Monday, May 02, 2016

Things I didn't learn in medical school: Vertigo

About two years ago I had a sudden onset of vertigo. Between my wife (a family doc), my family doc, and me (also a family doc, albeit lapsed) we couldn’t tell whether it was “viral” labyrinthitis or “benign” positional vertigo. The more I read and experienced the less I felt there was a clear difference; there’s an ENT folk belief that the “benign” condition follows the “viral”.

Yes, the “quotes” are there for the usual reason. The more I get to experience diseases from the inside (yay oldness) the more my textbooks seem delusional. The semicircular canals (labyrinths) have a circumference around a cm. I couldn’t find any diameter on the average cross-section diameter of the actual canal, but illustrations suggest it’s on the order of microns. Even the very best research scanners cannot resolve these canals, much less the microscopic hair cells within them. The otoliths within our utricle and saccule are about 3 to 30 microns and can only be seen with a high resolution microscope. 

We really have very little idea what’s going on in the canals of someone with vertigo. We’re making this stuff up. (Hain’s article is more honest than most.)

My acute vertigo lasted a day or so. I had to delay a trip and I put off driving for several days. It was just as unpleasant as one might imagine, but short-lived. Many people live with far worse vertigo for much longer. 

Except it wasn’t as short-lived as I expected. After the first few days I couldn’t induce the characteristic nystagmus eye movements but I still felt “off”. I could induce a feeling of imbalance by shaking my head. My walking required much more attention than I was used to, though I had no problems with running. I couldn’t close my eyes and balance on a single leg (bit of a severe test for many at my age).

Most days I no longer notice these symptoms. I think that took about a year of extremely slow improvement with occasional worsening; Epley exercises (there are many variants) might have helped. I don’t know if the (presumed) insult to the hair cells resolved or my brain compensated for them or both; I suspect it was at least as much compensation as it was healing. I don’t think my closed eye single leg balancing is as good as it once was. I’ve taken a step to the fall-prone imbalance of infirmity (yay, age).

Living inside my relatively minor (so far) experience with vertigo taught me two things I didn’t learn from my textbooks. One is that our classifications of transient vertigo (positional, inflammatory, viral, etc) are probably bogus (not the only example). Another is that the symptoms may take months (years?) to resolve - or adapt to. Even knowing this I couldn’t easily find references on duration of post-vertigo symptoms, I found very few references, and they seemed to only deal with acute symptoms.

Our system of producing and disseminating medical knowledge is quite broken.

Tuesday, April 26, 2016

World center of Eckankar cult is 1km from Prince's Paisley Park

Temple of ECK is top right, Prince’s Paisley Park facility and residence is bottom left, Lake Ann Park lies between them. The bland suburb of Chanhassen Minnesota has secrets.

Screen Shot 2016 04 26 at 9 58 40 PM

Tuesday, April 19, 2016

US programs for physicians reentering clinical practice.

I’ve been out of clinical practice for about 17 years. On the other hand I have a current license and I did well on my board exams a few months ago. I believe I could do above average work, but I’d want a few months of supervision. I can think of a few ways to manage this, including designing a mini-curriculum and following the post-employment path of a fresh physician assistant. 

A formal program for physician reentry would be interesting, but there aren’t any in Minnesota. Which sort of suggests we don’t have a serious shortage of primary care docs. We do have some local fellowships that might be interesting reentry paths, but they currently fill well with post-residency candidates.

I haven’t decided to pursue this direction, but at a recent meeting I asked the Minnesota Medical Association’s president what he knew of. Their policy counsel made up a short list, and as I’ve not seen it online I’ll share it here:

There’s a longer list in a Federation of State Medical Boards PDF, many of the programs deal with “ethics”, “boundaries”, “disruptive behavior”, prescribing controlled substances, and “anger management”, but a few simply focus on “reentry” (though, on visiting the web sites, even they seem mostly to deal with what we call “disciplinary issues”). The Cedars-Sinai program seems closest, but it’s primarily focused on hospital privileges.

