1. Protocol: Benefits and harms of remdesivir for COVID-19 in adults: A systematic review with meta-analysis
- Author
-
Matthew J. Page, Asger Sand Paludan-Müller, Andreas Lundh, and Klaus Munkholm
- Subjects
Viral Diseases ,Epidemiology ,Study Protocol ,Database and Informatics Methods ,Medical Conditions ,Mathematical and Statistical Techniques ,Health care ,Medicine and Health Sciences ,Database Searching ,Multidisciplinary ,Alanine ,Pharmaceutics ,Statistics ,Alanine/analogs & derivatives ,Research Assessment ,Metaanalysis ,Systematic review ,Infectious Diseases ,Reporting bias ,Research Design ,Meta-analysis ,Physical Sciences ,Medicine ,Adult ,Risk ,medicine.medical_specialty ,Systematic Reviews ,Clinical Research Design ,Death Rates ,Science ,MEDLINE ,Research and Analysis Methods ,COVID-19/drug therapy ,Adenosine Monophosphate/analogs & derivatives ,Drug Therapy ,Population Metrics ,medicine ,Humans ,Statistical Methods ,Intensive care medicine ,Adverse effect ,Protocol (science) ,Population Biology ,business.industry ,Biology and Life Sciences ,Covid 19 ,Publication bias ,Adenosine Monophosphate ,COVID-19 Drug Treatment ,Medical Risk Factors ,Adverse Events ,business ,Publication Bias ,Mathematics - Abstract
Background Effective drug treatments for Covid-19 are needed to decrease morbidity and mortality for the individual and to alleviate pressure on health care systems. Remdesivir showed promising results in early randomised trials but subsequently a large publicly funded trial has shown less favourable results and the evidence is interpreted differently in clinical guidelines. Systematic reviews of remdesivir have been published, but none have systematically searched for unpublished data, including regulatory documents, and assessed the risk of bias due to missing evidence. Methods We will conduct a systematic review of randomised trials comparing remdesivir to placebo or standard of care in any setting. We will include trials regardless of the severity of disease and we will include trials examining remdesivir for indications other than Covid-19 for harms analyses. We will search websites of regulatory agencies, trial registries, bibliographic databases, preprint servers and contact trial sponsors to obtain all available data, including unpublished clinical data, for all eligible trials. Our primary outcomes will be all-cause mortality and serious adverse events. Our secondary outcomes will be length of hospital stay, time to death, severe disease, and adverse events. We will assess the risk of bias using the Cochranes Risk of Bias 2 tool and the risk of bias due to missing evidence (e.g. publication bias, selective reporting bias) using the ROB-ME tool. Where appropriate we will synthesise study results by conducting random-effects meta-analysis. We will present our findings in a Summary of Findings table and rate the certainty of the evidence using the GRADE approach. Discussion By conducting a comprehensive systematic review including unpublished data (where available), we expect to be able to provide valuable information for patients and clinicians about the benefits and harms of remdesivir for the treatment of Covid-19. This will help to ensure optimal treatment for individual patients and optimal utilisation of health care resources. Systematic review registration CRD42021255915.
- Published
- 2021