Chemical catalogs is a monoclonal B cell malignancy that largely afflicts older adults, the median age at diagnosis is approximately 72 years. In the United States, over 15,000 new cases of CLL are diagnosed annually and over 4000 deaths each year are attributed to the disease.1 Many patients have an indolent disease course and do not require therapy. Others with progressive disease may present with symptoms that require treatment including lymphadenopathy, splenomegaly, hepatomegaly, fatigue, symptomatic anemia, immune related cytopenias or infection. Current drug therapies for CLL are intended to relieve symptoms and may slow disease progression, but are non curative.1,2 Chlorambucil, an alkylating agent, has been considered the standard first line therapy for symptomatic, progressive CLL for many years.3 Recently, drug screening libraries several new therapeutic options have become available including additional alkylating agents, monoclonal antibodies, purine analogs, and combination regimens comprised of these and other products. Many of the currently available treatment options have been evaluated in randomized controlled trials against chlorambucil, but they have not been directly compared against each other.
Different treatment approaches for CLL are common and there is currently no agreed upon standard regimen for previously untreated sodium channel patients with symptomatic CLL.4 Network meta analysis is an extension of traditional metaanalysis and is a method that synthesizes available evidence to allow for simultaneous comparisons of different treatment options that lack direct head to head evaluations.5 8 Individual pair wise studies are,linked, to create a network of studies on which statistical inference is based. When the network consists of a mixture ofdirect and indirect evidence with comparable study and patient characteristics, the relative treatment effect of drug B vs. drug C may be indirectly estimated by comparing peptide synthesis studies of drug A vs. drug B and drug A vs. drug C.8,9 The value of a network meta analysis is that it can include both direct and indirect evidence and it preserves the strength of randomization within individual RCTs.
However, the method has limitations as it is based on model simulation, and the method could result in biased estimates if there are systematic differences across comparisons. The objective of this study was to conduct a network meta analysis to compare relative treatment effects of therapies for previously untreated CLL. Methods Overall approach We performed a systematic literature review to identify RCTs of therapy options for symptomatic, previously untreated CLL. We used a Bayesian statistical framework to estimate relative treatment effects applied on the shape and scale parameters of survival curves, which provides a more flexible method and allows relaxation of the proportional hazards assumption.8,9 Systematic literature review We identified therapy options for treatment naïve CLL using National Comprehensive Cancer Network Clinical Practice Guidelines and UpToDate 19.3, an electronic resource that provides evidence based clinical recommendations. For each primary firstline CLL agent, we conducted an independent literature search in the Medline database and The Cochrane Library for RCTs published prior to November 2011 using search terms.