips for writing an article he terms a “symbol of the woe-ful role of the media in the course of the MMR controversy”, and to claim that “The recent publication of a Cochrane systematic review concluding that there is "no credible evidence" of a link between the measles, mumps, and rubella (MMR) vaccine and either inflammatory bowel disease or autism provoked demands that the British tabloid newspaper the Daily Mail apologise for its role in promoting the MMR-autism scare“ as it is not clear whether Dr Fitzpatrick actually read the Cochrane review since it does not appear to evidence his claims nor to have “provoked demands” Fitzpatrick speaks of. The Cochrane review is extraordinary in that there are certainly statements in that paper which, as Fitzpatrick argues, might lead readers to believe that the “MMR causes autism” debate can finally be laid to rest and that MMR is basically a safe intervention; I refer to the authors’ “No credible evidence of an involvement of MMR with either autism or Crohn’s disease was found”….”but the impact of mass immunisation on the elimination of the diseases has been demonstrated worldwide”…”the safety record of MMR is possibly best attested by its almost universal use”…”given the existence of documented elimination of targeted diseases in large population by means of mass immunisation campaigns however we have no reason to doubt the effectiveness of MMR” yet the review does not appear to identify any concrete scientific proof for those statements. The objectives of the review are clearly stated to be “To review the existing evidence on the absolute effectiveness of the MMR vaccine in children (by the effect of the vaccine on the incidence of clinical cases of measles, mumps and rubella). To assess in children worldwide occurrence of adverse events including those that are common, rare, short and long term, following exposure to MMR”. The team searched 5000 articles and pared them down according to their own criteria until there were only 31 studies that met the criteria for complete analysis – included in the ‘rejected’ 4969 studies were all those attributed to Wakefield et al – therefore his evidence of alleged MMR-induced IBDs and papers of Vijendra Singh et al with powerful evidence of alleged measles virus (and later measles vaccine virus) induced autism. Rejection from the final 31 had 4969 articles discarded by the team’s specific criteria; of course one cannot claim that the 4696 studies were invalidated by rejection, therefore the team cannot claim for example that evidence for IBD/Crohn’s- induced colitis does not exist as they ignored specific studies making that claim. The findings of the Cochrane review are therefore founded on careful analysis of the 31 studies that met criteria for study; only they provide evidence for conclusions drawn by the team about their objectives on “absolute effectiveness” and “worldwide occurrence of adverse events” for MMR. I was therefore surprised, on analysing this paper for some considerable time, that it appears to almost exclusively project the inadequacies of the 31 studies and not their inherent ability to prove or evidence the objectives set by the authors! In fact the authors make it perfectly clear that none of the 31 studies can be safely relied upon to evidence their objectives. Perhaps I can show this most readily by referring readers to a simple statistical representation derived from the authors’ critical comments on the value of the 31 studies from which they attempt to attain their objectives: - 1. NO study reported complete vaccine identification e.g. lot numbers, adjuvants etc. 2. 39% failed to report ANY vaccine strains 3. 10% reported the strain for only one component of MMR 4. 84% failed to give complete information on schedule, doses, route of administration 5. 58% failed to report definitions for all possible outcomes; 23% were single event specific 6. 19% had NO definitions for safety outcome measurements beyond a description of temperature range measurements; only 13% had ONE outcome with description, and 16% more than one outcome with description 7. 48% of those monitoring temperature gave NO further description of either numerical range or base reading 8. 19% reported NO participants missing for ADR monitoring; for 3% it was NOT POSSIBLE to determine if participants were missing; 55% had ‘clearly missing unintended event data’ of which 18% had under 10% missing from all areas, 24% had between 11 and 20% missing, 47% had between 20 to 60% missing from all areas and 12% the number of child subjects missing from all areas COULD NOT BE DETERMINED. 9. 26% of the studies had inadequate explanation for missing data and for 12% no explanations were offered 10. 6% had discrepancies in reporting denominators 11. 3% excluded more than 33% of cases 12. 32% had insufficient information on study population and enrolment 13. 23% had population descriptions that raised doubts as to the generalisability of their conclusions to other settings 14. 