The Ferryman

OpenTox API (Second Version) Published

The second version (Version 1.1) of the OpenTox API has been published and is available for review under http://www.opentox.org/dev/apis

For submission for inclusion in testing activity, please add/update your web service template summary descriptions on the OpenTox Test Web Services page:

http://www.opentox.org/dev/testing/testtoxservices

Satisfying REACH Requirements in Predictive Toxicology

The OpenTox workshop on "Satisfying REACH Requirements in Predictive Toxicology" to be held at the ISS in Rome 10-11 September 2009. 

Participants at the workshop will involve cross-industry users and regulatory experts in addition to solution developers and providers who will discuss the requirements and use cases of users in chemical toxicology evaluation and risk assessment, and including satisfaction of current and future requirements of the REACH legislation using alternative testing methods. The workshop format involves short presentations to provide user, regulatory and solution needs perspectives, followed by knowledge cafe discussions discussing use cases, challenges, issues, solutions, collaboration opportunities and ways forward in small groups.

PROGRAM

Thursday 10 September

08.30 Welcome Coffee

09.00 Introduction & Workshop Overview, Barry Hardy (OpenTox and Douglas Connect, Switzerland)

09.15 The Use of Computational Methods for the in silico  Prediction of Chemical Properties in REACH, Andrew P Worth (Systems Toxicology Unit, Institute for Health and Consumer Protection, European Commission -Joint Research Centre, Italy)

09.40 Automated Workflows for Hazard Assessment, Elena Fioravanzo (S-IN Soluzioni Informatiche, Italy)

10.05 OpenTox Predictive Toxicology Use Cases, Barry Hardy (OpenTox and Douglas Connect, Switzerland)

10.30 Coffee Break

11.00 Knowledge Café Discussions

12.30 Group Discussion

13.00 Lunch

14.00 Opportunities for using  Systems Biology Data for in silico  Modeling of Personalized Medicine, Richard D. Beger  (Division of Systems Toxicology, National Center for Toxicological Research, Food and Drug Administration, USA)

14.25 A Framework for Using Structural, Reactivity, Metabolic and Physicochemical Similarity to Evaluate the Suitability of Analogs for SAR-based Toxicological Assessments, Joanna Jaworska (Procter & Gamble, Modeling & Simulation, Biological Systems, Brussels Innovation Center, Belgium)

 14.50 Integration of Integrated Assessment Tools for Environmental Risk Assessment, Willie Peijnenburg (National Institute for Public Health and the Environment, The Netherlands)

15.15 Prediction of Animal Toxicity Endpoints for ToxCAST Phase I Compounds using a Combination of Chemical and Biological in vitro Descriptors, Alex Tropsha (Carolina Center for Computational Toxicology and Carolina Environmental Bioinformatics Research Center, University of North Carolina at Chapel Hill, USA)

15.40 Coffee Break

16.00 Knowledge Café Discussions

17.30 Group Discussion

18.00 Close

 

Friday 11 September

08.30 Welcome Coffee

09.00 Predictive Toxicology for Cosmetics - An Industry Perspective, Stephanie Ringeissen (Safety Research Department, L’Oréal R&D, France)

09.25 OECD (Q)SAR Application Toolbox: Progress and Ongoing Developments, (OECD, Paris, France)

09.50 Italian Specialty Chemical Industry Perspective on Predictive Toxicology, Maurizio Colombo (Health & Safety Evaluation, Industrial Regulation Management, Lamberti S.p.A., Italy)

10.15 Coffee Break

10.45 Knowledge Café Discussions

12.00 Group Discussion

12.30 Lunch

13.30 The Italian Chemical Industry and the REACH impact on SMEs, Antonio Conto (Chemsafe Srl, Italy)

13.55 Classification- and Regression-Based QSAR of Chemical Toxicity on the Basis of Structural and Physicochemical Similarity, Oleg Raevsky (Department of Computer-Aided Molecular Design, Institute of Physiologically Active Compounds of Russian Academy of Sciences, Moscow, Russia)

14.20 Analysis of Toxcast Data and in vitro / in vivo Endpoint Relationships, Romualdo Benigni (Istituto Superiore di Sanità, Italy)

14.45 Coffee Break

15.15 Knowledge Café Discussions

16.30 Group Discussion

17.00 Close

More Information including Abstracts:

http://www.opentox.org/data/blogentries/public/opentoxworkshoprome09

Collaborative Development of Predictive Toxicology Applications

I enclose here an abstract and copy of the presentation for the Plenary Lecture "Collaborative Development of Predictive Toxicology Applications" that I presented in Istanbul on 6 July 2009 at the Fifth International Symposium on Computational Methods in Toxicology and Pharmacology Integrating Internet Resources (CMTPI 2009).

