General Comments / Chat, page-13047

The Role of EQUIPOISE in the ETHICS of CLINICAL TRIALS!

I think the ethical dilemna that people find themselves in comes from the conviction that many have; that RC220 is an improved version of Bisantrene RC110, and as such, it is as effective and as safe as the original Bisantrene, in humans! It may well be, but where is the data?

If RAC have evidence of superiority of the Dox+RC220 combo versus Doxo alone (etc), it becomes unethical to experiment with this in humans: we should just apply for approval and present the evidence we have. The FDA even has a pathway that we can use: its ths 505(b)2 regulatory pathway, which Telix used successfuly with their first product (Illuccix), but failed with a second (they were told to bring more data). No need to dwell on that - the data is not there.

Belief without data is Faith, not Science! Even the folks at IMU swear by their product, with little care about evidence. A BP company had a great cancer killer made out of a giant antibody (huJ591) armed with a powerful warhead Actinium 225: It killed cancer, for sure; but I dont know who died first, the cancer cells or the unfortunate hosts!

What if RC220 gives Doxorubicin some Superpowers? How is that not possible?

Anyhow, I want to discuss a concept that is super important in Cliinical Research Ethics: The State of Equipoise!

Equipoise is the Ethical Green Light for clinical research. Its a situation where, the clinicians who are proposing to undertake the research in question (a human experiment), have real uncertainty about whether a new treatment is better than the current standard. For RAC researchers to gain ethics approval, the clinicians would have presented a statement that describes their being in a state of equipoise, indirectly or directly.

If you already know which drug is better, you cannot ethically randomize patients to a control arm that misses out on effective treatment. For RC220, despite being a reformulation of Bisantrene, there is no evidence yet that, when used in humans, Dox+RC220 is superior to Dox alone, or that Dox+Other+RC220 is superior to Dox+Other.

RAC would have also told the Ethics committes that the safe and effective dose of RC220 (especially in combinations) is not known yet. Even if RC220 is based on the same active pharmacological ingredients as the original Bisantrene, formulation tweaks (solubility improvements) can change how the drug behaves in humans. I know that people reject this - but thats how regulators will have seen it (and we have to accept that its the regulators who decide).
Frankly, RAC would not have been allowed to use a dosage that they (RAC) would have marked as a zero effect dose on patients! You may as well give the patient sterile water or something similar (as is done with controls). A dose determination study does not have an inactive arm. Even if it may not be efficacious at this dose, it can still cause side effects: thats important safety data! That, folks, is precicely why RAC lauded the success and safety from the first dosing, and why Mason is celebrating the absence of phlebitis in patint 1. It was not water!

Because of these uncertainty, Equipoise exists, thereby justifying the Clinical trial that RAC is doing, in the way that it is being done. Thats how regulators would have seen it.

Its a Risk-Benefit balance. Imagine starting with a high dose without safety data, and hitting serious adverse events in patients 1 and 2! Do you drop to a lower dose? But, how do you even do that when there was no lower dose plan? Suddenly, there is a risk of premature failure of a promising therapy, leaving Doxorubicin’s “red terror” unchallenged.

In God We Trust - All Others Must Bring Data!

Now, the RAC Scientists and Management are all convinced that this will work, and have convinced us, and we now beleive the same and have backed the company. But, we must present data to prove it, before we can save lives enmasse. Ethics will allow us to do that, while stopping products that are just hyped up from reaching patients. (Even is not 100% successful at that!)

Safety Review Committees will have early access to data, so they will help. If a new treatment is clearly effective, they make the call, so that the researcher may look at other ways. They do that too if the new treatment is causing harm, and also when there is no chance of achieving a desired outcome.

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Regards to you all!