в трагической истории Кокрановского обзора эффективности и безопасности антипапилломавирусной вакцины.
27 июля BMJ Evidence-Based Medicine опубликовал статью известных участников Кокрейн Lars Jørgensen, Peter C Gøtzsche, Tom Jefferson. The Cochrane HPV vaccine review was incomplete and ignored important evidence of bias. https://ebm.bmj.com/content/early/2018/07/27/bmjebm-2018-111012.
В ней они указывают на значительные погрешности в длительном процессе подготовки обзора, приведшие к крайне несовершенному результату. Главред Кокрейн Давид Тови ответил — после расследования — все ОК, идите лесом. Читать тут (https://www.cochrane.org/sites/default/files/public/uploads/cochrane_hpv_response_3sep18.pdf).
Поскольку я знаю беспрецедентную принципиальность ПГ и ТД, равно как и их методическое совершенство, я изначально на их стороне. Но читаем ответ:
«The Cochrane Review included 26 trials (73,428 participants) that matched the predetermined study criteria. As a result of our investigations we believe that five eligible completed studies with available data representing 5267 women may have been missed from the Cochrane Review, as a consequence of the search being based on bibliographic databases rather than trials registers. Details
of these studies are available in Appendix B. This finding contrasts with the calculation of 20 studies (48,276 women) missed, as suggested by Jørgensen et al in their BMJ Evidence-Based Medicine article. Once we have the data from the authors we will seek to understand the difference between these assessments»
Ну, далее. Как в таких случаях пишут, запасаемся попкорном.
«The use of surrogate outcomes in the HPV vaccine trials is, as Jørgensen et al note, «in line with WHO recommendations». This was explained by the authors in the Cochrane Review. Transition from CIN 2 and CIN 3 to cancer is not inevitable if untreated, but it is a clear risk, and for this reason both of these interim states are subject to treatment, which carries its own morbidity. The risk of progression to cancer increases as the lesions progress. Cervical cancer is a malignancy that can be prevented effectively through detection and treatment of the precursor states. Plainly there is no ethical means by which researchers could leave untreated the presence of the precursor states, so that the near complete absence of cervical cancer in any arm of the trials is inevitable. In our judgement it is impossible to see how it could be feasible or ethical to undertake a trial that was large enough and of sufficient duration for cancer outcomes to be reliably demonstrated and where women were denied interventions that are known to prevent cancer.»
Проблема-то неразрешимая… Про то, что она не решена, и писали.
«In relation to harms more generally, we acknowledge that there is a case for including other forms of evidence. The ‘Discussion’ section of the Cochrane Review and the accompanying Editorial both noted the importance of national surveillance programmes to identify and report harms.2,8 This is particularly true when it comes to harms such as autonomic dysfunction syndromes and other syndromes that are not reported (positively or negatively) in most of the journal-published reports, but about which concerns have been raised subsequently from observational reports. This underlines the importance of systematic reviews being used in conjunction with the evidence from national surveillance programmes. Finally, we believe that this Cochrane Review has raised broader questions for Cochrane in relation to reporting harms. We propose to initiate work aimed at providing updated guidance for author teams on identifying and reporting harms in the current and future data and research environment, as part of our ongoing implementation of Cochrane’s content strategy.»
Да-да, все знают, что в Кокрейн эта проблема решена нехорошо (в других местах совсем плохо). И в обзоре — плохо.
«Scientific debate is to be welcomed, and differences of opinion between different Cochrane ‘voices’ is not unexpected. However, public confidence may be undermined, unnecessary anxiety caused, and public health put at risk, if that debate is not undertaken in an appropriate way. This is especially true when such debates take place in public. There is already a formidable and growing anti-vaccination lobby. If the result of this controversy is reduced uptake of the vaccine among young women, this has the potential to lead to women suffering and dying unnecessarily from cervical cancer.»
Ага. Кругом антивакцинаторы, поэтому проблемы наших аргументов в пользу вакцинации надо обсуждать за закрытыми дверями.
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