Extrapolation from studies with laboratory animals to humans

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
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cave76
Posts: 3182
Joined: Sun 12 Aug 2007 2:27

Extrapolation from studies with laboratory animals to humans

Post by cave76 » Fri 10 Apr 2009 1:13

Extrapolation from studies with laboratory animals to humans should be done with caution.
A quote from Wormser ( according to Joe Ham)
But since there were three authors of the article:

http://aac.asm.org/cgi/content/full/46/1/132

----- I'm not sure how it's determined just who wrote that sentence.

However, I think it's a good idea even if it DID come from Wormser
.

Fin24
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Joined: Sat 8 Mar 2008 20:14

Re: Extrapolation from studies with laboratory animals to humans

Post by Fin24 » Fri 10 Apr 2009 4:18

actually I dont think ANY scientist medical or otherwise ever assumes the absolute cross relativity between animal studies and human outcome speculation.

here are a few articles that are of similar topic and note they go back very far meaning this has been standard accepted fact for decades--that you cant automatically and without severe limitations extrapolate results from animal tests to human otucomes.


http://www.shockjournal.com/pt/re/shock ... 28!8091!-1

ANIMAL MODELS OF SEPSIS AND SHOCK: A REVIEW AND LESSONS LEARNED.

Review Article

Shock. 9(1):1-11, January 1998.
Deitch, Edwin A.
This review focuses on the concept that the preclinical trials of many of these agents were conducted using models of sepsis and shock that do not adequately reflect the clinical realities of these conditions
J Infect Dis. 1988 Oct;158(4):831-47.

Correlation of antimicrobial pharmacokinetic parameters with therapeutic efficacy in an animal model


Animal models for the study of anti-anxiety agents: a review.
Neurosci Biobehav Rev. 1985 Summer;9(2):203-22
Although there are important exceptions, in general, most early animal models have not provided a reliable basis for identifying compounds with potential anxiolytic action, or for delineating the mechanisms of anxiolytic drug action
PRO animal studies with antimicrobials:
Animal model pharmacokinetics and pharmacodynamics: a critical review
D Andes, WA Craig - International journal of antimicrobial agents, 2002
Animals have been extensively used in the evaluation of antimicrobials. The value of animals in the pharmacokinetic and pharmacodynamic characterization of antimicrobials is critically reviewed. Animal studies have demonstrated that the pharmacokinetic/pharmacodynamic (PK/PD) target determining efficacy can vary for different classes of antimicrobials. However, the magnitude of the target required for bacteriological efficacy is relatively similar for various sites of infection, various pathogens and various drugs within the same class, provided free drug levels are used.
and here are a few others
Clinical Infectious Diseases 1998;26:1–10
DOI: 10.1086/516284
State-of-the-Art Clinical Article: Pharmacokinetic/Pharmacodynamic Parameters: Rationale for Antibacterial Dosing of Mice and Men
William A. Craig

J Infect Dis. 1990 Jul;162(1):96-102
Widmer AF, Frei R, Rajacic Z, Zimmerli W.
Correlation between in vivo and in vitro efficacy of antimicrobial agents against foreign body infections
part of the abstract I found very interesting
In vivo studies were performed with the guinea pig tissue-cage animal model; in vitro studies with minimum inhibiting and bactericidal concentrations, time-kill studies of growing and stationary-phase microorganisms, the killing of glass-adherent S. epidermidis. Drug efficacy on stationary and adherent microorganisms, but not minimum inhibiting concentrations, predicted the outcome of device-related infections. Rifampin cured 12 of 12 infections and was also the most efficient drug in any experimental in vitro test. Similarly, the failure of ciprofloxacin to eradicate foreign body infections correlated with its low efficacy on stationary-phase and adherent S. epidermidis.
this study shows the confusion over in vivo vs in vitro--in VIVO here means using a guinea pig tissue model and NOT humans or even human tissue cultures!! so just because you read "in vivo" you still must read the methodology section to see what they actually did!!
AND the fact that the MICs had NO predictive value!!
( and curiously ,the Rifampin beating Cipro in antimicrobial activity too)

some models( animal or culture plate) can have an extremely close correllation to humans meaning the study will be useful, while other models are less reliable.
Often before an animal study is undertaken it has to go through many layers of approval not the least of which is proof of absolute need of an animal model ( for at least 2-3 decades there has been a limitation); also required is proof of how well it has already been shown that the animal model planned to be used will in fact mimic the conditions needed for human outcome estimations, and finally furhter solid evidence that at the end of the study the information will have usefulness of specific parameters ( in other words you cant simpl,y say "I wanna use mice and I think it may end up helping some people")

so using animal models MAY or may NOT mean a thing when looking for correllation to human cases and even the use of IN VIVO vs In VITRO may not mean much either-- in vivo may not mean 'in the human who has the targeted specific illness' which is the ONLY 'absolute' test of a specific drug against a specific pathogen

so much for the frustration of a few members looking for black and white definitions to always mean the same thing!!

