Meta-analysis, technique

In contrast, systematic reviews employ a comprehensive, reproducible data search aud selectiou process to summarize all the best evidence. They follow a rigorous process to appraise and analyze the information, quantitatively (through the meta-analysis technique) or qualitatively, to best answer adeflned clinical question. Systematic reviews are a useful means of assessing whether findings from multiple individual studies are consistent and can be generalized. ... 

This chapter adds the socio-economic dimension to the medical or technical perspectives of the proceeding contributions of this book. As its health economic terminology and approach might be unfamiliar to some readers, we start with a section on methodology. In particular, we present an overview of the concept of Cost-of-Illness (COI) and of relevant health economic evaluation techniques. In Sect. 2, we present the basic findings of a meta-analysis of the socio-economic costs of HIV/AIDS and of the socio-economic impact of antiviral intervention. The major findings are reflected in Sect. 3. The chapter closes with a speculation on long-term socio-economic costs of antiviral intervention. 

In 1995 Guy Sapirstein and I set out to assess the placebo effect in the treatment of depression. Instead of doing a brand-new study, we decided to pool the results of previous studies in which placebos had been used to treat depression and analyse them together. What we did is called a meta-analysis, and it is a common technique for making sense of the data when a large number of studies have been done to answer a particular question. It was once considered somewhat controversial, but meta-analyses are now common features in all of the leading medical journals. Indeed, it is hard to see how one could interpret the results of large numbers of studies without the aid of a meta-analysis. 

Meta-analysis (meaning analysis among ) is being used increasingly in biomedical research to try to obtain a qualitative or quantitative synthesis of the research literature on a particular issue. The technique is usually applied to the synthesis of several separate but comparable studies. 

Usually, the main purpose of meta-analysis is quantitative. The goal is to develop better overall estimates of the degree of benefit achieved by specific exposure and dosing techniques, based on the combining (pooling) of estimates found in the existing studies of the interventions. This type of meta-analysis is sometimes called a pooled analysis (Gerbarg and Horwitz, 1988) because the analysts pool the observations of many studies and then calculate parameters such as risk ratios or odds ratios from the pooled data. 

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. ... 

However, another large meta-analysis study found no difference between different viability testing methods for predicting survival after revascularization, suggesting that decisions driven by viability studies are clinically equivalent and have similar outcomes, irrespective of the technique used [88]. While improved LV function is a major factor affecting... 

The technique can also address whether or not the studies provide a consistent result and exploring heterogeneity is a key element of any meta-analysis. 

Using meta-analytic techniques based on the means and the standard errors presented graphically in the poster, we estimated pooled data of the four effective dosages of quetiapine both for the BPRS and the CGI severity of illness change scores from baseline to endpoint. Quetiapine produced an improvement of 0.43 effect-size units in comparison with placebo, a difference that was highly statistically significant and about the same improvement as haloperidol. Thus, based on the BPRS or PANSS, quetiapine was similar to neuroleptics in efficacy (i.e., differences were nonsignificant). Based on our meta-analysis, quetiapine is clearly superior to... 

Two kinds of publication can help make sense of a set of differing, and even conflicting, conclusions from a collection of articles on a given topic. One is a systematic review. The strategy in this case is to describe, summarize, and collate the studies in a nonquantitative manner to look for emerging patterns or pictures of evidence. A quantitative approach is provided by the technique of meta-analysis. The results of the different studies are combined according to certain rules, and an overall test statistic is provided. The interpretation of this test statistic leads to the overall message of the meta-analysis. 

Structure-activity correlations were carried out using least-squares regression analysis techniques on an IBM 360 computer. As in the accompanying publication (6), the data in Tables I and II were fitted to Equation 3 in stepwise fashion. Standard statistical tests were carried out at each stage of fitting to determine the over-all goodness of fit of the x and o- data to the various equational forms examined. As in our previous study (6), the most statistically significant correlations were always obtained when activity data for meta-substituted and para-sub-stituted TFMS herbicides were divided into two discrete series and fitted separately. 

Emla cream causes minor local adverse effects, such as itch, burning, and localized purpura (SEDA-19, 131) (SEDA-20,127) (SEDA-22,140). A meta-analysis of the use of Emla cream in the elderly (over 65) showed that the technique is generally safe, with only mild transient effects (pallor, redness, and edema) at the apphcation site there were no systemic effects (1). 

Systematic reviews are recent additions to the medical literature. In contrast to traditional narrative reviews, these reviews aim to answer a precisely defined clinical question and to do so in a way that is transparent and designed to minimize bias. Some of the defining features of systematic reviews are (1) a clear definition of the clinical question to be addressed, (2) an extensive and explicit strategy to find ail studies (published or unpublished) that may be eligible for inclusion in the review, (3) criteria by which studies are included and excluded, (4) a mechanism to assess the quahty of each study and, in some cases, (5) synthesis of results by use of statistical techniques of meta-analysis. By contrast, traditional reviews are subjective, are rarely well focused on a clinical question, lack explicit criteria for selection of studies to be reviewed, do not indicate criteria to assess the quality of included studies, and rarely can use meta-analysis. 

Chalmers has clearly restated the principles on which meta-analysis is based and discussed some of the empirical evidence that enables the validity of the technique to be considered. In particular, meta-analysis uses objective statistical procedures, specifies how the choice of studies to include was made, and describes the results of the studies on which the analysis was based. Sometimes, studies are designed with the specific intention of being combinable with each other, a strategy that can be referred to as a prospective meta-analysis. This is sometimes the case in drug development. However, when a meta-analysis is retrospective , that is a search has to be carried out to identify studies which address a particular question, the problem of publication bias has to be considered, in that studies with positive results may be more likely to be submitted and accepted for publication. Hence, meta-analyses based solely on published work may be biased in favour of finding an effect. 

One criticism against the use of informative priors is their subjective nature, which may be perceived to introduce bias into the upcoming analysis. The choice of priors and assigning an appropriate level of informativeness is therefore of considerable importance. For population PK/PD studies, there may well be explicit, quantitative data that describes the parameter values in populations that are similar to the population in the current study. In this case it is possible to pool the available information in a meta-analytic technique to provide an appropriate level of prior information. Some care must be taken to assess for heterogeneity between studies and for applicability of studies to the current population under consideration. A brief summary of an approach is shown below. It would be impossible to include an exhaustive treatment of elicitation processes within the confines of this chapter. 

A recent meta-analysis was performed to assess the evidence for the efficacy of both RD and URD to determine their role among the available treatment options for opioid dependence. Analysis was performed on 12 studies of RD and 9 studies of URD. The authors concluded that more research is needed using more rigorous research methods, longer-term outcomes, and comparisons with other methods of treatment for opioid dependence before these techniques can gain widespread acceptance. ... 

There are a number of techniques which may be used. If the studies involved have a similar structure and use the same outcome variables and the meta-analyst has access to the original data (which is usually the situation of the drug developer), then an analysis of these raw data is both possible and (almost invariably) desirable. This has been referred to as a type A meta-analysis (Senn, 2000b). The situation is then very like that in a multicentre trial, with trials rather than centres forming the strata. In principle all the controversies, issues and difficulties which arise with multicentre trials may be attendant on such an analysis but there is no particular reason why new difficulties should present themselves. 

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