How We Go from Animal Model to Clinical Trial
Summary
TLDRSciShow explores the critical role of animal testing in medical research, emphasizing its necessity despite ethical concerns. Rodents, due to their genetic, behavioral, and biological similarities to humans, are often used to test treatments before human trials. The video highlights the complexity of translating animal results to humans, the importance of in vitro tests, and the implementation of safety measures in clinical trials. It also discusses the challenges and the evolution of safety protocols, including the use of computer models to predict drug interactions.
Takeaways
- đ Animal studies are crucial for testing new treatments in living organisms before human trials.
- đŹ Results from animal studies, like those in mice or rats, may not directly translate to humans due to biological differences.
- đ§Ș In vitro tests are conducted before animal testing to ensure potential efficacy and minimize animal use.
- đ Many countries have regulations to ensure the humane treatment of animals used in research.
- đ Rodents are commonly used in medical research due to their genetic, behavioral, and biological similarities to humans, and their ease of breeding.
- 𧏠Scientists can create genetically identical or 'knockout' rodents to enhance the reliability of research results.
- đ While primates are closer relatives, ethical and logistical concerns limit their use in research, making rodents suitable substitutes.
- đ Drug trials in animals are conducted with safety measures, starting with the minimum effective dose (MABEL) to minimize risks.
- đ Researchers define primary and secondary outcomes to avoid false positives and ensure the drug's effectiveness is accurately measured.
- â ïž Adverse event guidelines are established to determine when to stop a trial based on the severity and prevalence of side effects.
- đ Despite precautions, unpredictable reactions can occur, as seen in the 2006 TeGenero trial, highlighting the challenges in drug testing.
- đ ïž Modern trials incorporate more safety measures and technologies, like computer models, to improve the prediction of drug interactions with human proteins.
Q & A
Why are animal studies important in scientific research?
-Animal studies are crucial as they allow scientists to test new treatments in living organisms before trying them in humans, which helps identify potential complications or issues.
Why can't findings from animal studies be directly applied to humans?
-Animals are not mini humans, and their biological responses to treatments can differ significantly from humans, meaning that a treatment effective in mice may not necessarily be effective in humans.
What are in vitro tests, and how do they relate to animal studies?
-In vitro tests are experiments conducted in dishes and tubes rather than in living organisms. They are performed before animal studies to establish potential efficacy, as the use of animals in research is limited and regulated.
Why are rodents commonly used in medical research?
-Rodents are used because they are small, easy to breed, relatively cheap to maintain, and share enough genetic, behavioral, and biological similarities with humans to be useful for research.
What is a 'knockout specimen' in the context of animal research?
-A 'knockout specimen' refers to animals, like rodents, that have been genetically manipulated to lack specific genes, allowing researchers to study the effects of treatments more precisely.
Why are other primates not always used for drug testing despite being closer relatives to humans?
-While primates are used in some cases, ethical and logistical concerns limit their use. Rodents are often sufficient substitutes, and testing in primates does not guarantee a smooth transition to human trials.
What is the minimum anticipated biological effect level (MABEL) in drug testing?
-MABEL refers to the smallest dose of a drug that showed effectiveness in animal studies, which is used as a starting point for human trials to minimize potential adverse effects.
What are primary and secondary outcomes in clinical trials?
-Primary and secondary outcomes are predefined measures of effectiveness for a drug in a clinical trial. They help researchers determine whether the drug is working as intended and avoid false positives or missed benefits.
How do researchers handle unexpected adverse reactions during clinical trials?
-Researchers establish guidelines for adverse event outcomes, detailing what reactions necessitate stopping the trial and which are tolerable. They also plan for unexpected reactions using data from preclinical animal experiments.
What safety measures have been implemented in recent years to improve clinical trials?
-Recent safety measures include more time between dosing participants, use of computer models to predict drug interactions, and enhanced protocols for working with animals to ensure the clinical testing process is as safe as possible.
Why is animal testing still necessary despite advancements in computer modeling?
