Comparing medication adherence in patients receiving bisphosphonates for preventing fragility fractures: a comprehensive systematic review and network meta-analysis.

BACKGROUND: Bisphosphonates are effective in preventing fragility fractures; however, high rates of adherence are needed to preserve clinical benefits. OBJECTIVE: To investigate persistence and compliance to oral and intravenous bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate). METHODS: Searches of 12 databases, unpublished sources, and trial registries were conducted, covering the period from 2000 to April 2021. Screening, data extraction, and risk of bias assessment (Cochrane Collaboration risk-of-bias tool 1.0 & ROBINS-I) were independently undertaken by two study authors. Randomised controlled trials (RCTs) and observational studies that used prescription claim databases or hospital medical records to examine patients' adherence were included. Network meta-analyses (NMA) embedded within a Bayesian framework were conducted, investigating users' likelihood in discontinuing bisphosphonate treatment. Where meta-analysis was not possible, data were synthesised using the vote-counting synthesis method. RESULTS: Fifty-nine RCTs and 43 observational studies were identified, resulting in a total population of 2,656,659 participants. Data from 59 RCTs and 24 observational studies were used to populate NMAs. Zoledronate users were the least likely to discontinue their treatment HR = 0.73 (95%CrI: 0.61, 0.88). Higher rates of compliance were observed in those receiving intravenous treatments. The paucity of data and the heterogeneity in the reported medication possession ratio thresholds precluded a NMA of compliance data. CONCLUSIONS: Users of intravenously administered bisphosphonates were found to be the most adherent to treatment among bisphosphonates' users. Patterns of adherence will permit the more precise estimation of clinical and cost-effectiveness of bisphosphonates. TRIAL REGISTRATION: PROSPERO 2020 CRD42020177166.

A demonstration of using formal consensus methods within guideline development; a case study.

BACKGROUND: Recommendations within guidelines are developed by synthesising the best available evidence; when limited evidence is identified recommendations are generally based on informal consensus. However, there are potential biases in group decision making, and formal consensus methods may help reduce these. METHODS: We conducted a case study using formal consensus, to develop one set of recommendations within the Neonatal Parenteral Nutrition guideline being produced for the National Institute for Health and Care Excellence. Statements were generated through identification of published guidelines on several topics relating to neonatal parenteral nutrition. Ten high quality guidelines were included, and 28 statements were generated; these statements were rated by the committee via two rounds of voting. The statements which resulted in agreement were then used to develop the recommendations. RESULTS: The approach was systematic and provided transparency. Additionally, a number of lessons were learnt; including the value of selecting the appropriate topic, giving adequate time to the process, and ensuring methodologies are understood by the committee for their value and relevance. CONCLUSION: Formal consensus is a valuable option for use within guideline development when specific criteria are met. The approach provides transparent methodology, ensuring clarity on how recommendations are developed.