Working in a TBI lab means countless animal testing. What are your opinions on the issue? I believe it is very needed however I can't stop asking myself if using artificially created organic materials can do the trick. It can be a lot more expensive but closer to human specifications. Then again mice are 'worthless' (because as humans we are at the top of the chain and put a price on anything) and a lot cheaper than finding another way of testing.
1. Why was a need to overdose animals?
2. What measures were taken to avoid future overdosing to animals?
3. How were the dead animals disposed?
4. Any care was taken during disposing, considering bio hazards?
Sorry to reply to you guys (@ppp23 @scott) so late. So, I deal with the samples that are taken from these monkeys or other animals, plasma/blood and check the dosage of drug and how much amount worked the max at what time using different extraction method. As far as what I have heard through my superiors, this is one of the common problem because sometimes monkeys/rats/beagles cannot take that much amount of dosage and they die. These animals are usually tested and screened, but at the end of they day there are no guarantees given. I am truly not sure of disposal of animal but I am sure they have to follow the rules and regulations according to FDA. These are big pharmaceutical companies so they can not just dispose the dead animals in a garbage.
When conducting research on animals, you have to be very careful, because you want the experiment to succeed, I've only conducted research on rats previously, and sometimes, we did not know why the animal died. The animals were put under so that they did not experience any pain, and sometimes we found that some of the animals would die from anesthesia. this did not happen often but we did see it. This caused the repetition of several experiments because we could not count on the ones that died. One of the ways we try to investigate the failure of the experiments was that we did a mortality rate study, evaluating in what phase the animal died, how long after the experiment, in what conditions etc. I liked that we did this because it intrigued me to find patterns in their cause of death and it was something I learned from research in academia.
There are a number of subjects and variables at play when potential research fails in the post clinical trial. For example the animals you receive may have some sort of toxin that makes them sick before the experiment starts and can completely obscure data. Or if not the subject were at fault then the researchers may have not taken special precaution in administering of vaccinations or medications and caused complication with in the subject physiology.
I have also never been a part of a team doing pre-clinical or clinical research, however I do know that there are many things that can have detrimental effects on this stage of development. For example, a simple equipment failure could cause a delay due to requiring additional time for procurement, resulting in a delayed time frame for FDA approval, and in turn clinical trials not being able to be completed. There is a long list of minute details that can be executed wrong that can cause a major problem in the overall development of a project. Long story short, that is why all the stages of development that we went over in lecture one, such as planning, initializing, and executing are very important for great detail to be taken.
I am currently starting to do clinical trials and I have been doing a pre-clinical trial for my project. Anything you could think about can be a reason for this step to fail or prolong the process. For example, it took us forever to get the equipment(For us it is setting up a gait lab) purchased and set up. There are other people you have to rely on in order for a project to move forward. Usually, the administration of any organization takes forever to purchase the specific equipment and for them to install it. Therefore, project leads and members have no way in order to accelerate this process but wait patiently. And without the equipment set up the pre-clinical and clinical trials can not move forward. And once the equipment is installed you have to wait for the administrator to come and label them and inventory the equipment which adds to the wait time before you can actually start using equipments.
I personal have not been part of such a thing but can guess why this kind of thing happen. It might be because of poor study design. Reason of failing can also be not choosing correct biomaterial that is compatible with the test subject and not knowing something might be compatible for one part of the body but will be incompatible with other part as mentioned in the lecture. Also, the application of the device, material property, tissue property, physiological response, surface interactions these are all the factors of biocompatibilility which can cause failure if not picked correctly. Also, not following ISO requirement can cause failure as ISO guide lines help avoid these kind of failures by letting you know what you have to do in order create and commercialize medical devices so you avoid this kind of issues.
I haven't had to directly participate in pre-clinical research involving animals. However, as the research administrator for my area, I have had more than one experience of test mice and rats dying unexpectedly through human error. In one case, it was a blunder in the PI not budgeting enough to maintain the animals, which is a waste of resources on all sides. In the other case, correct instructions were lost in the translation from the PI's lab to our core animal maintenance laboratory. The wrong intervals for the injection of compounds were given to monitor the progression of atheriosclerosis and obesity in the WT and transgenic rats.
Both examples were very preventable and demonstrated how important clear and explicit communication is the execution of pre-clinical research. It's one thing when the animals die as a result of simulating the adverse effects of cardiovascular disease, but after incurring expenses to order, purchase and nurture the animals for a particular study then mortally harm the animals due to misapplied research protocol can be devastating to a research project, a department/grant budget and is a blemish on the treatment animal subjects.
These scenarios are all the more disappointing, because our animal laboratory management is very good at implementing stated protocols and adhering/surpassing industry standards, despite being smaller in capacity than the peer academic institutions in our area.
The emergence of Covid-19 certainly affected Pre-Clinical/Clinical research in many ways. Lab protocols were modified according to the new regulations. It led to the failure of research involving human contact. Such studies were temporarily paused until the situation became better. The students had to re-think of ways to keep the research going as the studies were based on human contact trails and it couldn't proceed further.
Although it was a simple procedure the participants couldn't attend and it has caused some major delays.
During my assistance in the lab, the major failures in the experiments occurred due to incorrect data collection especially increasingly noisy data. The implants made in the animals for the signal collection would give errors if incorrectly placed or when the animal has tried to tamper with the area repeatedly. Getting them ready (shaving a portion of their hair) where the electrode has to be placed is another tedious task as they are very finicky.
Another cause of failure is not getting the clearance at times from authorities for taking the experiments further.
I've never had the opportunity to conduct or be a part of a team doing pre-clinical / clinical research. For those of you who have done it in the past or are currently working in this type of research, what have been some of the reasons experiments, animal testing, or human testing has failed?
Although I have not had the opportunity to do pre-clinical or clinical research, from the numerous studies that I have read, there are several reasons as to why testing on animals or humans can fail. Humans are typically harmed by certain drugs due to misleading animal results. Although the anatomy of the average animal model used is similar to the human body, it does not necessarily mean that the outcome of the results will be the same. Common failures in human trials occur typically due to lack of efficacy, safety, lack of funding to complete a trial, and delay or failure to meet predetermined criteria and timelines set by the FDA. Trial designs that are inconsistent with clinical endpoints is another factor as to why both human and animal testing may fail.
I used to work with ferrets in the influenza division. So I know a great deal about failing animal tests. And I can say that a huge cause of reasons why animal tests fail is the lack of effectiveness and safety problems that were not predicted by animal tests.
@dipanpatel That's a good idea to use artificial ways to study animals. But I wonder what the pros and cons would be in comparison to using real animals?
One thing I have seen is the screening portion of the project not being done properly. Not having your control groups vs your experimental groups labeled/organized properly. My research project in college failed because the data was skewed due to the groups being mismanaged. It was something we realized following the internal review of the project. It was too late to fix the issue seeing as though the project was on a time crunch to begin with.
In pharmaceutical companies and academic institutions, advancing a drug candidate into phase I clinical trials after drug candidates are rigorously optimized at preclinical stage is a huge achievement. Long, costly, and high-risk processes can take years to complete. For each new drug approved for clinical use, the average cost is over $2 billion, and the average cost is over $1 billion.. However, the majority of drug candidates fail during phase I, II, and III clinical trials and drug approval, regardless of whether they have entered clinical studies. Additionally, the 90% failure rate applies only to drug candidates that have already advanced to phase I clinical trial, excluding preclinical drug candidates. It is even higher than 90% if preclinical drug candidates are included in the analysis.
