Performing meta-analysis with incomplete statistical information in clinical trials

<p>Abstract</p> <p>Background</p> <p>Results from clinical trials are usually summarized in the form of sampling distributions. When full information (mean, SEM) about these distributions is given, performing meta-analysis is straightforward. However, when some of the sampling distributions only have mean values, a challenging issue is to decide how to use such distributions in meta-analysis. Currently, the most common approaches are either ignoring such trials or for each trial with a missing SEM, finding a similar trial and taking its SEM value as the missing SEM. Both approaches have drawbacks. As an alternative, this paper develops and tests two new methods, the first being the prognostic method and the second being the interval method, to estimate any missing SEMs from a set of sampling distributions with full information. A merging method is also proposed to handle clinical trials with partial information to simulate meta-analysis.</p> <p>Methods</p> <p>Both of our methods use the assumption that the samples for which the sampling distributions will be merged are randomly selected from the same population. In the prognostic method, we predict the missing SEMs from the given SEMs. In the interval method, we define intervals that we believe will contain the missing SEMs and then we use these intervals in the merging process.</p> <p>Results</p> <p>Two sets of clinical trials are used to verify our methods. One family of trials is on comparing different drugs for reduction of low density lipprotein cholesterol (LDL) for Type-2 diabetes, and the other is about the effectiveness of drugs for lowering intraocular pressure (IOP). Both methods are shown to be useful for approximating the conventional meta-analysis including trials with incomplete information. For example, the meta-analysis result of Latanoprost versus Timolol on IOP reduction for six months provided in <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> was 5.05 ± 1.15 (Mean ± SEM) with full information. If the last trial in this study is assumed to be with partial information, the traditional analysis method for dealing with incomplete information that ignores this trial would give 6.49 ± 1.36 while our prognostic method gives 5.02 ± 1.15, and our interval method provides two intervals as Mean ∈ [4.25, 5.63] and SEM ∈ [1.01, 1.24].</p> <p>Conclusion</p> <p>Both the prognostic and the interval methods are useful alternatives for dealing with missing data in meta-analysis. We recommend clinicians to use the prognostic method to predict the missing SEMs in order to perform meta-analysis and the interval method for obtaining a more cautious result.</p

Adoptive T-cell therapy improves treatment of canine non–Hodgkin lymphoma post chemotherapy

Clinical observations reveal that an augmented pace of T-cell recovery after chemotherapy correlates with improved tumor-free survival, suggesting the add-back of T cells after chemotherapy may improve outcomes. To evaluate adoptive immunotherapy treatment for B-lineage non-Hodgkin lymphoma (NHL), we expanded T cells from client-owned canines diagnosed with NHL on artificial antigen presenting cells (aAPC) in the presence of human interleukin (IL)-2 and IL-21. Graded doses of autologous T cells were infused after CHOP chemotherapy and persisted for 49 days, homed to tumor, and significantly improved survival. Serum thymidine kinase changes predicted T-cell engraftment, while anti-tumor effects correlated with neutrophil-to-lymphocyte ratios and granzyme B expression in manufactured T cells. Therefore, chemotherapy can be used to modulate infused T-cell responses to enhance anti-tumor effects. The companion canine model has translational implications for human immunotherapy which can be readily exploited since clinical-grade canine and human T cells are propagated using identical approaches

Microarray-based identification and RT-PCR test screening for epithelial-specific mRNAs in peripheral blood of patients with colon cancer

BACKGROUND: The efficacy of screening for colorectal cancer using a simple blood-based assay for the detection of tumor cells disseminated in the circulation at an early stage of the disease is gaining positive feedback from several lines of research. This method seems able to reduce colorectal cancer mortality and may replace colonoscopy as the most effective means of detecting colonic lesions. METHODS: In this work, we present a new microarray-based high-throughput screening method to identifying candidate marker mRNAs for the early detection of epithelial cells diluted in peripheral blood cells. This method includes 1. direct comparison of different samples of colonic mucosa and of blood cells to identify consistent epithelial-specific mRNAs from among 20,000 cDNA assayed by microarray slides; 2. identification of candidate marker mRNAs by data analysis, which allowed selection of only 10 putative differentially expressed genes; 3. Selection of some of the most suitable mRNAs (TMEM69, RANBP3 and PRSS22) that were assayed in blood samples from normal subjects and patients with colon cancer as possible markers for the presence of epithelial cells in the blood, using reverse transcription – polymerase chain reaction (RT-PCR). RESULTS: Our present results seem to provide an indication, for the first time obtained by genome-scale screening, that a suitable and consistent colon epithelium mRNA marker may be difficult to identify. CONCLUSION: The design of new approaches to identify such markers is warranted

Selective laser trabeculoplasty for primary angle closure with persistently elevated intraocular pressure after iridotomy

PURPOSE: To determine whether selective laser trabeculoplasty (SLT) can lower intraocular pressure (IOP) in eyes with chronic primary angle closure, elevated IOP, and a patent iridotomy. PATIENTS AND METHODS: Patients with chronic angle closure who had underwent iridotomy, had an IOP greater than 21 mm Hg and a gonioscopically visible pigmented trabecular meshwork for at least 90 degrees were enrolled. SLT was applied to open angle segments. Duration of follow-up was 6 months. RESULTS: Sixty eyes of 60 patients were enrolled. The mean baseline IOP was 24.6±2.5 mm Hg. At 6 months, IOP reduction of ≥3 mm Hg or 4 mm Hg was measured in 82% and 72% of eyes, respectively, and IOP reduction of ≥20% or 30% was measured in 54% and 24% of eyes, respectively. When only eyes that were treated with the same number or fewer medications were considered, these IOP reductions were measured in 67%, 58%, 43%, and 15%, respectively. During the study period 1 eye (1.7%) required trabeculectomy owing to IOP elevation shortly after the SLT. There were no other significant complications attributable to SLT. CONCLUSIONS: SLT seems to be a safe and effective method of reducing IOP in many eyes with primary angle closure and a patent iridotomy in which there is a sufficient extent of visible trabecular meshwork. © 2009 Lippincott Williams & Wilkins, Inc.link_to_subscribed_fulltex