eLetters

138 e-Letters

  • What actually happened to 'R' in March 2020 as a result of school closures in the UK??

    The article by Alastair Munro and colleagues (to which this is a rapid response) is of great value and importance, as we can now see, since this article was published, that there has been considerable discussion and interrogation by the COVID inquiry (https://covid19.public-inquiry.uk/), about whether the closure of schools, ordered on 18th March 2020 by Boris Johnson's government, and put into effect two days later on 20th March, was ever necessary.

    The rationale for the closure of schools was that it was imperative that the transmission rate of the COVID-19 pandemic, then rapidly spreading in the UK, was brought down at pace. Only three days later, a full, mandated, "lock down" was imposed. This was in the context of a suite of increasingly draconian measures to impose Non-Pharmaceutical Interventions (NPIs) on an increasingly fretful population - on March 12th, 16th, 20th and 23rd.

    The question we pose of the authors of the current paper under discussion is a simple one. What is the actual, real world, evidence that the 'R' value fell as a result of the closure of schools? Is there any real-world, UK-based, 2020 information we can use to answer this question. This question cannot remotely be answered by reference to other countries, or, to mathematical models. The impact of school closures must also be analysed independently of all of the other contemporaneous NPIs.

    If the o...

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  • What about acces to innovative radiopharmaceutical l products

    As French Nuclear Medicine representatives, we read with great interest the article by Le Guludec et al. entitled: Rapid access to innovative medicinal products while ensuring relevant health technology assessment: Position of the French National Authority for Health. In this interesting and important position paper from the French Independent Health Technology body (HTAb) called “Haute Autorité de Santé” (HAS), the authors state that its recommendations derive from consultations with academics. Although we understand that accessibility to innovative drugs used for Positron Emission Tomography (PET) could be considered as a very ancillary issue by the HAS board that authored the paper, these PET imaging molecules are still considered as medicinal products from a regulatory standpoint and should be evaluated as such.
    We regret that, to our knowledge, none of the academic members of the French Nuclear Medicine Society (SFMN) board were given the opportunity to draw attention to some of the specific features of the drugs commonly used in nuclear medicine by answering the questionnaire sent to the panelists (cf supplemental material). Indeed, we would clearly have answered “Yes” to the following questions:
    - Are there specific methodological issues for Health Technology Assessment you wish to bring to our attention?
    - Do you identify methodological issues relative to the assessment of innovative drugs in specific therapeutic areas?
    We would also have be...

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  • Multiple problems with reporting and interpretation of the results

    Dear Editorial Office,

    I want to express my concern regarding “Curcumin and proton pump inhibitors for functional dyspepsia: a randomised, double blind controlled trial” by Kongkam et al(1). It was published against the journal’s editorial policy and has serious issues with reporting and interpretation of results.

    The article shouldn’t have been published in the first place. It lacks prospective registration, which directly contradicts the BMJ Evidence-based medicine editorial policy stating that a prospective registration is mandatory for any clinical trials(2). The Thai Clinical Trials Registry(3) registration TCTR20221208003 is retrospective which is clearly stated in the registry. The registration was submitted on 07 December 2022, just before a preprint was posted on medRxiv on 09 December 2022, while the study was completed on 30 April 2020.

    On top of that, there are serious issues with the reporting and interpretation of results.

    According to the authors an equivalence design was used with the equivalence margin of 2 points in the SODA score. Nine comparisons of SODA scores in the curcumin plus omeprazole (C+O), curcumin only (C), and omeprazole only (O) groups were reported. For three of those confidence intervals include equivalence margin. The only available interpretation here is that the trial failed to demonstrate equivalence. To demonstrate equivalence the confidence intervals should be between the two equivalence margins rath...