-Animal testing remains necessary because bodies are complex, and real living organisms are needed to observe how treatments interact within a biological system, something that computer models cannot fully replicate.
Outlines
đ Animal Studies in Medical Research
This paragraph discusses the significance of animal studies in the development of new medical treatments. It explains that while animal models, particularly rodents, are used to test potential treatments before human trials due to their genetic, behavioral, and biological similarities to humans, it's important to note that animals are not perfect substitutes for humans. This is because the results from animal studies may not always translate directly to humans. The paragraph also touches on the ethical considerations and regulations in place to ensure humane treatment of animals used in research, and the limitations of animal models, emphasizing the need for caution when transitioning from animal to human trials.
đŹ The Complexities of Transitioning from Animal to Human Trials
The second paragraph delves into the complexities of moving from successful animal trials to human trials. It highlights the safety measures put in place to minimize risks, such as starting with the smallest effective dose (MABEL) and defining clear primary and secondary outcomes to avoid false positives. The paragraph also discusses the challenges of predicting adverse reactions, the importance of setting guidelines for adverse event outcomes, and the need for contingency plans. It mentions the 2006 TeGenero trial as an example of an unexpected severe reaction in human participants, despite successful primate trials. The paragraph concludes by acknowledging ongoing efforts to enhance safety measures in clinical trials and the continued reliance on animal testing due to the limitations of computer models in fully replicating human biology.
Mindmap
Keywords
đĄAnimal studies
đĄIn vitro tests
đĄRodents
đĄGenomes
đĄKnockout specimens
đĄPrimates
đĄMinimum Anticipated Biological Effect Level (MABEL)
đĄPrimary and secondary outcomes
đĄAdverse event outcomes
đĄTeGenero trial
đĄClinical testing process
Highlights
Animal studies are crucial for testing new treatments before human trials.
Animals are not mini humans, so results from animal studies may not directly translate to humans.
In vitro tests are conducted before animal testing to ensure potential of treatments.
Rodents are commonly used in medical research due to their similarities with humans and ease of breeding.
Rodents can be bred with identical genomes for more uniform research results.
Knockout specimens, lacking specific genes, help researchers understand treatment effects.
Primates are used in some cases, but ethical and logistical concerns limit their use.
Human trials involve safety measures like starting with the minimum anticipated biological effect level (MABEL).
Primary and secondary outcomes are defined to avoid multiplicity issues in trials.
Researchers set guidelines for adverse event outcomes to determine when to stop a trial.
Preclinical animal experiments provide insights into potential adverse reactions.
Clinical trials have improved safety measures over the years, including more time between dosing.
Computer models are used to predict how human proteins interact with potential drugs.
Researchers continue to develop better protocols for working with animals in research.
Despite technological advancements, animal testing remains necessary for understanding complex biological systems.
Animals, particularly rats, play a vital role in ensuring the safety of treatments for humans.
Transcripts
[â©INTRO]
When we talk about cool new research here on SciShow, you might hear us say
something like: âThis study was done on rats.
And rats arenât people.â
Itâs nothing against them personally.
Animal studies allow scientists to test new treatments in living, breathing
organisms before they try them out in people,
which helps spot complications or potential pitfalls.
But animals arenât mini humans,
so what happens in a mouse may not happen the same way in a person.
And that means two things.
For one, it means we canât always assume a cure in mice
will be effective in human patients.
But it also means that safely going from animal to human trials
is a lot more complicated than you might think.
Before any animals even get involved, pharmaceutical researchers run a bunch
of what are called in vitro tests,
basically anything done in dishes and tubes rather than animals.
What theyâre doing has to have a lot of potential since, as you can imagine,
the use of animals in research can be unsettling for a lot of people.
Many countries have formal institutions in place which try to limit the use
of animals for cases where theyâre really needed, and they have regulations
which specifically ensure these animals are treated in a humane way.
Now, a lot of medical research is conducted in rodents.
