Have you heard about the Cochrane HPV controversy?
What controversy?
Well, yeah, but anti-vaccine folks are crowing about what is essentially a letter that was published in BMJ Evidence-Based Medicine journal.
About the Cochrane HPV Controversy
What’s the controversy?
Seems that the folks at Cochrane Reviews recently published a review, Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors, which concluded that the HPV vaccines work and that they are safe.
That doesn’t sound controversial…
Well, it seems that some other folks, associated with the Nordic Cochrane Center, disagreed. They published an “analysis” in BMJ Evidence-Based Medicine, The Cochrane HPV vaccine review was incomplete and ignored important evidence of bias.
So who do we believe when we have Cochrane vs Cohrane?
Who is the Nordic Cochrane Centre?
Some people will be familiar with the Nordic Cochrane Centre because of their involvement in complaints about the HPV vaccine that were investigated by the European Medicines Agency.
Complaints that were initially triggered by a case series that was published by Dr. Louise Brinth, when she was head of the Danish Syncope Group, but who is now part of the Nordic Cochrane Centre.
Complaints that were not approved by the Cochrane Collaboration and that were not an official Cochrane viewpoint!
“…we highlight here how academic colleagues, under the purported banner of a respected authority, raise concerns about the HPV vaccine but they cite an evidence base of small and poor quality studies and ignore the extensive wealth of global literature that vividly demonstrate the excellent efficacy and safety record of the vaccine.”
Head et al on Inadvisable anti-vaccination sentiment: Human Papilloma Virus immunisation falsely under the microscope
Complaints that had already been investigated and dismissed by the European Medicines Agency.
“In conclusion, in clinical trials conducted in the 9 to 26-year- old age range, vaccination was generally well tolerated with no apparent adverse health impact following completion of the vaccination regimen.”
Block et al Clinical trial and post-licensure safety profile of a prophylactic human papillomavirus (types 6, 11, 16, and 18) l1 virus-like particle vaccine.
Complaints that are also refuted by many other studies.
So we don’t actually have Cochrane vs Cochrane…
The Cochrane HPV Review
Once you read the complaint against the Cochrane HPV review, you realize that this isn’t even just about the Cochrane HPV review.
The main faults that the Nordic Cochrane Centre folks found is that the Cochrane review left out a bunch of what they consider to be eligible HPV vaccine trials, even though “twenty-six randomised trials were identified that contained data on vaccine efficacy and/or safety, which all together enrolled 73,428 women.”
But if this was just about a systemic review which didn’t stick to protocol about which studies to include, then why do the Nordic Cochrane Centre folks go on and on about placebos and active comparators?
“The Cochrane authors mistakenly used the term placebo to describe the active comparators.”
Lars Jørgensen et al. on The Cochrane HPV vaccine review was incomplete and
ignored important evidence of bias
Would you be surprised to know that one of Nordic Cochrane Centre’s arguments to the EMA was about placebos?
“In all the vaccine trials apart from a small one, the “placebo” contained aluminium adjuvant, which is suspected of being neurotoxic.”
Cochrane Nordic Complaint to the European Medicines Agency (EMA) over maladministration at the EMA
Why do they talk about placebos?
Most of these folks want pure saline placebos to be used in clinical trials, even though doing so would make it hard to keep the trials blinded.
Placebos don’t have to be inert though. The BMJ and the Nordic Cochrane Centre authors mistakenly corrected the Cochrane authors on their use of the term placebo.
They make plenty of other mistakes too.
“The Cochrane authors did not mention a study from 2017 by the WHO UMC that found serious harms following HPV vaccination overlapping with two syndromes: postural orthostatic tachycardia syndrome (POTS) and complex regional pain syndrome (CRPS).”
Lars Jørgensen et al. on The Cochrane HPV vaccine review was incomplete and
ignored important evidence of bias
What study?
Jørgensen cites a commentary that describes “a signal based on both spontaneous reports and published case series that is best characterized as a potential association between HPV vaccination and dysfunction of the autonomic nervous system.”
“There is currently no conclusive evidence to support a causal relationship between the HPV vaccine and POTS. It is of utmost importance to recognize that although temporal associations may be observed, conclusions of causality cannot be drawn from case reports and case series due to the small sample size and lack of control population inherent to this type of scientific literature. If POTS does develop after receiving the HPV vaccine, it would appear to do so in a small subset of individuals and would be difficult to distinguish from the normal prevalence and incidence of the disorder.”
Butts et al on Human Papillomavirus Vaccine and Postural Orthostatic Tachycardia Syndrome: A Review of Current Literature
So who do you believe?
Researchers who published a systemic review as part of the Cochrane Review Groups that confirms that the HPV works and that it is safe, or a group who seems to have an axe to grind against the HPV vaccines?
Update on the Cochrane HPV Controversy
Apparently, Cochrane has taken the Nordic Cochrane Centre complaints seriously enough to launch an investigation.
“Our current investigations appear to show that there may be a handful of missed but potentially eligible studies, but that this falls substantially below ‘nearly half of the eligible trials’.”
David Tovey, editor-in-chief of the Cochrane Library
And not surprisingly, Tovey stated that “To date, we also have no reason to believe that the main conclusions of the review relating to benefit and serious adverse effects are unsafe.”
And yet, as with their complaints to the EMA, resources get wasted as the attacks are put down.
