The Ferryman

Collaborative development of predictive toxicology applications

The following initial paper on OpenTox has now been published and is available in preliminary form:

Collaborative development of predictive toxicology applications
Barry Hardy, Nicki Douglas, Christoph Helma, Micha Rautenberg, Nina Jeliazkova, Vedrin Jeliazkov, Ivelina Nikolova, Romualdo Benigni, Olga Tcheremenskaia, Stefan Kramer, Tobias Girschick, Fabian Buchwald, Joerg Wicker, Andreas Karwath, Martin Gutlein, Andreas Maunz, Haralambos Sarimveis, Georgia Melagraki, Antreas Afantitis, Pantelis Sopasakis, David Gallagher, Vladimir Poroikov, Dmitry Filimonov, Alexey Zakharov, Alexey Lagunin, Tatyana Gloriozova, Sergey Novikov, Natalia Skvortsova, Dmitry Druzhilovsky, Sunil Chawla, Indira Ghosh, Surajit Ray, Hitesh Patel and Sylvia Escher
Journal of Cheminformatics 2010, 2:7 (31 August 2010)
http://www.jcheminf.com/content/2/1/7

Please feel free to circulate in the community and to your contacts who might be interested. Thanks!

And a special thanks to all who have contributed to advancing this work, including our advisors, and growing community of friends, interactions and partners!

Barry 

OpenTox Workshop in Potsdam to discuss collaborative approach to linking resources to improve human safety

On Sunday May 30 we host an OpenTox Workshop near Berlin in Potsdam that will bring many leading international research program directors and leaders together to discuss how collaboration and the increased linking of resources over the World Wide Web could progress human safety research and safety assessment.  By linking resources and data increasingly powerful computer-based models can be built for predicting and avoiding unwanted adverse toxic side effects of drugs, chemicals, ingredients in soaps and cosmetics, pesticides etc. thus enhancing human safety and protecting the environment better.  Such methods should also eventually lead to the replacement of many animal experiments.

More details on program can be located at:

http://www.opentox.org/data/blogentries/public/opentoxworkshoppotsdam2010

Neglected diseases, HIV, and development work on the ground in communities

Neglected diseases such as parasitic infections reek havoc on many communities in different parts of the world.  As part of our committment to responsible, sustainable development and a community culture, we will make neglected disease problems, where we evaluate we can make a significant difference, a goal of our collaborative virtual organisations in years to come.  Please contact me to discuss your ideas and also consider joining the new Collaboration Pools summarised at bottom of this post.  We can also work together on new funding opportunities.

However and also, my experiences in Africa, for example on our conservation trip to the remote Caprivi Delta region of Namibia:
http://barryhardy.blogs.com/theferryman/2009/02/experiences-from-expedition-work-in-the-caprivi-delta.html
(please keep in mind this post was based on a summary for my younger son for awareness!), was that "small contributions" can make a big difference.  One story from that trip was the inability of a local clinic to deal with the torn foot of one of our party, and we ended up stitching him up with a veterinary kit back at base camp. Once that was done, how would he get around we asked, as there were no crutches to be had locally?!  Discussing the incident around the camp fire afterwards, we came up with the simple solution of each throwing some money into a "needles and crutches" hat, and that was able to buy needles and crutches for the local clinic to keep them going for a couple of years, and it could be directly organised.  So in this reality-focused context something like $200 made a bigger difference on the real problem for the future than a (possibly failed) major $100m program.  A bit of a stretched analogy, but you probably get the point.

We intend to continue our support of sustainable development work in the community in Caprivi in community-involved wild life conservation development, and look forward to our next trip, and others in the community who might be interested.  Let me know, if this might be for you too.

Here I would like to draw attention to a new local initiative in the area to help support the families affected by a widespread HIV infection epidemic.  There is need for education, healthcare, and support of the many orphans left behind by parents who simply die from untreated HIV infection.  Consider what you might do by volunteering some simple help and support to the work out there.  The new center is called TAG Volunteers (TAG for think-act-grow):
 
http://www.tagvolunteer.com/
 
I vouch this is a real legitimate project as Ronel, the woman setting it up, was also very much involved in competently running the important activities at our base camp on our last visit, such as getting something to eat when we got back very tired and hungry from our trips into the bush!