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  • The main claim in this paper is not even wrong

    Dear Prof. Franco,

    I am writing to request further clarification on the paper “Likelihood ratio interpretation of the relative risk”. The “key messages” section of this paper states that the study adds the following to the literature:

    ⇒ It is demonstrated that the conventional interpretation of the relative risk is in conflict with Bayes’ theorem.
    ⇒ The interpretation of the relative risk as a likelihood ratio connecting prior (unconditional) intervention risk to outcome conditional intervention risk is required to avoid conflict with Bayes’ Theorem

    I will refer to the first bullet point as “Doi’s Conjecture”. Doi’s Conjecture is also stated in the second section of the main text, where it is claimed that “the usual interpretation (33% increase in the +ve outcome under treatment) contravenes Bayes Theorem”.

    No attempt is made within the text to prove Doi’s Conjecture. But perhaps more worryingly, no attempt is made to define the term “interpretation”, a term which is not defined in standard probability theory. The meaning of Doi’s Conjecture is therefore at best ambiguous. Moreover, the manuscript relies substantially on claims about how effect measures are “perceived”, another term which is defined neither in probability theory not in the manuscript.

    The relative risk is defined as the risk of the outcome under treatment, divided by the risk of the outcome under the control condition; that is, as a ratio of two probabilities. Thi...

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  • Claims about the main claim

    Title: “Claims about the main claim”
    Author: Suhail A, Doi, Polychronis, Kostoulas, Paul, Glasziou
    In response to the published article "Likelihood ratio interpretation of the relative risk"

    Rapid response :
    September 16, 2022

    The problem in evidence-based medicine arises when we port relative risks derived from one study to settings with different baseline risks. For example, a baseline risk of 0.2 and treated risk of 0.4 for an event in a trial gives a RR of 2 (0.4/0.2) and the complementary cRR of 0.75 (0.6/0.8). Thus the ratio of LRs (RR/cRR) is 2/0.75 = 2.67. If applied to a baseline risk of 0.5 the predicted risk under treatment with the RR “interpretation” is 1.0 but with the ratio of LRs “interpretation” is 0.73. Here, the interpretation of the risk ratio as a likelihood ratio, using Bayes’ theorem, clearly gives different results, and solves the problem of impossible risks as clearly depicted in the manuscript and the example.
    If, in our effort to highlight the need of this correct interpretation, we have used strong wording that annoyed the commentator we feel the need to express regret. We hope that the commentator could also feel similarly for his scientifically unbecoming choice of wording that culminated with “Doi’s Conjecture”.
    Conflict of Interest
    None declared

  • Dr.

    I would like to congratulate Dr. Abbott and her team in generating this piece of important and interesting article, which applied the methods of meta-science to the early systematic review articles and the infodemics related to COVID-19.

    Indeed, the COVID-19 pandemic came quick and ferocious, starting early 2020 and lasted till recently and with new possible variants emerging, it still presents the medical community and indeed the scientific circles with challenging question. Thankfully to the selfless work of researchers, patients and frontline medical staffs, we now have some valuable means to deal with this Pandemic.

    The research community was presented with a rather challenging task of designing and conducting researches to answer important questions relating to the new infectious diseases at the time of early 2020. The “new” corona virus was ravaging parts of our world without checks. So studies were conducted at pace, which unfortunately resulted in much duplicated and poor methodological studies conducted. But on the other hand, the sheer volume of studies itself may be useful as it generated evidence to inform us of what does and what does not work in terms combating the COVID-19. For example, dexamethasone (RECOVERY trial) was found to be essential for severe COVID-19 patients and the use of Hydroxychloroquine is ineffective for COVID-19.
    Having said this, I must state that I am not in support of the generation of poor quality clinical studi...

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  • Letter to the editor

    Dear Editor,
    This response is in relation to the titled article above published in June 2019. Firstly, I would like to commend the outstanding work of research done. While reading the article, I understood the correlation between the nursing field, evidence-based research, and ways in which patients benefit from current health practices. Furthermore, the research conducted a wide range of research benefits in other nursing career paths globally. It showed experts views on teaching evidenced based prospectus, evidence-based deliberations, and stakeholders’ engagement which can impact patients involved. I agree with the study conducted and how research is essential for future advancements as well as improvements in care to patients. Unfortunately, there aren’t as much published research work in The Bahamas on evidence-based practices from an expert view. Through further research this thesis can become widespread to obtain more views on this pressing matter.