3% had uncertainty about power and generalisability of findings from single case only design study 15. For 2 GPRD-based studies the precise nature of controlled unexposed subjects to MMR their generalisability was IMPOSSIBLE to determine. When one applies the above error-inducing factors to their respective studies it is difficult to find one study devoid of sufficient error likely to invalidate its findings. Is it any wonder the authors of the Cochrane review also concluded “external validity of included studies was low”, that ”descriptions of the study populations, response rates (particularly in non randomised studies), vaccine content and exposure (all important indicators of generalisability) were poor and inconsistently reported”, and that there was in addition “inadequate and inconsistent descriptions of reported outcomes, limited observations periods (maximum 42 days) and selective reporting of results”? The question must be; why were supportive statements made by the authors regarding safety and effectiveness of MMR which their detailed dismantling of the validity of the 31 studies so obviously invalidate? One detects almost ‘bipolar’ outpourings when comparing, for example, a statement like “Existing evidence on safety and effectiveness of MMR vaccine supports current policies of mass immunisation” with “the design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, need to be improved and standardised definitions of adverse events should be adopted”. Perhaps the most damning statement for MMR vaccination the team makes appears in their ‘Background’. They state “ despite its worldwide use, no systematic reviews of the effectiveness and safety of MMR are available”. Clearly, and despite the Cochrane review, the worlds’ children continue to be afflicted by lack of a review which provides essential evidence of effectiveness and safety of MMR vaccination.. Regards John H. Competing interests: None declared |
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Charles R Whiting, purchasing agent Wheeling, WV 26003
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Onisillos Sekkides states: "(measles) which is still among the top 10 global killer diseases." One cannot compare the situation in Africa with the situation in the UK or US (apples to apples and all that); what the children in Africa really need is not vaccinated for measles as much as help with the AIDs crisis, better malaria control, an end to the constant flare-ups of civil war, and most importantly reliable sources for potable water and nutritious food. In the US, according to statistics kept by the US Government, deaths attributable to measles had declined by nearly 85% a full 20 years before the introduction of the monovalent measles vaccine and 30 years+ before the introduction of the MMR. I do not suggest that the MMR vaccine is impotent in reducing the frequency of occurance of measles. I do question the frequent parroting of disingenuous "facts" to "prove" the position of no connection between the MMR and autism (ends do not justify the means), more so when it is so easy in our cyber-society to show the flaws, misconsceptions and falsehoods is said arguments. The bottom line is the MMR-autism controversy remains unresolved, and stonewalling and misrepresentation of the limited facts by government personnel and public health authorities does a disservice to society at large. It may well be that there is indeed no link between the MMR and autism. The preliminary clinical studies however seem to support a link in some cases. What our public health officials should be doing is exploring that link so we can determine how to screen out the vulnerable infants, properly compensate the "allowable loss" should it be deemed a good risk/benefit trade-off from society's perspective, and eliminating those products which cause more damage to society than the disease they are developed o prevent. Competing interests: father of an autistic child (non-regressive) |
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John Stone, none London N22
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Where are the passages in Cochrane that prove that MMR does not cause autism or bowel disease? Competing interests: Middle-class (autistic son) |
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Lisa C Blakemore-Brown, Psychologist UK based
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Simple: Look at the biological and cognitive profiles of the children who parents consider have been damaged by this or any other vaccine, instead of: ignoring them or blaming them; doing everything possible to prevent this happening; year in year out re-hashing irrelevant epidemiology and trashing those professionals who dare to also consider some children have suffered adverse reactions to vaccines. Competing interests: Specialist Psychologist in Autism and the spectrum of disorders associated with it |
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Hilary Butler, freelance journalist. home 1892 N.Z.
