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Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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January 20, 2010

A Database of Side Effects

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Posted by Derek

There's probably a lot of undiscovered information sitting out there in clinical trial data sets. And while I was just worrying the other day about people with no statistical background digging through such things, I have to give equal time to the flip side: having many different competent observers taking a crack at these numbers would, in fact, be a good thing.

Here's one effort of that sort, as detailed in Molecular Systems Biology. The authors have set up a database of all the side-effect information released through package inserts of approved drugs, which was much more of a pain than it sounds like, since the format of this information isn't standardized.

Looking over their data, the drugs with the highest number of side effects are the central nervous system agents, which makes sense. Many of these are polypharmacological; I'm almost surprised they aren't even worse by a wider margin. Antiparasitics have the fewest side effects (possibly because some of these don't even have to be absorbed?), followed by "systemic hormonal preparations". To be fair, the CNS category has the largest number of drugs in it, and those other two have the least, so this may be just a sampling problem. At a glance, one category that seems to have a disproportionate number of side effects, compared its number of approved drugs, is the "genitourinary/sex hormone" class, with muskoskeletal agents also making a stronger showing than their numbers might indicate.

Comments (15) + TrackBacks (0) | Category: Clinical Trials | Toxicology


1. PharmaHeretic on January 20, 2010 11:01 AM writes...

In previous ages "side effects" were developed into new drugs.. now MBAs and lawyers make sure that it does not happen (admitting liability).

Consider that anti-pyschotics, tricyclic antidepressants and the first synthetic anticholinergics were developed from the antihistamine pharmacophore, as was the accidental discovery of synthetic opioids. Mustard gas led to
Mechlorethamine. Heck even the cytotoxic effects of radiation were discovered as a "side effect"

The adverse effects of anti-bacterial sulfonamides led to carbonic anhydrase inhibitors and sulfonylureas.

The use of PDE5 inhibitors for ED and the usable immunosupressive effects of low dose anti-cancer nucleotides were also a new use of "side effects"

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2. Strauss Wagner on January 20, 2010 11:39 AM writes...

Exactly, what we must avoid is that television is not a negative influence on our children as they rely on the attitude and performance of individuals who are on television, there are many cases like the House that by their addiction vicodin has led to people using this medication and this is proven in the U.S., since 40% of the American population is assiduous to this medicine and is caused by the influence that Dr. House at the time, as indicated findrxonline in his article that this medicine is dangerous if not properly due to moderation.
Hopefully, the media are aware that an important means of educating future generations.

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3. anonymous on January 20, 2010 12:12 PM writes...

How exactly posts like #2 struuss wagner are generated ? Must be some software running through blogs related to medecine/drugs etc. and composing some random sentences which incorporate a key name of the medication. But what is the purpose of this activity ? does it really work and promote stuff ?

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4. SP on January 20, 2010 12:34 PM writes...

Reading such gibberish gives you such a painful headache that you want some Vicodin.
Almost every HTS we've run has at least one tricyclic antidepressant come up as a primary screening hit.

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5. Cloud on January 20, 2010 12:41 PM writes...

anonymous #3- I'd guess that the purpose of those semi-coherent machine generated posts is not to fool human readers, but to fool other software. Modern search engine algorithms use links to a web page page to help determine how high up in the search results it is displayed. They also look at the context of the link.

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6. David on January 20, 2010 1:26 PM writes...

I'd guess that CNS drugs have the highest number of Adverse Effects (the correct term) partly because we have a diverse experience of brain function. If function is disrupted in different parts, we get different effects. In contrast, for example, if you get ischemia anywhere in the heart, you get pain. The number of terms we have to describe brain-related disorders is much greater, reflecting that we are "CNS splitters" and "everything else lumpers."

It is grossly unjustified to compare AEs accross studies of different designs, in different populations, and in different sociologic contexts.

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7. barry on January 20, 2010 1:49 PM writes...

one of the other great stories of an "adverse effect" exploited is cyclosporin-A, first found in an anti-fungal screen. Not as profitable as sildenafil, but perhaps more important in the grand scheme of healthcare.

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8. Anonymous on January 20, 2010 1:51 PM writes...

#3 - These things remind me of that automatic computer science paper generator thats been running around for a while now. Step 1) Pick random prases with big words step 2) string'em together and hope for the best.

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9. darwin on January 20, 2010 2:55 PM writes...

Rough day today. I think I will open my desk drawer for a jigger of side effect.

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10. CMCguy on January 20, 2010 3:36 PM writes...

RE statement "much more of a pain than it sounds like, since the format of this information isn't standardized." I would take observation a step further because often terms and definitions can not be precise/identical at different companies/departments and even within FDA/individual reviewers. I have seen MDs argue about AEs but (to me at least) was all about semantics not substance. I know there are many guidelines for Clinical Trials reporting however such conventions appear to get scrambled in label claims after others groups have their say.

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11. biobug on January 20, 2010 4:14 PM writes...

Quick comment on the database, after a short look it appears they don't capture any black box data, and are missing some other things... Probably better to have no database and just stick to checking labels.

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12. Late Fred on January 20, 2010 5:06 PM writes...

anonymous (#3), those posts are not intended to fool people. Their purpose is just to generate a lot of hyperlinks from reputable sites to their sales one. Google's index considers sites "better" when they are linked from a lot of places, so the idea is that the sales site will move higher in the Google rankings and improve its sales that way.

This doesn't work very well, for a few reasons. One is that Google's crawler is slowly getting better at detecting and ignoring comment spam. Another is that humans are so good at noticing and deleting it before it ever has any effect on the rankings.

If you want details on how the text is built, do a web search for: Markov text generator

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13. Vittorio Montanari on January 20, 2010 6:54 PM writes...

There is a post by Google's Director of Research on the nature of "effects" on his site

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14. befuddled on January 21, 2010 9:00 AM writes...

Surprising. I had always thought of the antiparasitics as pretty nasty drugs as a class.

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15. PeterC on January 21, 2010 1:07 PM writes...

I'd say one of the reasons antiparasitics aren't that harmful is that they are ment to bind pathogen protein.

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