30 e-Letters

published between 2016 and 2019

  • Evidence maps: a tool to guide research agenda setting

    This is Cancun Lu, is a master from the Evidence Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, China. Here, I thought the 17th citation in the references of this paper with a mistake. And it should be——Schulz KF, Altman DG, Moher D, et al. CONSORT statement: updated guidelines for reporting parallel group randomised trials. BMJ 2010;2010:c332.
    Conflicts of interest
    I declare that I have no conflicts of interest.

  • Re: Defamation: no evidence required

    Sergey Tarasov responded to our article “Drug discovery today: no molecules required” with claims of mistakes in our analysis. We are sure that we did not conceal anything of relevance or make any mistakes. This is a response to the claims by Sergey Tarasov.

    1. Tarasov claims that one of us has an undeclared conflict of interest: “However, one of the authors of the article, Khromov-Borisov NN, is a defendant in a defamation lawsuit brought by Materia Medica (June 28, 2018). Materia Medica has sued Khromov-Borisov NN <…> this therefore raises serious doubts over the objectivity and impartiality of one of the authors of the article, who also carried out the data analysis presented in supplementary letter 1”. However, the analysis provided by Khromov-Borisov NN was sent to the editor of International Journal of Diabetes Research on Dec 13, 2017 (Supplementary Letter 1). Then editors of Drug Discovery Today (Feb 5, 2018, Supplementary Letter 5), BMJ (Apr 2, 2018), and BMJ EBM assessed the article including analysis mentioned above. Thus Tarasov presented the chronology completely wrong. First we have submitted our criticism of release-activity (RA) to scientific journals and only then Materia Medica sued one of our co-authors.

    2. We don’t see how any of our previous criticisms of RA drugs and homeopathy creates a conflict of interest or are relevant to the reception of our article.

    3. We have stated that RA drugs contain no active substance. Simple...

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  • Defamation: no evidence required

    The article “Drug discovery today: no molecules required” (2018) (by Panchin AY, Khromov-Borisov NN, Dueva EV) questions the imperfections in reviewing scientific publications. The authors use the example of publications on released-active drugs (RA-drugs) as a basis for the paper and their accusations against journal editorial boards. The authors postulate that these drugs do not contain any active ingredients due to the technology used and therefore come to the conclusion that the reviewers and journal editors who have published articles on RA-drugs carried out their work appallingly and made gross mistakes. So the authors state «…the vast amount of flawed publication claiming therapeutic properties and physiological effects of drugs with no active components can highlight the problems of peer-review standards and policies in biomedical journals».
    This particular conclusion is based on approximate theoretical calculations and not on experimental evidence: «If one assumes a 1M initial antibodies concentration (though this is usually not disclosed in release-activity papers) and takes into account Avogadro’s constant (~6.02×10^23 mol^(−1)), then even C12 dilutions are unlikely to contain any antibody molecules». In their article, the authors present these calculations as the main argument to complain to journals. It is noteworthy that in the article the authors do not provide any data or references to any studies conducted by themselves. Neither do the authors provid...

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  • 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...

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  • 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.

    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...

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    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.


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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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