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Dear Sir, If vaccine trials were done properly in the first place, we wouldn't be in this position today. When you study the Cochrane Review you can see very clearly part of the shortcomings that lead to this situation. But there is something else as well. Not one vaccine that has been used today, has been trialled correctly. Not the DPT, not the meningitis ones... not the MMR ... not the influenza vaccine. A vaccine to be tested, needs to take two large groups representative of society, diseases, immunodeficiencies, cancers, the lot, and without reference to their medical histories, split them into two groups. One group get the vaccine, the other gets absolutely nothing. No placebo, and certainly not the recently mockery of a placebo, which is a comparable vaccine with an assumed safe profile. Both groups are then compared. And the scientists are set to repeat their mistakes yet again. Here are the protocols for a new smallpox vaccine: http://www.clinicaltrials.gov/ct/gui/show/NCT00079820 They asked for participants and here was the criteria. >>>adult males or females who provided informed consent for the study. >>>adults 18 and 31 years (inclusive). >>>good general health, >>>female subjects must not be pregnant or lactating and be on appropriate contraception or be a female unable to bear children. >>>subjects be available for participation during the entire study. ~~~~~~~~~~~~~~~~~~~~~ OKAY? BUT>>>> They didn't want you in the study if ----- ~~~~~~~~~~~~~~~~~~~~~ >>>>>military service prior to 1989 or after December 13th, 2002. >>>>>history of previous smallpox vaccination >>>>>known/suspected history of immunodeficiency, or with current radiation treatment or use of immunosuppressive or anti- neoplastic drugs. >>>>>subjects with a household member or intimate contact with the same conditions listed above. >>>>>known or suspected impairment of other immunologic function. >>>>>malignancy, including squamous cell or basal cell skin cancer at vaccination site >>>>>active autoimmune disease. >>>>>subjects with known eye diseases or other conditions that require the use of corticosteroid eye drops. >>>>>known/history of cardiac disease. >>>>>subjects who have been diagnosed with 3 or more of the following risk factors for ischemic coronary disease: a) high blood pressure b) elevated blood cholesterol levels c) diabetes or high blood sugar d) first degree relative (for example, mother, father, brother, or sister) who had a heart condition before the age of 50 e) smoke cigarettes >>>>>subjects with a history of palpitations or abnormalities of cardiac rhythm. >>>>>subjects with odd ECG patterns >>>>>subjects with a ten percent or greater risk of developing a myocardial infarction or coronary death within the next 10 years. >>>>>positive or elevated creatinine kinase, CK-MB, or Troponin I laboratory test levels. >>>>>abnormalities of clinical laboratory assessments. past history or current diagnosis of chronic renal disease, adverse reactions to drugs characterized by renal impairment, a serum creatinine > 1.5 mg/dL, or presence of 1+ protein in urinalysis at screening and a calculated creatinine clearance of not less than 80 mL/min. >>>>>current diagnosis or past history of eczema. >>>>>subjects with a household member or intimate contact with the same conditions listed above. >>>>>presence of acute, chronic, or exfoliative skin conditions, open wounds, or burns. >>>>>history of keloid formation. >>>>>known allergies to MVA or to any known components (Neomycin, Gentamycin) of the vaccine. >>>>>known allergy to eggs or egg products. >>>>>known allergies to any component of the Dryvax® vaccine. >>>>>Antibiotics in Dryvax® include neomycin, streptomycin, chlortetracycline, and polymixin B. >>>>>known allergies to any known component of the Dryvax® diluent (i.e., glycerin and phenol). >>>>>known allergies to any known component of VIG, (i.e., thimerosal or previous allergic reaction to immunoglobulins). >>>>>known allergies to cidofovir or sulphur containing drugs, including probenecid, trimethoprim, and sulfonamide antibiotics. >>>>>transfusion of blood or treatment with any blood product, including intramuscular or intravenous serum globulin within 6 months of the screening visit. >>>>>positive serology result for HIV, hepatitis B surface antigen, or hepatitis C. >>>>>current diagnosis or history within six months of the screening visit of drug or alcohol abuse disorders. >>>>>significant acute or chronic psychiatric illness. >>>>>female subjects with a positive serum pregnancy test result >>>>>subjects with a household member or direct contact with someone who is pregnant or lactating. >>>>>temperature or acute illness within 3 days prior to vaccination >>>>>inoculation with an inactivated vaccine with 14 days of Day 0 or with a live attenuated vaccine within 30 days of Day 0. >>>>>subjects who have participated in another investigational drug or vaccine trial within 30 days of Day 0. >>>>>subjects who are planning on donating blood or organs within 30 days of vaccination. ~~~~~~~~~~~~~~~~~~~~~~~~~~~ If the vaccine proves satisfactory in this trial, it will not show that it is suitable for the whole population at large. It will only show that in that very restricted population it did not appear to cause too many problems. If the FDA, or anyone else, then releases it to the general public, then as Thomas Pynchon says in “Gravity’s Rainbow” .... “If they can get you asking the wrong questions, the answers don’t matter.” That is the problem with the MMR issue, which must be seen in the context of all the vaccines that went before as well. Vaccine trials have always asked the wrong questions. Therefore, the protestations of those who say any vaccine is "safe" have to be analysed, because if the questions the safety studes asked were wrong in the first place, all other "answers" and jury-rig explanations are largely irrelevant. Hilary Butler. Competing interests: None declared |