I haven’t decided to go down this path, but it’s helpful to know the landscape.

Monday, April 18, 2016

My project management tools - April 2016

Early in my post-corporate days I wrote a detailed post on how I expected to do project management going forwards. Since then I’ve experimented with various tools and services.  

Today I updated a Simplenote/nvAlt [1] summary of my project management tools including how I archive completed (or abandoned) projects. All of these tools have multiple substitutes on iOS, Android, Windows and MacOS so I’m hopeful this toolset approach should work for years to come. Sometime I’ll write an update on my methodology, it basically shifts between Agile-Kanban and Agile-Scrum. Lately more Kanban than Scrum, but I go back and forth.

- minimize proprietary data formats and data lock (or at least tool lock) - always have an exit strategy
- archived indexable by Spotlight
- easy backup and restoration [Trello fails here, it’s the tool I’m most likely to replace.]
- integrated with Google Calendar
- scales to single person or team projects
- formal project archiving process

- create a folder in Project hierarchy
- in some cases also have a shared Google Drive folder
- I don’t make much use of Tags in MacOS at this time.
- Mac file folder has aliases to nvAlt Simplenote, Trello (URL), MindNode (in iCloud Drive), may contain Scrivener files if a writing project, presentation files, etc.

Simplenote/nvAlt (iOS, Web, MacOS)
- Create a simplenote entry for the project, tag it with project.
- Simplenote title has prefix “Project: “
- Describe the project and where things are
- Define project tags: use tags in OS X file system
- project tags have prefix p_
- save as text file in project folder when completed

Trello - Agile Project Management (iOS and Web) (review)
- create Board for Project
- 2 lists: Queue, Active
- when Task/Card Done archive it
- Milestone Cards have dates
- Cards can have checklists
- Subscribe to Calendar on gCal
- Print as PDF when completed and export JSON

MindNode (MacOS and iOS)
- release planning, hierarchy, overview of project (alt OmniOutliner)
- store in iCloud drive but create shortcut
- export to PDF when completed

Scrivener (MacOS)
- for writing projects

Google Calendar (Trello project calendar, iOS, MacOS)
- scheduling and time/capacity management
- project calendar to PDF when completed

Google Drive (iOS, MacOS)
- for collaborative file sharing projects

Email (iOS, MacOS)
- Gmail with web interface and MacOS IMAP client.
- Drag and drop selected emails from to desktop (creates standard file) to a folder in MacOS project (“Mail Archive”) 
- Careful use of Subject lines to optimize search, typically I don’t file emails or use tags with emails. 

- fn - 

[1] nvAlt is post-maintenance but it still works on El Capitan. Simplenote still has active development, but search has been broken on the Mac app for over a year. I’m not worried because I keep all my notes in plaintext; I have multiple exit strategies. (Not including Apple, it needs an exit strategy, a backup strategy, and significant updates. None of which I expect from Apple in its current state).

See also:

Sunday, April 17, 2016

Boxer shorts for bicycling

Cyclists are supposed to ride ‘commando’ — nothing between cycling short padded lining and the butt.

Me, I don’t like to wash my cycling shorts that often, and sometimes I just ride with regular shorts. I prefer to wear synthetic fabric boxer shorts without seat area seams. I have a few pairs I’ve picked up over the years, but they’re no longer sold. I’ve had a hard time finding seamless shorts. Web sites generally show the front, not the back.

