Incomplete Documentation in Pharmaceutical R&D Lab Notebooks
I came across this excellent article in the Oct. issue of Scientific Computing and wanted to make people aware of it.
This article by Robin Y. Smith comments on the elephant in the room for most pharmaceutical companies as well as fine chemicals companies in R&D. The problem is the incomplete and sloppy notebooks. This is the elephant in the room that no one wants to talk about.
He found, based on auditing 10 years of lab notebooks from a top 10 pharmaceutical company, that 15% of the pages had major problems such as being illegible, incomplete, or had some other error meaning the experiment could not be reproduced.
In some of the worst cases, 60% of the pages were deemed not reproducible and this did not count vague phrases such as “worked up in the usual fashion”. If there was ever an area in R&D that could is ripe for improvement, this is it.
Cases of scientists being judged on the number of notebooks filled leading to “dry labbing”. This is where lab notebooks are padded with many planned experiments which are never carried out. Just looking at the number of notebooks filled these scientists appear to be very productive.
I’ve always been frustrated when trying to find info in others lab notebooks. Lack of table of experiments in the front resulting in having to flip through the notebook until you find the right result. Not knowing which of dozens of lab notebooks contains the information you need. Experimental results such as chromatograms or NMR printouts not being in the notebook or even worse, being in another 3 ring notebook that isn’t identified by anything other than a volume number. I have spent too much time trying to find information rather than analyzing and coming up with new experiments.
The problem is at its worst in discovery or med chem groups but I will note that even in most process development groups it is better but still not great.
The article doesn’t comment on stats for use of phrases such as “typical work-up procedure”, “standard procedure”, etc. without referencing some other document or lab notebook page. As a process development chemist, I always found this sort of documentation mind boggling. I had one case were I was repeating a drug discovery process on a small scale to become familiar with the process and at one point encounter a horrible emulsion. I went to the discovery chemist and asked if this is what he saw and if so, what did he do about it. He said yes, he saw that too and he just left it to sit overnight until it separated. This was NOT noted in his lab notebook! Needless to say, this required a lot of work in process development to get a process that would work on even a 22L scale.
The other complaint I have is even when a work-up procedure it listed, most of the time in my experience, the procedure did not list volumes of solvent or aqueous washes used. In another case, it said the organic layer was washed repeatedly with water. I found out that it was washed 15 times with huge amounts of water each time!!! None of that was documented. When I asked the chemist, they said all these washes with that large of volume of water was indeed required to get rid of some inorganic salts. Ends up, using equal volumes and doing 3 washes worked fine.
All of these are huge problems and I do indeed think that electronic notebooks are needed. I’d like to see them used much more widely than they are currently and think this could go a long way towards increasing R&D productivity.
I should point out that the author, Robin Y. Smith is Vice President of Product Strategy at Symyx Technologies and they make software for electronic notebooks.
Technorati Tags: documentation, lab notebooks, R&D productivity
Related Posts:
Bookmark it with:
| 
del.icio.us
| 
Digg it
| 
Furl
| 
Simpy
| 
Spurl
| 
My Yahoo!
|
May 30th, 2008 at 9:15 am
y published on www.brainblogger.com
The Human Injury of Lost Objectivity
If I were to rate the corruptive tactics performed by big pharmaceutical companies, the intentional corruption of implementing fabricated and unreliable results of clinical trials by pharmaceutical companies by hired third parties who manipulate these trials they sponsor because of their power to control others involved in such trials that is largely absent of regulation would be at the top of the list, and likely the most damaging to the requirement of authenticity and, more importantly, assuring the safety of the public health, as I understand that this does in fact occur.
Decades ago, clinical trials were conducted at academic settings that focused on the acquisition of knowledge and the completely objective discoveries of meds. Then, in 1980, the Bayh-Dole Act was created, which allowed for such places to profit off of their discoveries that were performed for pharmaceutical companies in the past. This resulted in the creation of for-profit research trial sites, called Contract Research Organizations, which is often composed of community research sites with questionable investigators possibly void of necessary research experience or quality regarding their research purpose and ability. Since they are for- profit, with some CROs making billions of dollars a year. The trials conducted at such places are sponsored by pharmaceutical companies that control and manipulate all aspects of the trial being conducted involving their med being studied in the trial. This coercion is done by various methods of deception in subtle and tacit methods. As a result, research in this manner has been transformed into a method of marketing, which includes altered results of the trial to favor the sponsor’s med. Their activities are absent of true or applied regulation, and therefore have the autonomy to create whatever they want to benefit what may be a collusive relationship between the site and the sponsor.
Further disturbing is that once the creation of the trials is completed, they are then written by ghostwriters often, although no one seems to know how often. These people are not identified and acknowledged by the sponsor, and may not be trained in clinical research overall, as they are simply freelance writers, as one does not need research training or certification in order to perform this function. Rarely do trial ghostwriters question their instructions about their assignment, which is clearly deceptive and undocumented by the sponsor. Also, these hired mystery writers are known to make about 100 grand a year. This activity removes accountability and authenticity of the possibly fabricated clinical trial even further. The corruptive act is finally completed by the sponsor hiring an author to be placed on the trial that likely had no involvement with the trial, and, along with others, was paid by the sponsor for doing this deceptive act.
To have the trial published, the sponsor pays a journal to do this in various ways, I understand, such as purchasing thousands of reprints of their study from the journal. Again, how often this process is performed is unknown, yet frequent enough to create hundreds of such false writers and research sites to support the pharmaceutical industry. So benefits of meds studied in such a malicious way potentially can harm patients and their treatment options and safety risks. The purchased reprints are distributed to the sponsor’s sales force to share the content with prescribers which may lack validity.
Such misconduct discussed so far impedes research and the scientific method with frightening ethical and harmful concerns, if in fact true based on reports by others. If so, our health care treatment with meds is now undetermined in large part with such corruptive situations, as well as the possible absence of objectivity that has been intentionally eliminated. Trust in the scientific method in this type of activity illustrated in this article is absent. More now than ever, meds are removed from the market are given black box warnings. Now I understand why this may be occurring.
Transparency and disclosure needs to happen with the pharmaceutical industry for reasons such as this as well as many others, in order to correct what we have historically relied upon for conclusive proof, which is the scientific method. More importantly, research should not be conducted in a way that the sponsor can interfere in such ways described in this article, requiring independent sites with no involvement with the drug maker. And clearly, regulation has to be enforced not selectively, but in a complete fashion regarding such matters. Public awareness would be a catalyst for this to occur, after initially experiencing a state of total disbelief that such operations actually are conducted by such people, of course. We can no longer be dependent on others for our optimal health. Knowledge is power, and is also possibly a lifesaver.
“Ethics and Science need to shake hands.” ……. Richard Cabot
Dan Abshear