Alternatives to placebo-controlled designs

Given the ethical concerns about placebo-controlled study designs, several alternative procedures to reduce bias in clinical trials have been proposed  

This option assumes a comparable or even standard placebo response rate for historical data and the current trial. The historical improvement rate (on placebo or without any treatment) is then used for purposes of comparison with results of subsequent non-placebo-controlled studies involving the same investigator and protocol design but different drugs. For historical placebo response data it is recommended that a small placebo treatment arm is used for safety data purposes and to avoid observer bias although this proposal may resolve or diminish some ethical concerns, it raises a number of scientific problems  

In summary, and as supported by the shilling placebo response rates quoted earlier, use of historical placebo or no-treatment data does not appear to be a reliable alternative to the use of concurrent placebo. 

Comparison of Current Treatment with Waiting List 

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