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John Stone, none London N22
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I have had passed on to me an article of March 2004 by John Grimley Evans, the retiring Coordinating Editor of the Cochrane Dementia and Cognitive Improvement Group (CDIG): 'Morality and Respectability, The Face and the Mask'. The article considers how the funding by the Department of Health for the British Cochrane Groups might be replaced. And it places the immediately preceding events of February 2004, in which Andrew Wakefield was pilloried by government and in the media for alleged non- disclosure of interest in a revealing light: "CDIG has always taken the view that it is in their own interest that employees of drug companies should not be authors of a Cochrane Review. They would inevitably be at risk of accusations of either bias or disloyalty, whatever the scientific quality of their work. As the witch- hunt over MMR illustrates, the mob goes for the man not the ball. But we also believe that a global ban on funding from pharmaceutical companies would be neither just nor wise. It would not be just because there are many other sources of potential conflict of interest in Cochrane reviews that escape similar damnation. Charities have donors wih pre-conceived notions who must be kept sweet. Government research money is now heavily under political influence; it would be a brave academic hoping for future grants who used govenment funds to conclude the latest Downing-Street- trumpeted health sevice initiative was garbage..." [1] This puts the contradictions and lacunae of the present Cochrane Review and its rather patchwork effect in alarming context. As John Grimley Evans points out Cochrane is heavily dependent for its future survival in finding favour with the industry, and industry funded institutions. It would also be naive to suppose that the charities he refers to are also not dependent on government and pharmaceutical industry backers: in reality it all goes back to exactly the same sources, and the linkage is there irrespective of a lack of specific connections between particular products and their reviews. The apparently easy going attitude of Evans contrasts notably with the recent House of Common's Health Committee report 'The Influence of the Pharmaceutical Industry'[2]. In the meantime it is revealing to read that a medically senior observer regards the contemporaneous MMR episode as a "witch-hunt". And though not in the same breath he talks about the influence of Downing Street in determining the outcome of research: "...it would be a brave academic hoping for future grants who used govenment funds to conclude the latest Downing-Street-trumpeted health sevice initiative was garbage...". In this context it ought not to be forgotten that one of the first voices to be heard in the "witch-hunt" was that of the Prime Minister: "There's absolutely no evidence to support this link between MMR and autism...I hope now that people see that the situation is somewhat different to what they were led to believe, they will have the triple jab because it is important to do it." [3] The catastrophe, I suggest, is that government has given up more than the pretence at seeking objective science in determining policy. The present study actually gives no basis at all for confidence in the safety of the MMR. All we have is the empty mantra: "The safety record of MMR is possibly best attested by its almost universal use; it evaluation cannot be divorced from its effectivenes and the importance of the targeted diseases" and the admission that the real work has never been done. What a terrible dereliction after 17 years. The public, however, have been told something different. [1] CDIG Newlsetter 10, p.8: http://www.cochrane.org/newslett/CDCIG_Mar_2004.pdf [2]http://www.parliament.the-stationery- office.co.uk/pa/cm200405/cmselect/cmhealth/42/42.pdf [3] BBC News, 'Top doctor wades in to MMR debate':http://news.bbc.co.uk/1/hi/health/3512195.stm Competing interests: Autistic son |
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John Stone, none London N22
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Fiona Godlee's powerpoint presentation to a British National Formulary on 18 May 2004 "The Next MMR - can we do better?" can still be downloaded from the web [1]. But it begs the important question what do we do about the present one? Admittedly, the public relations behind the the present Cochrane document have been rather a success. What is not a success is the yawning gap of reality. Even the six papers included the review relating to autism and bowel disease were found to be defective. The review did not look at anything which might establish a link between MMR autism and bowel disease, so its proclaimed negative finding is of no significance. The substantial matters are the issue of total failure: "The design and reporting of safety outcomes in MMR vacccine, both pre and post-marketing,are largely inadequate." "The safety record of MMR is posssibly best attested by its almost universal use; it evaluation cannot be divorced from its effectiveness and the importance of the targeted diseases." This last statement - and I apologise for returning to it - is a complete appeal to unreason, and a statement of research bias. What, then, is the point of having a review? So, yes the media control is a great success: you can tell journalists anything and they do not want to contradict the scientists, but the true picture is not one of success but of irrationality and ignorance. When the PR is over the medical profession ought to ask itself some serious questions about what it is doing, and why? [1]http://bnf.org/bnf/extra/current/noframes/450050.htm Competing interests: Autistic son |
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John Stone, none London N22
