phase I ... addressing sub-therapeutic doses

[Guest guest]

Phase I ... addressing sub-therapeutic doses of a new drug

Greetings,

There is so much that I want to share regarding the role of advocates in

clinical research - which can range from providing input on the rationale of

the study, to the tests that are given, but also the informed choice

process.

One of the many challenges of early-phase research is how to start to

evaluate a new drug that was never given to any person. Here, to protect

the participants, the starting dose must be VERY low and therefore almost

certainly it will be sub-therapeutic - too low to have a beneficial

treatment effect.

At the Methods Workshop - actually prior to the meeting - I asked if it's

feasible to allow participants in the low-dose phase of a study to have

access to the maximum dose that is later found to be well tolerated -- this

to increase the chance (even if statistically pretty low) that the

participants may actually get some clinical benefit.

Anyhow, I was very pleased to learn during an amazing lecture by Dr. Rick J.

Chappell about a dosing schedule that allows just that. It's called

Accelerated Titration.

There's no need to remember the fancy term for it, but I think it could be

helpful for the community to know that this type of dosing schedule can

exist in early-phase trials and that it can make participation more

reasonable.

So following Dr. Chappell's presentation I made a comment about how

important this could be to potential participants; and asked if this method

is commonly used in phase I studies? My purpose for making the comment was

to raise awareness among the junior investigators about the potential

importance of the Titration scheme on phase I enrollment and also the ethics

of such trials.

To my great satisfaction, two protocols developed by junior investigators in

my group were modified in this way based also on further discussion, which

took place in the protocol development group meetings to which I was

assigned as a member of the patient advocate faculty.

However, there are some study designs that cannot use Accelerated Titration

- one being when you add a new agent to a standard therapy in a step-wise

manner - such as when the study goal is to find the right dose of a Btk

inhibitor when added to standard chemotherapy . because that would require

giving more of the standard dose of the chemo as well, causing unacceptable

cumulative toxicity.

All the best,

PS. For more on my workshop experience, see http://bit.ly/qXgqUW