Tag: hierarchy of evidence

The BMJ Asks If Injections Are Part of the “Mystery” of Acute Flaccid Myelitis/AFM…

Yes, the BMJ, formally the British Medical Journal, just published a piece, Are injections part of the “mystery” of acute flaccid myelitis/AFM? Is the CDC interested in finding out?

Those familiar with the BMJ understand that this is not a real editorial or article though.

It is one of their Rapid responses to another article – basically a letter to the editor. Unfortunately, some folks use these Rapid responses as evidence for their anti-vaccine talking points and arguments.

The BMJ Asks If Injections Are Part of the “Mystery” of Acute Flaccid Myelitis/AFM…

We know vaccines are not associated with AFM.

It is no mystery that AFM isn’t associated with vaccines – experts review patient vaccination records.
It is no mystery that AFM isn’t associated with vaccines – experts review patient vaccination records.

The AFM patient summary form asks for a vaccination record and current studies have found no association with recent vaccines.

“They also say that they are continuing to investigate the possibility of an association, but the AFM Patient Summary Forms that they supply to US state health departments contain no questions about injections or vaccinations.”

Allan S. Cunningham on Are injections part of the “mystery” of acute flaccid myelitis/AFM? Is the CDC interested in finding out?

We know that vaccines are not associated with AFM.

“According to patients’ vaccination records, all but one had been vaccinated according to Advisory Committee on Immunization Practices recommendations. The median interval between receipt of the last vaccination and onset of neurologic symptoms was 1.9 years (range = approximately 2 months–7 years).”

Acute Flaccid Myelitis Among Children — Washington, September–November 2016

But it is understandable that some folks are still trying hard to push the idea that vaccines are associated with AFM, as to some of them, everything is a vaccine injury.

What is really baffling though, is why does BMJ give them a platform to spread their wild ideas and misinformation?

More on the BMJ

About the Cochrane HPV Controversy

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.

Cochrane Nordic has been filing multiple complaints with the EMA about HPV vaccine safety for years.
Cochrane Nordic has been filing multiple complaints with the EMA about HPV vaccine safety for years.

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.

While the Cochrane Collaboration has a very good reputation, you can't really say the same about the Nordic Cochrane Centre.
While the Cochrane Collaboration has a very good reputation, you can’t really say the same about 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

Hierarchy of Evidence and Vaccine Papers

Evidence is evidence, right?

Nope.

There is a hierarchy of evidence, from weakest to strongest, that help folks make decisions about science and medicine.

That’s why you can’t just search Google or PubMed, read abstracts, and say that you have done your research.

Hierarchy of Evidence

For any study, you have to review and judge the quality of the evidence it provides.

A meta-analysis with over 1.2 million kids found that vaccines were not associated with autism, while Wakefield's retracted case series included only 12 children.
A meta-analysis with over 1.2 million kids found that vaccines were not associated with autism, while Wakefield’s retracted case series included only 12 children.

Is it a case report (a glorified anecdote), case series, or animal study (lowest quality evidence)?

Or a systemic review or meta-analyses (highest quality evidence)?

“The first and earliest principle of evidence-based medicine indicated that a hierarchy of evidence exists. Not all evidence is the same. This principle became well known in the early 1990s as practising physicians learnt basic clinical epidemiology skills and started to appraise and apply evidence to their practice. Since evidence was described as a hierarchy, a compelling rationale for a pyramid was made.”

Murad et al. on the New Evidence Pyramid

What about case control studies, cohort studies, and randomized controlled trials?

They lie somewhere in between on the hierarchy of evidence scale or pyramid.

And there are other factors to consider when judging the reliability of a study.

“Ultimately, the interpretation of the medical literature requires not only the understanding of the strengths and limitations of different study designs but also an appreciation for the circumstances in which the traditional hierarchy does not apply and integration of complementary information derived from various study designs is needed.”

Ho et al. on Evaluating the Evidence

For example, you might also have to take into account the sample size of the study.

A study can be underpowered if it doesn’t have enough subjects. Unfortunately, even an underpowered study will give you results. They likely won’t be statistically significant results, but folks don’t always realize that.

Even a meta-analysis, usually considered to be at the top of the hierarchy of evidence pyramid, can have problems that make their results less useful, such as not using appropriate inclusion criteria when selecting studies and leaving out important studies.

All in all, there are many factors to look at when reading a medical paper and considering if the results are valid and should influence what you do and how you think. This is especially true when looking at low quality vaccine papers, many of which the anti-vaccine movement uses to scare people, even though they are often poorly designed, and several of which have been retracted.