Today I searched harder. After digging past the typically useless few pages of Google pay-to-play-adsearch results here are the options I found, mostly in comments on a Lazy Randonneur blog post

  • BOSS cyclist stretch cotton boxer briefs. These are cotton unfortunately. $28 for 3.
  • ExOfficio Give-N-Go Boxer Briefs 1241-0020: Blog post. Designed for easy wash/dry, supposedly no seams in contact zone. $23 each. Top selling mens boxer briefs on Amazon. (Amazon has several versions of this underwear, but only one appears on the ExOfficio site. I think a number may be counterfeit, this one is sold by Amazon itself so probably genuine.)
  • MEC merino briefs/T1 boxer briefs: Canada only alas.
  • Devold multi sport boxer briefs: Blog post. Expensive Norwegian merino wool briefs sold by Rivendell cycle. About $40.
  • Bent Scivvies: no longer sold as far as I can tell, once a Target store brand label. These sounded ideal

I ended up ordering one pair of ExOfficio and the set of 3 BOSS underwear. I’d love to find a Target or Walmart equivalent…

PS. I have a vague memory that back in the 70s male cyclists used to wear seamless women’s panties? Probably a false memory. Was a long time ago. I never had the nerve to try.

Monday, April 11, 2016

Apple's CareKit (HealthKit) - what kinds of clinical data does it work with?

I thought Apple had given up on HealthKit, but recently we learned that it’s been rebranded as CareKit and it seems to be going forward.

Since my professional work is in “health informatics”, specifically medical knowledge applications, I was curious what “ontology” (data dictionary, terminology, etc) Apple was using for it’s CareKit work. The concept set is somewhat hidden within Apple’s HealthKit Constants Reference documentation. I auto-expanded the symbols (nice web app Apple!) and make a quick pass at organizing the strings.

For someone like me it’s a fascinating set. The discussion of privacy and FDA device identifiers is noteworthy — in an early implementation it was apparently possible to trace HealthKit data to an individual device (not good, obviously - bold below).

I liked the use of Fitzpatrick Skin Type instead of trying to describe ethnicity/race.

It’s a fun list to scan:



HKBiologicalSexNotSet = 0

HKBloodTypeNotSet = 0


HKCategoryValueCervicalMucusQualityDry = 1

HKCategoryValueMenstrualFlowUnspecified = 1



HKFitzpatrickSkinTypeNotSet = 1



HKWorkoutActivityTypeAmericanFootball = 1

HKWorkoutSessionLocationTypeUnknown = 1

Wednesday, April 06, 2016

Old broken person CrossFit - it's fun. Really.

The experimental results are in. Under optimal conditions I can do a CrossFit WOD 4 times in five days and not be obviously injured. 

That’s no trick for under 30, but over 55 there’s a fuzzy border between enough and too much. Shoulders, knees, wrists (again), butt tendons and backs take turns being funky. Not to mention errant barbell strikes. And the unrelated arthritis.

Yeah, that does sound kind of grim, but the body does some of that just sitting around. The knees were from mountain biking, and the piriformis problem was hockey. With my genes, being old* and active is experiential sports medicine.

I like it though. I even like putting a toe over that fuzzy border once in a while.

I don’t want injuries to bench me though, so here’s my year 3 of CrossFit recipe for staying more or less out of trouble. 

  • 3 “Workout of the Day” (WOD) every week. Sometimes 4, but I was pushing things this week.
  • My WOD target is “Women’s Rx”. I can do that for some movements and weights. This tends to be close to the men’s “master’s Rx” of competitive CrossFit. Muscle fatigue is my main weakness, I think that’s true of most 40+.
  • I listen to my coaches. They have good advice.
  • 1-2 Open Gym workouts - a light version of a WOD or a special movement or muscle group. Like $*&^% double-unders or bar muscle ups or handstand pushups.
  • I started taking one of those whacky protein supplement powders after my big workouts. You can blame that on a recent publication that showed it helping in a small trial of exercise and weight loss. It includes magical arthritis supplements that I’m supposed to take anyway (though they probably don’t do anything)
  • Hockey and/or Mountain Biking 1-3 times a week (sub Nordic Skiing**, road biking, swimming, running, underwater hockey, etc)

I think I can keep that going for a few years more, depending on what surprises age brings. I’ve learned that the researchers are right, the body adapts to exercise by increasing energy efficiency — diet is still a challenge. I can’t survive doing CrossFit at the frequency needed to balance my calorie intake, so it has to be supplemented by calorie burning activities that are easier on the old body (bicycling, hockey, etc)

It really is fun.

