Commentary on Cochrane review of neuraminidase inhibitors for preventing and treating influenza in healthy adults and children

Abstract

In recent years there has been much debate and controversy surrounding the efficacy and safety of neuraminidase inhibitors for influenza, in part because the data underlying certain efficacy claims were not available for independent scrutiny. In 2014, a Cochrane review was published, based exclusively on an almost complete set of clinical study reports and other regulatory documents. Clinical study reports can run to thousands of pages, providing an extensive amount of information on the planning, conduct and results of each trial. After a protracted campaign to obtain the reports, the manufacturers of the medications provided them unconditionally. The review authors subsequently published the underlying documents simultaneously with the Cochrane review, endorsing the concept of open science. In the following commentary, the background to and results of this review are summarized and put into clinical context.

Grey literature in systematic reviews: a cross-sectional study of the contribution of non-English reports, unpublished studies and dissertations to the results of meta-analyses in child-relevant reviews

“…One review included only unpublished studies; therefore, no effect estimate was available without the unpublished studies. The topic of the review was neuroaminidase inhibitors for preventing and treating influenza, a particularly high profile topic that relied heavily on industry reports and other regulatory documents [24]. …”

“…In an additional case (of the eight meta-analyses), there were no published studies included; this review relied on unpublished industry reports and regulatory documents because of questions raised about the credibility of the published reports. The authors of this review had been questioned about the findings of an earlier version for which the conclusions were based on a pooled analysis, conducted by the manufacturer of the manufacturer-sponsored trials [24]. To address the concern, the authors set out to obtain the unpublished data from the drug manufacturer [24].…”

“…The authors of this review had been questioned about the findings of an earlier version for which the conclusions were based on a pooled analysis, conducted by the manufacturer of the manufacturer-sponsored trials [24]. To address the concern, the authors set out to obtain the unpublished data from the drug manufacturer [24]. We might argue that this was a special case, and advise reviewers to seek unpublished data when the manufacturer has been heavily involved in a substantial proportion of published reports identified for inclusion.…”

Treatment of influenza with neuraminidase inhibitors

“…Mortality was therefore a rare event, and the trials were not methodologically designed or powered to reliably detect differences in complications including hospitalisation [15,17]. The Cochrane review analyses therefore does not evaluate the patient groups who are most likely to benefit from influenza treatment, i.e.…”

On neuraminidase inhibitors and evidence-based medicine

“…Quite astonishingly, 60% of the patient data (3145 of 5267 patients randomized) were never published. In the current issue, the review authors provide explanations [3]. In response to critiques that the review addressed only healthy adults, the authors clarify that the review included all adult patients, including those with comorbidities that were included in the RCTs, except for patients with primary immunodeficiency and cancer.…”