cave76
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Joined: Sun 12 Aug 2007 2:27

Re: Extrapolation from studies with laboratory animals to humans

Post by cave76 » Fri 10 Apr 2009 15:23

In case some haven't read all the information Fin wrote, at the bottom is a pithy comment.
so using animal models MAY or may NOT mean a thing when looking for correllation to human cases and even the use of IN VIVO vs In VITRO may not mean much either-- in vivo may not mean 'in the human who has the targeted specific illness' which is the ONLY 'absolute' test of a specific drug against a specific pathogen

so much for the frustration of a few members looking for black and white definitions to always mean the same thing!!
If we had wanted 'black and white' --- we'd have all gotten a staph infection instead of Lyme.

And:
in vivo may not mean 'in the human who has the targeted specific illness' which is the ONLY 'absolute' test of a specific drug against a specific pathogen
Thereby hangs the crux of the matter. Each and every one of us has so many different variables in our body that what drug works for one may not (often doesn't) work for the next person.

[personal non contributory, non substantial commentary removed]
Last edited by cave76 on Thu 16 Apr 2009 1:55, edited 1 time in total.

Fin24
Posts: 1699
Joined: Sat 8 Mar 2008 20:14

Re: Extrapolation from studies with laboratory animals to humans

Post by Fin24 » Fri 10 Apr 2009 19:32

maybe its me, but it looks like even more clarification may be needed

In VIVO means "in life" -- in the living organism, BUT that can mean in any living animal model and not necessarily in a human or in a human having the same disease target the drug is being tested on/for.

in vitro means " in glass" but can mean any artficial environment

and more confusion: many assume "in vitro" means in the lab BUT what about using animals in a lab?? isnt that " in vivo" and "in vitro"???

cave76
Posts: 3182
Joined: Sun 12 Aug 2007 2:27

Re: Extrapolation from studies with laboratory animals to humans

Post by cave76 » Fri 10 Apr 2009 19:45

[personal non contributory, non substantial commentary removed]
Last edited by cave76 on Thu 16 Apr 2009 1:49, edited 1 time in total.

minitails2
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Joined: Sat 3 Nov 2007 10:27

Re: Extrapolation from studies with laboratory animals to humans

Post by minitails2 » Sat 11 Apr 2009 9:58

Now here's some more interesting information about extrapolation. This one includes animal models as well as the extrapolation of dose amounts:

http://www.atsdr.cdc.gov/toxprofiles/tp160.html

On page 54, a concept called Psyiologically Based Pharmacokinetic models is introduced. Such models are being used more and more
...in risk assessment, primarily to predict the concentration of potentially toxic moieties of a chemical....
snip
These models are biologically and mechanistically based and can be used to extrapolate the pharmacokinetic behavior of chemical substances from high to low dose, from route and route, between species, and between subpopulations within a species.
snip
The numerical estimates of these model parameters are incorporated within a set of differential and algebraic equations that describe the pharmacokinetic processes.
Certainly no easy task to apply research from one study to another.

Fin24
Posts: 1699
Joined: Sat 8 Mar 2008 20:14

Re: Extrapolation from studies with laboratory animals to humans

Post by Fin24 » Sat 11 Apr 2009 20:00

major problem--" being used" doesnt = " checked for safety and validity"

meaning a LOT of the time methods are adopted for less than admirable reasons ( cost, ease, drug compnay agenda)

look at the recent crap with the post surgical pain management based upon one Drs studies that for YEARS became the " accepted" way to do it and come to find out his studies were FALSIFIED and had to be rescinded and now the state of anestesiology and pain mgt was set back decades!!

so Im very wary of any mathematical model that " extrapolates" data cross species and even most times within species--I have worked with animals and have experienced the very frustrating variances within an animals system--meaning that we often didnt get what we expected after injecting a group of animals with some experiemental treatment--

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