  • Level of reporting bias shown to be lower in homeopathy trials than in trials on conventional medicine

    We fully agree that „non-publication of trial results and selective outcome reporting…is not a phenomenon that is limited to homeopathy.”
    Previous reviews in conventional medicine, such as the study by Kosa et al. in 2018, report „…substantive disagreement in reporting between publications and current clinical trial registry, which were associated with several study characteristics”.[1]

    In 2019 The Lancet commented on the reporting of clinical trial data for 30 European universities that sponsor the largest number of trials governed by EU clinical trials regulation: “The report shows that 778 (83%) of 940 clinical trials sponsored by these universities due to post their results on the EU Clinical trials Register (EudraCT) had not done so”.[2]

    The International Committee of Medical Journal Editors (ICMJE) announced in 2005 that “… trials that begin enrolment of patients after 1 July 2005 must register in a public trials registry at or before the onset of enrolment to be considered for publication …”.[3] EU rules took effect in 2014, which require all clinical trials registered in EudraCT to post summary results within 12 months of study completion.[2] Hence, the inclusion of studies on homeopathy published before and in 2005 by Gartlehner et al. 2022 does not seem reasonable respectively of those published before and in 2014 is debatable.
    Notwithstanding the above, precise information on sub-groups of studies was not given by Gartlehner et al. 202...

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  • Reflecting trial registration status does not change the conclusions from two previous homeopathy reviews

    In their recent paper, Gartlehner et al [1] reached the headline conclusion that ‘effect estimates of meta-analyses of homeopathy trials might substantially overestimate the true treatment effect of homeopathic remedies’. Their conclusion is based on having re-analysed one of the systematic review papers’ data published by Mathie et al [2] by taking into account the possible impact of a trial’s registration status. Gartlehner et al analysed a sub-set of 19 trials of non-individualised homeopathic treatment, comparing 6 trials that were registered with 13 trials that were not registered. They observed a statistically significant difference between homeopathy and placebo only for the non-registered trials; however, the difference in effect sizes between registered and non-registered trials did not reach statistical significance.

    In conducting their re-analysis, Gartlehner et al have failed to recognise that the meta-analysis by Mathie et al [2] was primarily based on a sensitivity analysis of trials that comprised reliable evidence (effectively, low risk of bias): the effect-size estimate collectively for those 3 trials yielded a statistically non-significant result. Those 3 trials are amongst the 6 registered trials in Gartlehner’s re-analysis, and so it is no surprise that they contributed to a non-significant pooled effect size. A majority of the other 13 trials, now defined as non-registered [1], had previously been categorised by Mathie et al as high risk of bias...

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  • Context is everything: Conclusions of Gartlehner et al should be interpreted with caution.

    The new study by Gartlehner et al. (1) claims that the benefits of homeopathy may have been over-estimated due to high levels of reporting bias. However, as this problem is well-known to affect all areas of medical research, context is everything.

    Although the authors state that, “non-publication of trial results and selective outcome reporting …. is not a phenomenon that is limited to homeopathy”, they failed to provide adequate context for their results by making any direct comparison to other areas of clinical research. Homeopathy is arguably out-performing conventional medicine, or, at the very least, has comparable levels of reporting bias. Using representative examples of high-impact studies on reporting bias across all medical fields, when compared with the data presented by Gartlehner et al.(1) it is clear that:
    1) half of all registered clinical trials (2) in conventional medicine fail to report their results within 12 months; whereas 62% of all registered homeopathy trials reach publication, and
    2) inconsistencies in reporting of primary outcome (3) occur in 43% of conventional medical studies; whilst this happens in only 25% of published homeopathy trials.

    The potential impact of unregistered/unpublished results on estimates of treatment effects is well known (4), yet for homeopathy, according to Gartlehner et al.(1), the impact may be minimal, or nothing at all: “the difference in effect sizes between registered and unregistered stud...

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