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HPV vaccine safety: Cochrane launches urgent investigation into review after criticisms

BMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k3472 (Published 09 August 2018) Cite this as: BMJ 2018;362:k3472

Cochrane HPV vaccine review severely compromised by conflicts of interest

The recently published Cochrane HPV vaccine review[1] is severely compromised and cannot be trusted due to the conflicts of interest of authors on the original protocol and the final review document.

Due to serious conflicts of interests, Cochrane should withdraw this review.

In February 2016, I challenged David Tovey, Editor in Chief of Cochrane, directly about protocol author Lauri Markowitz's conflicts of interest.

Catherine Riva et al raised the problem of conflicts of interest in December 2014 in a comment on the original protocol[2], specifically pointing out the failure to properly disclose conflicts of interest by Lauri Markowitz and Marc Arbyn. Arbyn remained an author throughout all stages.

Lauri Markowitz is an employee of the US Centers for Disease Control and Prevention (CDC), and is involved in HPV vaccination promotion.

The US Government benefits from the sale of HPV vaccine products, i.e. a letter to Dr Eric Suba from the US National Archives and Records Administration (November 2010) discusses royalties the US National Institutes of Health (NIH) receives from the sales of HPV vaccines. (See a copy of the letter via this link: http://www.vietnamcervicalcancer.org/dmdocuments/ogis%20suba%2024%20nove...)

Indicating a stunning lack of transparency, it appears the value of these royalties is kept secret, i.e. it is protected from disclosure under the US Freedom of Information Act.

The NIH Office of Technology Transfer (OTT) oversaw the patenting of the HPV vaccine technology and licensed the technology to Merck, the maker of Gardasil, which sought approval for Gardasil around the world, working with the PATH group, with support from the Bill and Melinda Gates Foundation, in distributing the HPV vaccine in developing countries.[3] The HPV vaccine technology was also licensed to GlaxoSmithKline[4].

The Bill and Melinda Gates Foundation has been very influential in promoting HPV vaccination[5]. In regards to the Cochrane HPV vaccine review, Cochrane has a conflict of interest in that it is a beneficiary of Bill and Melinda Gates Foundation funding, i.e. to "support the development of Cochrane's next generation evidence system, with a specific focus on maternal and child health".[6] The World Mercury Project has provided critical analysis of Cochrane's conflicts of interest via the Bill and Melinda Gates Foundation and other organisations[7].

As a matter of urgency, Cochrane needs to consider conflicts of interest in its undertakings, as these are compromising Cochrane's mission to provide credible and unbiased information to support informed health decision-making.

In regards to the Cochrane HPV vaccine review, it's alarming that an employee of a US government agency promoting HPV vaccination was involved in the Cochrane protocol to evaluate the immunogenicity, clinical efficacy, and safety of HPV vaccines when there is a clear conflict of interest, i.e. it is in the US Government's interest to justify and defend the use of HPV vaccine products.

How and why was Lauri Markowitz's participation in the protocol approved by Cochrane?

In my previous correspondence to Dr Tovey in February 2016, I noted Markowitz is an author on many papers about HPV vaccination, for example Prevalence of HPV After Introduction of the Vaccination Program in the United States[8], a paper which received acclaim in the mainstream media, see for example this article published in Forbes magazine: HPV Infection Rates Plummet in Young Women Due to Vaccine[9].

I also noted Markowitz was on the US Advisory Committee on Immunization Practices' Human Papillomavirus Vaccine Working group in 2006, and that she is the 'corresponding preparer' on the ACIP's document recommending implementation of HPV vaccination[10].

I queried how Markowitiz could possibly be an objective and independent reviewer of the literature regarding HPV vaccination, and also queried on what basis Lauri Markowitz was engaged to conduct the Cochrane review of HPV vaccines.

Dr Tovey's response to me on 1 March 2016 included: "We can’t govern the opinions that review authors hold although we are stricter than other journals about conflicts of interests – in that declaration is not always sufficient. We have safeguards in place to avoid bias due to non financial conflicts although I acknowledge these cannot currently be fully controlled – but these include insisting on teams of authors, peer review at both the protocol and review stage, detailed editing by the appropriate Cochrane Review Group plus oversight by my Editorial Unit."

It appears that Cochrane does not have an effective system to evaluate conflicts of interest either of Cochrane itself or its authors.

Dr Tovey did not clarify on what basis Lauri Markowitz was engaged to conduct the Cochrane review of HPV vaccines.

It is not clear who initiated the HPV vaccine review protocol.

Subsequently Lauri Markowitz was not listed as an author on the title page of the Cochrane HPV vaccine review, so it appears there was recognition that it was not appropriate that she continue as an author of a review on HPV vaccines.

But the fact remains she was influential in the development of the protocol, which was acknowledged in the final review, along with her "invaluable advice and contributions by reviewing the results and discussion sections".

As a citizen interested in HPV vaccination I had hoped to rely on a review by Cochrane which was untainted by any allegation of bias, but I do not trust this review and do not consider it to be a document of value.

The Cochrane HPV vaccine review is severely compromised. Based on Markowitz' involvement, at least, it is demonstrably not independent and therefore cannot be trusted.

The Cochrane HPV vaccine review should be withdrawn.

Cochrane also needs to urgently consider its own position in regards to conflicts of interest, and the impact on Cochrane's credibility, independence and trustworthiness.

References:

1. Marc Arbyn, Lan Xu, Cindy Simoens and Pierre PL Martin-Hirsch. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Systematic Review. Published 9 May 2018.

2. Marc Arbyn, Andrew Bryant, Pierre PL Martin-Hirsch, Lan Xu, Cindy Simoens and Lauri Markowitz. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Protocol. Published 30 December 2013.

3. NIH Technology Licensed to Merck for HPV Vaccine: https://www.ott.nih.gov/news/nih-technology-licensed-merck-hpv-vaccine

4. HHS-Licensed Products Approved by the FDA: https://www.ott.nih.gov/reportsstats/hhs-licensed-products-approved-fda

5. See for example Summary of Bill & Melinda Gates Foundation-supported HPV Vaccine Partner Activities: http://www.who.int/immunization/sage/HPV_partner_info_gates.pdf

6. Cochrane announces support of new donor: https://www.cochrane.org/news/cochrane-announces-support-new-donor

7. Are Cochrane Reviews Truly "Independent and Transparent"? World Mercury Project. 5 June 2018: https://worldmercuryproject.org/news/are-cochrane-reviews-truly-independ...

8. Markowitz LE et al. Prevalence of HPV After Introduction of the Vaccination Program in the United States. Pediatrics. 2016 Mar;137(3):e20151968. doi: 10.1542/peds.2015-1968. Epub 2016 Feb 22.

9. Tara Haelle. HPV Infection Rates Plummet In Young Women Due To Vaccine. Forbes. 23 February 2016: https://www.forbes.com/sites/tarahaelle/2016/02/23/hpv-infection-rates-p...

10. Quadrivalent Human Papillomavirus Vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP): https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5602a1.htm

Competing interests: No competing interests

17 September 2018
Elizabeth M Hart
Independent
Adelaide, South Australia