eLetters

96 e-Letters

  • Cochrane: More transparency deficits

    Dear Sir or Madam

    With interest I read your letter concerning the Cochrane HPV vaccines review. However the result for all high-risk HPV-associated CIN 2+ in the “per protocol” analysis of only 16.9% was presented by the German independent drug bulletin arznei-telegramm in September 2008 already (1). At that time the underlying VBPAC background document could be accessed easily on the homepage of the FDA. Currently you can still find it there in the archived content (2).

    The way Cochrane handled your comments are consistent to our experiences: On 25 April 2018 I sent a comment on the updated Cochrane Review "Interventions for emergency contraception", published in Issue 8, 2017 (3). Without presenting any new data the authors had changed their conclusion about the effectiveness of ulipristal acetate (UPA) from “UPA may be more effective than LNG” (= levonorgestrel) in the former version (published 2012) to “UPA was more effective than levonorgestrel” in the actual review. This was based on a new approach to the comparison of UPA versus LNG which was neither discussed nor even mentioned: In the updated review the analysed time elapsed since unprotected intercourse had been extended from 72 hours to 120 hours. There are, however, good reasons to prefer the time window of 72 hours: The risk of pregnancy is significantly lower if LNG is administered within 72 hours of unprotected intercourse than if it is given later than this (3) and in Europe as well...

    Show More
  • Cochrane fails to respond

    I also submitted a criticism online about the review. While I have had email assurances from David Tovey that my contribution would be considered I have yet to hear anything at all.

  • effect sizes

    In general there is often not enough attention paid to the difference of clinical and statistical significance. I do not understand, however, how the authors of the letter conclude that the clinical effect in CASTE-AF was "tiny".
    The application of Cohen's d to a study with a discrete outcome is rather unusual. A more intuitive approach, if one is unfamilar with hazards, would be to use the relative risk as outcome measure. The risk of the primary outcome in the ablated group is 28.5%, the risk in the comparison group is 44.6%. The relative risk is 0.64. The absolute risk reduction is 16% and the number needed to treat is 6.25 (for three years). Not a tiny effect.

  • The first serious signal was in 1982

    The first report on 9 cases à of a specific malformation (spinabifida) appeared in the Lancet on October 23, 1982. I signed this letter (E.Robert) that indicated a risk ratio of 30 for mothers taking valproate. Following this alarm, hundreds of publications confirmed the risk, and others (other malformations, and autism know from 2000). A correct warning was given to women in childbearing age in 2015 in France, after the first lawsuits were initiated.

  • Inaccuracies within Lars J Jørgensen's Response to the Cochrane HPV vaccine review. Response to the Cochrane editors Lars J Jørgensen

    I realise there is a lot that has been written on this issue, more than it is possible for someone like me to work through in detail. However, I must point out some factual errors in the Jørgensen et al response dated 17th September.

    I was rather surprised at the level of detail of some of the critique, which even drilled down to cross-checking the exact number of reported deaths in dozens of individual trials. I therefore decided to look at one of the Jørgensen et al claims, and opted for one that I could verify pretty easily, namely the number of deaths in the VIVIANE study.
    https://www.ncbi.nlm.nih.gov/pubmed/27373900

    Jørgensen et al stated that they "found that the Cochrane HPV review gave an incorrect number of deaths for the VIVIANE study (HPV-015): 13 deaths in the HPV vaccine group and 5 deaths in the AlOH3 group; according to VIVIANE’s journal publication (8), there were 14 deaths in the HPV vaccine group and 3 deaths in the Al(OH)3 group."

    A check of their cited reference (8) demonstrates that Jørgensen et al have sourced the 48 week interim 2014 data analysis for this study, rather than sourcing the correct data from the final 84 week data analysis published in 2016, which is quite properly what the Cochrane Review authors sourced.

    The correct citation source states: "Data for serious adverse events related to the vaccine and deaths continued to be collect...

    Show More
  • 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...

    Show More
  • 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...

    Show More
  • 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...

    Show More
  • 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...

    Show More
  • 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...

    Show More

Pages