Pooled analysis

Some questions have been raised about the relative efficacy of the SSRls, particularly in severe depression. The pooled analyses of the data from blinded, controlled trials have tended to find similar levels of efficacy between the SSRls and the comparator TCA, imipramine. Paroxetine and fluvoxamine were both found in subanalyses of patients with severe depression included in large placebo- and imipramine-controlled studies to be more effective than imipramine in severe depression (S. A. Montgomery 1992a Ottevanger 1991 Tignol et al. 1992 Wakelin 1988]. However, imipramine may not be the TCA that is most effective in severe depression or may not have been used in the trials at an adequate dose. 

Additionally, current product labeling contains a boxed warning regarding an increased risk of suicidal ideation in children and adolescents. Pooled analyses of 12 short-term atomoxetine trials showed an average risk of suicidal ideation of 0.4% in patients taking atomoxetine, compared with none in patients receiving placebo (Strattera 2005). Patients should be advised of the risks associated with atomoxetine prior to treatment. 

Blettner M, Sauerbrei W, Schlehofer 6, Scheuchenpflug T, Friedenreich C (1999) Traditional reviews, meta-analyses and pooled analyses in epidemiology. Int J Epidemiol, 28 1-9. 

An analysis of each study and all the studies as a whole to demonstrate how they relate to each claim of effectiveness. If some studies are considered more important than others, this should be noted and an explanation given. Any pooled analyses should be explained and presented. Any major inconsistencies or areas needing further exploration should be identified. Dose-response and dose-duration/dose-frequency information as well as any differences in response among subgroups should be included. 

Phase IV studies can also take the form of retrospective pooled analyses which are designed to reflect the totality of clinical research experience with a new drug which is usually obtained via analysis of pooled clinical trial databases. Such data-mining efforts should not be considered inferior to data obtained from the conduct of an individual clinical trial. In fact, there are substantial benefits of such an approach, as the results of a given trial, especially if the end point is not prespecified to be primary because of power limitations, can be a function of chance. To assure that the results obtained from pooled analyses are not biased, a prespecified data analysis plan is often formulated as the first step, outlining the clear goals of the proposed analysis as well as its methodology. Key to this type of analysis is the definition of the outcome measure. Both efficacy and safety measures can be the focus of these types of analyses. 

Pooled analyses are commonly used to assess the safety of drugs that have been already evaluated on an individual subject level by adjudication committees. Such committees are usually comprised of a combination of clinicians, epidemiologists and statisticians, who meet to discuss the specifics of prespecified, suspected adverse events, in order to... 

Meta-Analysis. Meta-analyses (or pooled analyses) synthesize and compare studies that investigate similar health effects and risk factors. These analyses examine sources of heterogeneity and may clarify relationships between exposures and health effects. Inclusion and exclusion criteria and data analysis methods must be transparently described. Meta-analyses are not helpful when the relationship between exposure and disease is obvious, there are few studies, or the existing studies suffer from severe methodological faults (Blair etal. 1995). Dickersin... 

Table 9.1 Multivariate RRs° of CHD or Stroke Comparing the Highest vs. the Lowest Quintiles of Fruit and Vegetable Intakes in the Pooled Analyses of the Nurses Health Study and the Health Professionals Follow-Up Study...

Grob, M.K., et al.. Optimization of cellular nucleotide extraction and sample preparation for nucleotide pool analyses using capillary electrophoresis, J Chromatogr B Aiudyt Technol Biomed Life Sci, 788, 103, 2003. 

Adapted from data in Lanphear et al. (1998). Children 6—36 months of age. Pooled analyses of 12 id niolr ical studies from unban and mei allurgical industry sites. ... 

The matter of peak periods for neurotoxic vulnerability can be addressed by assuming much of early childhood is a high vulnerabihty/high toxic risk period, with one or more parts of this age band being somewhat more sensitive to Pb exposure. Large, pooled analyses indicate that no childhood Pb exposure period is free of elevated poisoning risks. 

The Lanphear et al. Pooled Analyses of Soil and Dust Pb Exposures in U.S. Children... 

TABLE 23.10 Descriptive Data for Dust Pb Pooled Analyses of Urban and Extractive Industry Community Children Exposed to Lead " ... 

Systematic reviews The major studies on the safety and tolerability of rufinamide were reviewed [157 ]. In placebo-controlled trials and pooled analyses, the most common adverse effects reported with rufinamide were somnolence and vomiting. Headache and pyrexia were also reported more frequently with rufinamide compared to placebo. In terms of drug-drug interactions, rufinamide may slightly increase the clearance of CBZ and lamotrigine and may slightly decrease the clearance of phenytoin and phenobarbital. VPA may significantly decrease the clearance of rufinamide. 

Tzellos T, Kyrgidis A, Trigoni A, ZoubouUs CC. Association of ustekinumab and briakinumab with major adverse cardiovascular events. An appraisal of meta-analyses and industry sponsored pooled analyses to date. Dermatoendocrinol 2012 4(3) 320-3. 

Log-phase cells were subjected to a 350nM pulse of [1- C]acetate, (for acyl-CoA pool analyses [ C-acetate] = 700nM) for 30 mins, after which the pulse was diluted 100 fold with unlabelled acetate. Samples were removed from the vessel, the cells freeze-dried and lipids extracted and analysed as above. 

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