5 ms·

QSAR sounds very interesting, if I encounter a failure in later stages of drug development - can I feed that information back to the model? See I'm trying to un

• dalke 10y ago
  As with just about everything to do with chemistry and drug development, the answer is "maybe". It depends on the model, it depends on the failure, it depends on so many different factors. For example, it may be that in human trials the new drug X is better than nothing, but not as effective as an older, generic drug A, which costs $0.10 per pill. That's a market failure, but it's not possible to feed that back into the model. Or, look at the TGN1412, where all 6 volunteers for first-in-man Phase 1 tests has to be hospitalized; 4 with multiple organ disfunctions and may never fully recover. That doesn't require a simple fix to the existing model, but a investigation into how the underlying mechanism works. But in general, yes, absolutely the information is fed back into the development process. That said, I can make no sense of your analogy to unit testing. Drug molecules aren't meaningfully decomposed into individual units that can be tested, and a modification in one structure which may be deleterious may be beneficial if done to another structure. There are rules of thumb ("Rule of 5", "magic methyl"), and more statistics-based model ("Free-Wilson model", "matched molecular pairs"), but they do not ensure that there will/won't be a problem, only enrich the likelihood of finding what you are looking for. Hopefully. Based on what you've written, including your lack of knowledge of QSAR, no, I don't think you know much about drug development. You have a new account, so I will explain what my comment means. At HN, the readers are also semi-moderators. By making my comment, I was doing the first step towards "contact[ing] the administrator", and letting the submitter (that is, you), know that it is a poor fit for HN. The HN guidelines say that topics should be on "Anything that good hackers would find interesting." I am a good hacker. I also write software for drug development. I did not find the piece to be interesting. I found it to be dismissive of the hundreds of thousands of people who have worked in drug development, and long ago put iterative processes and quality control methods in place. I guess if you don't like my comments, you too can file a complaint with the administrator. I will continue to criticize articles that I think have little understanding of topics that I know something about.
  • osharav 10y ago
    Fair enough, although I think that discussing and further thinking about that analogy might be able to create new insights. I find it unfortunate that in addition to highly interesting information you've shared, you have also chosen to make destructive criticism about my attempt to find touch points between software and drug development. See, software development, the way I see it, is based on sharing, via open source, but not only. The culture it induces is of being open, to new ideas and to constructive criticism. > Drug molecules aren't meaningfully decomposed into individual units It's not about the molecules - it's about the tests. Envision a state where you could say - "oh dear, 6 volunteers for first-in-man Phase 1 tests had to be hospitalized - let's find a lab test, or a change in the model which would predict a positive result for the structure we've tested and negative result for other structures which do not cause that condition". The individual units don't have to be the molecules, they can also be the tests. You would argue, and rightly so, that finding such a test is hard/impossible. And I would agree but the whole article is about defining the problem - and because in software development, when making a small bug fix - you are not after making the entire system work, rather a tiny fraction of it better apt for a new condition you did not take care of earlier. > the answer is "maybe" When uncertainty is high - wouldn't you want to strengthen the tools that allow you to know at least that the failures you've already encountered won't happen again? I find it also unfortunate that you think my article is dismissive of efforts made by countless people before me. I had and have no such intention.
    • dalke 10y ago
      If you think my comments are "destructive criticism" then I invite you to post to a medchemist's site, like Derek Lowe's, or present at a medchemist's conference and see the responses you get. By giving you all these pointers I am trying to provide the "constructive criticism" you say you want. I am also trying to establish my bona fides, so you might have a chance of accepting as true my statement that you've offered no insights which were not already known a century ago. It's not like the concepts underlying unit testing didn't exist before CS developed them. And I have no wish to put up with an eternal September here on HN when some enthusiastic engineer thinks the methods from that field can be moved over to drug development. It very similar to what Lowe, above, calls the 'Andy Grove fallacy' - http://blogs.sciencemag.org/pipeline/archives/2015/04/02/silicon_valley_sunglasses http://blogs.sciencemag.org/pipeline/archives/2015/04/02/sil... . Also, there's an entire field for the theory of the design of experiments: https://en.wikipedia.org/wiki/Design_of_experiments https://en.wikipedia.org/wiki/Design_of_experiments . These are used in drug development. Perhaps it's software development which should incorporate ideas drug development, and not the other way around.