Irreverent Moment

One of the interesting things about my job is the chance to meet the staff of many different company in the pharmaceutical and life sciences sector. Just sitting in a meeting you can sense the culture of the company, and dare I say it, even the quality/skills/smarts of the company staff – there are tremendous variations. Some companies would be interesting to work for, and some would be very painful. In chatting about one such latter company with a colleague, it occurred to me that if they ever offered me a job I’d be tempted to say something like, “I’m sorry, stupid companies hire stupid people, so I’m not qualified!” Like I said, its irreverent and perhaps a lot of other things, but…

My How Things Have Changed

I first joined the commercial world in 1984 when I joined the biotechnology company Allelix in Mississauga, Canada. By 1985 I had moved from the lab to the business side in the company, getting involved in business development, marketing and sales support. In the early 90’s I went back to the lab, but that’s another story.

Anyway, in going from an office to a lab I gained the part-time support of a secretary (as assistants were more commonly referred to in those days). That was the first time I had a secretary, except when I had a thesis to be typed – as an interesting aside the secretary who typed my Masters thesis is now the mayor of our town!

I’ve been reflecting on the work process in those days. While the company had a few word processors they were only used by the secretaries – they used 8” floppy disks and printed out on a daisy wheel printer that was kept in a somewhat soundproof cabinet. When I wanted to send a letter I first typically wrote it out by hand and gave the draft to the secretary. She did her best to decipher my scrawl and produced a first ‘typed’ draft, with blank areas where she couldn’t figure out words. I’d then correct that and she’d produce another draft; after a few more possible iterations the letter was finished and was mailed. After a couple of weeks I would typically receive a reply.

If a faster mode of communication was required, we usually used the phone – yes they existed way back then J, but phone rates were much higher and one used them somewhat selectively. If I was out of the office, the secretary would answer my phone and record the message on a special piece of paper. At various periods we also allowed paging via the company intercom if a call was on hold, but as other people found paging to be irritating this approach was sometimes banned for a while, only to be resurrected with a management change.

We also had a teletype, but mostly used this for communication with Japan.

My how things have changed! I work remotely for a software company now, although I do have an office I try to visit once a week to keep it from feeling abandoned. Since we sell a collaborative content management system (Livelink) I think we are probably on the leading edge of new practices, but not that far out. I still run into dinosaurs in the pharma industry that have secretaries to print out their e-mails, but they are in the minority.

I do all my own typing – which I am profoundly bad at – but with a rich, personal auto-correction library in MS Word I don’t have to fix many words. I’d guess that I mistype perhaps one word in four – it’s fun to watch Word fixing as I go. You can tell how bad I am if you communicate with me by instant messaging (IM) – so far the IM clients don’t have auto-correction, but I’m waiting... Probably at least a third of my day is spent with e-mails and much of the rest preparing documents. I’m bemused by people who complain how long it takes to do their e-mail before they can get to their job – in my case it IS a large part of my job. I can’t remember the last time I send a printed letter by mail.

IM has its place – mostly we use it typing people for a quick question or to see if they are free to talk by phone as the majority of my colleagues are also remote workers. There are different camps in the company – I’m in the Yahoo IM camp. But recently Open Text introduced an integrated IM function in Livelink so we are starting to move to that as the company standard.

Then we get to phones and telephony… I have a phone in my office, but it uses our FirstClass product. If you phone me and leave a voice message, that message is forwarded by e-mail to me wherever I am. It is always fun to reply to someone’s v-mail by e-mail and attach the sound file and hear their response. People tend to feel that voice mails are somehow trapped in limited phone system so only you can hear them and will then destroy them. If you choose not to leave a voice mail, you can select from a menu and have the call forwarded to my cell phone or home office. And when I remember, I may have one of these auto-forwarding to the other – each has voice mail too.

I also have access to a standing conferencing facility where I can have up to 16 people dial in toll-free to a teleconference at any time.

We also sell a meeting support tool called MeetingZone, which I use almost once a day to support virtual web meetings; it can also support physical meetings and the dynamics there are very interesting (perhaps the subject of a future posting).

