Keeping up to date and increasing precision

Evidence from cardiovascular medicine has shown that doctors failed to use effective treatments, such as intravenous streptokinase, for acute myocardial infarction even when there is overwhelming evidence for their effectiveness.5 Conversely, they continued to recommend medicines such as intravenous lidocaine for post-infarction arrhythmias long after the evidence suggested that they were ineffective or even harmful.6 With over 200 specialist dermatology journals, it has become increasingly difficult for the dermatologist to

Figure 54.2 As dermatologists, we must overcome our slavish obsession for dividing the results of all clinical trials into those that are statistically significant at the 5% level and those that are not, and instead use confidence intervals to estimate a range of likely effects

keep up with the literature.7 Systematic reviews such as those supported by the Cochrane Skin Group that track down all possible published and unpublished studies are needed to keep us up to date.

Such systematic reviews can reduce uncertainty produced by the conflicting results of several small inconclusive studies by combining their results - provided they are sufficiently similar. This may overcome our current obsession with dividing all clinical trials into those that are significant at the arbitrary 5% level and those that are not (Figure 54.2), instead of estimating a range of plausible treatment effects by means of confidence intervals and pooling studies that are sufficiently alike in terms of patients, interventions and outcomes. Studies that reach the "magic" P<0-05 significance are commonly claimed as being "positive" and those that fail to reach that level are often considered "negative",

Figure 54.3 The Cochrane Collaboration logo depicts a systematic review of seven placebo-controlled trials evaluating the efficacy of a short course of oral corticosteroids for women in premature labour to prevent fetal death. Each horizontal line represents a single RCT - the shorter the line the more certain are the results. If an RCTs touches the vertical line, it means that particular trial found no clear evidence of treatment benefit. The diamond at the bottom represents the combined results, and its position to the left of the vertical line of no treatment difference indicates that the treatment was clearly beneficial in reducing premature infant mortality by 30-50%.

Figure 54.3 The Cochrane Collaboration logo depicts a systematic review of seven placebo-controlled trials evaluating the efficacy of a short course of oral corticosteroids for women in premature labour to prevent fetal death. Each horizontal line represents a single RCT - the shorter the line the more certain are the results. If an RCTs touches the vertical line, it means that particular trial found no clear evidence of treatment benefit. The diamond at the bottom represents the combined results, and its position to the left of the vertical line of no treatment difference indicates that the treatment was clearly beneficial in reducing premature infant mortality by 30-50%.

The first of these RCTs was done in 1972. The figure depicts what would have been revealed had a systematic review of the available evidence been done a decade later. By 1991, another seven RCTs had been done. Because no systematic review of these studies had been produced until 1989, most obstetricians had not realised that the treatment was so effective, but instead, interpreted each individual study as "conflicting". As a result, tens of thousands of premature babies around the world have probably died or suffered unnecessarily. This is an example of the human costs of failing to perform an up-to-date systematic review of apparently "conflicting" studies

Source: The cochrane collaboration whereas in reality many of the latter trials are far too small to detect even quite large changes.8 Instead of concluding that such studies are "conflicting", a meta-analysis performed within the context of a carefully conducted systematic review may show that they are all compatible with a clear overall treatment benefit. The Cochrane Collaboration logo shows a good example of this (Figure 54.3).

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