Thursday, August 27, 2009

Dr. Naomi Kleitman from the NIH

Title of her talk is Getting On With Clinical Trials

What's the process? She's trained in basic science . .. we heard this morning that there are lots of potential targets. Slide is showing all the good targets, including neuroprogection, replacement of lost cells, repair of axons to promote regeneration and remove inhibition, remyelination, and retrain remaining circuits through rehab.

So many good targets!

And it's not care vs. cure anymore . . .they have to go together because rehab will be part of whatever works.

So, is walking the realistic target? Go look at clinicaltrials.gov -- of the 238 trials listed in sci at that website, what are they addressing?

sensory, bladder and bowel, sexual function, spastiticy, brething, pain, pressure ulcers, cardiovascular conditions. Her point is that we're somewhere along the path -- we're not het able to translate.

Ack! Image of a rat spinal cord and a human one, both kind of hemp-colored; against a purple background (image came fromDr. Bruce Dobkin, going to try to find it so you can see.)

The point is that what workds in the skinny little rat cord might be worthless in the human cord. Issues include the length of the cord, the size of the lesion, anatomy of each, and functional things, like walking on 2 leg vs. on 4.

Some fundamental questions -- neurological disorders are complex, and we need complex strategies to deal with them. The thing that researchers have to confront is, how much information is enough???

And there is disagreement about that among scientists themselves. There's no gold standard for cellular therapies and very little consensus about what that would be. How much recovery in animals justifies tests in humans?

Okay, so what is translation? It's changing one thing to another (thought to action) or carrying something from one place to another (bench to bedside)

It's not about doing a trial that isn't anything like what happened in the lab, and not using a therapy without some kind of rigorous assessment of what you knew.

What are the targets again?

neuroprotective strategies, neurorepair strategies (anti-nogo, NgR, cethrin, rolipram) -- you have to know what the outcomes mean.

The basic flow from thought to trial is:
ID the target, do an assay, do screening, establish proof of concept with animal models, do preclinical testing, do safety studies, take it to the clinic

she's talking about the difference between clinical reearch and clinical trials. Clinical research is basic science done with humans or human tissues, like epidemiology, physiology, pathology. Clinical trials test treatments in people for safety, efficacy and compared to other treatments.

What the FDA does is define three phases in the testing process. 1 is for safety, 2 is for safety and bioactivity, and 3 is for efficacy.

There was a spinal cord injury locomotor trial done recently on people with relatively new injuries. The trial "failed" because everybody walked and everybody in the control group walked, too!

Joking about how dumb some trials are with a phony randomized trial to see if it's dangerous to jump out of a plane with no parachute.

When will clinical trials begin?
They already have. There are currently 118 sci trials recruiting at clinicaltrials.gov

She says she can't talk about anything she knows about pending grants -- and asks us not to believe rumors that nothing is ever going to be tested.

There's a lot going on right now in sci -- more than in brain or stroke. the key is to figure out how to measure outcomes.

ICCP, ASIA/ISCoS, SCOPE, SCIQOL, EM-SCI, China SCINet, CDRF NOA, NETT . . . these alphabet soup nuggets are about planning collaborations. When I have some time I'll go find em and put the hyperlinks in.

Don't be fooled by clinical trials with bad designs. The problem is that when a design is bad you won't be able to tell if the drug failed or the trial failed. What you want from trials is reliable information.

She's talking about the icord document that tells people how to know whether or not they should think about enrolling.

Why does the FDA delay Phase I trials? Safety, safety, safety.

Getting to translation is hard. But we know much more than we ever have before, and my grad school advisor was wrong when he said that "spinal cord is boring."

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