Phase II trials are also small investigations, which have been designed to test the efficacy and safety of a given treatment (this treatment will, of course, have been required to pass the Phase I stage). Phase II clinical trials require very close monitoring to determine whether all of a particular tumour type will respond to the drug at the dosage etc. as determined in its Phase I stage. It is also here that the patient is likely to be introduced to such terms as “complete response” (meaning that all evidence of the tumour has disappeared) “partial response” (meaning that the volume of the tumour has reduced to at least 50% of their original size). The distinct advantage here to patients is the knowledge that whereas their tumour may not be responding to standard treatments, there is a distinct chance of a response to the drug currently being tested.
Once a drug or treatment has been shown to be reasonably effective, it becomes essential to compare it with the current standard treatment for that same combination. However, this time, a substantial number of patients will be needed for participation; hence a Phase III trial, which in terms of all scientific clinical investigations is the most rigorous and extensive of all. It follows that all treatments started in Phase III trials will have successfully negotiated Phases I and II.
The first priority for good research is quite simply that it should be based on good ideas, leading to viable and testable hypotheses for improving treatment. Another basic rule of Stage III trials is that they are comparative; i.e. used to compare one group of patients on the new treatment, with a control group receiving standard treatment (or where available, untreated patients). And it is here that we come across a necessary and crucial part of the entire procedure, yet one that has been known to cause real concern for patients and their loved ones – namely “randomization”. The overriding concern of patients must surely be that they receive the ‘best bet’ so far as treatment is concerned. The question that we need to address here, therefore, is: does randomization in any way compromise this understandable and laudable aim? Let me explain.
Randomization is a well-proven statistical device for ensuring that patients are assigned to one or other ‘arms’ (research groups) of the study, i.e. experimental (the “new drug” group) and a control (standard treatment group) on a purely chance basis, not tainted by other factors such as patient, doctor (or any other) preference or prejudice, leading to bias. The purposes of randomization are therefore twofold: i. it guards against such human judgments causing error through bias (where the case for either treatment is as yet unproven; hence the case for a trial) and ii. It provides a sound basis for standardization of statistical analysis, i.e. tests for statistical significance which will clearly separate chance results from those which can, on the basis of statistical validity and reliability, be attributed to the treatment under test.
(There is a selection of methods of randomization, the most common being the assignment of random numbers from a neutral and dependable pre-prepared table. However, such methods will not be pursued here, other than to add that all questions concerning the ethics of randomization would in every case of credible research, have been very carefully weighed at an earlier stage of protocol design and construction).