By Helen Petousis Harris 23/06/2016 13

Last month members of the Nordic Cochrane posted a letter of complaint to the European Medicines Agency (EMA) on their website. Does this mean that members of the Nordic Cochrane have uncovered previously undiscovered evidence about the HPV vaccine?

No! The vaccine has an excellent safety profile and as of todays date the scientific community are unanimous about that fact.

But what is ironic is that anti-vaxxers, generally resolute in their ignorance of Cochrane-level evidence are, in contrast, zealous about a letter from a few members of the Cochrane’s Nordic faction, one complainant appears miffed that her case reports have not been interpreted as evidence for causality. This behaviour is called hypocrisy. The anti vaxxers have elected to ignore systematic reviews and meta-analysis under the name of the Cochrane but when a bellyaching letter of complaint by a few individuals gets sent to the EMA whinging about processes and perceived lack of attention to some published case reports then I am inclined to call them a bunch of hypocrites.

So what happened?

A complaint has been made by members of the Nordic Cochrane Collaboration against the EMA claiming that their review of the safety of HPV vaccine was not transparent and did not take in to account case reports that document onset of complex regional pain syndrome (CRPS) and postural orthostatic tachycardia syndrome (POTS) as evidence for causality.

If I have bitched about anything then I have bitched about the use of spontaneous reporting in the assessment of causality. DON’T DO IT, this practice is not science.

Who are the Nordic Cochrane?

The Cochrane Collaboration is an international independent non-profit NGO group of over 37,000 volunteers. They are committed to preparing, maintaining and disseminating systematic reviews and meta-analysis of the effects of health care.

The Nordic Cochrane is an independent centre and part of the Cochrane Collaboration.

Who are the EMA?

The EMA are a regulator. They monitor compliance with the law and regulations. Their job is to remind the companies of their responsibilities. The EMA can ask the company to respond to questions and then then they review the answers. This is the usual process for all safety concerns in every country. In New Zealand these functions are performed by MedSafe.

Who ensures that the company provides the correct information?

This is done through pharmacovigilance inspections.

The authors complain that the EMA has not been open and accountable to citizens, not lived up to professional and scientific standards, not treated Louise Brinth fairly for raising concerns, not treated fairly the Danish Health and Medicines Authority, not ensured proper safety evaluations and that they have conflicts of interest.

The Nordic Cochrane expectation that the EMA would do the work of the companies to review the safety of their products demonstrates a misunderstanding.

It would therefore appear that the authors of this complaint do not fully understand the regulatory process.

Anyway, the main gripe of this Complaint appears to be about a perceived lack of transparency and process at the EMA. The data at the centre of the complaint consist of spontaneous reports, not even observational studies, so in other words there is no scientific evidence at the centre of their report.

The more I look at the letter the more fluff I see, and by fluff I politely mean classical anti-vax rhetoric. In fact there is a gaffe so spectacular it deserves a round of applause.

Gripe about conflicts of interest

The Complaint highlights Julie Williams as having undeclared conflicts of interest. The CVs and conflicts of interest of the EMA Pharmacovigilance Risk Assessment Committee (PRAC) members are in the public domain on the EMA website. Dr Julie Williams’s details indicate she is from the United Kingdom, has degrees in biochemistry and training in pharmacovigilance and pharmacoepidemiology, is an Expert Assessor at Medicines and Healthcare Products Regulatory Agency and declares no conflicts including industry involvement. See for yourself here.

Now this bit is hilarious! The Complainants must have googled Julie Williams and found Julie Williams from Wales, who is a Professor of Psychological Medicine and Clinical Neurosciences. They must have thought “she will do nicely” and then gone on to document Julie from Wales’s activities and conflicts. But the bloody muppets have the wrong woman! I think this howler really draws in to question the validity of the other claims but let’s look at a few of them anyway.

In terms of transparency. There is a big moan about lack of transparency on the part of the EMA. Just what do these complainants expect? The regulator and experts must be able to communicate freely and confidentially. This is vital if the topic is to be thrashed out thoroughly. People must be able to speak their minds and be challenged in a safe environment without risk of having things taken out of context and manipulated. They made their rationale and conclusions public.

What are the responsibilities of PRAC? If you check out the rules and responsibilities you will find that the complaint has not specified that any of these have been broken.

So what are they complaining about exactly?

