One of the the core accusations of this blog is that cancer patients are pushed toward clinical trials in spite of alternatives with demonstrated safety and efficacy, which takes advantage of two patient biases: new (if unproven) means better and your physician has your best interests at heart.
Physicians are paid to participate in clinical trials. Let’s get that out of the way. There is nothing objective about recommending trials to patients; you only need to notice how often a physician points a patient toward a trial outside his or her practice to deduce that trial suggestions are not without bias.
I have a few stories, spread out at multiple centers over several years. They vary in egregiousness.
- MM-302, which was in phase Ib at the time, was pitched to me as a Big Deal. It’s liposomal doxorubicin, with a new delivery mechanism that exploits the HER2 pathway to deliver a sad, old red agent. As I had no particular interest in sad, old red agents, I had to Google whether the drug was truly as sad as it seemed. In fact, there was early phase I data that showed the drug did not work in patients who had been treated with an anthracycline. I had been treated with an anthracycline. The marker TOP2A is also not amplified in my cancer, which is associated with lack of clinical benefit from anthracyclines. This drug was never going to work. Naturally, I declined to enroll. In the phase II HERMIONE study, prior anthracycline exposure is an exclusion criterion.
- Then there was the Voldemort of studies: so shady I dare not speak its name. Suffice it to say I was informed that one particular oral agent, whose name had changed about seventeen times, one for each of the prior indications where it had failed, worked better than any other drug in its class, ever. Yeah. I’m sure. I didn’t last long at this practice. The study sponsor subsequently wiped its breast program from its website, so I’m guessing the drug didn’t work out great in that indication, either.
- I got booted from a study for toxicity on a day the PI was traveling, so the PI was not part of the decision. I got a call later that I could stay in if I wanted. Why? There were similar drugs already on the market in different indications, so couldn’t I take one of those off-label? I was warned that “something bad” could happen to me if I started messing around with off-label drugs. This was a phase I study. Of an experimental agent that was poisoning me. But I should be afraid of an off-label alternative that had already been proven safe and effective? I laughed.
I go through cancer centers the way other people go through paper towels.
Clinical trial enrollment is not pure. There is lots of money at stake, and investigators (and their centers) are both financially inclined and under extreme pressure to recruit subjects. Physicians disclose their financial conflicts to one another, via their default disclosures slides, but not to patients. Investigators in a clinical trial are tasked with identifying patients who meet eligibility criteria, with zero presumption of efficacy. This clarification doesn’t benefit the center, and it is entirely possible that the physician wants the agent to work as badly as the subject does, or believes, based on his or her experience and knowledge, that the drug will perform.
Not all my clinical trial stories have dark ethical undercurrents. There’s one story I love: I was looking at an expanded access study (where the drug is made available to enrolled subjects in exchange for data; these types of projects generally occur when FDA approval is pending) for a drug I especially wanted. The same drug was available in a well-designed randomized study from the same sponsor and being conducted at the same clinical site. The PI was happy to sign me up for the expanded access, but cautioned, dead serious, before I consented that I would not be furthering science in an expanded access; the big randomized study would advance the body of knowledge. LOL. I didn’t come all this way to be randomized.
Science is not the priority.
B4 U Consent 