eLetters

61 e-Letters

  • DOES THE HPV VACCINE CAUSE NON-VACCINE TYPE PRECANCERS?

    The Cochrane Review of the HPV vaccine states :

    "In older women, vaccinated between 25 to 45 years of age, the effects of HPV vaccine on precancer are smaller, which may be due to previous exposure to HPV. The risk of precancer associated with HPV16/18 is probably reduced from 145/10,000 in unvaccinated women to 107/10,000 women following HPV vaccination (moderate certainty). The risk of any precancer is probably similar between unvaccinated and vaccinated women (343 versus 356/10,000, moderate certainty)."

    Cochrane estimates a significant effect of the vaccine on HPV 16/18 associated precancer in the 25-45 age group, but that effect disappears when risk of precancer of all (HPV) types is calculated. It is a matter of simple logic that for the positive (desired) effect on type 16/18 precancer to be offset in this way, the vaccine must have a corresponding negative (undesired) effect on precancer associated with other HPV types.

    The observation holds for all age groups, but is more pronounced in the older group. It is reasonable to assume that if one took, say, a 35 to 45 years old group, the total undesired result of the HPV vaccination could be statistically significant.

    If my reading of these numbers is too simplistic, it would be good to get a clarification, since the quoted passage appears right in the Summary with no further comments.

    In Europe, the vaccine is routinely recommended to women of all ages.

    Reference...

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  • This is a public matter and not just an institutional one

    Back in May I submitted a comment to the review by Aubyn et al, and when it was not published received an assurance from Cochrane admin that was because the site was undergoing up-date. I am dismayed but not surprised to find that it never appeared, though it is still germane:-

    "It concerns me that the authors of this study failed to contest the validity of trials that did not mostly take place against genuine placebo (i.e. saline), and even use the term "placebo" repeatedly. Do they not bear a huge responsibility by not taking this issue on, as if it is all right for this kind of methodology to become a norm of modern "scientific" practice and as something which does not affect the meaning and usefulness of the safety results?

    "Ordinary citizens, most of whom will have learned about good scientific practice at school, might assume that these trials were against genuine placebo and I find no clear explanation of the issue here, let alone in the "Plain Language Summary"."

    I was obviously stating the issue in a simplistic manner. The public probably mostly believe that the science behind these products would have been conducted at the highest standard before marketing, but this is very far from evident - and evident at a level which they are more than capable of understanding. Yet they continue to be shielded from the truth. The authors and this journal ought to be commended for standing against the profession...

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  • The Cochrane HPV vaccine review was incomplete and ignored important evidence of bias: Response to the Cochrane editors

    The Cochrane HPV vaccine review was incomplete and ignored important evidence of bias: Response to the Cochrane editors

    Lars Jørgensen, LJ (lj@cochrane.dk), 1
    Peter C. Gøtzsche, PCG (pcg@cochrane.dk), 1
    Tom Jefferson, TJ (tj@cochrane.dk), 1

    1Nordic Cochrane Centre, Rigshospitalet 7811, Tagensvej 21, 2100 Copenhagen, Denmark.

    Summary

    In a report uploaded on the Cochrane.org website on 3 September 2018 (1), Cochrane’s Editor in Chief and Deputy Editor in Chief responded to our analysis published in BMJ Evidence-Based Medicine on 27 July 2018 (2) of the Cochrane review of the HPV vaccines published on 9 May 2018 (3).

    The Cochrane editors acknowledge (1) that our analysis (2) addresses the importance of the selection of data sources for reviews, and we hope that Cochrane will take the threat posed by reporting bias (4) more seriously by using clinical study reports, rather than journal publications.

    The Cochrane editors claimed that we had “substantially overstated” our criticisms and they concluded that “Jørgensen et al made allegations that are not warranted and provided an inaccurate and sensationalized report of their analysis” (1).

    Here we address the Cochrane editors’ findings and present our further assessment and additional findings.

    In summary, we found that our analysis (2) was appropriat...

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  • Strongly support the conclusions of this article written by Jørgensen et al.

    The authors addressed important limitations in the Cochrane HPV vaccine review and stated that the Cochrane HPV vaccine review authors should make every effort to identify all trials and the trials' limitations in their conclusion. We (members of Medwatcher Japan [YAKUGAI Ombusperson], an NGO that was launched in 1997 to monitor and prevent drug-induced disasters) strongly support their conclusions.
    Medwatcher Japan released an open letter (original Japanese document) ‘Critical Opinion on Cochrane Review of HPV Vaccines’ dated on June 8th, 2018 and raised some comments concerning the content of the Cochrane HPV vaccine review and the governance of the Cochrane organisation. We have submitted the open letter (English translation of the original Japanese document) to some relevant parties in charge of Cochrane on August 13th, 2018. Furthermore, we have submitted the short version which was limited to the specifics of the contents of the Cochrane HPV vaccine review via the feedback system on The Cochrane Library on August 31st, 2018. It has been confirmed that the short version was published via the Cochrane Library feedback system. We have not, however, received any responses directly from the Cochrane.
    Therefore, in addition to the points raised in this article by Jørgensen et al., we would like to address the following key comments concerning the content of the Cochrane review in this response:

