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  "path": "/t/statin-related-side-effects-the-recent-lancet-publication-is-biased-toward-false-negatives/28635?page=2#post_25",
  "publishedAt": "2026-06-14T20:16:03.000Z",
  "site": "https://discourse.datamethods.org",
  "textContent": "ESMD:\n\n> Asking the Oxford authors to word their findings as follows might be a reasonable “middle ground” that would not risk aggravating a serious public health problem (statin denialism):\n>\n> _“Many of the AEs currently listed in statin product monographs were added to labelling many years ago because of a reported temporal relationship to statin use in individual patients in the postmarket setting. Rigorous evidence for a causal role of the statin in individual cases was not required to include these AEs in the label. Rather, many AEs were added as a precautionary measure, because a causal role for the drug “could not be excluded.” But we have now accrued high numbers of reports of many of these AEs in the context of decades of statin clinical trials. Trial-level evidence allows us to see that many of the AEs reported over the years in the postmarket setting (outside the context of trials) have occurred with**similar** frequency in statin-treated and placebo-treated trial subjects. We can draw the following conclusion from this observation: IF statins are capable of causing these AEs, they would **only** do so at rates **so low that the signal has been undetectable after decades of clinical trials. This fact suggests that that the risk for the labelled AEs in question would have to be so low that it would not be expected to influence clinical decision-making**. AEs that occur at very low rates are often those that occur unpredictably in idiosyncratically-vulnerable patients, for reasons we don’t understand- as such, these AEs can usually not be avoided through pre-treatment patient screening. If no safety signal for an AE has been observed after many accrued AEs of this type in statin clinical trials, we can conclude that IF statins are capable of causing this AE (perhaps in idiosyncratically-vulnerable patients), the risk is likely to be lower than 1 in …”_\n\nI think we need to separate two distinct issues.\n\nFirst, the Oxford headline does not merely refer to statins in general: it presents the findings of a study conducted by Oxford researchers in a way that appears to turn trial-level non-detection of excess adverse events into causal evidence of absence of such effects. That is the core problem, especially considering the strong bias towards false negatives.\n\nThis is not a minor wording issue, as it legitimizes a pseudo-methodological move (in pharmacovigilance) that has no sound basis and is inconsistent with decades of warnings in epidemiology and statistics: _absence of evidence_ is not _evidence of absence_. Importantly, we are not imposing an external standard: the authors themselves have acknowledged this distinction.\n\nSuch a methodological and infodemiological problem has consequences as serious as those associated with statin denialism. It may even be more insidious, because it often goes unnoticed given that the error is technically subtle, accessible to relatively few people, and at the same time it is amplified and given credibility by a major academic institution such as Oxford (of course, Oxford is not the only institution where this type of problem has occurred). Again, the literature I have already mentioned in this thread reports striking examples of these phenomena.\n\nThe targeted failure is independent of the specific topic - statins, vaccines, cancer drugs, or any other medical intervention. Indeed, we are talking about a general principle of evidence communication. Institutions should not disseminate this kind of severe misinformation, especially when it concerns causal interpretation of safety evidence.\n\nA second issue is why such miscommunication occurred. There are several competing or alternative explanations, and these should be considered analytically rather than dismissed as speculation. One possibility is simple incompetence: that Oxford researchers and/or communication officers failed to recognize the difference between “absence of evidence” and “evidence of absence.” Another possibility is that ordinary academic dynamics contributed to the overstatement of the findings: the incentive to present results in stronger, more visible, and more prestigious terms. A further possibility is that the long list of declared conflicts of interest that can have influenced, directly or indirectly, the framing and communication of the results. These are not “conspiracy theories”, but explanatory hypotheses for the observed “data”.\n\nAs for the specific discussion about statins, the “middle ground” solution seems to ignore what has already been repeatedly discussed in previous comments: again, the proposed narrative is only one of several possible narratives compatible with the observed data. Its persuasive force is substantially reduced once we consider well-known sources of bias, including the influence of pharmaceutical companies, selective framing of trial evidence, under-ascertainment or under-reporting of adverse events, and the persistent myth that randomized trials are the only legitimate source of causal evidence.\n\nNone of this means that statins lack important cardiovascular benefits when they are properly evaluated and appropriately prescribed - and, in some respects “paradoxically”, I reach this conclusion only after integrating information derived from the direct (observational) experience of the clinicians who prescribe them. The crucial question is that, in light of a highly controversial landscape that continues to rely on ritualistic practices and to perpetuate striking errors such as the one shown here, the scientific community should make a collective effort both to estimate and to limit the impact of these biases on the production of medical evidence.\n\nIf methodologists themselves fail to do this because they are misled by formal plausibility - not unlike the plausibility generated by a large language model - or because they are influenced by ideological, political, social, or economic pressures, then I do not see who else can realistically do it. And that would cause serious, unavoidable, reputational damage to medical research. What I (have to) expect, as a researcher, is not to be reassured with a convenient narrative; I expect serious countermeasures to prevent similar failures from **continuing** to occur.\n\nIn this respect, when explanations are produced for the public, we should stop attributing responsibility for claims to abstract formal entities such as “the evidence” or “the studies.” Evidence and studies acquire meaning only through human interpretation, validation, and judgment. Therefore, if Oxford wishes to communicate health recommendations to the public, it should state more explicitly that its analysts judge the underlying uncertainty to be sufficiently low to support those recommendations. At the same time, it should engage openly with those raising substantive methodological concerns, rather than leaving those concerns unanswered.",
  "title": "Statin-related side effects: the recent Lancet publication is biased toward false-negatives"
}