No secretary, no written voice mail messages, no teletype… Big changes, much faster, and in the end I think more efficient.


I was at a conference in Philadelphia yesterday on the eCTD and CTD – these are new standards for the submission of drug and other life sciences applications to regulatory authorities. Pharmaceutical and other life sciences companies cannot test new candidate drugs on humans or market tested drugs without the permission of government regulatory authorities such as the Food and Drug Administration (FDA) in the United States, or Health Canada’s Therapeutic Products Directorate (TPD). The Common Technical Document (CTD) and its electronic equivalent (eCTD) is a global quasi-standard format for such submissions. Maybe in a future posting I’ll describe this more, but for the moment I thought I’d focus on an element of the talk that I gave – I can’t remember the last time I went to a conference as an attendee – either I’m a speaker or I man a company booth.
Most of the speakers were from pharmaceutical companies and so talked about aspects of implementing the CTD or eCTD. As a member of a software company that sells a solution to help such companies prepare eCTD submissions (i.e. Livelink for Collaborative Submissions), I wanted to talk about software. Now no one at these conferences wants to hear a commercial from a software company, so I decided to give a talk entitled, “Applying the eCTD Standard to Internal Business Processes.” The talk was well received and I was asked by a number of people for copies. One aspect of the talk was how people confound the potential benefits of an electronic system.
As a first example, I talked about the steps involved in the review of a document:


In the paper world, a request for an action (e.g. a draft report for review) by a user takes time to arrive by internal mail. When that user has completed their review, then it takes time to hand-off or mail to the originator or next person required to act. In theory, with electronic content, distribution at the beginning and end is essentially instantaneous. But in the real world, the expected time savings are often not achieved. While the worker may have been notified that they have to perform an action, they may not be ready to do so. Consider the scenario were the worker has decided that on Fridays he/she will perform all their reviews for that week. A request that arrives electronically on Monday will be addressed on Friday, just like a request that took until Wednesday to arrive by internal mail. So the actual time involved is longer:


But it gets worse. Very often people prefer to review on paper – if they receive a request for review of a paper document, they can begin work immediately. If the request is electronic, they have to ‘find time’ to print it out, before beginning their review, and then at the end they have an extra step transferring their comments back to electronic form:


Another potential benefit of electronic systems is that they can allow multiple workers to perform tasks on the same material at the same time (i.e. in parallel). Technologies exist for people to be adding comments to a document and in real-time see the comments added by their colleagues – each worker is seeing the latest version of a document. In the paper world, serial processes are much more common – only one copy circulates and one person at time makes comments:


But frequently, as electronic systems are adopted, a pre-existing paper process is mapped unchanged to the electronic system, reducing the potential time saving benefits. And then ‘people factors’ enter the equation again – we may find that a final manager is less motivated to perform the his task because he got the request sooner – he doesn’t think it is so urgent!:


Simple examples from personal experience, but I’ve found they resonate well


The Past Marches On

Many years ago (about a decade…), when I was at the biotechnology company Allelix Biopharmaceuticals (acquired by NPS), I worked with Dr. Dan Drucker at Toronto General Hospital (TGH; now part of The Toronto Hospital) to develop derivatives of the hormone GLP-2. Dan had discovered that GLP-2 has a powerful effect in stimulating the development of intestinal epithelium cells, i.e. the lining of the gut. I remember being there when he ‘opened up’ some experimental mice – you didn’t even need to take a measurement to see the marked difference in the bowels of the experimental mice versus the controls as the differences were so significant.

Dan had indications from earlier experiments that one of the glucagon family of hormones had this effect, and he had tried various elegant engineering experiments to determine which one. As the Allelix research director I had sponsored a collaboration with Dan and provided him with synthetic samples of these hormones. Near the end of the collaborative period, with little success, Dan decided to take the simple, direct approach – he simply gave series of injections to mice with each of the hormones – which is when GLP-2 ‘jumped’ out.

