Meta-analysis safety assessment

Meta-analysis is a method often used to determine the effectiveness of a drug but to date it has rarely been used to assess safety. One case illustrates how this technique can help. Six studies examining the use of intravenous lidocaine for acute myocardial infarction did not, on an individual basis, give strong enough evidence to support the hypothesis that this technique could cause excess mortality. The meta-analysis, however, was able to demonstrate this. ... 

Determination of efficacy and safety is an ongoing process usually based on results from multiple randomized, double-blind, controlled trials. A meta-analysis of similarly designed studies that measured the same endpoint can be used to better assess possible significance of drug treatment by narrowing confidence limits they can strengthen the hkehhood that an apparent effect is (or is not) due to the drug rather than chance. 

Cardiovascular The cardiovascular safety of tiotropium (combining dry powder, Handi-Haler, and soft mist, Respimat, formulations) has been assessed in a meta-analysis of 30 double-blind, randomized, placebo-controlled trials of tiotropium in 19545... 

Product-line safety assessment typically generalises from individual safety analyses to produce a configurable analysis result that is then customised to the particular product in question. The process may involve annotation of an existing model, such as fault trees (Dehlinger and Lutz 2005), or it may involve the creation of a new model (Stephenson et al. 2004). In contrast to diese relatively simple approaches, (Habli 2009) describes a complex meta-model diat relates design variation, context variation, events, consequences and severities. It is important to note that each of these bodies of work assumes the existence of hazard assessment in-... 

The comparative safety of salmeterol versus formoterol was assessed in another Cochrane meta-analysis [37 ]. Based on four studies involving 1116 adults and 156 children, the investigators did not find any between group difference in the serious adverse effects in adults (Peto OR = 0.77, 95% Cl = 0.46,1.28), children (Peto OR = 0.95, 95% Cl = 0.06,15.33). Only one death was reported in the included studies. Although methodologically correct, the results of this study may be limited by the lack of available data. 

Upper Respiratory Tract A Cochrane meta-analysis studied the effect of intranasal ipratropium versus placebo on the severity of rhinorrhea and nasal congestion in children and adults with the common cold [45 ]. Seven trials, studying 2144 patients were included in the study. Safety assessment showed an association of ipratropium with nasal dryness (OR = 2.55, 95% Cl = 1.50, 4.33), mouth dryness (OR = 3.59, 95% Cl = 1.38, 9.38) and epistaxis (OR = 3.21,95% Cl - 1.68,6.13). 

Since all of the information gathered during the Change Safely Analysis is contained in the hazard log, it seems logieal to utilise the hazard log to actively support further analysis, not only as a repository of results of the analysis. If the hazard log is stmetured in such a way as to preseut the data iu a form of a Meta-model of the hazard universe , it eotrld then be trsed in support of further analysis, for example in support of qrralitative risk assessment, review for completeness, or constraction of safety argrrments. 

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