102 e-Letters

  • Game keepers, poachers, thin ice and disease definition

    The fine paper by Moynihan et al moves the goal posts in terms of how changes in disease definitions are made.1 They identify many of the problems involved, including financial conflicts of interest. Their proposal fails to address two issues. First, only the most problematic vested interests are dealt with and second, they fail to acknowledge and address the necessarily flawed evidence base they must work out of.
    The authors find that the present financial arrangements in industry almost inevitably introduce unacceptable biases to its advocacy positions. Interests, so compromised, must be excluded from panels determining disease definitions. On the other hand, Moynihan et al. allow for participation by medical specialists deeply in the related fields. Such groups can have compelling financial and/or professional interests, particularly where private practice or turf battles prevail. This situation, though noted in passing, is inadequately challenged, and it is at least arguable, that the professions are too influential. The biases of many professional groups identified (and others not mentioned) can be just as problematic as those of the industry.
    The paper favours an evidential approach without noting the endemic medical evidence crisis of the last decade.2 This must be part of any serious discourse in which the wider public is, inevitably, included. Among the problems, in no particular order are poor choice of question; biases and poor quality in study desig...

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  • Yes, bias is pervasive . .

    I find this discussion unbalanced. Yes, bias is pervasive, and - unfortunately - primary care organizations are not exempt. Like, "the public" can be mislead - about chlorinated water and measles vaccination. But most importantly, put simply, expanding disease definitions usually means more patients to treat, and more cost to account for - this can be a negative incentive in health systems. I have witnessed on several occasions - including WHO BP treatment panels - a strong, explicit bias by primary care organizations to resist the evidence of benefit to treatment at lower levels of BP because it would increase patient loads. Historically the call to "not over-treat" goes back to the '60's, when many argued that "high BP was just like a fever - a symptom not a cause", and every step of progress has been to adopt lower targets. In my view, like it or not, pills are a new era in public health - much like vaccination. And, yes, wide use of safe, effective pills is being resisted for many of the same reasons. But progress cannot be denied, BP goals have declined from "never treat" to SBP of 120, with 80-90% decline in CVD - esp stroke. The US may have the bias toward more treatment (some doctors get patient for more visits . . ) but stroke rates are much lower than in Europe, and many dozens of US health systems have achieved the goal of 80% of treated patients with BP < 140, with excellent results. It shoul...

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  • Expanding the scope – pursuing a fully integrated discourse on health

    Expanding the scope – pursuing a fully integrated discourse on health

    Thank you for starting a long overdue discussion about the largely “insidious vested interest driven” activity of disease redefinition. Clearly this is causing high risks to the health and well-being of people and communities [1]. However, I think, there is a need to expand the emerging discourse on three front right at the beginning, especially the complex adaptive epistemology of health, a clear elaboration of the limitation of statistics as a means to “prove the truth”, and more fundamentally, the consideration of “biological plausibility”, i.e. the need to focus on integrated network physiology, in considering what are healthy “normal” indicators across the lifespan.

    (1) The paper tangentially alludes to the epistemic issues of defining health, illness, dis-ease and disease. Putting it in this way infers as a presupposition that health, illness, dis-ease and disease are distinctively “different things” – essentially a reflection of the reductionist tradition of thought of the past 350 yrs. In the first instance health in all it’s forms is subjective in nature [2], and must be distinguished from the objective features of pathology we use to define disease. As most generalist health professionals know at the end of a consultation patients fall into one of four principle clusters:
    • Subjectively healthy with no identifiable pathology
    • Subjectively health with well-defined path...

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  • 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.