That period was one of the most exciting in my professional career. Dan had new results almost every day that he e-mailed to me and I kept designing and sending him new samples to test. I’d e-mail him at 1:00am and he’d respond at 1:30am! We were having fun and were driven. In drug development you want to find a new approach to treating disease. Here we had a powerful effect by a natural hormone. We wanted to know if there was any disease that we could effectively treat and if we could make a more effective version of the hormone.

I made literally dozens of derivatives of GLP-2 and passed them on to Dan. Experiments looked at the minimal size of the hormone and the critical regions. We were also very interested in improving the activity of the hormone. That family of hormones are quickly inactivated by an enzyme (DPP-IV) that chops-off one end. By testing different ends we were able to make versions of GLP-2 that resisted that degradation and were therefore several times more potent, i.e. you could get the same effect with less hormone. Besides improving the economics of the drug it gave Allelix a proprietary product – a key requirement in commercial drug development. Of the dozen of so patent applications in my name that were made over the years, the only issued patent that I bothered to frame and hang on my office wall was one for those derivatives of GLP-2.

There are lots of diseases involving the intestinal lining. But the most obvious one to look at was Small Bowel Syndrome (SBS) – a condition where patients have had to have large portion of their intestines surgically removed and must be maintained on intravenous feeding, often for the balance of their lives, which may be significantly shortened.

Why these reminiscences? While NPS has been testing one of my derivatives (ALX-0600), which they subsequently called Teduglutide, over many years, they just announced that they have initiated pivotal Phase 3 clinical studies on patients with SBS. If these studies are successful they will be a giant step closer to getting approval for the drug and being able to make a meaningful difference in peoples’ lives.

It’s been years since I worked on the project, and literally dozens of other people have contributed, but it’s still something I recall fondly and am especially proud of.


A Hoffnung Moment

My family moved into what Karina call New House last August (2003). At the time New House was new, but hardly finished. It wasn't until late November or early December that most things were done, as in the there weren't workmen somewhere in the house at least once or twice a week. Of course, as anyone who has moved into a new house knows, that simply means that there are lots of things that are left for you to do yourself. One such little thing I have to do is to put up a shelf in our shower stall; for the moment the various shower accessories are piled in a corner on the floor - and so is set the scene for our little tale...My wife and I usually shower together. Last weekend as I started to straighten up after bending over, she started to bend down - the inevitable happened. I was reminded later of Gerard Hoffnung famous address to the Oxford Union in 1958, where he presented the Bricklayers Story, but in this case, "Halfway up, Martin met Lindy coming down; she received a severe blow to her nose." I felt a rather unpleasant crunch against my skull, but of course no pain. The same cannot be said for Lindy. While I didn't actually break her nose, I certainly came close to doing so. She can still hardly touch it without pain several days later.Hardly funny at the time, but then neither would the events described by Hoffnung have been, and yet it is one of the funniest comedy monologues I've heard. Reading the words alone does not convey Hoffnung's superb comedy timing which really make the piece. He gives enough of each sentence so that you could anticipate what is coming before he actually says it - it engages you in a way that makes you picture the events clearly in your mind while you almost feel like you are telling the story from personal experience. There are audio copies of the talk on the Internet - enjoy if it is your taste. Interestingly the story is not original, versions going back to as early as 1918 have been tracked. But I doubt anyone else has ever told it as well as Hoffnung.

Dead Parrot

Yesterday the FirstClass Division of Open Text held a Monty Python's Tea Party. I have an office there which I use occasionally, but I didn't want to miss the party being a longtime Python fan - after all I was growing up when they were current. There wasn't time for a fancy costume so I decided to wear my oldest suit, my old British school tie and a Norwegian Blue shagged out after a long squawk:




New Daughter Look

After years and years (at least a large percentage of her life) Karina has had her hair cut - it looks great to the unbiased father...