Welcome your feedback.  If you do decide to take some time out to volunteering in some way, I suspect you will find it rewarding.  And it is also at the same time such a special and beautiful country to experience!

Barry

Collaboration Pools:

OpenTox - predictive toxicology
https://www.surveymonkey.com/s/M7TFM6C

eCheminfo - drug discovery
https://www.surveymonkey.com/s/V6T2YSD
 
InnovationWell - life science innovation and knowledge management
https://www.surveymonkey.com/s/782L9DZ

InnovationWell Collaboration Pool Formation

We are establishing an InnovationWell Collaboration Pool of individuals and organisations who have an interest in collaborating together in areas of healthcare and life science innovation. For example, a selection of Pool members could participate in a collaborative life science, systems biology or predictive toxicology project, develop a funding proposal or response to a call opportunity together, or develop an innovation or best practice.

To join the InnovationWell Collaboration Pool please complete the short form located at https://www.surveymonkey.com/s/782L9DZ

Collaborations will take a virtual organisation approach, i.e., partners can bring contributing knowledge, computational or experimental capabilities to a partnership for the duration of a project or other endeavour.

We will run two such virtual organisation (VO) projects for the first time this year starting later this Spring:
A) Drug Design project which will examine the application of a variety of leading modelling and design approaches to novel target kinases, to experimentally test predictions, and to initiate a best practices virtual screening resource.
B) Predictive Toxicology project to apply a combination of in silico and in vitro approaches to predict in vivo toxicity including exposure.

Both VOs will be supported by a variety of leading modelling and design software, informatics infrastructure, and collaborative content management and electronic lab notebook systems.

The VOs will be supported by knowledge-oriented collaboration services developed under the FP7 Synergy research project, including a reactive complex event driven engine, collaboration moderator, collaboration pattern services and partner knowledge base.

The Predictive Toxicology VO will be supported by distributed REST-driven web services for data management, model building, validation and reporting, developed under the OpenTox Framework (http://www.opentox.org/)

We will also consider incorporation of Case Studies into the eCheminfo Drug Discovery and Predictive ADME/Tox workshops to be held in Oxford this summer. See http://echeminfo.com/

Barry Hardy PhD
InnovationWell 

Douglas Connect
Switzerland

Growing significance of communities and collaboration in discovery and development

Just saw an article I wrote for Future Science has come out as a Perspective:

Growing significance of communities and collaboration in discovery and development
Barry Hardy, Future Medicinal Chemistry, June 2009, Vol. 1, No. 3, Pages 435-449.
http://www.future-science.com/toc/fmc/1/3

Sorry, but I don't have the budget just right now to take the Open Access option, but there is some other open material available at the above link.

In summarising the drivers for the growing significance of communites and collaboration I introduced:

The benefits of community participation or collaboration should outweigh the costs to support a rational decision to pursue such routes.  Lions usually prefer to hunt as a group as the shared food from group kills offers a better return and lower risk than hunting alone; in a similar manner organisations may also choose to collaborate to have greater success in acquiring new resources or income. The current convergence of a number of factors appears to be driving up the R&D collaboration benefit/cost ratio. The drivers include:

1.      Scientific research is becoming more complex and multi-disciplinary, requiring researchers to move more away from “working in the expert’s box”.

2.      Our work, economy and society are becoming more knowledge-oriented. (I define knowledge here as including understanding gained from experience and involves individual and collective knowledge in addition to explicit knowledge such as intellectual property (IP).)

3.      Business models in the chemistry and pharmaceutical industry that worked fine historically, e.g., manufacturing products based predominantly on patents related to chemistry, appear to be increasingly lacking.

4.      The goals of translational and personalized medicine have stronger requirements for networked and collaborative approaches over discipline and time than the historically relatively linear drug discovery and development process.  Integrated services offer greater future value creation than stand-alone products.

5.      Patient Safety has become an issue of growing concern requiring new more integrative approaches to data, knowledge and disciplines.

6.      Computational Science continues to grow in importance, fueling overlaps and interactions between scientific disciplines including that of computer science.

7.      The maturing of the Internet-based World Wide Web including enhanced usability, services, social software and the semantic web, provide new community and collaboration resource opportunities.

8.      Challenging problems we face as a race such as global warming, energy management, population growth, and sustainable development are often linked to healthcare issues and are demonstrating the need and benefit for greater cooperation and at larger scales.

9.      Continuing education and learning throughout life has been growing in importance as knowledge workers go through greater numbers of career and job changes than in the industrial age.

10.  Work can increasingly be done anywhere on the planet where the best combination of costs and skills are available.  As Thomas Friedman discussed in his recent book, the “world is now flat” (1). A work objective can be broken into a workflow of numerous tasks, each of which may be done in different locations or by different organizations or individuals.

And I will add three more uncertain or controversial factors here:

11.  There is a growing importance of small and medium size enterprises (SMEs) collaborating in knowledge-oriented activity and growth in the global economy.

12.  As our modern life seems increasingly less rewarding beneath the surface, we need, search for and find new happiness from the benefits of taking advantage of new collaboration opportunities through interacting with others more.  In addition to needing better conversations for learning, work and self-development, we also simply need them psychologically and to feel good.  (Happier workers are also more productive ones.)

13.  Enabling international cooperation, collaboration and knowledge transfer in socio-economic areas such as healthcare, including building shared cultural meaning between different countries, races and cultures will significantly progress the security and prosperity of the world we leave to our children, whereas other current flawed political, military and unsustainable economic strategies will not.

Welcome your feedback and additions...

The Ferryman

(1) Friedman TL, “The World is Flat”, Picador, (2005).

Trident Missiles, Drugs and Shoe Choices

The question I am asking here is "How can lessons from Trident Missiles improve future patient healthcare treatment?" or more prosaically "What is the business case for knowledge management in healthcare product and service development and delivery?"

A number of times in recent weeks the topic of the business case for knowledge management (KM) has arisen in my interactions, conversations and activities, and from which some initial reflections are convincing me of the need and importance for new work, approaches and applications in this area.  Personally I would like to develop the case approaches in the life science/pharmaceutical/healthcare area but new approaches may apply across sectors and cross-industry comparisons may be insightful. 

Before getting into the challenges let me mention one story I came across recently that really brings home the future benefits of KM applied to technology development over the long term.  It is the one of how the knowledge required to refurbish Trident missiles has been literally lost: http://kerrieannesfridgemagnets.posterous.com/did-we-throw-out-that-fogbank-stuff-no-probs  Ignoring the question of why the missiles are being refurbished and whether that should be done, you can simply focus on the issue of huge cost gain and loss of investment through inadequate KM. This case involves not only inadequate explicit knowledge management of data, procedures and processes, but also the loss of human and social capital knowledge associated with the technology due to worker loss and retirement unaccompanied by tacit knowledge sharing, transfer and alumni retainment measures.  So there simply has been an almost complete organizational memory loss of a key competency; lack of KM is now costing tens if not hundreds of millions of dollars of squandered taxpayers’ money to reinvent the wheel.

In this time of cost-cutting responses to the finance industry triggered economic recession and mass follow-me psychological depression, it would be pertinent for long-term investment stakeholders to consider the above lesson in lack of KM.  As executives are cutting costs and jobs to survive and human and social capital in the organization is being lost or destroyed, one should ask what is the impact of knowledge loss on the long term value and growth of the organization.  What KM measures are being taken so that the organization is simply not forgetting what it can do?

Let’s return to focus on the challenges with formulating the business case for KM in the life science/pharmaceutical industry case.  If the case is for a small tactical project and we concentrate on short term benefits and localised returns, then one can probably do a reasonable job with existing best practices.  However this is of very limited value in assessing the impact on factors that are really strategically important – e.g., longer term overall financial performance, sustainable development, stakeholder value, innovation success etc.

If we accept the statement that no major organisation in the life science/pharmaceutical industry has yet implemented a successful quantified global organisation-wide KM strategy, then we are immediately and obviously in the situation of having no previous data or case study as reference.  (I welcome exceptions even if partial cases added as comments and links to this initial post.)

Moreover the situation is even worse in terms of complexity.  The current industry business models are in their old age years; the current approaches of pharma mergers and biotech acquisitions are intermediate strategies, and the models of the future e.g., service oriented approaches combining knowledge, diagnostics and interventions for population segmented personalised medicine are currently plans and pilots.  Such factors will certainly distort many of our calculations for mid and long term returns.

According to the Economist’s 2020 study Pharma industry executives considered KM as the greatest potential source of productivity gains between 2005 and 2020. (Reference:
“Foresight 2020: Economic, Industry and Corporate Trends”, The Economist, (2005).
http://www.eiu.com/site_info.asp?info_name=eiu_Cisco_Foresight_2020&rf=0)  Although looking promising at first sight, my concern is what definition of KM was understood by respondents to this survey.  If the understanding was similar to what I have often encountered, there will be a great spectrum of definitions included in the survey sample and unseparated in the results analysis.   So we need to consider the question (and our business case ones) in the light of considering all KM impacts on value including structural, human and social capital values, and hence needing consideration of intellectual capital approaches.  Of course the current impact of mergers and acquisitions and associated job cutting complicates significantly an intellectual capital analysis applied over time.

A further significant complication in pharma is the long development cycle and time gap between initial R&D and market returns.   There will in general be a lag between gains in an intellectual capital index and a stock market financial metric, but the long lag time in drug development with complexities such as mentioned above make a clear return analysis very difficult.  We know at least anecdotally that many pharmaceutical companies often face knowledge loss issues similar to that depicted above for the Trident with their drug products.  The loss of personnel associated with mergers, acquisitions or recessions exasperates the already challenging issue of knowledge integration, sharing and translation across the life cycle.

The Dow Jones Sustainability Index has now been applied to pharmaceutical, biotech and healthcare companies for a few years and provides some initial insight on the KM business case problem for this sector as it includes some KM-oriented components such as human capital and talent management valuations.  However it appears that several extensions and elaborations to such indexes are necessary.  The ideal would be a KM index component that predicted future stock market index gains for organization or sector which could guide both current strategy and investment decisions. 

However as KM increasingly becomes integrated with operations and work processes, it will become more challenging to separate out components as suggested above and inter-dependency may favor smartly aggregated multidimensional metrics.

Finally, there is the issue of the prospect of the increasingly collaborative approach to work in life science R&D, translational medicine and healthcare service provision.  If infrastructures increasingly involve virtual organization approaches sharing risk, practices and value creation across organizations, the KM evaluation and measurement situation has a further series of differences in these contexts.  At this stage one might just think one should give up on a detailed approach to intangibles and a quantitative KM business case for the industry.

However, let’s finish on an optimistic note.  What we may be happy to settle for here are metrics which can successfully guide decision making rather than scientifically rigorous ones.  We should therefore remind ourselves of the bounded rationality theory of Herbert Simon, which would point to our only needing to guide the non-optimal decision making of managers, based on metrics which are good or useful enough.  There should only be so many pairs of shoes for me to choose from in the shop before I decide; for me 2 or 3 good pairs are enough!  We can also remind ourselves that although Herbert Simon was awarded his Nobel in economics, he spent much of his life working in AI.  (If you are an economist expert reading this post and encountering imponderable conjunctures, please reach out to correct, extend, enlighten and collaborate…!)

So for now I will conclude it looks like an interesting problem to work on.  Please a) add relevant comments and links to this post and/or b) contact me at Barry.Hardy -(at)- douglasconnect.com if interested in joining a (probably initially small) practice group interested in discussing and developing approaches in this area.

Barry Hardy
InnovationWell Community of Practice & Research Manager

Computer-based Predictive Toxicology: Advances and Impact of Cheminformatics on the Safety-oriented Design of New Products

Current advances in computer-based predictive toxicology offer the potential to create more advanced environments for the screening and prediction of safety issues due to chemical and drug adverse side effects, drug-drug and chemical-system interactions, and chemical and drug toxicologies in the environment and the human body.  Advances in this growing field also offer the potential to replace or reduce the need for animal testing and to reduce later stage clinical trial failures or new product development rejection. Acceleration of progress in practical applications requires the creation of interoperable environments, knowledge sharing, data integration, algorithm development, and extensive validation and testing. 

Numerous opportunities exist in this field for scientific advances, but also for innovation, service and product development, and value creation. Additionally, significant collaboration approaches are a scientific, industry and society imperative to advance this field and the safety of new products and all society members.  Collaborative approaches need to support the multidisciplinary networking and collaboration between computer scientists, biologists, chemists, toxicologists, product development and clinical and environmental researchers, and to network groups, centers, initiatives, projects and data into interoperable semantic frameworks, systems, knowledge bases and virtual organisations.

At our Predictive Toxicology session chaired by Artem Cherkasov (University of British Columbia) running 17 October 2008 at Bryn Mawr recent developments in the field of predictive toxicology will be presented and discussed.

The session will be preceded the evening of October 16 by a Knowledge Café to discuss Collaboration Opportunities in Predictive ADME & Predictive Toxicology.

A description of the session with presentation abstracts follows.  Please add your comments, discussion or questions at the end of the post.

Predictive Toxicology

http://innovationwell.net/COMTY_confprogr08predtox

(Please follow continuation here to read abstracts.  Comments can be made at the end.)

InnovationWell Membership & Workshop Activity for 2007

During November I will be planning the program for the following InnovationWell workshop in Oxford (cross-industry sector) and InterAction Meeting in Bryn Mawr (life science/pharma/healthcare sector). Please contact me with your interests and proposals!

Knowledge Assessment & Performance Improvement of Collaborative Work and Innovation Activities
InnovationWell Workshop & Innovation Café, accompanied by pre-meeting
2 day hands-on workshop activities on collaborative systems and ELNs
20-22 June 2007, Oxford University, Oxford UK

Innovation in Life Science & Healthcare Research & Product Development
InnovationWell Community of Practice InterAction Meeting
15-18 October 2007, Bryn Mawr College, Philadelphia, PA, USA
Themes: FDA Critical Path Themes, Knowledge Management, Translational Research, Biomedical Informatics, Metabolomics, Biomarkers, Toxicology, Patient & Drug Safety

InnovationWell Gold membership
This entitles members to access InnovationWell meeting proceedings including audio, access to our Executive Insights reports from meeting and community of practice activities, and additional member discounts on meeting and training registration fees.

Download InnovationWell2007MembershipForm.pdf

Barry Hardy

Email: barry.hardy *[at]* douglasconnect.com

InnovationWell meeting workshop conference management executive Bryn Mawr Philadelphia Critical Pathbiomarkers metabolomics toxicology personalised medicine KM Life Sciences Pharma Drug Discovery Drug Safety Research and Development Drug Development Healthcare Innovation Knowledge Management events

InnovationWell Interest List and Signup

You can join our InnovationWell interest list (managed by Constant Contact) to be kept posted on news related to our community of practice activities using the following signup form:

Join Our Mailing List

Email:

Barry Hardy

InnovationWell Community of Practice

European InnovationWell InterAction Meeting Final Program (9,10 November 2005)

The European InnovationWell InterAction Meeting "Knowledge-based Innovation in Life Science Product Development" takes place in Basel, Switzerland next week (November 9-10).  The schedule with list of presentations and discussion sessions is available at:
http://echeminfo.colayer.net/files/SpeakerTopcSchedule-IA05-Basel-v5.pdf

Included in the meeting will be a one day session running November 9 on Knowledge Management in R&D with further details being made available at:
http://innovationwell.net/COMTY_randd

The eCheminfo Drug Discovery meeting runs concurrently with our InnovationWell Community meeting; registrants are welcome to attend sessions from either program.  Further details, such as abstracts and speaker bios, can be viewed in the Program areas of either the innovationwell.net or the echeminfo.com websites.

We will be closing registrations shortly, so please let us know quickly if you'd like to come.  Register through the websites or contact Nicki Douglas (nicki.douglas at douglasconnect.com, +41 61 851 04 61)

And if you can't make the meeting, you can access the recordings and presentation materials if you become a member of one of these communities. You will also have access to all previous sessions (including those from last month's US InterAction meetings in Philadelphia being released this month which also included a 1 day Knowledge Management in R&D program).

Barry Hardy
Community of Practice Manager
Douglas Connect, Switzerland
tel: +41 61 851 0170

InnovationWell meeting workshop conference management executive drug safety KM Life Sciences Pharma Drug Discovery Research and Development Drug Development Healthcare Innovation Knowledge Management events