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Why huge gains in drug discovery tech have led to longer drug development times

73 点作者 blaurenceclark大约 9 年前

9 条评论

tominous大约 9 年前
The authors argue for using better predictive models to screen drugs at an early stage, because too many drugs are failing at costly clinical trials.<p>In my opinion we already know the best predictive model to use, but we choose not to use it. When Jenner developed the first vaccine back around 1800 he didn&#x27;t use any petri dishes or mathematical models: he just found some nearby children and tested his theory directly.<p>Now you may find this ethically repulsive but from a consequentialist point of view it was the right thing to do at the time. This line of research saved hundreds of millions of lives.<p>I say we have gone too far in the other direction. The problem with failed costly clinical trials is not the failure per se but the cost: in money spent, time, reputation, commercial return, legal consequences, etc. And the hidden cost of how long the whole process takes even if successful.<p>Take the field of monoclonal antibodies. We now have almost off-the-shelf technology to develop drugs that specifically block certain biological mechanisms. But it still takes 10-15 expensive years to progress through different lab and animal models, then healthy humans, before clinical trials on actual patients.<p>Instead we should reduce the cost of human trials: have a network of terminally ill volunteers to test mabs at an early stage. Fail fast to move fast. Use the money saved to offer defined compensation when things go wrong.<p>The drugs that we really want to find are the ones with an obvious effect on real patients. This process would find those drugs much faster, and save lives overall.
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skyhatch1大约 9 年前
In the early days, most drug discovery (while amazing for its time) covered comparatively simpler diseases with arguably less complex physiological and pharmacological models i.e. low hanging fruit. Many of these diseases (e.g. Type 2 Diabetes) are still improperly addressed to this day. But they are not as lucrative for today&#x27;s pharmaceutical company as they used to be in simpler times.<p>Governments and insurers are too astute to pay excessively for incremental improvements in mass or lifestyle disease categories. It makes more business sense for Big Pharma to target complex, hard-to-cure diseases that affect a small population set. While the success rate for such molecules is much lower, it&#x27;s also much harder for payers to apply their usual mass-oriented drug economics to them.<p>One of the better examples of this is the recent introduction of Hep C &quot;curing&quot; drugs. Sponsors are going uncontested in pricing their molecules up to $84,000 per patient year[1,2].<p>With 3 million patients in the US alone, that&#x27;s a TAM of $252 billion per year. For one drug category.<p>References:<p>[1] <a href="http:&#x2F;&#x2F;hepatitiscresearchandnewsupdates.blogspot.com&#x2F;2014&#x2F;03&#x2F;democratic-leaders-request-briefing-by.html" rel="nofollow">http:&#x2F;&#x2F;hepatitiscresearchandnewsupdates.blogspot.com&#x2F;2014&#x2F;03...</a><p>[2] <a href="http:&#x2F;&#x2F;www.grassley.senate.gov&#x2F;news&#x2F;news-releases&#x2F;senators-seek-details-sovaldi-pricing" rel="nofollow">http:&#x2F;&#x2F;www.grassley.senate.gov&#x2F;news&#x2F;news-releases&#x2F;senators-s...</a>
refurb大约 9 年前
<i>Gerhard Domagk tested his few hundred drug candidates in live mice with bacterial infections. The recent attempts started with single bacterial proteins in a tiny dish.</i><p>This goes back to the phenotypic screening argument.<p>Unless your biological model captures most of the factors involved in a biological system, it&#x27;s not worth much. You might get a great hit, then put it in an animal model and get nothing.<p>There are a ton of examples of the value of phenotypic screening in past drug discovery. The discovery of benzodiazepines (Valium, etc) was completely random. Hoffman created some new molecules and just injected them into mice. When the mice fell asleep, he followed up on it.<p>Of course, phenotypic screening is not a panacea. It&#x27;s expensive and has problems of it&#x27;s own.
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blaurenceclark大约 9 年前
My co-founder and I interviewed Jack Scannell and Jim Bosley, two renowned researchers, for this article on the state of drug development and Pharma.<p>If you have any follow on questions, we&#x27;re meeting with Jack again next week and would be happy to add any more information on this topic!
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kumarski大约 9 年前
In short, this paper calls for &quot;Do more math on the front-end of the pipeline.&quot;<p>The core issue is that CEOs of biopharmas aren&#x27;t compensated as such, so if you were to go to one with mathematical techniques that would take 3 to 6 months to run, (Combining research, bioinformatics, and diff EQ) they would look at you like you&#x27;re crazy because the timeline and their incentivization is skewed toward not failing a trial.<p>Trials exceed CEO lifetime, and that&#x27;s one core issue as to why pharma development isn&#x27;t done this way today.
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cvarjas大约 9 年前
Great article. I&#x27;ll be sharing this with some colleagues that work in drug discovery.
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kidsil大约 9 年前
We&#x27;d like to think that we&#x27;re a modern civilization, with systems in place, and the right priorities when it comes to life saving research &amp; development.<p>In reality, we&#x27;re barely out of the caves.
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mirimir大约 9 年前
tl;dr They can look for the wrong things, very quickly.<p>This is the classic <a href="http:&#x2F;&#x2F;quoteinvestigator.com&#x2F;2013&#x2F;04&#x2F;11&#x2F;better-light&#x2F;" rel="nofollow">http:&#x2F;&#x2F;quoteinvestigator.com&#x2F;2013&#x2F;04&#x2F;11&#x2F;better-light&#x2F;</a>
searine大约 9 年前
Wow that is one amazing PLOS one article.