* 50 is not the new 30. Sorry. Don’t talk about 80. Please.
** Nordic Skiing was my all-time favorite exercise. I’m not a global warming fan.

See also:

Thursday, March 17, 2016

The Obama doctrine -- I will so miss our Vulcan President

From the Obama Doctrine, quoting the President:

… Right now, across the globe, you’re seeing places that are undergoing severe stress because of globalization, because of the collision of cultures brought about by the Internet and social media, because of scarcities—some of which will be attributable to climate change over the next several decades—because of population growth…

… As I survey the next 20 years, climate change worries me profoundly because of the effects that it has on all the other problems that we face. If you start seeing more severe drought; more significant famine; more displacement from the Indian subcontinent and coastal regions in Africa and Asia; the continuing problems of scarcity, refugees, poverty, disease—this makes every other problem we’ve got worse. That’s above and beyond just the existential issues of a planet that starts getting into a bad feedback loop.

By “collision of cultures” I think he means “existential threats to patriarchy” — because he’s obviously reading my mind. Must come with his Vulcan heritage.

We are never ever going to get another President this good (even though he’s wrong about encryption). HRC isn’t bad, but she’s no Obama.

Using Gmail and the link to correspond with patients -- HIPAA 2013 clarification

HIPAA is designed to protect patient confidentiality. It’s widely misunderstood, not least because of the scary fines for violations. I think on balance it’s a good law, but it needs regular adjustment.

Happily in 2013 a major adjustment was made. Rule makers allowed use of conventional email applications, perhaps without robust encryption, for patient communications if informed consent is given and recorded. I recently put together a set of references on this:
Covers the 2013 final rule changes.
Pretty good discussion of implications
Example of a patient consent to receive unencrypted email‐2013‐01‐25/pdf/2013‐01073.pdf
HIPAA language is on page 5634 (I didn’t confirm this, just copied from the Austin Med Clinic consent form.

I’d still worry about risks associated with using Gmail (though communication is now actually well encrypted for most users) — the message will be both sender and receiver’s server forever unless it’s deleted. Tricky business!

Still, it’s encouraging to see this clarification. I hope the HIPAA rules continue to be adjusted. Having robust encryption built into laptops helps — at least until the FBI forces backdoors which will, of course, be widely exploited by hackers.

Tuesday, March 15, 2016

Phenazopyridine (pyridium, AZO) - yet another example of missing research

Phenazopyridine is an old drug, discovered in the 1930s. Chemically it’s classified as an “azo dye”, these chemicals are usually used to color clothing. Phenazopyridine will stain clothing orange. Another Azo dye was once used a seizure med

Two-thirds of a dose is excreted unchanged in the urine (and sweat and tears), the rest is metabolized to unknown substances. It has some sort of anesthetic action on the urinary tract, we don’t know how that works. “Trace amounts” may enter the cerebrospinal fluid. With prolonged use there is injury to both liver and kidney.

Historically phenazopyridine was prescribed for use in the very early stages of a bladder infection, before antibiotics did their job (since it’s older than antibiotics I suspect it was used heavily in the past). It’s over the counter now, to be used for one to two days.

Except some patients use phenazopyridine for longer than a few days. Interstitial cystitis is particularly nasty syndrome. Like many poorly understood disorders (osteoarthritis, autism, etc) it’s probably several different disorders that share common features. One pattern of interstitial cystitis causes severe sleep disruption; patients wake up to void every 10 to 60 minutes with very small volume urination. On bladder biopsy the protective lining of the bladder has been disrupted. 

Sleep deprivation is a well understood and effective form of torture, so it’s not surprising that IC patients get a bit desperate (you would too). Phenazopyridine may allow sleep when all else fails. So it’s used more than it should be, especially since it’s available without a prescription.

Since phenazopyridine has an anesthetic effect, we presume it interacts with the peripheral nervous system.  So what happens to the brain with large lifetime doses of phenazopyridine? I can’t see that this has ever been investigated, even in animal models.  Tartrazine, another azo dye used in food coloring, was associated with oxidative brain damage in one rat study.

