Placebo risk/benefit analysis

The UK Committee of Safety of Medicines has previously warned that paroxetine appeared to be no more effective than placebo in the treatment of depression in adolescents and might be associated with a greater risk of self harm (SEDA-28, 16). In a meta-analysis of both published and unpublished placebo-controlled trials of SSRIs in childhood and adolescent depression, only fluoxetine seemed clearly to be associated with a positive benefit-harm balance (26). The evidence of efficacy for sertraline and citalopram was doubtful, while the risk of serious adverse events was significantly increased. Additionally, for both drugs the risk of suicidal behavior was numerically increased. In regard to venlafaxine, the risk of suicidal behavior was significantly greater than placebo. 

In a meta-analysis of 10 studies of the use of amiodarone in patients with heart failure, the overall odds ratio for mortality with amiodarone compared with placebo was 0.79 (95 % Cl = 0.68, 0.92). The corresponding odds ratio for adverse effects was 2.29 (1.97,2.66) (36). The benefit to risk ratio of the use of amiodarone in these patients is not yet clear. The dosage of amiodarone in these studies varied from 50 to 400 mg/day, with an average of around 250 mg/day. 

Data from the previous three randomized controlled trials on postoperative nausea were appropriate for meta-analysis. The pooled absolute risk reduction for the incidence of postoperative nausea proved the difference between the groups treated with ginger and placebo to lack significance. These values indicate a point of the number-needed-to-treat of 19 and a 95% confidence interval that also includes the possibility of no benefit (16). 

Unfractionated heparin (UFH) inhibits platelet aggregation and fibrin formation by accelerating the action of antithrombin, which in turn inactivates factors Ha, IXa, and Xa. The benefit of heparin in UA has been well defined in early trials (48,49). In the RISC trial, a combination of aspirin and heparin reduced the incidence of MI and death during the first five days by 75% when compared with placebo. This result was successfully replicated in several small trials examining the role of heparin in UA. A meta-analysis of these trials revealed a 33% reduction in the combined risk of death or MI in patients treated with aspirin plus heparin compared with those treated with aspirin alone (66). With benefit of heparin clearly established in UA patients, later trials attempted to expand the role of heparin in NSTEMI. 

In an analysis of the Valsartan in Heart Failure Trial (Val-HeFT), focusing on chronic kidney disease, the benefits and harms of dual blockade of the RAAS have been explored [29. Compared with the addition of placebo to ACE inhibition, the addition of valsartan led to higher rates of discontinuation and hyperkalemia in those with chronic kidney disease at baseline. However, the authors argued that the overall benefits of combined therapy would outweigh the risks even in those with chronic kidney disease. 

A quantitative benefit-harm balance analysis of alosetron for the treatment of irritable bowel syndrome from the patient s perspective has been reported pS "]. There was greater than 99% chance that both the incremental benefit and the incremental risk associated with alosetron are greater than with placebo. The incremental net benefit of alosetron was greatest in patients with the worst quality of life at baseline. 

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