Clinical trials: the larger the better?

A chronobiologic approach is much more than fine-tuning that may perhaps be considered after a drug has been identified as useful; at very little cost at first, a Phase 0 chronobiologic trial may show that there is danger that a given drug may do more harm than good when administered at the wrong time. At least equally important, the chronobiologic approach may recognize the usefulness of a drug that is active only at the proper time. When different chronobiologic timing results in opposite effects from the same total weekly dose of the same drug, it is clear that timing cannot be separated from dosing. The time structure-adjusted pattern of drug administration can make the difference between the undesired stimulation of a malignant growth and shortening of survival time and the desired growth inhibition and prolongation of survival. The experience with lentinan, namely that this immunomodulating drug can stimulate as well as inhibit the development of a cancer, may apply to many more therapeutic agents in a day and age of biologic response modifiers. It is a point of particular importance that an immunostimulator ought not be given at a time when it can be an immunosuppressor. What is surprising to many under these circumstances is that chronobiologic designs are also cost-effective. Most scholars believe that if a test is carried out at six times, it will cost six times more, will require six times more patients and six times more work. We believe we have shown that the reverse holds true: if so, the discussion of the pros and cons of chronobiometry and of neglect thereof becomes one of ethics. Figures 1-5 depict the status quo. Examples have been given to show that some effects can be obtained only at certain times with the dose used. Figure 8 reveals the doubling of the desired anticancer effect by timing treatment according to an unspecific marker rhythm. The recognition of the power of chronobiologic designs coupled to the discovery of large-amplitude rhythms in non-invasively determined marker chronomes is a challenge that can be exploited, particularly in the treatment of cancer. Marker determinations are still expensive, but once the cost of their development is paid, a market is established, and the community is trained in self-help, the responsibility now assumed by most diabetic patients for themselves can also be shouldered by cancer patients.(ABSTRACT TRUNCATED AT 400 WORDS)