title: Safety and effectiveness of long-acting versus intermediate-acting insulin for patients with type 1 diabetes: protocol for a systematic review and individual patient data network meta-analysis.
abstract: BACKGROUND
  The choice of a basal insulin regimen to manage type 1 diabetes mellitus (T1DM) may have different risks of adverse events and effectiveness, due to the difference in the effectiveness of these agents across patient characteristics (eg, baseline glycosylated haemoglobin; A1C). Currently, there is a lack of high quality evidence to support the tailoring of insulin regimens according to an individual's needs. The aim of this study is to update our previous systematic review and perform an individual patient data network meta-analysis (IPD-NMA) to evaluate the comparative safety and effectiveness of long-acting versus intermediate-acting insulin in different subgroups of patients with T1DM.
  
  
  METHODS
  We will update our previous literature search from January 2013 onwards searching relevant electronic databases (eg, MEDLINE), as well as perform grey literature search through relevant society/association websites, and conference abstracts, and scan reference lists of the eligible studies. We will include randomised clinical trials of any duration examining long-acting versus intermediate-acting insulin preparations for adult patients with T1DM. We will focus on A1C and severe hypoglycaemia outcomes. For each pairwise treatment comparison, we will combine all IPD from all studies in a single multilevel model, where each study is a different cluster. For a connected network of trials, we will perform an IPD-NMA to identify potential effect modifiers, and estimate the most effective and safe treatments for patients with different characteristics. If we are not successful in obtaining IPD for at least one study, we will include aggregated data (AD) abstracted from the included RCTs in our analysis, combining IPD and AD into a single model. We will report our results using the PRISMA-IPD statement.
  
  
  BACKGROUND
  The results of this systematic review and IPD-NMA will be of interest to stakeholders and will help in improving existing guideline recommendations.
  CRD42015023511.
authors.affiliation: Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Areti Angeliki
authors.initials: AA
authors.lastname: Veroniki
authors.affiliation: Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada Department of Geriatric Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Straus
authors.affiliation: Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Huda M
authors.initials: HM
authors.lastname: Ashoor
authors.affiliation: Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jemila S
authors.initials: JS
authors.lastname: Hamid
authors.affiliation: Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Yu
authors.affiliation: Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada Epidemiology Division, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Tricco
mesh_terms: D002985:Clinical Protocols; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D049528:Insulin, Long-Acting / Q000627:therapeutic use*; D061266:Insulin, Short-Acting / Q000627:therapeutic use*; D000078202:Systematic Reviews as Topic; D015201:Meta-Analysis as Topic
chemical_list: D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D061266:Insulin, Short-Acting
keywords: glycosylated hemoglobin; hypoglycemia; individual participant data; insulin; multiple treatments meta-analysis