Acute Vs Chronic trials some more truth

[paolocipolla]

Here below a recent experience I wanted to share. You can also listen to the audio recording I have posted on youtube.



http://www.youtube.com/my_videos_edi...id=N1BjFIomo58



Context:
At the ISCOS meeting in London on sept 3rd 2012 in the morning there have been several presentations explaining the problems of running acute trials and then were presented the results of the Stem Cell Inc. trial (chronic).
The advantages of running a trial on chronic SCI were very clear even to a lay person after the presentations.
In the final discussion at the end of the morning session a person with SCI from the audience has asked to a well know researcher (my summary): given the advantages to run a clinical trial on chronic SCI people wouldn’t be convenient to focus more on chronic to move forward faster to find a cure for SCI and then once efficacy is proved in chronic SCI move back to acute patients?

Research answer:
1 -There is not enough preclinical data to justify doing more chronic SCI trials. The preclinical studies are being done mainly on acute SCI animals because it is easier and because it is cheaper.
2- (A load of BS here) To keep an animal with chronic SCI for SEVERAL years (2/3 years he said at the end) is very expensive (but we all know that 2-3 months is already chronic for a rat or a mouse – my note).
3- but there are few groups working on chronic
4- The advantages of doing a clinical trial for chronic are well known

My comment:
So the problem is just getting more preclinical data on chronic SCI, so it’s just a problem of

1- some money
2- (above all IMO) WILL by scientists to do chronic studies.

I hope many CC members get the problem and get angry like me.

Remember that:
Aristotle does not deny anger a place in the behavior of a good person, but says it should be "on the right grounds and against the right persons, and also in the right manner and at the right moment and for the right length of time"

I agree with Aristotle.

Paolo

[GRAMMY]

Paolo, your link didn't seem to come up, so I posted it here.

[paolocipolla]

Thanks Grammy!

The audio is not great, but that was the best I could do.

Paolo

[GRAMMY]

Paolo, I don't recognize who is talking in the audio. Who was the research person talking?

Several points to consider...yes, it's expensive to keep chronic animals alive for long periods of time but serious researchers have labs and staff that are very capable of doing it with some added funding. We're seeing research papers for chronic SCI projects that show results and recovery with rats that are chronic one to 1.5 years old. That's pretty extraordinary considering the lifespan is around 2 yrs old. It doesn't make any sense to say there's no trials or shouldn't be because it's too hard to gather preclinical data on chronics. The scientists will tell you that after a few months they are considered chronic and their work begins. Some are even being left more than 1/2 their lifespan and then various therapies are being tested.

Perhaps the person on the video hasn't kept up on the accomplishments being achieved in the chronic sci labs. The old world thinking dies hard.

We could surely use more sci labs working on chronic projects to gain the necessary preclinical data that is required to go to human trials. We should support the ones who really are working on the chronic piece.

[jsilver]

Originally Posted by GRAMMY

Paolo, I don't recognize who is talking in the audio. Who was the research person talking?

Several points to consider...yes, it's expensive to keep chronic animals alive for long periods of time but serious researchers have labs and staff that are very capable of doing it with some added funding. We're seeing research papers for chronic SCI projects that show results and recovery with rats that are chronic one to 1.5 years old. That's pretty extraordinary considering the lifespan is around 2 yrs old. It doesn't make any sense to say there's no trials or shouldn't be because it's too hard to gather preclinical data on chronics. The scientists will tell you that after a few months they are considered chronic and their work begins. Some are even being left more than 1/2 their lifespan and then various therapies are being tested.

Perhaps the person on the video hasn't kept up on the accomplishments being achieved in the chronic sci labs. The old world thinking dies hard.




We could surely use more sci labs working on chronic projects to gain the necessary preclinical data that is required to go to human trials. We should support the ones who really are working on the chronic piece.

Hi Grammy,

It's John Steeves. His voice is unmistakable. I disagree with much of what he said about chronic injury research and agree with your and Paolo's assertions

[JenJen]

I remember being at RIRC and having to leave early because of wildfire evac. They were discussing who would stay behind to care for the chronic animals. Research for Cure raised a lot of money to ensure that chronically injured animals would be available for appropriate study. I even recall once knowing how much it cost... correct me someone, but is it not something like $11,000 per year per chronic rat? That was a few years ago. Probably more now.

[rjames]

I just read where the Miami Project just raised close to $18million from their recent Legends Gala....maybe they could afford to care for some Chronically injured rats???

By the way My foundation paid for some chronic injury rat care at RIRC a few years back...money well donated IMHO

[jsilver]

Originally Posted by JenJen

I remember being at RIRC and having to leave early because of wildfire evac. They were discussing who would stay behind to care for the chronic animals. Research for Cure raised a lot of money to ensure that chronically injured animals would be available for appropriate study. I even recall once knowing how much it cost... correct me someone, but is it not something like $11,000 per year per chronic rat? That was a few years ago. Probably more now.