Medicine is full of things like phenazopyridine. Medications that were adopted long ago, and have received minimal research review since. We could employ an army of scientists studying these drugs. But then we’d have to figure out how to pay for them…

Saturday, March 05, 2016

The Man's Book (1978)

I remember the early 1970s as quite odd - particularly based on the books of the time. I like to pick them up if I can find them, but I think others share my interest. I rarely see them in used book stores.

I remembered on recently. Actually, it’s late 70s, so not nearly as odd, but still quite a long time ago. The topic is what makes it interesting…

Blog  1

The Man’s Book was published in 1978 (ISBN-13: 978-0380018994). There were no later editions, though suspiciously similar books with the same name have been published more recently. I wonder if they just pilfered the original.

It’s a real cultural artifact, required reading for a historian of the era …

Blog  3


Blog  4

Some of the contents are very 1970s…

Blog  5

Most of it, however, still works today. That surprised me a bit, but really a lot changed between 1968 and 1978 and the book is written from a liberal perspective. It would have been a very different book if it were written in 1973.

The advice to a man on how to support a working wife is the most dated …

… If you say, “No wife of mine is going to work,” you’ll be considered antiquated …when you both work, something or someone is always getting neglected … The household is often on the brink of chaos …

… To make a two-career marriage work, you both need sensitivity, cooperation, flexibility, and a boundless sense of humor…

… In spite of women’s lib [ed note: at the time that would not have been meant sarcastically] when you run out of catsup … there’s no question, in your mind or hers, whose fault it is … you’ll make it easier on both of you if you pitch in and share responsibility for the household …

… it’s necessary to be willing to share power…

Dated, but perhaps not as dated as we might wish it to be. The rest of the book still kind of works. I’m going to hand it off to my #2 son…

Thursday, March 03, 2016

Everyone needs an AI in their pocket

Two articles from my share feed today …

Transit systems are growing too complex for the human mind

… “What makes it messy is the presence of different possibilities," Barthelemy says. "When you arrive at a specific point, you have many choices."

The Paris system has 78 such choice points. The New York subway, the most complex in the world, has 161. New York's system is so sprawling and interconnected, Barthelemy and colleagues Riccardo Gallotti and Mason Porter concluded in a recent analysis, that it approaches the maximum complexity our human minds can handle, the equivalent of about 8 bits of information.

“But then if you add the bus,” Barthelemy warns, “the 8-bit limit is exploded."...


Google Research: An Update on fast Transit Routing with Transfer Patterns

What is the best way to get from A to B by public transit? Google Maps is answering such queries for over 20,000 cities and towns in over 70 countries around the world, including large metro areas like New York, São Paulo or Moscow…

… Scalable Transfer Patterns algorithm [2] does just that, but in a smart way. For starters, it uses what is known as graph clustering to cut the network into pieces, called clusters, that have a lot of connections inside but relatively few to the outside…

… Frequency-Based Search for Public Transit [3] is carefully designed to find and take advantage of repetitive schedules while representing all one-off cases exactly. Comparing to the set-up from the original Transfer Patterns paper [1], the authors estimate a whopping 60x acceleration of finding transfer patterns from this part alone….

Humans can’t manage modern transit complexity — but the AIs can. Including the AI in your pocket.

Everyone needs a portable AI, including people with no income and people with cognitive disabilities. That’s one reason I’m writing my smartphone for all book.

See also:

Wednesday, March 02, 2016

Minnesota explained: Rubio, Sanders and the President Gordon agenda.

My home state of Minnesota, most annoyingly, uses caucuses. I attend the Dem variety in the bluest of neighborhoods. They are crowded, disorganized and well meaning. When I ride my bike to caucus cars slam to a stop as though I were a family of 5 on foot. Which is wrong and dangerous, but I appreciate the sentiment.