The complaint begins by outlining the case of Dr Louise Brinth’s article that describes some cases of chronic fatigue-related syndromes along with a hypothesis. This article presents a series of cases and the only case provided in detail had an alternative explanation of viral illness at the time of vaccination. Only a very high level overview is provided in the paper for the other cases and no comparison with unvaccinated cases is included, despite the author suggesting that they had a very long experience of diagnosing these cases which would presumably pre-date the start of the vaccination programme. Below is the EMA conclusion on the Brinth paper, which they reviewed:

Overall, the case series reported by Brinth and colleagues (2015) is considered to represent a highly selected sample of patients, apparently chosen to fit a pre-specified hypothesis of vaccine-induced injury. The methods used to ascertain the trigger and time to onset of specified symptoms of autonomic dysfunction may inherently bias patient recall. Whilst Brinth and colleagues (2015) acknowledge that their cases series cannot prove a causal association with HPV vaccine, they do not acknowledge or discuss the possibility that their case series simply reflects the expected characteristics and prevalence of POTS and autonomic dysfunction amongst a population cohort with 90% vaccine uptake. The authors speculate that high intensity physical exercise may be a risk factor for development of HPV vaccine-induced illness, but do not reflect upon the available medical literature suggesting that this is a commonly-reported characteristic in POTS patients, regardless of putative trigger. Finally, Brinth and colleagues (2015) now propose that their case series should be considered as having CFS induced by HPV vaccine and that this requires further, robust study, but dismiss an existing study that has already tested this hypothesis and found no association.

I think this whole thing boils down to one author disgruntled that their case series data (and that of others) has not being found to imply causality.

If the Cochrane Collaboration are all about evidence as a whole then why would they argue the value of a series of case reports when no other evidence supports them? They don’t tend to include case reports. A whingey letter in no way constitutes scientific evidence.

Just one final footnote

I have criticised Brinth as having sour grapes about her work, however Tom Jefferson is a bit of a surprise.

Tom Jefferson is one of the authors of the complaint and he has published loads of Cochrane Reviews of influenza vaccines – by no means our most effective vaccines to be sure, and Jefferson has enjoyed publishing on the limitations inherent in trying to study annual influenza vaccines. For years he has pointed out the lack of high quality studies evaluating influenza vaccine effectiveness (he does have a point), while avoiding the overall evidence from other study designs. Interesting how a purveyor of the randomised controlled trial, meta-analysis and systematic review can turn tail and add his name in support of the relevance of a series of case reports with no controls, no denominators and no baselines. But that is effectively what Tom Jefferson has done. Not the first time he has drawn criticism for double standards.

Featured image: Gardasil vaccine and box. CC Wikimedia

13 Responses to “Nordic Cochrane, the medical regulator and anti-vax hypocrisy”

  • You have attempted to discredit, minimise and misrepresent the details of the Nordic Cochrane Complaint and you have failed miserably. Anyone reading the complaint themselves and hopefully they will and not believe your jaundiced impressions of it, will understand the concerns and have questions of their own. Anyone literate person, will understand what the word ‘placebo’ means and what it is not supposed to do. Anyone who can read, can understand there have been omissions and a paucity of scientific evaluation and some pretty unconvincing word polishing in the Product Monograph itself. Finally, any parent who has had to sit with their daughter in agony for hours all night, watching their child suffer from a multitude of new debilitating symptoms, as a result of the HPV vaccine Gardasil, whose daughter now has gynaecological, neurological, cardiological and gastroenterological medical conditions, will understand, that the safety profile of Gardasil needs a robust review. These girls were happy, healthy, functioning and well adjusted, prior to this vaccine. They are not just a coincidence. They are medically unwell and no one is able to help them. Even their CARM case reports are not being treated seriously. What a disgrace. Where is the duty of care?Will you be giving the Gardasil 9 to your family? Overseas reports are describing young boys and men with erectile dysfunction following Gardasil..did you know this?Limited male fertility studies… and girls are indeed experiencing severe menstrual disturbances.. NO ovarian studies done in the clinical trials..that was wreckless. Wilful ignorance is no excuse. You will be aware of the serious allegations that have been made to the WHO Director General regarding Scientific Misconduct and Malfeasance. May I ask why this was not disclosed when you were asked for comment about Gardasil, by RNZ recently, or why you did not comment on the Nordic Cochrane Complaint to the media?

    • Regarding the comment about Tom Jefferson and no baselines..really …you are talking about someone not using a that is when you do a test, say a blood test ..before you start looking at something right.. so that when you have carried out your study or whatever.. you have something to compare it with..

      • A baseline is usually a term used to refer to the rates or incidence that existed prior to the exposure. In the case of a vaccine this would be the rates or incidence of some sort of condition in the population of interest prior to the use of a vaccine. There is no baseline reported in the Brinth paper.She should have had one because she claims to have treated the conditions for years. This has nothing to do with blood tests but a baseline could serve a purpose in a before and after study. This would still be limited but have a lot more validity that case reports. I am sorry but case reports are hypothesis generating and nothing more. That is a fact. Jefferson likes randomised controlled trials. These studies take a groups of volunteers and randomise them to intervention or control and measure the outcome in each group.