Time and Time Again

It must be mid-life crisis but I've detected a recurring theme of time in all of my postings to date:
New Daughter Look = "After years and years..."
Buggy Customers = Time zone offset in software
The Past Marches On = Time-themed title, even though the post had to do with drug development
Watery Strings = How electronic systems can fail to save time
It Starts, Parts 1 & 2


Buggy Customers

Yesterday was one of those crazy days which start out with too much to do and end with you having done none of it despite being furiously busy. I participated in two web meetings (one in Italy and one in Boston) and a conference call and produced two documents – most of which were not on the plan as the day started. One of those documents was a quick position paper that essentially said, "No, there's nothing wrong with our software – you just have to think..."
There are strict requirements in the pharmaceutical industry to ensure that crucial events performed with software managing electronic records are captured and time stamped. An inspector from the FDA or other regulatory agency may want to know exactly what happened, who did it and when it occurred. Open Text Livelink runs a comprehensive audit trail and timestamps all of the events.
But in the process of validating their Livelink system according to regulatory requirements a customer discovered that when they viewed the same audit trail using two different computers as web clients the recorded times differed, and not even by an exact number of hours --> Big red flag waving, major problem, slam on brakes, system can’t be validated, panic, it is the software vendor’s problem, make them fix it yesterday, call Martin, fix it or make it go away…
Martin looks at problem, takes deep breath, answer simple = client hasn’t thought this through.
So what was the problem you ask Dear Reader (if there even be one!)? Well Livelink gets its time from the server(s) on which it runs (both application and database server(s)). Typically systems are configured to get their time from a time-server – this may be internal or external, in either case an atomic clock available on the Internet (e.g. at NIST) is usually the final authoritative source of information (good overview). As long as the servers from which Livelink gets time information have accurate and synchronized clocks, then the timestamps are fine.
So where’s the problem? Well users get confused – that old ‘human factor’ thing I keep running into. Livelink has an option to either represent time to users exactly as ‘known’ to Livelink (i.e. ‘server time’) or to reinterpret this time to each user’s local time – this feature is called the “Timezone Offset” and is a configured by a Livelink Administrator and applies to any client computer accessing a given Livelink system. The aim of this function is to enable users to conveniently understand events according to their local time.
To illustrate the usability benefits (i.e. trying to address the human factor) of the Timezone Offset feature consider the following example:
A Livelink server is configured to record and display times according to Eastern Standard Time but does not have Timezone Offset enabled.
A user working in Pacific Time adds a document as 10:00am.
If that user subsequently refers to the audit log they will see that their document was added at 1:00pm, not 10:00am.
However, if Timezone Offset is enabled, then whenever Livelink sends time and date information to the user in the Pacific Time zone it reinterprets the time to their local setting, so the user would see that they added the document at 10:00am as expected, not 1:00pm. This reinterpretation of time applies to all time events, not just those related to a particular user.While the Timezone Offset feature can aid users, it presents particular challenges in a validated system. In order for Livelink to reinterpret server time to a user’s local time, it has to determine the user’s current time. It does this by querying the time as known to the user’s client computer and compares this to the Livelink server time, calculating the difference between these two. This calculated time difference is then applied to all time references provided to a given user. The times in the authoritative Livelink record are not being changed, only their representation to users to keep them happy. If a given user’s computer clock is accurate then the times shown to the user correspond exactly to the times in the Livelink record, although they are adjusted to the corresponding local time equivalent.
In the real world unless adequate controls are enforced this can lead to unexpected variations. It is of course essential that the clock of any computer accessing Livelink be correct – not only must the ‘displayed time’ be correct (e.g. 05:13:12pm), but also the correct time zone must be set. In general the clocks employed in PCs are not accurate. Also, when users travel they often fail to reset their computer clocks or reset the displayed time but not the time zone. As a simple example, in a Livelink system when the Timezone Offset feature is activated and two computers differ by 2 minutes and 12 seconds, then all time events shown by Livelink will differ by this amount when compared between the two computers.
So how to address this? 1.) Ensure that the clocks of client computers are correctly set or, 2.) Establish procedures to deal with apparent time variations. If neither of these can be achieved, then the Timezone Offset feature should not be used. Is simple is it not?
So Martin writes this all out in more formal form (i.e. passive voice, qualified sentences, using official corporate template, converts to secure PDF, etc.), e-mails to sales and technical people on account, and then gets back to serious work on the next unscheduled task. Sigh…


It Starts - Part 2

This just in (based on my earlier comment):

To: Karina Sumner-Smith
Subject: Please Forward to your Dad
Dear Mr. Karinasdad: Yes, other online journalers do get a little freaked out when their parents start talking to them about their journal. Really. We just get over it.Hmmm...


