CT scan series part 10 - Clinical Trial CT scan Context
There is solid rationale for CT-scanning in a Clinical Trial setting that cannot be avoided but is it adequate or overkill? Who decides?
There are so many newer drugs that promise better efficacy with less toxicity that it is hard to keep up with them. All these drugs will require Clinical Trials that must produce evidence of efficacy and safety. Ibrutinib and Idelalisib are two drugs that illustrate the difficulty for obtaining that evidence. These two drugs initially cause an increase of cancer cells in the peripheral blood, unlike standard chemo and mAbs that show an immediate decrease as the cells are killed off. Many lymphnodes are not visually observed or felt by palpation but can be used as evidence of efficacy if objectively measured to prove reduction of the total tumor burden, even while ALC (Absolute Lymphocyte Count) is on the rise. Is this objective measurement of lymphnodes via CT scanning necessary to the drug developer in order to convince the FDA of a drug's efficacy which will lead to approval?
Just yesterday I made contact with an NCI researcher who provided a number of insights. I asked who is responsible for setting the criteria that involves CT scans for the evidence of drug efficacy and safety that will be required for FDA approval? He explained that the gold standard for drug approval is OS (Overall Survival) and in the absence of that there are surrogate endpoints. I remember Dr. Byrd musing on the dilemma of quantifying the “feeling Great” reaction of so many Ibrutinib patients soon after taking the drug in the early Trials. Is patient subjective reaction regarding quality of life a valid endpoint?
The TKIs (Ibrutinib and Idelalisib) have made endpoint evaluation an important goal for FDA approval and may be a major factor behind frequent CT use. I am still working on who is setting the CT use agenda and what is really necessary as opposed to what is being done. Questions I have not received adequate answers for revolves around who decides how many scans a Clinical Trial Lab-Rat will get and is there a patient advocate perspective in the decision process? Even if frequent scans are deemed necessary, is anyone setting out guidelines for institutions conducting Clinical Trials assuring that Lab-Rats like you and me are getting those scans on the lowest radiation dose machines?
A recent personal story illustrating my concerns occurred during the recent Needham, MA LRF Conference where one of the two Dana Farber Oncologists giving a formal presentation gave the now familiar nudge to the audience on participating in Clinical Trials and the also familiar warning off of inappropriate CT scanning. Both subjects I had planned to ask questions about. At questions from the audience, I emphasized the doctor's push for Clinical Trial participation by describing my experience with PCI-32765 (Ibrutinib) and finished up by saying I wished to pick up on an issue related to unnecessary CT scanning in the Clinical Trial context. I said I had not been treated at Dana Farber and since I assumed that he was involved in Clinical Trials, what was Dana Farber, as an institution or he as an investigator doing to minimize ionizing radiation to Clinical Trial patients and what could he tell the audience about CT machines used at Dana Farber that used low dose technology?
His reaction was to look down at his watch in an uncomfortably long pause and finally he blurted out “I don't know what machines are used but if you have a problem with radiation exposure you should take it up with the pharmaceutical company – next question.”
I don't know about you but at that point I no longer had a problem with just radiation exposure but a problem with who is looking out for the patients who are being asked to endure frequent scanning. For the record, I volunteered for the NIH Natural History Study in which I knew I would be scanned and at a time where I had a record of scan refusal by local oncologist recommendation. I believe in the progress of advancing medical breakthroughs by Trial participation but I want to know somebody has our back on safety issues. That Dana Farber Doc did not inspire confidence that Clinical Trial patients were indeed anything more than Lab-Rats.