Clinical trials are a process by which different treatments being evaluated against each other, or a brand new drug, to decide which is the best treatment for that particular disease, for that particular stage.
All current treatments have been selected as the standard of care, because they went through a clinical trial, and were found to be better that what they were being compared against. At any time, patients are offered “current standard of care” or enrollment in a clinical trial, to see if something better is out there.
Phase 1 trials are conducted after laboratory development of a new drug. At this stage, only safety testing is taking place. Doses of the medicine are increased in stepwise fashion in successive patients, with testing of blood tests, etc, to see what is the maximum tolerated dose. Any disease response is a bonus, not the primary function of a Phase 1 trial.
Phase 2 trials have the mandate to see if the drug shows reasonable activity against that disease being studied.
Phase 3 trials study the relative benefit of the treatment under study against current standard of care. Patients who are participating are assigned into the study group or the control (current standard of care) group. They are followed closely and the relative outcomes in the group are studied. If one group does much better than the other, that treatment becomes the recommended treatment.
For this process to work, the groups have to be matched in patient characteristics (age, gender, race, stage of disease, etc), so that we have a level playing field for the treatments being studied. The treating physician cannot make the decision to assign the patient to one group vs. the other; that would introduce bias into the result.
Phase 1, and mostly 2 trials are only offered at major referral centers. Phase 3 trials are available at participating Community Cancer Centers. Each trial has to go through each hospital’s Institutional Review Board to make sure that the patient’s interests are protected, and the study is being ethically conducted, per local standards.
Patients participating in the trial need to fully understand that their expected outcome is unknown. They need to give informed consent. They may be on the winning team, or not, but they will be contributing to an overall body of knowledge.
Patients who have participated in previous trials have brought us to our current stage of knowledge, and we are forever grateful for their contribution.
This information is then taken to the regulatory authorities (the FDA in the US), and approval is obtained for the drug being developed. Often, if the data are not enough, the companies have to do more studies to establish efficacy.
Biostatistics is a major component of study design. How many patients need to be enrolled at each phase to show actual improvement in results, rather than chance alone? (Statistical significance). How long should the participants be studied? At what point will treatment A be declared a winner over treatment B? At what point should the trial be closed? All of these questions are carefully thought through before patients are enrolled.
After all this, one has to use common sense in interpreting data. If you decrease the recurrence rate from an absolute number of 4% to 2%, you have a 50 % risk reduction. Is that a meaningful improvement for the individual? That is part of the discussion and decision making process. Every individual patient can make very different decisions based on the same numbers, depending where they are in their life situation.