Watery Strings

I was involved in a customer demonstration today showing the regulatory affairs group of a small pharmaceutical company our new software offering to support the preparation of electronic submissions to regulatory agencies. There is a classic paradigm shift underway in this space – that’s a well worn cliché, but in this case quite true. In a future entry I’ll expound on this a bit, or even a lot, more. But the point here is that the staff of the potential customer neither understands what technology can do for them nor do they realize how much that technology will change the way they do things. And it’s not like they will have choice – the regulatory authorities are moving inexorably to require electronic submissions in a new format called the eCTD from the ICH that incorporates XML.
After a two hour web demo I felt like I’d been through a wringer. How do you sell something to someone who doesn’t even know enough to know what they don’t know, or to understand the issue and how they will have to address it at some time? Obviously the answer is you don’t. Clearly this company is not one of the early adopters ready to ‘cross the chasm’, they aren’t even a member of the mainstream – they are clearly a laggard – so onto the next prospect for me.
I felt like we were trying to, “Push water up a slope” or “Push on a string” as the sayings go.
Today’s experience leaves a number of half formed questions in my mind, mostly related to the ‘human factor’. At times I’ve watched how electronic systems have failed to yield the expected benefits because human behaviour works to confound them. As an example, in many companies it can take a month or two to collect the required signatures on a formal document such as a standard operating procedure (SOP). If you analyze the time involved, something like 30-40% of that time is taken by the process of moving the document around in internal mail. So you’d think that if the document was circulated electronically you could immediately get a 30-40% time saving; but no such luck. People notice that they get the document quicker so they feel a lower sense of urgency to sign it – they procrastinate. Or they have structured their work week to only sign procedures on Friday, so whether they get a document on Monday electronically, or on Wednesday by internal mail, there is no time saving by the time they sign.
Most people know that saving time will benefit their company, but in today’s experience, we couldn’t even talk about benefits when the people on the call didn’t understand the issue or the problems associated with it. One day they will, but not until I’ve moved onto another career – and I don’t have any current plans to do so…


It Starts

I've had fun reading my daughter's weblog, Spontaneous Things, but whenever I mention that I've just read something or comment on what I read she feels uncomfortable. Hmmm.... Lots of anonymous people on the Internet can read it, but when Karina's father reads it she's uncomfortable. And she says that other web bloggers understand how she feels. There's nothing like personal experience, so here goes...While that’s certainly one of the reasons I thought I give this online journal ‘thing’ a try, there are others that may emerge on these pages in the future…
What to talk about he muses… Well, being half-a-century old (“But only just,” he feels compelled to add) certainly gives plenty of historical fodder: things I’ve done, professions I’ve had (more than one), things I’ve seen, relationships, and so on. Not to mention thoughts of the Future, of which I personally will undoubtedly have less of than I've already had of the Past.
So who is this guy (or bloke - note subtle reference to English birth)? I could be lazy and simply say “Google me’” by clicking this link. In looking at the results right now there are 129 hits – what a grab bag of my Past and a little of my Present. None of my Future though of course; what a scary thought that is: Imagine going to www.futuregoogle.com, searching on your name and seeing things that you will do that will make it on the web. But I digress. I’m very happily married, have two great children (including the aforementioned Karina), and live in Palgrave, Ontario, Canada. I’m a molecular biologist by training (Ph.D. University of Toronto, 1982, Postdoc Yale to 1984), spent many years in biotechnology with a company called Allelix (subsequently acquired by NPS). In 1996 I founded a bioinformatics company called Base4, which was ultimately acquired by Open Text, my current employer.
But enough for now; let’s see where this goes over time…