The Dem caucus is not representative of the Dem voter. You have to be very persistent to fight through traffic and crowds to hit the narrow window for voting. Only the most committed can get there. The caucus system is a bad, bad idea. I think the same is true of the GOP caucuses here.

So the caucus results last night were not too surprising.

The GOP, as usual, went for the extreme right candidates. This year there were three of ‘em - Trump, Rubio and Cruz. Since we have one of the strongest economies in the US, with unemployment under 5% for years, Trump didn’t have his usual vote-of-despair left-behind advantage. So the three extremes ended up with fairly similar numbers, but the anti-Trump movement focused on Rubio and he won.

My team went, as usual, for the more left candidate. Sanders won by 20%, so he might even have won a primary. I voted for HRC, but the MN DFL is effectively to the left of me — which is saying a lot.

I’m backing HRC but, in truth, we need to go down some variation of the Sanders road over the next two decades. We’re going to have to bias the post-AI globalized economy to generate jobs for the non-college — even at the cost of economic efficiency. We have to build more social supports for people who aren’t working, with some kind of rethinking of what we do for disabled workers. We may end up with a non-binary definition of disability, or even some kind of guaranteed income.

We will end up taxing wealth in one form or another and we’ll do a  lot more government redistribution. We should also, and this is not so much Sanders, execute on the old Gore “reinventing government” mission, refactoring regulatory systems. We need to break the accounting, tax and regulatory frameworks the mega-corporations (“neo-Chaebol is a term I like) have built; the foundations of a great stagnation ecosystem wherein new companies are built only for acquisition.

We need to build supports that enable entrepreneurial types to pick business designs off a shelf and implement them. We need to strip benefits from employment completely, and both fix and finish the mission the ACA started — while breaking the corporatization of that great compromise.

Phew. It’s a big mission, but it is doable. We have to do it, or we get President Trump. Or worse. Sooner or later. 

So I don’t feel that bad that Sanders won Minnesota. It’s a good sign for the future. I don’t want him to go up against the GOP though. By the time their attack machine is done with him he’ll be hiding in a stone shelter in the wilderness. HRC’s great strength is she’s lived that machine for decades. Nobody short of Obama can equal that. (And, of course, I would love him to keep his job. Alas, even if our constitution allowed that I think he’s ready for a change.)

See also:

Tuesday, March 01, 2016

Pediatric TMJ disorder and Developmental Dysplasia of the Hip: Separated at birth?

Early onset disruption of the Temperomandibular Joint (TMJ) reminds me of what we once called Congenital Dislocation of the Hip (CDH). That syndrome has since been better named as Developmental Dysplasia of the Hip. Untreated DDH is thought to result in severe early arthritis of the hip.

I wonder if early-onset (pediatric) TMJ syndrome should be renamed Developmental Dysplasia of the Temperomandibular Joint (DDTMJ).

I don’t see any hint of this in my PubMed searches though.


Saturday, February 20, 2016

Why Johnny can't make drugs any more ... we need better science from government.

I think of In the Pipeline’s Derek Lowe as a small ‘m’ marketarian. He has more confidence in the “invisible hand” of markets than I, but he’s not a believer in Rand’s Market Divine (the market that can do no evil, so long as government snakes are avoided). He combines critiques of big pharma CEOs with a robust defense of antibiotic development process.

Which may explain why he sort-off calls for more government funding of basic research — without quite getting there…

A Terrific Paper on the Problems in Drug Discovery | In the Pipeline

… Jack Scannell and Jim Bosley … “These kinds of improvements should have allowed larger biological and chemical spaces to be searched for therapeutic conjunctions with ever higher reliability and reproducibility, and at lower unit cost … in contrast many results derived with today’s powerful tools appear irreproducible; today’s drug candidates are more likely to fail in clinical trials than those in the 1970s … some now even doubt the economic viability of R&D in much of the drug industry [22] [23].

