Undisclosed Conflicts of Interest in Vaccine Research

Conflicts of interest (COIs) are very important considerations in research. The most obvious COIs are financial; the researcher may receive financial gain for one result versus another, or they will at least avoid losing current or future income if they get a specific result. But COIs could also be non-financial. Perhaps they have family or close friends that would prefer one outcome versus another. Or they might hold a volunteer position of authority in the sponsor's organization. Whatever form they take, COIs may not necessarily invalidate a study, they hold the potential to influence scientists' behavior during a study, their analysis of the data, and the conclusions they draw from their research. Sometimes, the researcher may not even be fully aware of the influence of their COIs on their work. Blinding can help reduce the influence of conflicts of interest, but any COIs must be disclosed so that anyone who reads the study can think about how they may have influenced the study design, the methods, the analysis, and the conclusions.

When it comes to published research, most journals require authors to disclose both financial and personal relationships with other organizations or people that could bias their study. Failure to disclose COIs can be grounds for refusal of a manuscript or retraction of a paper that has already been published. It can really damage the researcher's reputation, but it can also harm the reputation of the journal.

This all brings us to a study that was originally published as an uncorrected proof in the journal Vaccine, and later withdrawn by the journal: Behavioral abnormalities in young female mice following administration of aluminum adjuvants and the human papillomavirus  (HPV) vaccine Gardasil, by Rotem Inbar, Ronen Weiss, Lucija Tomljenovic, Maria-Teresa Arango, Yael Deri, Christopher A. Shaw, Joab Chapman, Miri Blank, and Yehuda Shoenfeld.

I was fortunate enough to get a copy of the full paper. I'm not going to go into any of the numerous flaws in this study, as that has already been done (far more ably) by others. Instead, I want to focus on the conflicts of interest. Here is the entirety of the statement from the paper:

Yehuda Shoenfeld has acted as a consultant for the no-fault U.S. National Vaccine Injury Compensation Program. L.T. has served as an expert witness in cases involving adverse reactions following qHPV vaccine administration. The other co-authors declare nocompeting interests.

Here are some COIs that are missing from that statement. While Lucija Tomljenovic declares her having served as an expert witness in cases involving HPV vaccine, Dr. Christopher Shaw does not declare that he has also been an expert in a case involving Gardasil. In 2012, Dr. Shaw gave expert evidence for a coroner's inquest into the death of a young woman named Jasmine Renata. He was sent samples of her brain tissue for testing, ultimately claiming that he found aluminum and HPV in her brain, though reports do not state how he got his results. (The coroner ultimately failed to find a connection between her death and Gardasil.) Dr. Shaw should have declared his past involvement as an expert in a case involving alleged injury from Gardasil.

That's not the only undisclosed COI, though. Dr. Shaw is also the chair of the Scientific Advisory Board for the Children's Medical Safety Research Institute (CMSRI). What, you might ask, is CMSRI? It is a registered 501(c)3 charity whose primary activity is to "Address eroding public confidence in national vaccine policies" (from the 2013 form 990 for the Children's Medical Safety Research Institute Endowment Fund, accessed via Guidestar). The organization also seems to view vaccine-induced brain injury and immune dysfunction as established fact, with a focus on the "toxic potential" of vaccines. CMSRI was founded by Albert and Lisa Claire Dwoskin, who also sit on the governing board. The Dwoskins funded this particular study via their family foundation:

Funding

This work was supported by the grants from the Dwoskin Foundation Ltd.

Dr. Shaw has a professional relationship with the funding sponsor of this study, yet this does not appear in the conflict of interest statement, nor in the author information. Nor is Dr. Shaw the only author involved in this study with such a connection to CMSRI. The corresponding author, Dr. Yehuda Shoenfeld, is also on the Scientific Advisory Board of CMSRI.

I've written a bit about the Dwoskins few years ago, pointing out that despite their objections that they are not anti-vaccine but rather "vaccine safety advocates", their words suggest otherwise. As Claire Dwoskin wrote to John Stossel following a segment he did on vaccines (emphasis added):

I just saw the show and am so sorry to hear that other than what Chris had to say, not a word of truth was spoken by Stossel or Offitt. What a travesty – I hope someday he will recognize the error of his ways and realize the fear and damage that he is contributing to by allowing falsehoods to rule the air. At least his daughter is alive, smiling, educated and enjoying life. That cannot be said for the hundreds of thousands of vaccine injured children in the US. What his daughter went through is NOTHING compared to what the families of autistic children go through every day of their lives. No disease can match this record of human devastation. Vaccines are a holocaust of poison on our children’s brains and immune systems. Shame on you all.

We have an anti-vaccine sponsor for this study, conducted, in part, by two board members of an organization formed, funded, and directed by the anti-vaccine sponsor. This sponsor also happens to be one of the primary sources of funding for Dr. Shaw's vaccine research activities overall. Yet neither author thought they ought to disclose this connection. This is reminiscent of Mark and David Geier forming their own Institutional Review Board, stacked with their family and business partners, to approve their own research.

Despite the flaws in the study that I linked to above, and despite the failure to disclose competing interests that could bias or influence the study (in violation of Elsevier's conflict of interest policy), Dr. Shaw stands behind the study and seems shocked and perplexed that it was withdrawn.

As I mentioned at the beginning of this article, conflicts of interest do not necessarily invalidate a study, but they do give reason to view the study with an extra measure of scrutiny. When the authors fail to disclose their COIs, it does not speak well for the authors, the reviewers, or the journal, and it casts further doubt on the conclusions drawn in the study. The irony in all of this is that anti-vaccine activists are very quick to claim that research in support of vaccines is horribly biased due to real, but disclosed, COIs or due to COIs that only exist in their imaginations, yet here we have real conflicts of interest on the part of anti-vaccine authors that they failed to disclose.

This represents a significant lapse in research ethics. Even if there were no methodological or statistical flaws in this study, there are still grounds for the journal to withdraw the paper.

[Edited to Add (2/24/16): The journal has put up the following statement regarding this paper:

This article has been withdrawn at the request of the Editor-in-Chief due to serious concerns regarding the scientific soundness of the article. Review by the Editor-in-Chief and evaluation by outside experts, confirmed that the methodology is seriously flawed, and the claims that the article makes are unjustified. As an international peer-reviewed journal we believe it is our duty to withdraw the article from further circulation, and to notify the community of this issue.

In other words, the article no longer exists. (h/t to Skeptical Raptor for the update)] 

[Edited to Add (9/11/16): The paper was submitted to and published by Immunologic Research, with reportedly altered statistics, but the same data. Likewise, the Conflict of Interest and Funding statements remain unaltered. Unfortunately, the original
Vaccine paper is no longer available to compare the details of the statistics and data.]