What to Know About the Hierarchy of Evidence

Learning about the hierarchy of evidence can help you better evaluate medical studies and vaccine papers and understand that there is more to doing your research about vaccines than searching PubMed and reading abstracts.

More on the Hierarchy of Evidence

 

Can Vaccines Cause POTS?

Have you ever heard of POTS?

“In POTS, the lightheadedness or fainting is also accompanied by a rapid increase in heartbeat of more than 30 beats per minute, or a heart rate that exceeds 120 beats per minute, within 10 minutes of rising.”

NIH Postural Tachycardia Syndrome Information Page

POTS or postural orthostatic tachycardia syndrome was first identified in the early 1990s and can cause many debilitating symptoms, such as dizziness, headaches, and fatigue.

What Causes POTS?

We don’t know what causes POTS.

“The term “POTS” was coined in 1993 by a team of researchers from Mayo Clinic, led by neurologist Dr. Philip Low. However, POTS is not a new illness; it has been known by other names throughout history, such as DaCosta’s Syndrome, Soldier’s Heart, Mitral Valve Prolapse Syndrome, Neurocirculatory Asthenia, Chronic Orthostatic Intolerance, Orthostatic Tachycardia and Postural Tachycardia Syndrome.”

Dysautonomia International on POTS

Well, we know that POTS is caused by a malfunction of the patient’s autonomic nervous system (dysautonomia), but we don’t know always know what causes or triggers that malfunction.

Sometimes we do though, as POTS has been associated with other types of dysautonomia, like Ehlers-Danlos Syndrome and Mast Cell Disorders.

And genetics may play a role in some people with POTS.

Can Vaccines Cause POTS?

It shouldn’t be surprising that some folks think that vaccines could be associated with POTS.

“Anyone at any age can develop POTS, but the majority of individuals affected (between 75 and 80 percent) are women between the ages of 15 to 50 years of age.”

NIH Postural Tachycardia Syndrome Information Page

That’s right.

As more people were becoming aware of POTS, some of them were getting vaccinated for HPV.

But that correlation certainly doesn’t mean that vaccines cause POTS.

“POTS is a condition that causes lightheadedness or fainting and a rapid increase in heartbeat upon standing. The cause is unknown, but doctors think POTS may be associated with a number of risk factors and syndromes, including: a recent viral illness, physical deconditioning, chronic fatigue syndrome and nervous system problems.”

CDC on Can HPV vaccines cause POTS?

And studies have confirmed that, including:

  • In 2015, the European Medical Association confirmed evidence that HPV vaccines do not cause complex regional pain syndrome (CRPS) and postural orthostatic tachycardia syndrome (POTS)
  • A review of VAERS reports that “did not detect any unusual or unexpected reporting patterns that would suggest a safety problem” with HPV vaccination, including extra cases of POTS
  • A study in the UK using the MHRA’s Yellow Card passive surveillance scheme found no increase in reports of chronic fatigue syndromes following the introduction of Cervarix
  • A large, nationwide register-based study from Norway found no indication of increased risk of chronic fatigue syndrome/myalgic encephalomyelitis following HPV vaccination
  • A large cohort study of over 2 million young girls in France found no risk for autoimmune diseases (including neurological, rheumatological, hematological, endocrine, and gastro-intestinal disorders)
  • A large cohort study of girls in Sweden with pre-existing autoimmune diseases found that HPV vaccination was not associated with increased incidence of new-onset autoimmune disease (49 types of autoimmune diseases)

Contrast those large studies that are evidence against any association between vaccines and POTS with the case reports, anecdotal evidence, and vaccine scare stories that say there is.

“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

What about other vaccines? Could they cause POTS?

Folks should remember that a case report is basically a gloried anecdote and is not the kind of evidence you should use to make decisions about vaccinating and protecting your kids.
Folks should remember that a case report is basically a gloried anecdote and is not the kind of evidence you should use to make decisions about vaccinating and protecting your kids.

While the focus has been on the HPV vaccines, an issue with other vaccines causing POTS would have been picked up with our current vaccine safety systems.

But why has the focus been on the HPV vaccines?

It is an easy association to notice, after all POTS begins to occur right around when the HPV vaccines are given (teen years) and the HPV vaccines are given in many different countries. Most other vaccines that we give to teens in the United States, including Tdap and the meningococcal vaccines, aren’t as widely used in other countries.

But remember, POTS isn’t a new diagnosis. That anti-vaccine groups are latching onto it to scare parents away from vaccinating and protecting their kids is.