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The Cochrane Review of 2005 regretted: “We were disappointed by our inability to identify effectiveness studies with population or clinical outcomes. Given the existence of documented elimination of targeted diseases in large population by means of mass imunisation campaigns, however, we have no reason to doubt the effectiveness of MMR." [1] Remarkably the review came up with no scientific evidence that MMR eliminated measles, so it remains a proper question whether it has? In its report of a new study by Baird et [2] al last week the BBC carried the following statement: "The number of confirmed measles cases has risen from 56 in 1998 in England and Wales to just under 1,000 in 2007, according to provisional data. "However, the impact of MMR on these figures is not clear." [3] The most prominent instance of a measles outbreak last summer was reported in Hackney by Michael Fitzpatrick himself in an article in on- line Guardian "Right jabs: Before rejecting the MMR vaccination for their children, middle-class parents should think of the risks measles can present to the wider community" [4]. It was surprising that Fitzpatrick focussed not on the vaccination status of the cases, but of another: "the middle classes", omitting to mention that in many cases they would have had single jabs. The likely conclusion was that this outbreak was occuring in a vaccinated population. When quizzed about this Fitzpatrick offered the following elucidation: "Could I clarify a few points. "There have been 150 cases of measles in Hackney (population >200, 000) over the past three months. "There have been 3 cases of measles in my practice (population >10, 000). These children had not received MMR. "Though I do not have the data on the other cases, I understand that the vast majority had not been fully protected against measles (with MMR at 12 -15 months and a pre-school booster). "As this number of cases exceeds the number expected, this constitutes an epidemic. "The decline in middle class uptake of MMR has contributed to a population coverage well below that required to protect against outbreaks of measles. "When an outbreak of measles occurs it is more likely to spread rapidly among socially disadvantaged children. This is what we have seen in recent weeks." [5] You cannot, of course, deduce anything from this unless you knew the ages of those who had not been vaccinated or not received their "pre- school booster". This was not, however, the original polemical slant of the article. I note as a parallel example the study by Harnden et al [6] on whooping cough in which a one-time deadly disease is presumed eradicated because of vaccination, but is simply commonly unrecognised. It is regrettable if both the profession and the public are being given less than transparent information about the effectiveness and usefulness of vaccine. [1] http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD004407/frame.html [2] Baird et al, 'Measles vaccination and anti-body response in autistic spectrum disorders', http://adc.bmj.com/cgi/content/abstract/adc.2007.122937v1 [3]http://news.bbc.co.uk/1/hi/health/7226763.stm [4]http://commentisfree.guardian.co.uk/michael_fitzpatrick/2007/08/right_jabs.html [5]http://commentisfree.guardian.co.uk/michael_fitzpatrick/2007/08/right_jabs.html#comment -789052 [6] Harnden et al, 'Whooping cough in school age children with persistent cough: prospective cohort study in primary care' http://www.bmj.com/cgi/content/full/333/7560/174 Competing interests: Autistic son |
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Ian Fleming, parent Rowansoft
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Mumps was not even notifiable as a disease until 1988 when the MMR was introduced. In 1985 in the British National Formularly it stated that there was no justification to introduce a mumps vaccine in to the schedule as it is a benign childhood illness, rarely any complications. when there were 16 cases of mumps in Wales in recent months it turned out that 15 had received two doses of MMR - the health officials admitted that the mumps component was not effective. While MMR may be safe many parents want to use single vaccines if for no other reason than they are more effective vaccines than MMR conferring a higher level of protection. What is really important is that children ARE vaccinated; not that they are vaccinated by "brand x" MMR or by single vaccines. If parents want to use single vaccines then they should be supported. It's not as if they were refusing to vaccinate their children merely that they wish to use a different route. Department of Health should be encouraged to act responsibly and encourage the current licence holder to restart production immediately or licence its production to another company as a matter of urgency http://petitions.number10.gov.uk/mumps-vaccs/ Competing interests: None declared |
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Peter J Flegg, Consultant physician Blackpool FY3 8NR
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Mr Fleming is incorrect in his assumption that single vaccines "are more effective vaccines than MMR conferring a higher level of protection." History proves him wrong. Before the introduction of MMR, children received monovalent measles vaccine, and (girls) monovalent rubella vaccine. The year MMR was introduced, there were 86,000 cases of measles and 16 deaths (despite the widespread use of single measles vaccine). In the 17 years between introduction of single rubella vaccine and the introduction of MMR there were over 730 cases of congenital rubella syndrome and thousands of terminations performed. I don't wish to see a return to the level of illness and mortality we experienced 20 years ago. Combined MMR is more effective and as safe (and possibly even safer) than the individual vaccines. The vaccination schedule is also more likely to be completed with combination vaccines meaning better protection for vulnerable children. Competing interests: None declared |
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