Grant: Knowledge Synthesis Grant

Safety and effectiveness of long-acting versus intermediate-acting insulin for patients with type 1 diabetes: a systematic review and individual patient data network meta-analysis (IPD-NMA)

Effectiveness; Glycosylated Hemoglobin; Hypoglycemia; Individual Patient Data; Insulin; Network Meta-Analysis; Safety; Systematic Review; Type I Diabetes Mellitus

<html> <body> <p>&nbsp; &nbsp; &nbsp;The foundation of Type 1 Diabetes Mellitus (T1DM) glycemic management is a basal-bolus insulin regimen, for which two choices exist for basal insulin: long- and intermediate-acting insulin. These choices may have different risks of harm and effectiveness. To help patients and clinicians optimally select a basal insulin, knowledge regarding how the effectiveness of these agents differs across patient characteristics (e.g. baseline glycosylated haemoglobin (A1C), risk of hypoglycemia) is required. <strong>Our decision-maker partners from the Canadian Diabetes Association have identified this as a critical issue, which led directly to this proposal for a systematic review and individual patient data</strong> <strong>network meta-analysis (IPD-NMA).</strong> Globally, the incidence of T1DM is increasing by approximately 3% per year, and is a challenging disease to live with, thereby impacting quality of life. The objective of this study is to evaluate the safety and effectiveness of long-acting insulin vs. intermediate-acting insulin for patients with T1DM.<br> </p> <p>&nbsp; &nbsp; &nbsp;NMA enables the evaluation of the comparative effectiveness or safety of multiple competing interventions, even for treatments that have not been directly compared in a head-to-head study. A key assumption in NMA is that the included randomized clinical trials (RCTs) are sufficiently similar across comparisons. Different distributions of a treatment effect modifier (TEM) can threaten the validity of results, and cause network inconsistency. <strong>When the TEM is a patient characteristic, consistency can only be examined using IPD.</strong> This can be due to potential aggregation biases, which may occur if one (incorrectly) assumes that relationships observed at the group level also hold at the individual level.<br> </p> <p>&nbsp; &nbsp; &nbsp;Our previous NMA suggested that long-acting insulin is statistically significantly superior to intermediate-acting insulin for glycemic control and severe hypoglycemia. Although this NMA provided important results, we were unable to make recommendations about tailoring the insulin to specific patients presenting with T1DM. <strong>Imagine a male patient with T1DM comes into a clinic with A1C level of 8.6%; our results will allow us to determine that glargine once daily (for example) is the most effective treatment for this type of patients in contrast to a man with a lower A1C value!</strong> <br> </p> <p>&nbsp; &nbsp; &nbsp;Using an integrated knowledge translation approach, we will conduct a methodologically rigorous systematic review and IPD-NMA following the highest standards put forth by the Cochrane Collaboration. We will update our previous systematic review published in the BMJ, include RCTs that assessed A1C and/or severe hypoglycemia in adults with T1DM administered long- or intermediate-acting insulin. For each eligible study, we will contact the corresponding author and request IPD<strong>.</strong> <strong>Members of our team have experience in contacting authors and successfully obtaining IPD, which highlights the feasibility of our proposal</strong><strong>.</strong> If we are not successful in obtaining IPD for at least one study, we will include aggregated data (AD) in our analysis as reported in the original articles, and we will combine both IPD and AD in a single model. <strong>It has been shown that</strong> <strong>combining IPD with AD minimizes the chances of confounding bias evident in NMA and leads to more information that can be used in clinical decision-making</strong>. Results from our IPD-NMA will be used to update the CDA guidelines, improving the health of Canadians suffering from this debilitating disease.</p> </body> </html>