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Facilitating healthcare decisions by assessing the certainty in the evidence from preclinical animal studies.

ABSTRACT: Laboratory animal studies are used in a wide range of human health related research areas, such as basic biomedical research, drug research, experimental surgery and environmental health. The results of these studies can be used to inform decisions regarding clinical research in humans, for example the decision to proceed to clinical trials. If the research question relates to potential harms with no expectation of benefit (e.g., toxicology), studies in experimental animals may provide the only relevant or controlled data and directly inform clinical management decisions. Systematic reviews and meta-analyses are important tools to provide robust and informative evidence summaries of these animal studies. Rating how certain we are about the evidence could provide important information about the translational probability of findings in experimental animal studies to clinical practice and probably improve it. Evidence summaries and certainty in the evidence ratings could also be used (1) to support selection of interventions with best therapeutic potential to be tested in clinical trials, (2) to justify a regulatory decision limiting human exposure (to drug or toxin), or to (3) support decisions on the utility of further animal experiments. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach is the most widely used framework to rate the certainty in the evidence and strength of health care recommendations. Here we present how the GRADE approach could be used to rate the certainty in the evidence of preclinical animal studies in the context of therapeutic interventions. We also discuss the methodological challenges that we identified, and for which further work is needed. Examples are defining the importance of consistency within and across animal species and using GRADE's indirectness domain as a tool to predict translation from animal models to humans.

SUBMITTER: Hooijmans CR

PROVIDER: S-EPMC5764235 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Facilitating healthcare decisions by assessing the certainty in the evidence from preclinical animal studies.

Hooijmans Carlijn R CR de Vries Rob B M RBM Ritskes-Hoitinga Merel M Rovers Maroeska M MM Leeflang Mariska M MM IntHout Joanna J Wever Kimberley E KE Hooft Lotty L de Beer Hans H Kuijpers Ton T Macleod Malcolm R MR Sena Emily S ES Ter Riet Gerben G Morgan Rebecca L RL Thayer Kristina A KA Rooney Andrew A AA Guyatt Gordon H GH Schünemann Holger J HJ Langendam Miranda W MW

PloS one 20180111 1

Laboratory animal studies are used in a wide range of human health related research areas, such as basic biomedical research, drug research, experimental surgery and environmental health. The results of these studies can be used to inform decisions regarding clinical research in humans, for example the decision to proceed to clinical trials. If the research question relates to potential harms with no expectation of benefit (e.g., toxicology), studies in experimental animals may provide the only ...[more]

PMID: 29324741

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Project description:BackgroundThe implementation of evidence-based healthcare interventions is challenging, with a 17-year gap identified between the generation of evidence and its implementation in routine practice. Although contextual factors such as culture and leadership are strong influences for successful implementation, context remains poorly understood, with a lack of consensus regarding how it should be defined and captured within research. This study addresses this issue by providing insight into how context is defined and assessed within healthcare implementation science literature and develops a definition to enable effective measurement of context.MethodsMedline, PsychInfo, CINAHL and EMBASE were searched. Articles were included if studies were empirical and evaluated context during the implementation of a healthcare initiative. These English language articles were published in the previous 10 years and included a definition and assessment of context. Results were synthesised using a narrative approach.ResultsThree thousand and twenty-one search records were obtained of which 64 met the eligibility criteria and were included in the review. Studies used a variety of definitions in terms of the level of detail and explanation provided. Some listed contextual factors (n = 19) while others documented sub-elements of a framework that included context (n = 19). The remaining studies provide a rich definition of general context (n = 11) or aspects of context (n = 15). The Alberta Context Tool was the most frequently used quantitative measure (n = 4), while qualitative papers used a range of frameworks to evaluate context. Mixed methods studies used diverse approaches; some used frameworks to inform the methods chosen while others used quantitative measures to inform qualitative data collection. Most studies (n = 50) applied the chosen measure to all aspects of study design with a majority analysing context at an individual level (n = 29).ConclusionsThis review highlighted inconsistencies in defining and measuring context which emphasised the need to develop an operational definition. By providing this consensus, improvements in implementation processes may result, as a common understanding will help researchers to appropriately account for context in research.

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Dataset Information

Facilitating healthcare decisions by assessing the certainty in the evidence from preclinical animal studies.

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Facilitating healthcare decisions by assessing the certainty in the evidence from preclinical animal studies.

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