Thatâs because rodents are small, easy to breed,
and relatively cheap to care for in large numbers.
And rodents have enough similarity to humans in a lot of areas,
including genetics, behavior, and biology, that they can help scientists suss out
whether a drug has real potential.
Also, we can breed them to be optimized for research.
Large numbers of rats can have almost identical genomes, for example,
allowing for more uniform and reliable results.
And scientists know how to manipulate their genomes to get what we call
knockout specimens: ones that lack specific genes.
This lets them dig deeper into what a treatment is actually doing to the body,
which helps minimize any surprises that might happen when a drug is given to
humans instead.
You might think itâs strange that so many trials are done in mice or rats
when weâd get the most reliable information from animals
that are closer relatives, especially other primates.
But while primates are the right choice in some cases, there are ethical and
logistical concerns with conducting research on them, and for the most part,
rodents are pretty good substitutes.
Besides, testing a drug in primates doesnât guarantee a smooth transition to
human trials, because the only animals with all the right cells and proteins to
perfectly predict what happens in a human body are, well, humans.
Thatâs why, even when a drug has passed animal tests with flying colors,
researchers build in a number of safety measures to minimize the risk of adverse
reactions in people.
Itâs considered important to use as little of the drug as possible, for example.
That usually means starting with the smallest amount that seemed to work in animals,
called the minimum anticipated biological effect level, or MABEL.
If that doesnât cause any problems, but doesnât work, either,
then researchers can dial up the dosage.
They also lay out exactly what their definition of âworkingâ is ahead of time.
These are what are called primary and secondary outcomes.
If theyâre too lofty or unfocused,
like if there are dozens of things the drug could do,
then youâre likely to perceive a benefit that isnât really there.
This is whatâs called multiplicity in a trial, and it arises because the statistics used
to determine whether something has made an impact or not
have a certain margin of error.
On the flip side, if your trial outcomes are too narrow or impossible to obtain,
you might not realize a drug is actually doing something good.
And at the same time as theyâre determining primary and secondary outcomes,
researchers also set guidelines for adverse event outcomes,
basically, what reactions mean itâs time to call it quits, and what reactions,
though perhaps unpleasant to experience, arenât really that big a deal.
The good news is that they already have an idea what might happen
from those preclinical animal experiments.
But they also have to make plans for things that come out of left field.
So, they make guidelines to determine how to react if things go wrong,
which take into account everything from the number of participants
affected to the severity of their reactions.
Of course, it doesnât help matters if companies are overzealous
about their hopeful cures.
In many cases, when a failed clinical trial makes headlines,
investigators later discover corners that were cut along the way.
But sometimes, researchers do everything right and the worst still happens.
Take the 2006 trial for TeGenero,
an antibody that researchers hoped would be the next cure
for a set of autoimmune diseases.
For the first human test, 6 of the otherwise healthy participants
were given 1/500th the dose used during primate trials, but within an hour,
all experienced severe inflammatory reactions requiring hospitalization.
The drug was supposed to activate certain cells in the immune system,
so in a sense, it was doing its job, it just did it a little too well.
The human cells the drug targeted turned out to be way more sensitive
than any of the animals tried.
And that kind of uniquely human reaction to a drug is really hard to predict.
Nowadays, trials build in a lot more safety measures than they did a couple
decades ago, like taking more time between dosing each participant
to see if something bad happens.
And they can take advantage of newer technologies like computer models
that can better predict how human proteins interact with potential drugs.
But researchers and regulators are still working on ways to make the clinical
testing process even safer.
And a big part of that is making better protocols for working with animals.
Thatâs because, despite all the amazing things we can do with computers,
bodies are really complicated.
So we still need animal testing to see how things work in real living things.
So even though rats arenât people, we still need their help to keep people safe.
Thanks for watching this episode of SciShow!
If you enjoyed learning more about the importance of animals in research,
you might like our episode about 5 times researchers gave animals drugs
and what we learned from those experiments.
[â©OUTRO]
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