    • I actually paid to give my sons the opportunity to receive the Gardasil vaccine and am delighted that my youngest will be able to get Gardasil 9 on top of Gardasil 4 for free.

      I think it is fair to say my money is firmly where my mouth is.

  • And so Ms Lynch goes on, narrative and rhetoric at its best with evidence notably absent. Next blog commentator a moon landing conspiracist with a 48 year history claiming the moon landing occurred in a TV studio perhaps? An equally irrelevant comment as we read above of course.

    • I would gladly point you in the direction of evidence..start with the Product Monograph, and the Nordic Cochrane Report, then have a look at the serious allegations made by Dr Lee. Study the work of Professor Christopher Exley, who is an authority on aluminim and its effects on the body. He has studied this for 30 years. Look at the CARM data base and see what is not recorded there. I can provide evidence that a medical expert requested his name not be disclosed to the Health and Disability Commission, as having advised on an ACC case for a CARM report for a Gardasil injury. You might like to personally meet the girls and their families face to face and hear what they have to say..They are not just a coincidence. Would you meet with them? I will arrange this for you. Ad Hominem attacks do nothing to add to you response.

      • And in return I’ll point at the overwhelming body of evidence that the vaccine is safe and effective.

        CARM is not an evidence base – its open access makes it way too unreliable. It at best would indicate areas for further investigation or research.

        Despite your claims, there are no recorded deaths or serious injuries resulting from gardasil in New Zealand, and I’m not aware of any overseas – and permanent or serious injury from any vaccination is vanishingly rare.

        One professor with a pet theory on aluminium is not a credible source, especially in the face of overwhelming evidence of vaccine safety including vaccines with aluminium content.

        You claim an ability to provide evidence – so do so. Otherwise you are all talk.

        Personally meeting someone is the last thing I would do if I wanted to dispassionately assess if they have or have not been injured by something – the human condition is to identify with people who are suffering. Perhaps you should consider the problem your personal association with these individuals represents to your clarity of thought.

        • What a feeble attempt once again to disregard global evidence of serious adverse events and deaths due to Gardasil. Perhaps if you took you eyes off the resources you provide and started reading what is actually going on in reality around the World? As for NZ, you are of course forgetting the cases that have occurred. Your comments regarding this and those of your support crew, cement the absence of compassion you have for those who have lost loved ones, or whose lives have been devastated by vaccines. Please give Dr Lee has correct title. Your offensive references to the credibility of Dr Lee and Professor Exley, once again put you in a very poor light. As for disregarding scientific method, you are really not in a position to state this. Interesting to hear the take on CARM and its open access making it way too unreliable. We are supposed to have the best reporting system in the World right..would you and Ashton have this reporting system dispensed with the new?As far as not wanting to meet those whose lives are affected and continue to be so, you and Ashton might learn a lot from these people. I doubt either of you would have the courage to face these people. It’s all too easy to dismiss vaccine injury, until it happens to you or someone you know. These children were fully vaccinated in keeping with NZ schedules, not against vaccines…If you ever find that courage, you ought to face these families..

          • More noise, more hollow claims of inside knowledge, no light. I’m sorry Fiona, but you have not provided a single source for any of your claims. For me, that’s tantamount’ to making it up.

            Thanks for your input such as it is, but as a lay person watching this site, I’ll go with the people who give straight, concise, unemotional and verifiable information.

          • Fiona, while dissent is most welcome here, trolling is not. Please refrain from these types of comments, they do nothing to serve the advancement of scientific discourse. Lets remain on topic.

        • Just to clarify, the evidence you requested, presumably the evidence relating to the CARM report and the request for name ‘non disclosure’.?..this will be addressed by the appropriate authorities. Better to let the right people investigate this don’t you think?

      • Christopher Exley and Sin Hang Lee are well established Anti Vaxxers who have complete disregard for the scientific method. A real expert on aluminium adjuvants was Stanley Hem and although sadly he is no long alive I would refer anyone genuinely interested in aluminium adjuvants to his work.

        As Ashton has pointed out, there is no place for personal relationships when you are being objective. Casualty can only be established through carefully controlled studies. It does not matter how much we believe something, it does not make it so. Perhaps consider a religion you do not subscribe to, or all of them for that matter.

  • I read that letter and while I glazed over at some of the regulatory stuff, I did notice that the author confused the fringe conservative American College of Pediatricians with the much more influential American College of Physicians in the text. Not very carefully written.