There's a lot of problems with it, though. Even if advancing medical research was the main goal-- ad hoc use in dying patients provides unclear data. Medical research wants clear inclusion criteria, metrics, reduced statistical noise from similar patients, predeclared outcome measures, and economies of scale in running trials.
We already let terminal patients participate in medical research, but only inviting patients at times and meeting criteria that optimizes the research. Also, only where IRBs have found it to be ethical-- this means not replacing a drug with proven benefit with an experimental treatment with unknown benefit recklessly.
But terminally-ill patients push for inclusion beyond this: to be dosed when there is not an active trial, or to be dosed when they are so sick that the outcome would be difficult to interpret or compare, etc. This isn't for medical research, this is for self-preservation.
>There's a lot of problems with it, though. [...] Medical research wants clear inclusion criteria, [...] , but only inviting patients at times and meeting criteria that optimizes the research [...] But terminally-ill patients push for inclusion beyond this: to be dosed when there is not an active trial, [...]
Your objections are sensible but that's beyond the scope of this author's argument. I'm just taking author's following comment at face value:
">The FDA was loathe to approve initial mRNA human trials, even when those trials would have been full of people like me: those who are facing death sentences anyway."
If it's the drug researchers who don't want the author as a test subject, that's understandable. But he's arguing the _FDA_ shouldn't be the one blocking his participation.
For the situations where there's "no active trial" caused by the FDA not greenlighting the experiments, then of course, the complaint will be that "terminally ill patients want to participate in trials that don't exist". That's sort of a circular argument -- caused by the FDA.
Again, if there's no active trial because the medical researchers themselves are not yet ready, that's understandable. But if the drug scientists are ready but the FDA is not, that's a different issue and it's the focus of the author's essay.
All that said, I don't know how much scientific progress the FDA holds back because of "safety". I'm just trying to explain the author's position.
> I'm just taking author's following comment at face value
Plenty of mRNA human trials of cancer treatment are in progress. Indeed, as he stated, he wants into two that are underway, but that he is probably too far along for. He wishes that they had been greenlit even earlier and perhaps made their way to be approved drugs that he could just be given by his local doctor.
> For the situations where there's "no active trial" caused by the FDA not greenlighting the experiments,
There's compassionate use exceptions for circumstances like this.
The big thing is, there's two big bars to cross with getting a trial together:
- You probably want to be doing human research in a way that will produce evidence that will convince the FDA to grant you approval. (Hence, drug companies often are nervous that compassionate use will pollute their data).
- The FDA wants to protect human subjects, and if there's a drug that results in 15% survival for a year, vs. 5% for doing nothing and ???% for your new experimental treatment: they want that drug to be tested as part of a protocol that minimizes potential harms, not to randomly replace the 15% survival treatment. Most experimental treatments end up failing.
> Indeed, as he stated, he wants into two that are underway, but that he is probably too far along for.
The author is incorrect on this, he’s not too far along but he does not meet inclusion criteria for either of the studies he cited as both require systemic therapy.
mRNA is not being pitched or tested as a first-line mono therapy by Moderna. I’m not sure why the author is jumping the gun here and ignoring approved systemic treatment options.
I’m ignoring that part because it is nearly impossible to prognosticate prior to initiation of systemic therapy, with the exception of some phenotypes but we don’t have the pathology report in this case.
My point is that he doesn’t even meet the inclusion criteria for these studies, regardless of aggressiveness. This has nothing to do with the FDA, he can’t join the studies because Moderna doesn’t want to study him at this point and not because he won’t survive long enough to enroll.
Whether or not his prognosis statement is correct.
Excellent explanation, parent is also correct. I think the author’s position is misinformed.
The FDA doesn’t hold back researchers on inclusion/exclusion criteria.
Inclusion for the Moderna trial he linked to:
> Must have primary refractory or acquired secondary resistance to prior immune checkpoint treatments. Primary refractory is defined as prior exposure to anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) antibody for at least 6 weeks but no more than 6 months with demonstration of progression on 2 separate scans at least 4 weeks apart but no more than 12 weeks apart and progression occurring within 6 months after first dose of anti-PD-1 antibody. Acquired secondary resistance must have confirmed objective response or prolonged stable disease (SD) (>6 months), followed by disease progression in the setting of ongoing treatment and confirmed progression on scans at least 4 weeks apart.
Exclusion criteria:
> Participant has received treatment with prohibited medications (that is, concurrent anticancer therapy including other chemotherapy, radiation [local radiation for palliative care is permitted with approval from the Sponsor]…
From the description of the patient’s treatment course it sounds like he had curative intent radiation (given he subsequently had surgery) and would probably not meet this study’s criteria making the limiting factor Moderna not the FDA.
He also doesn’t mention whether he’s starting immunotherapy/checkpoint inhibitors (or his tumor status) and may be lumping immunotherapy with chemotherapy which is a good new treatment option and would typically be offered if eligible. Definitely better than being enrolled in a dose study and in fact is required by Moderna.
We already let terminal patients participate in medical research, but only inviting patients at times and meeting criteria that optimizes the research. Also, only where IRBs have found it to be ethical-- this means not replacing a drug with proven benefit with an experimental treatment with unknown benefit recklessly.
But terminally-ill patients push for inclusion beyond this: to be dosed when there is not an active trial, or to be dosed when they are so sick that the outcome would be difficult to interpret or compare, etc. This isn't for medical research, this is for self-preservation.