Treatment effects/differences meta-analysis

Each trial that is to be included in the meta-analysis will provide a measure of treatment effect (difference). For continuous data this could be the mean response on the active treatment minus the mean response in the placebo arm. Alternatively, for binary data the treatment effect could be captured by the difference in the cure rates, for example, or by the odds ratio. For survival data, the hazard ratio would often be the measure of treatment difference, but equally well it could be the difference in the two-year survival rates. 

A recent meta-analysis was performed on all published human trials that used low-dose dopamine in the prevention or treatment of ARE20 A total of 61 studies were identified that randomized more than 3300 patients to low-dose dopamine or placebo. Results reveal no significant difference between the treatment and control groups for mortality, requirement for RRT, or adverse effects. 

These continuation trials tell a very different story from that told by relapse-prevention trials. They show that there is little difference between antidepressant and placebo even when the clinical trial is extended over a longer period of time. Across the eight continuation trials that have been published, 79 per cent of patients on placebo and 93 per cent of patients on active medication remained well throughout the treatment period. In these long-term studies, placebo treatment was 95 per cent as effective as drug treatment. The authors of a meta-analysis of these trials concluded that the widely held - and probably erroneous - belief that the placebo response in depression is short-lived appears to be based largely on intuition and perhaps wishful thinking .17... 

In 2001 two Danish researchers, Asbjorn Hrobjartsson and Peter Gotzsche, published an influential meta-analysis in which they estimated the difference between the effects of getting a placebo versus doing nothing at all.14 Although they found a significant placebo effect, especially in the treatment of pain, the overall effect seemed very small - much smaller than would have been expected of a powerful treatment. On the basis of these data, the researchers asked Is the placebo powerless and answered their own question by concluding that there was little evidence that placebos have powerful clinical effects. 

In contrast, another meta-analysis undertaken by Brzezinski et al., using 17 different studies involving 284 subjects, most of whom were older, concluded that melatonin is effective in increasing sleep efficiency and reducing sleep onset time (Brzezinski et al. 2005). Based on this meta-analysis the use of melatonin in the treatment of insomnia, particularly in aged individuals with nocturnal melatonin deficiency, was proposed. 

When possible, meta-analyses were computed to summarize the overall effects from controlled clinical trials. These summarized data are used to compute an effect size and to calculate the probability that a given drug is different from placebo and equivalent to or more effective than standard drug treatments. The goal is to estimate the extent of clinical improvement with a specific treatment as an aid to therapeutic decision-making. In one sense, a meta-analysis can be seen as a quantitative literature review using a more explicit and structured approach. Thus, it can complement a narrative review and often accompanies a literature summary (6). 

Different types of evidence can be ranked in term of importance when decisions about clinical interventions are made (Figure 19.1).13,14 For example, the confidence from randomized controlled trials gives stronger evidence for treatment effects than open studies. Moreover, apparently conflicting results between studies may be compatible when a statistical meta-analysis of the data has been performed. This chapter will give a brief summary of evidence on the treatment effects of common dry skin disorders with urea-formulations. Furthermore, data on the influence of urea on the skin barrier function will be reviewed. 

In a meta-analysis based on 9087 patients in 87 different randomized clinical trials fluoxetine was more effective than placebo from the first week of therapy (2). In bulimia nervosa, fluoxetine was as effective as other agents. It was as effective as clomipramine in the treatment of obsessive-compulsive disorder. 

Case series and reviews have suggested superior effectiveness of zuclopenthixol acetate in the acute management of disturbed behavior caused by serious mental illness. However, this seems not to have been supported by the evidence from an analysis of randomized controlled trials (88). A meta-analysis of five randomized comparisons of zuclopenthixol acetate with other neuroleptic drugs in patients with considerable behavioral disturbance showed that in all studies there was some improvement in mental state scores (BPRS CGI), but none showed statistically significant differences between zuclopenthixol acetate and standard treatment. In three studies there was more sedation in those who took zuclopenthixol acetate than in those allocated to haloperidol. With regard to adverse effects, the studies were not homogeneous one study showed that people who took zuclopenthixol acetate were more likely to need antiparkinsonian drugs (OR = 6.4 Cl = 1.5,17) other studies did not show any differences in this particular outcome. 

Individually, the cholinesterase inhibitors improve memory in patients with AD. There have been no head-to-head comparisons made of the drugs to determine w hether one is more effective than the others and no trials of agents in combination. The main know n differences are the side effect profiles, titration schedules and the dosing regimens (Table 39.1). The most common side effects of treatment with cholinesterase inhibitors are gastrointestinal and include nausea, vomiting and diarrhea. A meta-analysis of the efficacy and safety of these agents revealed that despite many clinical studies show ing... 

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