Article type
Year
Abstract
Background: Preclinical animal studies are used to develop new clinical treatments. The aim of animal studies (bench) ranges from unraveling pathophysiology and action mechanisms to investigating the clinical potential of selected interventions (bedside). Systematic reviews (SRs) can provide a reliable synthesis of the available evidence on the effect of interventions, but are relatively novel in laboratory animal research. SRs of animal studies can facilitate healthcare decisions, e.g. selection of interventions with therapeutic potential to be tested in clinical trials, regulatory decisions limiting human exposure (drugs or toxicants) or decisions on further animal studies. In addition, evidence from animal studies can inform clinical management decisions, if other evidence is lacking. Certainty in the evidence plays an essential role in these decisions, but guidance on the assessment is lacking.
Objectives: To apply the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach to preclinical animal studies, to adapt if needed, and to identify methodological issues.
Methods: A draft GRADE approach for animals studies was developed by a literature survey on how authors of SRs of animal studies address certainty in the evidence, and by applying the ‘human studies’ GRADE approach to three SRs of animal studies to flag challenges. The draft was discussed and improved in several rounds of expert meetings.
Results: In general, the GRADE approach applied well. The evidence is based on animal studies (bench), but the clinical question (bedside) is central. No factors other than the current GRADE domains were identified. Identified methodological challenges were choice of baseline risk, dealing with inconsistency within and across species, upgrading for consistency across species and specification of translating animal models to humans as part of GRADE’s indirectness domain.
Conclusions: GRADE can be applied to preclinical animal studies in the context of therapeutic interventions. Further work will concentrate on performing case studies, methodological issues and development of Evidence to Decision frameworks.
Objectives: To apply the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach to preclinical animal studies, to adapt if needed, and to identify methodological issues.
Methods: A draft GRADE approach for animals studies was developed by a literature survey on how authors of SRs of animal studies address certainty in the evidence, and by applying the ‘human studies’ GRADE approach to three SRs of animal studies to flag challenges. The draft was discussed and improved in several rounds of expert meetings.
Results: In general, the GRADE approach applied well. The evidence is based on animal studies (bench), but the clinical question (bedside) is central. No factors other than the current GRADE domains were identified. Identified methodological challenges were choice of baseline risk, dealing with inconsistency within and across species, upgrading for consistency across species and specification of translating animal models to humans as part of GRADE’s indirectness domain.
Conclusions: GRADE can be applied to preclinical animal studies in the context of therapeutic interventions. Further work will concentrate on performing case studies, methodological issues and development of Evidence to Decision frameworks.