More on the Nordic Cochrane Centre HPV Attacks
- The HPV Vaccine: A Critique of a Critique of a Meta-Analysis
- Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors
- HPV vaccine safety: Cochrane launches urgent investigation into review after criticisms
- HPV vaccines: EMA confirms evidence does not support that they cause CRPS or POTS
- EMA HPV Safety Review
- EMA to further clarify safety profile of human papillomavirus (HPV) vaccines
- HPV vaccine prevents cervical cancer – a systematic review
- Comment – Inadvisable anti-vaccination sentiment: Human Papilloma Virus immunisation falsely under the microscope
- Study – A Review of Clinical Trials of Human Papillomavirus Prophylactic Vaccines
- Study – Clinical trial and post-licensure safety profile of a prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine.
- Gardasil safety and efficacy – debunking the HPV vaccine myths
- Study – Bivalent human papillomavirus vaccine and the risk of fatigue syndromes in girls in the UK.
- Study – HPV vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis: A nationwide register-based study from Norway.
- Study – Human papillomavirus vaccination and risk of autoimmune diseases: A large cohort study of over 2million young girls in France.
- Study – Incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease after quadrivalent human papillomavirus vaccination: a cohort study.
- Study – Reports of Postural Orthostatic Tachycardia Syndrome After Human Papillomavirus Vaccination in the Vaccine Adverse Event Reporting System.
- HPV vaccines: EMA confirms evidence does not support that they cause CRPS or POTS
- European Medicines Agency concludes HPV vaccine doesn’t cause POTS, will that stop bad vaccine journalism?
- How the Toronto Star massively botched a story about the HPV vaccine — and corrected the record
- CDC – Can HPV vaccines cause POTS?
- WHO – Global Advisory Committee on Vaccine safety Statement on Safety of HPV vaccines
- Study – Human Papillomavirus Vaccine and Postural Orthostatic Tachycardia Syndrome: A Review of Current Literature.
- Study – Reports of Postural Orthostatic Tachycardia Syndrome After Human Papillomavirus Vaccination in the Vaccine Adverse Event Reporting System.
Nordic Cochrane are critical of the Cochrane systematic review by Arbyn et al for not including a number of studies that Nordic feel are relevant. They accuse Cochrane of being “influenced by reporting bias and biased trial designs.”
Yet sytematic reviews are designed in advance; the sources, the selection criteria and methodology is standardised; the articles are selected according to whether they fulfil criteria for consideration and not for other reasons, and reasons for exclusion are made apparent and documented. Simply put, the studies would not have biased trial designs or suffer reporting bias. It might be that the criteria for inclusion in a systematic review may not accord with the criteria that Nordic would have preferred to have, but looking at the criteria used by Arbyn et al in their review they appear very clear and definitive, and IMHO only someone who is regarding this from a position of bias themselves could call that biased.
What Nordic Cochrane would like is for the studies to be cherry-picked according to their own whim, and not according to predefined standards. That is patently ridiculous.
Your assertions are false and defamatory. If you actually read Nordic Cochrane’s paper, their complaint is that 42 studies with results met the inclusion criteria, yet only 26 were included in the study, with no explanation or mention of the missing 16 studies. That is fraud or incompetence. You cannot claim your review is systematic if you have excluded studies that meet the criteria without explanation.
Our current investigations appear to show that there may be a handful of missed but potentially eligible studies, but that this falls substantially below ‘nearly half of the eligible trials’. – It seems likely that Nordic folks picked every trials that they could find, even if it didn’t fit eligibility criteria. Even this handful that were missed would not have changed the results of the review.
16 is an awfully large handful. That’s 1/3 of eligible studies. The phrase ‘nearly half’ was probably used because there were 46 total trials, and the review only included 26/46, which is nearly half. But four of those did not have posted results yet, so 42 is the real number. The use of the term ‘nearly half’ is not important since they provide the actual numbers. And again, there is an insinuation that Nordic is picking just any trials when they specifically state that it was 46 trials that met the stated inclusion criteria. That is obfuscation. And whether that handful would have changed the results of the review is irrelevant to their criticism. Their criticism is that the review is not up to Cochrane’s standards. The missing trials are only one part of their critique.
Would it be possible to approve the other comments I made so that others can read a valid critique of this post? Or at least let me know what changes I could make to get them approved, rather than just leaving them in “awaiting moderation” status?
“Placebos don’t have to be inert though.” – Seriously?? inert, no therapeutic effect, inactive substance would all be ways to define placebo IMO. If utilizing the vaccine adjuvant (which by definition in this case is for the purpose of augmenting the immune response) as the “placebo” is not a fair criticism I’m not sure what would be.
One thing I recently learned that I did not know before. Nordic Cochrane’s criticism of the use of adjuvant as placebo is based on what they found in the clinical study reports. What they found from one manufacturer (I think GSK?) was that placebo was used at first. And they found excess harms in the vaccine group, so moving forward they switched to using the adjuvant as comparator to hide those harms. It was an active decision based on what they were seeing.
That’s convenient! Do you have any links you could post to where to read more about that? I also thought it was notable that some study exclusions were preexisting autoimmune or neurologic diseases…..this would seem a clear bias again.
I don’t know what is causing my comments to get flagged for moderation. I think maybe when I include links? I commented with a link to the article this appears in, but that is now awaiting moderation.
But, apparently two experts at the EMA had made this allegation and it was in the internal review that was leaked to the Nordic Cochrane Center. The full quote is:
Here is a link you can piece back together so the moderation filter does not block it:
dubya dubya dubya dot medscape dot com slash viewarticle slash 865686
Thank you!