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s_r_constantin's profile
Sarah Constantin
Sarah Constantin
Sarah Constantin
@s_r_constantin

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Sarah Constantin

@s_r_constantin

Math/ML/data-science person now working on solving aging...and helping with COVID19?! Founder, LRI and Daphnia Labs. Married to @oscredwin

Be
srconstantin.posthaven.com
Joined February 2019

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    1. Sarah Constantin‏ @s_r_constantin 10 Jun 2019
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      Eroom's Law is Moore's Law spelled backwards. It's the bitter name in the pharma industry for the fact that R&D costs per drug have been steadily rising since the 1950's.

      2 replies 11 retweets 35 likes
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    2. Sarah Constantin‏ @s_r_constantin 10 Jun 2019
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      The famous Nature review article "Diagnosing the decline in pharmaceutical R&D efficiency" offers a model as to why. http://lukemuehlhauser.com/wp-content/uploads/Scannell-Diagnosing-hte-decline-in-pharmaceutical-RD-efficiency.pdf …

      1 reply 0 retweets 4 likes
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    3. Sarah Constantin‏ @s_r_constantin 10 Jun 2019
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      Drug development is a series of experimental filters (the pipeline) that narrow down a huge collection of potential molecules to the few that actually can be used to treat a disease.

      2 replies 0 retweets 3 likes
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    4. Sarah Constantin‏ @s_r_constantin 10 Jun 2019
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      The development of high-throughput screening in the 90's automated the first few and allowed us to test far more molecules in parallel. BUT, the chance that any compound succeeds in clinical trials has been CONSTANT since the 1950's.

      1 reply 0 retweets 1 like
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    5. Sarah Constantin‏ @s_r_constantin 10 Jun 2019
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      The funnel has been made at least a thousand times larger; initial screens now look at millions of compounds, compared to thousands in the days before HTS.

      1 reply 0 retweets 0 likes
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    6. Sarah Constantin‏ @s_r_constantin 10 Jun 2019
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      Since there's been no improvement in the rate of clinical trial success, this tells us that the highly automated modern preclinical pipeline is thousands of times *less predictive* than the old manual process was.

      1 reply 0 retweets 3 likes
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    7. Sarah Constantin‏ @s_r_constantin 10 Jun 2019
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      The authors cite "molecular reductionism" as a related problem. "Nearly all drugs are sold with a biological story...“drug x works by binding receptor a, which influences pathway b, which adjusts physiological process c, which alleviates disease d.”"

      1 reply 0 retweets 2 likes
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    8. Sarah Constantin‏ @s_r_constantin 10 Jun 2019
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      Obviously, most hypotheses of this form turn out to be false. A drug discovery process that starts with screening for molecules that bind a target will be futile if the disease does not depend solely on that target (which is usually the case.)

      1 reply 0 retweets 2 likes
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    9. Sarah Constantin‏ @s_r_constantin 10 Jun 2019
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      Of course, this is what target validation is meant to discern, and there's a lot of good science in this field. But failure is normal in science.

      1 reply 0 retweets 0 likes
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      Sarah Constantin‏ @s_r_constantin 10 Jun 2019
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      The target-based paradigm means that, for instance, basic researchers were making discoveries that raised doubts about the amyloid hypothesis of Alzheimer's *decades* before amyloid-targeting Alzheimer's drugs failed in the clinic. That's expensive.

      9:25 AM - 10 Jun 2019
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