Effectiveness and cost-effectiveness of oral nutritional supplements in frail older people who are malnourished or at risk of malnutrition: a systematic review and meta-analysis

Current management of malnutrition can include prescribed oral nutritional supplements (ONS); however, there is uncertainty whether these supplements are effective in people who are older (≥65 years) and frail. We assessed the effectiveness, cost-effectiveness, and adherence and acceptability of ONS in frail older people who are malnourished or at risk of malnutrition. In this systematic review and meta-analysis, five bibliographic databases (MEDLINE, EMBASE, Cochrane Library, Scopus, and CINAHL) and grey literature sources were searched from inception to Sept 13, 2021, to identify studies assessing the effectiveness and cost-effectiveness of ONS (with or without other dietary interventions) in frail older people who are malnourished or at risk of malnutrition. Multiple reviewers independently did study screening, data extraction, and risk of bias assessment. Quality was assessed using version 1.0 of the Cochrane risk of bias tool for randomised controlled trials (RCTs), and the BMJ Drummond checklist was used to assess the quality of the included cost-effectiveness study. A meta-analysis was done for the effectiveness review; for the other reviews, a narrative synthesis approach was used. This systematic review and meta-analysis was registered on PROSPERO, CRD42020170906. Of 8492 records retrieved and screened, we included 11 RCTs involving 822 participants, six of which were fully or partly funded by industry. For the majority of the outcomes for which meta-analyses were possible (11/12), Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessments suggested that the evidence was of very low certainty. Results suggested that ONS might have a slightly positive effect on energy (kcal) intake (standardised mean difference 1·02 [95% CI 0·15 to 1·88]; I2=87%; four studies), protein intake (standardised mean difference 1·67 [–0·03 to 3·37; I2=97%; four studies), and mobility (mean difference 0·03 [0·02 to 0·04]; I2=0%; four studies), compared with standard care. Narrative syntheses suggested that the effect of ONS on quality of life, compared with standard care, was mixed. In the identified studies, there was very little information related to active components, determinants, or acceptability of interventions. One economic evaluation, done in a care home setting, showed that ONS could be cost-effective. We found little evidence of ONS reducing malnutrition or its associated adverse outcomes in older people who are frail. High-quality