
......................m......................... Specific guide to this web site for:
Additional Topics: Large Randomized Clinical Trials
 LIMITATIONS OF METAANALYSES The assumption that a metaanalysis uniformly represents the final and accurate viewpoint of an area of research is not warranted. The conclusions made by the authors of a metaanalysis are subject to the same potential for bias as the smallest of clinical studies.
The authors of the metaanalysis must assess the limitations of their
analysis and decide what conclusions to state. In addition, they need to
determine how broadly their conclusions can be applied and to what patient
groups. Conservative conclusions derived directly from the data with a realistic
assessment of the limitations of the study are optimal, but by no means
universal. A
metaanalysis is particularly subject to biased conclusions when it is created by advocates of a
controversial opinion regarding the same topic the metaanalysis is addressing.
See
critique
of oat bran metaanalysis, critique of ALLHAT metaanalysis,&
Metaanalyses Bearing False Gifts for
details.) Similarly, a metaanalysis written by employees or representatives of a pharmaceutical company will have an inherent and expected favorable bias towards the product of that company. This type of metaanalysis will always be an advocacy metaanalysis. A very large randomized clinical trial is the most reliable way of obtaining reproducible results. This means that if the same trial protocol was repeated with a similar patient population using a sufficient number of patients, the same trial results would be expected to occur. However, even a very large trial does not guarantee that the specific treatment protocol being studied has been constructed optimally or appropriate conclusions have been formulated. (See Tale of Two Large Trials.) A metaanalysis has a number of areas with the potential for bias (which are usually unintentional). The potential areas of bias in a metaanalysis include:
NETWORK METAANALYSIS There is a type of metaanalysis called network metaanalysis that is more subject to erroneous conclusions than a routine metaanalysis. A network metaanalysis adds an additional variable to a metaanalysis. Rather than simply summing up trials that have evaluated the same treatment compared to placebo (or compared to an identical medication), different treatments are compared by inference. ( If A is better than B, and B is equal to C, then A is better than C.) The problem with network analysis in regards to a metaanalysis, is that a network metaanalysis tends only to be valid for very similar studies. Since network metaanalysis combines studies with a higher degree of variability, there is even more potential for combining studies that are not adequately similar. The quality of some recent network analyses in the hypertension literature highlights the problems of this type of analysis. 1. Discrepancies Between MetaAnalyses and Subsequent Large Randomized, Controlled Trials. LeLorier J, Gregoire G, et al. NEJM, 1997; 337:53642

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