Replies to post #320600 on Innovation Pharmaceuticals Inc (IPIX)

[Jhawker]

And “different labs” implies that companies could shop labs for the highest SI. Luckily ours was done at an independent RBL lab.

[bradfordbros]

"Asking for a friend.?" I doubt it.

[KMBJN]

I'm not an expert, really, and just giving my opinion here.

Surely if one runs a test one time, one will get a result. Running it again in the same lab and same conditions will give a slightly different result. Running the same experiment in another lab, and all bets are off.

Science is messy, and it's really hard to replicate results across different labs, since there are so many variables, such as the amount and duration of virus applied to the cell culture, clinical isolate/source of SARS2 virus, suppliers of various instruments and supplies, etc..., not to mention the politics and human biases that go into doing "science" where the results matter and there are various incentives for finding the "right" results.

If an accountant wants to be frightened, take a look at "The Irreproducibility Crisis of Modern Science" below:

https://www.nas.org/reports/the-irreproducibility-crisis-of-modern-science/full-report

In 2005, Dr. John Ioannidis argued, shockingly and persuasively, that most published research findings in his own field of medicine were false. Contributing factors included 1) the inherent limitations of statistical tests; 2) the use of small sample sizes; 3) reliance on small numbers of studies; 4) willingness to publish studies reporting small effects; 5) the prevalence of fishing expeditions to generate new hypotheses or explore unlikely correlations; 6) flexibility in research design; 7) intellectual prejudices and conflicts of interest; and 8) competition among researchers to produce positive results, especially in fashionable areas of research. Ioannidis demonstrated that when you accounted for all these factors, a majority of research findings in medicine—and in many other scientific fields—were probably wrong.

Ioannidis’ alarming article crystallized the scientific community’s awareness of the reproducibility crisis. Subsequent evidence confirmed that the crisis of reproducibility had compromised entire disciplines. In 2012 the biotechnology firm Amgen tried to reproduce 53 “landmark” studies in hematology and oncology, but could only replicate six. In that same year the director of the Center for Drug Evaluation and Research at the Food and Drug Administration estimated that up to three-quarters of published biomarker associations could not be replicated. A 2015 article in Science that presented the results of 100 replication studies of articles published in prominent psychological journals found that only 36% of the replication studies produced statistically significant results, compared with 97% of the original studies.

Ioannidis is a truth teller, and I really enjoyed hearing him talk at my hospital a few years ago.

I don't think the FDA relies on the SI that much, but it's important to show a drug theoretically has a large "therapeutic window" where the drug works but doesn't cause harm.

Yeah, sure, but remember if a compound is so ineffective that it doesn't inhibit 50% of the virus compared to control (e.g. aviptadil/VIP), the SI is undefined.

Some reading on SI here:

https://www.researchgate.net/post/Why_do_we_have_to_measure_IC50_CC50_and_SI

We use IC50 to determine the minimum inhibition concentration for inhibiting 50% of the pathogen and CC50 as the Cytotoxic concentration of the extracts to cause death to 50% of viable cells in the host. These are measured through dilution assays of your extracts added to virus infected host cells.
In the Ideal situation you want to have your IC50 concentration below your CC50 concentration and your CC50 and MNTD as high as possible. This would mean that you kill the pathogen before killing the host; as an example - if the IC50 is 0.1g/L and the CC50 is 100g/L then your host won't suffer any adverse effects if treated with the extracts.
These are important factors to consider when developing anti microbial compounds.
SI = CC50/IC50
SI is a index value that gives you an idea about the selectivity. You need this to be a high value number which means that you achieve killing the virus before your host, i.e. the compound has selectivity towards your virus and not your host.

Safety of the 2200 SI was done in cells, not in animals, so no bloodstream involved. It was found to be safe in monkey kidney cells at doses that were effective in stopping SARS2 replication (or killing of the cells, depending on which "assay" or test they used). I think you are right though, that like brilacidin rinse in the mouth or other end, the dendrimers don't enter the bloodstream at doses used.