What to Know About Vaccines and POTS

There is no evidence that vaccines, especially the HPV vaccines, cause POTS.

More on Vaccines and POTS

Retracted Anti-Vaccine Studies

Everyone knows that Andy Wakefield‘s fraudulent MMR study was retracted.

Andrew Wakefield was the lead author on his retracted paper.
Andrew Wakefield was the lead author on his retracted paper.

That’s the study that got folks scared into thinking that vaccines are associated with autism.

Surprisingly, it’s not the only one…

Retracted Anti-Vaccine Studies

Actually, it shouldn’t be surprising at all.

Most studies that are touted by the anti-vaccine movement are poorly done and often flawed.

And they include these other papers and studies that have been retracted:

Is it a coincidence that all of the researchers who have had papers retracted seem to get funding from the CMSRI?

What else has been retracted?

The “Deadly Immunity” article by Robert F. Kennedy, Jr.

And the survey, “Vaccination and Health Outcomes: A Survey of 6- to 12-year-old Vaccinated and Unvaccinated Children based on Mothers’ Reports,” was originally retracted by Frontiers in Public Health before finding a home at another journal under a different name. That journal quickly retracted it too, but they then published the “fatally flawed” paper for some reason.

What to Know About Retracted Anti-Vaccine Studies

Many of the heroes of the anti-vaccine movement have published fatally-flawed studies that have been later retracted.

More on Retracted Anti-Vaccine Studies

Using Pubmed to Do Research About Vaccines

A lot of the vaccine research that folks do is on PubMed.

Using PubMed to Do Research About Vaccines

And that’s not necessarily a bad thing.

“PubMed comprises more than 27 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.”

All of the studies that say that vaccines are safe, that vaccines work, and that vaccines are necessary are in PubMed.

So are the studies that show that vaccines are not associated with autism, SIDS, and other so-called vaccine induced diseases, like ASIA.

Unfortunately, there are also poorly done studies in PubMed that do purport that vaccines are associated with autism and that ASIA is a real thing.

Can You Use PubMed to Do Research About Vaccines?

Kelly Brogan didn't make history in getting a case report published in a low impact journal who's editorial board includes a Reiki Master, chiropractors, and naturopaths.
Kelly Brogan didn’t make history in getting a case report published in a low impact journal who’s editorial board includes a Reiki Master, chiropractors, and naturopaths.

Just like anyone can put up a website or Facebook page and say whatever they want, almost anyone can get a study or article published in a journal and get it indexed in PubMed.

While PubMed is an index with over 27 million citations, it doesn’t do anything to evaluate those citations to see if they include studies with design flaws, conflicts of interest, or are simply fraudulent.

That means that you need to know that a study does not get a badge of legitimacy for simply being in PubMed!

And it does not automatically mean that the evidence and conclusions from the article are of high quality just because it is listed in PubMed.

So use PubMed to find articles to help you do research about vaccines, but then read the article from beginning to end, not just the abstract, and make sure it is an article you can trust:

  • Was it published in a legitimate journal, like Vaccine or Pediatrics, and some of these high-impact journals? (good)
  • Was it published in a predatory journals?  (bad)
  • Does it involve simply looking at VAERS data?  (usually bad)
  • Is it written by folks with a conflict of interest that makes the article biased?  (bad)
  • Has it already been refuted by other people because it wasn’t designed properly or had other major flaws?  (bad)
  • Is it written by people who have expertise on the topic they are writing about? (good)
  • Has it been retracted?  (very bad)
  • Is it a case report (a glorified anecdote), case series, or animal study (lowest quality evidence) or a systemic review or meta analyses (highest quality evidence)?
  • Is it a case control study, cohort study, and randomized controlled trial, which lie somewhere in between case reports and reviews on the hierarchy of evidence scale?

Are you ready to get educated about vaccines?

That’s great, but PubMed shouldn’t be your first stop, or your only stop.

As you do your research or get bombarded with a list of links or abstracts from PubMed, remember that there is a hierarchy of evidence to consider before deciding if a paper or study is really evidence of anything. And finding a case report, study on rats, or an invitro study won’t win you an argument about vaccines when there are randomized control trials and systemic reviews on the other side.

What to Know About Using PubMed to Do Research About Vaccines

PubMed is a giant index of journal articles, but simply being in PubMed doesn’t mean that an article or study is reliable or of high quality, whether it is about vaccines, a vaccine-preventable disease, or any other medical topic.

More on Using PubMed to Do Research About Vaccines