    1. Since the effectiveness claimed in the Cochrane revi...

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  • Cochrane review should be revised due to overlooked trials, toxicity of adjuvant, mortality in mid-adult women and lack of discussion on observational studies with serious healthy-vaccinee effect

    Dear Dr. David Tovey,

    I have read your response [1,2] to the paper by Jøorgensen et al. published in BMJ Evidence-Based Medicine [3] relating to the recently published Cochrane Review on HPV vaccines [4], and would like to give my feedback on this issue.
    The key findings of your investigations are as follows:

    1. The Cochrane Review did not miss "nearly half of the eligible trials". A small number of studies were missed due to the primary focus on peer-reviewed reports in scientific journals, but addition of these data makes little or no difference to the results of the review for the main outcomes;
    2. The trials comparators were unambiguously, transparently, and accurately described;
    3. The selection of outcomes for benefits was appropriate and was consistent with World Health
    Organization guidance;
    4. The review included published and unpublished data on serious harms, and the findings on
    mortality were reported transparently and responsibly;
    5. The review was compliant with Cochrane’s current conflict of interest policy;
    6. Cochrane’s media coverage was cautious and balanced, but we recognize that there could be
    improvements in relation to transparency where external experts are quoted;
    7. The BMJ Evidence-Based Medicine article substantially overstated its criticisms.

    I would like to comment on your findings 1, 2, 4 and lastly, I added comments as 8. Most observational studies neg...

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  • More than 20,000 systematic reviews were published in 2017

    The number of systematic reviews being published each year is actually much larger than the already impressive number of 10,000 quoted. In 2017 over 20,000 were published; 20,661 are cited in the KSR Evidence database in early August 2018. KSR Evidence, includes all systematic reviews and meta-analyses published since 2015 and for many reviews provides a critical appraisal and a short, accessible bottom line. www.ksrevidence.com

  • Problems associated with not using a true placebo in clinical trials

    The problems associated with NOT using a true placebo in clinical trials - in this case GSK's trial for Cervarix - were discussed way back in 2009:

    FOOD AND DRUG ADMINISTRATION CENTER FOR BIOLOGICS EVALUATION AND RESEARCH

    VACCINES AND RELATED BIOLOGICAL PRODUCTS ADVISORY COMMITTEE

    September 9, 2009

    Pg166

    DR. DEBOLD: I just think in the absence of having a true placebo in the entire study, it is very, very difficult to sort out what the effects are here, what is it that we are really dealing with, what is the baseline, versus what potentially is caused by the so-called controls.

    In this particular study, not only was there two different strengths of Havrix used, there was alum used. In the pooled analysis there were a number of other vaccines used as the control, which makes it scientifically very difficult to sort things out.

  • Retraction notices in PubMed

    I searched PubMed for the retraction notices. The 3 retracted articles published by Elsevier have no retraction notices in PubMed. Retraction notices for the 2 articles in the Journal of the American Society of Hypertension were published in vol. 9, issue 10, this issue is indexed in PubMed and articles citations are in PubMed but the two retraction notices are missing. "Publishers of journals in PubMed must submit citation and abstract" (PubMed FAQ for publishers), these two notices should normally have been submitted by the publisher. As for the article published in the European Journal of Pharmaceutical Sciences, no retraction notice was found, information about the article being retracted is available in the original article but, as no retraction notice seems to be available, there is no information about the retracted status in PubMed. As PubMed is often the source used by researchers doing a study on retractions of articles (e.g. PMID: 28683764, PMID 26797347, PMID: 24928194) it is important to find this information in the database. Publishers should always publish retraction notices for retracted articles and submit the citations to PubMed when the journal is indexed in this database.

  • Response to Brodersen et al’s ’Overdiagnosis: what it is and what it isn’t'

    In their editorial, Brodersen et al. present two types of overdiagnosis. Their two types appear to be identical to two types of overdiagnosis we identified in research published in 2016 (Rogers WA and Mintzker Y. Getting clearer on overdiagnosis. J Eval Clin Prac 2016;22: 580-587). In that paper, we provide a detailed account of maldetection overdiagnosis and misclassification overdiagnosis, together with an analysis of the relevance of these two different types.
    This matter, including our request for a correction, is fully explained in our letter published in this journal: Response to Brodersen et al’s ’Overdiagnosis: what it is and what it isn’t' (http://ebm.bmj.com/content/early/2018/03/29/bmjebm-2018-110948).

  • Re:DPP4is are safe
    Joshua J. Fenton

    Dear Editor,

    Andrea Giaccari asserts that I wrote in my editorial that sitagliptin in the TECOS trial "caused" 20% increase in the secondary outcome of congestive heart failure. That is not what I wrote. I wrote that "the study data remain consistent with" a 20% increase in this adverse outcome. While the wide confidence interval is also consistent with a reduction in heart failure risk, the primary goal of the TECOS tr...

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