The contrasts ..between huge gains in input efficiency and quality, on one hand, and a reproducibility crisis and a trend towards uneconomic industrial R&D on the other, are only explicable if powerful headwinds have outweighed the gains [1], or if many of the “gains” have been illusory …

Shaywitz and Taleb wrote something similar about ten years ago (via Hensley, WSJ, emphases mine)…

… The molecular revolution was supposed to enable drug discovery to evolve from chance observation into rational design, yet dwindling pipelines threaten the survival of the pharmaceutical industry,” say consultant David Shaywitz and Nassim Nicholas Taleb, author of “The Black Swan: The Impact of the Highly Improbable.”

“What went wrong?” they ask in the opinion pages of the Financial Times. “The answer, we suggest, is the mismeasure of uncertainty, as academic researchers underestimated the fragility of their scientific knowledge while pharmaceuticals executives overestimated their ability to domesticate scientific research.”

When you get right down to it, Shaywitz and Taleb say, we still don’t understand the causes of most disease. Even when we think we do, because someone found a relevant gene, we’re not very good at turning the knowledge into a treatment. “Spreadsheets are easy; science is hard,” they tell Big Pharma.

I lived through this, including the 2nd failure of the genomic revolution. In retrospect the years from 1945 through the 1970s were a Golden Age of medicine. I did my medical science in 1982; for my generation the Golden Age was a baseline. We thought we understood so much …

By 2008 we all knew we had a problem. I’d been long out of practice and I was having to catchup on 7 years of medicine for my licensing exam. That turned out to be easier than expected. I wrote then about medications…

  1. Lots of new combinations of old drugs, maybe due to co-pay schemes
  2. Many new drugs have suicidal ideation as a side-effect.
  3. Lots of failed immune related drugs re-purposed with limited focal impact on a few disorders.
  4. Probably some improvements in seizure meds. Lots of new Parkinson’s and diabetes meds, but they’ve had limited value. (metformin was a home run, but that was more than 7 years ago).
  5. Really lousy progress in antibiotics; there are fewer useful therapies now than 7 years ago. Actually, fewer every year.
With Lowe’s latest we learn what has come from 8+ years of digging into our research flail (emphases mine):
… this paper is also a great source for what others have had to say about these issues, too (and since it’s in PLoS, it’s open-access). But the heart of the paper is a series of attempts to apply techniques from decision theory/decision analysis to these problems …
… Let’s all say “Alzheimer’s!” together, because I can’t think of a better example of a disease where people use crappy models because that’s all they have. This brings to mind Bernard Munos’ advice that (given the state of the field), drug companies would be better off not going after Alzheimer’s at all until we know more about what we’re doing, because the probability of failure is just too high…
… I’ve long thought that a bad animal model (for example) is much worse than no animal model, and I’m glad to see some quantitative backup for that view. The same principle applies all the way down the process, but the temptation to generate numbers is sometimes just too high, especially if management really wants lots of numbers. So how’s that permeability assay do at predicting which of your compounds will have decent oral absorption? Not so great? Well, at least you got it run on all your compounds…
… there’s no cure for the physical world, either, at least until we get better informed about it, which is not a fast process and does not fit well on most Gantt charts. Interestingly, the paper notes that the post-2012 uptick in drug approvals might be due to concentration on rare diseases and cancers that have a strong genetic signature …
… in drug discovery, we have areas that where our models (in vitro and in vivo) are fairly predictive and areas where they really aren’t…
I think what Lowe is telling us that we need more basic science work because drug development has raced ahead of the science-road it runs on. On the other hand, being a believer in markets and enterprise, he doesn’t quite come out and say that government needs to fund this work, even though he knows pharma won’t.
Or perhaps he has such a low opinion of current US government funded research that he doesn’t think our NIH will help. I see his point.  So we need government, but we need better government science …
It’s a tough one.
But… I just did my board exams again. Seven more years have passed. This time I had to learn more things. Maybe, when we look back, we’ll say that genomics science began to pay dividends around 2010. I think that’s not enough though. If the US is ungovernable, maybe we need to look for others to lead…

See also: