Hormesis, biological plasticity, and implications for clinical trial research

The present paper identifies a critical factor that leads to false negative results (i.e., failing to indicate efficacy when beneficial results did occur) in randomized human drug trials. The paper demonstrates that human performance can only be enhanced by a maximum of 30-60% as described by the hormetic dose response which defines the limits of biological plasticity. However, human epidemiological/clinical trials typically contain such extensive variability that often requires responses greater than 2-3 times control group responses to show statistical significance. Thus, many potentially beneficial agents may be missed because the clinical trial fails to recognize and take into consideration the limits of biological plasticity. The paper proposes that this hormesisbiological plasticity-clinical trial conundrum can be addressed successfully via the use of a weight-of-evidence methodology similar to that used by regulatory agencies such as EPA in environmental assessment of chemical toxicity.

Automated summary

The paper identifies a critical factor that leads to false negative results in human drug trials. It demonstrates that human performance can only be enhanced by a maximum of 30-60% due to the limits of biological plasticity. Clinical trials often require responses greater than 2-3 times control group responses to show statistical significance, causing potentially beneficial agents to be missed. The paper proposes a weight-of-evidence methodology to address this conundrum.