You are way off. Rat care per diem is around a dollar per day. They cost about $35 per animal. So that is about $400 per year per animal. A typical experiment might entail 6-8 animals per group. Experimental drugs and various reagents can be costly but their amounts don't vary much between an acute or chronic experiment. I my opinion, the greatest impediment to doing chronic experiments is lack of creative ideas as well as fear of failure. We need spinal cord neuroscientists to step up to the plate and "just do it."

[GRAMMY]

Originally Posted by jsilver

You are way off. Rat care per diem is around a dollar per day. They cost about $35 per animal. So that is about $400 per year per animal. A typical experiment might entail 6-8 animals per group. Experimental drugs and various reagents can be costly but their amounts don't vary much between an acute or chronic experiment. I my opinion, the greatest impediment to doing chronic experiments is lack of creative ideas as well as fear of failure. We need spinal cord neuroscientists to step up to the plate and "just do it."

Thank you Dr. Silver for having the guts to just come right out and say how it is. If sci scientists aren't willing to get into the box to start swinging in the first place there's no chance for the team. We know there's going to be strikes along the way. I don't expect every research experiment to result in a home run, but without a sci neurobiologist willing to step up to the plate and really work at it, we may as well shut off the lights and go back home. Thank you so very very much for being part of a newly formed collaborative team working on chronic spinal cord injury research for us.

[Wise Young]

I agree with Jerry that $11,000 per chronic spinal injured rats is way too high but, in my opinion, $400 per year is too low because it doesn't include care of spinal-injured rats, the cost of surgery, behavioral evaluation, or histological assessment of the rats. The one dollar per day of per diem cost that the animal facilities charge for housing the rats just includes changing the bedding of the animals and providing food and water.

The cost of care depends on the spinal injury model that is used. If one hemisects the animals, they generally recover function within 2-3 weeks and there is no need for special care of their bladders. However, if the animal has a 25 mm weight drop contusion, which causes long-term bladder paralysis, the costs for daily animal care are much higher.

Labor is the most expensive part of animal care. A severely spinal-injured rat must be inspected and receive daily bladder expression, sometimes twice a day. Even with the best of care and prophylactic antibiotic administration during the first week after injury, about 25% of the animals will get a bladder infection and must receive additional antibiotics.

Let me give an example of the actual cost of a chronic study. Let's say that we are studying 48 rats, i.e. 4 groups of 12 rats and keeping them for 3 months after injury before treating them, and then observing them for 3 months for a total of 6 months. Note that the animals must be purchased at least 2 weeks before and the cost of purchase and shipping is about $50/rat. Because of mortality and problems with the injury one should purchase about 20% more animals, i.e. 60 rats.

Animal care. Even the most efficient animal care technician require more than 4 hours per day to take care of 48 spinal-injured rats. If the technician spends 5 minute per rat, that is only 12 rats per hour. If there are any problems with the rats, it can easily consume another several hours. The animals must also be evaluated for walking and other behavior every week, i.e. BBB scores for about 10 rats/day for 5 days a week. Incidentally, this care must be delivered 7 days a week and one technician cannot do this job. So, two technicians will be necessary to care for and evaluate recovery in 48 rats. Let's say that each technician salary is $55,750 per year ($40,000 annual salary and 35% fringe benefit costs).

Surgery. It takes about 2 hours of work to do spinal cord injury and post-operative care of a rat. So, an efficient surgeon typically does about 4 spinal cord injuries per day and requires about 3-4 weeks of work to do spinal cord injury on 48 rats. A 20% mortality rate over a 6 month survival period is typical. Then, if there is cell transplantation involved, another month of work will be required. Tract tracing, euthanasia and removal of tissues require another month of surgery time. If an experienced surgical technician costs about $60,000 per year, three months cost would be about $15,000.

Histological assessment of the animals. It takes a technician, student, or post-doctoral about 1 week to cut, stain, and analyze the spinal cord of a rat. A full-time person is needed to do this. Including reagents, this could easily be $30,000 for 48 rats. Of course, part of this work can be outsourced but just cutting and staining of sections by outside companies usually cost as much as $1000 per rat. This would add about $48,000 for 48 rats

Estimated budget for a chronic spinal cord injury experiment:
• Animal purchase and shipping ($50/rat • 60 rats) = $3000
• Animal housing (per diem of $1/rat/day • 60 rats • 200 days) = $12,000
• Animal care (6 months of two technicians effort) = $60,000
• Surgery (3 month of a surgical technician) = $15,000
• Histology (6 months of technician effort) = $30,000
Total $120,000

Note that the above does not include the investigator salary, which could easily add $60,000 to the cost of one chronic spinal cord injury study. In any case, if we divide the $120,000 by 48 rats, the cost per rat is $2500. It is less than $11,000 per rat but substantially more than $400/rats.

Wise.