Vaccines to prevent COVID-19: a protocol for a living systematic review with network meta-analysis including individual patient data (The LIVING VACCINE Project)

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes corona virus disease 2019 (COVID-19) which has rapidly spread worldwide. Several human randomized clinical trials assessing potential vaccines are currently underway. There is an urgent need for a living systematic review that continuously assesses the beneficial and harmful effects of all available vaccines for COVID-19.Methods/design: We will conduct a living systematic review based on searches of major medical databases (e.g. MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify relevant randomized clinical trials. We will update the literature search once a week to continuously assess if new evidence is available. Two review authors will independently extract data and conduct risk of bias assessments. We will include randomized clinical trials comparing any vaccine aiming to prevent COVID-19 (including but not limited to messenger RNA; DNA; non-replicating viral vector; replicating viral vector; inactivated virus; protein subunit; dendritic cell; other vaccines) with any comparator (placebo; ‘active placebo’; no intervention; standard care; an ‘active’ intervention; another vaccine for COVID-19) for participants in all age groups.Primary outcomes will be all-cause mortality; a diagnosis of COVID-19; and serious adverse events. Secondary outcomes will be quality of life, and non-serious adverse events. The living systematic review will include aggregate data meta-analyses, Trial Sequential Analyses, network meta-analyses, and individual patient data meta-analyses. Within-study bias will be assessed using Cochrane risk of bias tool. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) and Confidence in Network Meta-Analysis (CINeMA) approaches will be used to assess certainty of evidence. Observational studies describing harms identified during the search for trials will also be included and described and analyzed separately.Discussion: COVID-19 has become a pandemic with substantial mortality. A living systematic review assessing the beneficial and harmful effects of different vaccines is urgently needed. This living systematic review will regularly inform best practice in vaccine prevention and clinical research of this highly prevalent disease.Systematic review registration: PROSPERO CRD42020196492

Vaccines to prevent COVID-19: A living systematic review with Trial Sequential Analysis and network meta-analysis of randomized clinical trials

“…This review was carried out following recommendations outlined in the Cochrane Handbook of Systematic Reviews of Interventions [11]. More details on our methods can be found in our published protocol [8,12].…”

Antibiotics for hospital-acquired pneumonia in neonates and children

“…If the trialists do not use the ICH-GCP definition or this term, then we will include the data if the event clearly fulfils the ICH-GCP definition for a serious adverse event. We will exploratorily assess each type of serious adverse event separately (Korang 2020).…”

Potential therapeutic options for COVID-19: an update on current evidence

“…DCs related to immunotherapy and cell-based vaccination, are the next cell-based therapy candidate for the treatment of COVID-19. In the USA, an immuno-oncology company designing personalized vaccines has recently conducted a clinical trial (NCT04386252) of a vaccine of autologous DCs loaded with antigens from SARS-CoV-2, with or without GM-CSF, to inhibit COVID-19 in adults [ 121 , 122 ]. These DCs consist of peripheral blood monocyte-derived DCs collected from the blood samples of patients.…”