TY - JOUR
T1 - The use of single armed observational data to closing the gap in otherwise disconnected evidence networks
T2 - A network meta-analysis in multiple myeloma
AU - Schmitz, Susanne
AU - Maguire, Áine
AU - Morris, James
AU - Ruggeri, Kai
AU - Haller, Elisa
AU - Kuhn, Isla
AU - Leahy, Joy
AU - Homer, Natalia
AU - Khan, Ayesha
AU - Bowden, Jack
AU - Buchanan, Vanessa
AU - O'Dwyer, Michael
AU - Cook, Gordon
AU - Walsh, Cathal
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/6/28
Y1 - 2018/6/28
N2 - Background: Network meta-analysis (NMA) allows for the estimation of comparative effectiveness of treatments that have not been studied in head-to-head trials; however, relative treatment effects for all interventions can only be derived where available evidence forms a connected network. Head-to-head evidence is limited in many disease areas, regularly resulting in disconnected evidence structures where a large number of treatments are available. This is also the case in the evidence of treatments for relapsed or refractory multiple myeloma. Methods: Randomised controlled trials (RCTs) identified in a systematic literature review form two disconnected evidence networks. Standard Bayesian NMA models are fitted to obtain estimates of relative effects within each network. Observational evidence was identified to fill the evidence gap. Single armed trials are matched to act as each other's control group based on a distance metric derived from covariate information. Uncertainty resulting from including this evidence is incorporated by analysing the space of possible matches. Results: Twenty five randomised controlled trials form two disconnected evidence networks; 12 single armed observational studies are considered for bridging between the networks. Five matches are selected to bridge between the networks. While significant variation in the ranking is observed, daratumumab in combination with dexamethasone and either lenalidomide or bortezomib, as well as triple therapy of carfilzomib, ixazomib and elozumatab, in combination with lenalidomide and dexamethasone, show the highest effects on progression free survival, on average. Conclusions: The analysis shows how observational data can be used to fill gaps in the existing networks of RCT evidence; allowing for the indirect comparison of a large number of treatments, which could not be compared otherwise. Additional uncertainty is accounted for by scenario analyses reducing the risk of over confidence in interpretation of results.
AB - Background: Network meta-analysis (NMA) allows for the estimation of comparative effectiveness of treatments that have not been studied in head-to-head trials; however, relative treatment effects for all interventions can only be derived where available evidence forms a connected network. Head-to-head evidence is limited in many disease areas, regularly resulting in disconnected evidence structures where a large number of treatments are available. This is also the case in the evidence of treatments for relapsed or refractory multiple myeloma. Methods: Randomised controlled trials (RCTs) identified in a systematic literature review form two disconnected evidence networks. Standard Bayesian NMA models are fitted to obtain estimates of relative effects within each network. Observational evidence was identified to fill the evidence gap. Single armed trials are matched to act as each other's control group based on a distance metric derived from covariate information. Uncertainty resulting from including this evidence is incorporated by analysing the space of possible matches. Results: Twenty five randomised controlled trials form two disconnected evidence networks; 12 single armed observational studies are considered for bridging between the networks. Five matches are selected to bridge between the networks. While significant variation in the ranking is observed, daratumumab in combination with dexamethasone and either lenalidomide or bortezomib, as well as triple therapy of carfilzomib, ixazomib and elozumatab, in combination with lenalidomide and dexamethasone, show the highest effects on progression free survival, on average. Conclusions: The analysis shows how observational data can be used to fill gaps in the existing networks of RCT evidence; allowing for the indirect comparison of a large number of treatments, which could not be compared otherwise. Additional uncertainty is accounted for by scenario analyses reducing the risk of over confidence in interpretation of results.
KW - Evidence synthesis
KW - Network meta-analysis
KW - Relapsed or refractory myeloma
KW - Single armed studies
UR - http://www.scopus.com/inward/record.url?scp=85049153640&partnerID=8YFLogxK
U2 - 10.1186/s12874-018-0509-7
DO - 10.1186/s12874-018-0509-7
M3 - Article
C2 - 29954322
AN - SCOPUS:85049153640
SN - 1471-2288
VL - 18
SP - 66
JO - BMC Medical Research Methodology
JF - BMC Medical Research Methodology
IS - 1
M1 - 66
ER -