Presentation

Download OpenTox-CMTPI 2009 Presentation 90706

Abstract

Collaborative Development of Predictive Toxicology Applications

Barry Hardy*^a, Christoph Helma^b, Nina Jeliazkova^c, Romualdo Benigni^d, Stefan Kramer^e, Andreas Karwath^f, Haralambos Sarimveis^g, David Gallagher^h, Vladimir Poroikovⁱ, Sunil Chawla^j, Sylvia Escher^k

This lecture will provide a perspective on the growing significance of community and collaboration approaches in predictive toxicology.  In part these challenges are technical and involve progressing issues related to cross-organisational, enterprise and application interoperability. Additional challenges include the development and application of best practices related to knowledge management, culture, organizational and industry development.

The EC-funded FP7 project “OpenTox” (www.opentox.org) is developing an Open Source-based predictive toxicology framework that provides a unified access to toxicological data and (Quantitative) Structure-Activity Relationship i.e., (Q)SAR models. OpenTox provides tools for the integration of data, for the generation and validation of (Q)SAR models for toxic effects, libraries for the development and integration of (Q)SAR algorithms, and scientifically sound validation routines. OpenTox will support the development of applications for non-computational specialists in addition to interfaces for risk assessors, toxicological experts and model and algorithm developers.

OpenTox is relevant for the implementation of REACH as it allows risk assessors to access experimental data, (Q)SAR models and toxicological information from a unified interface that adheres to European and international regulatory requirements including OECD Guidelines for validation and reporting.  The OpenTox framework is being populated initially with data and models for chronic, genotoxic and carcinogenic effects. These are the endpoints where computational methods promise the greatest potential reduction in animal testing required under REACH. Initial research has defined the essential components of the framework architecture, approach to data access, schema and management, use of controlled vocabularies and ontologies, web service and communications protocols, and selection and integration of algorithms for predictive modelling.  The initial results of this research and next steps will be discussed.

OpenTox has been initiated as a collaborative project involving a combination of 11 different enterprise, university and government research groups to design and build the initial framework.  Additionally numerous organizations with industry, regulatory or expert interests are being included from the start in providing guidance and direction.  The goal is to expand OpenTox as a community project enabling additional expert and user participants to be involved in developments in as timely a manner as possible. To this end, our agreed upon intention is to carry out developments in an open and transparent manner from the early days of the project, and to open up discussions and development to the global community at large, who may either participate in developments or provide user perspectives.  Cooperation on data standards, data integration, ontologies, integration of algorithm predictions from different methods, and testing and validation all have significant collaboration opportunities and benefits for the community.  Additionally, practices for building effective collaborations from the OpenTox community approach will be discussed.

About OpenTox

OpenTox - An Open Source Predictive Toxicology Framework, www.opentox.org, is funded under the EU Seventh Framework Program: HEALTH-2007-1.3-3 Promotion, development, validation, acceptance and implementation of QSARs (Quantitative Structure-Activity Relationships) for toxicology, Project Reference Number Health-F5-2008-200787 (2008-2011).

Project Partners

Douglas Connect^a, In Silico Toxicology^b, Ideaconsult^c, Istituto Superiore di Sanita'^d, Technical University of Munich^e, Albert Ludwigs University Freiburg^f, National Technical University of Athens^g, David Gallagher^h, Institute of Biomedical Chemistry of the Russian Academy of Medical Sciencesⁱ, Seascape Learning^j and the Fraunhofer Institute for Toxicology & Experimental Medicine^k

Advisory Board
European Centre for the Validation of Alternative Methods, European Chemicals Bureau, U.S Environmental Protection Agency, U.S. Food & Drug Administration, Nestle, Roche, AstraZeneca, LHASA, Leadscope, University of North Carolina, EC Environment Directorate General, Organisation for Economic Co-operation & Development, CADASTER and Bayer Healthcare

*Contact Address: Dr. Barry Hardy, OpenTox Project Coordinator and Director, Community of Practice & Research Activities, Douglas Connect, Baermeggenweg 14, 4314 Zeiningen, Switzerland

 

InnovationWell 2009 Program

The fifth InnovationWell Community of Practice InterAction Meeting will take place from October 13-16, 2009 at Bryn Mawr College near Philadelphia, PA. This year's program has sessions on:

Translational Bioinformatics: Bridging Bioinformatics and Biomedical Informatics in Translational Medicine, chaired by Jake Chen (Indiana University)

Systems Biology and Biomarkers, Chaired by Darius Dziuda (Central Connecticut State University)

Modeling of the Blood–Brain Barrier in Drug Discovery and Development, Chaired by Roméo Cecchelli (Université d'Artois, France)

Predictive Toxicology: Combining in vitro and in silico Techniques in Predictive Toxicology Applications, Co-chaired by Richard Judson (US EPA) and Vladimir Poroikov (Institute of Biomedical Chemistry of Russian Academy of Medical Sciences)

Pre-Conference workshop
We will also hold a pre-conference forum on October 12 on Collaboration in Discovery and Development, Co-chaired by Peter Gates (Johnson & Johnson PR&D) and Barry Hardy (Douglas Connect).

Full details of the conference program including abstracts and speaker bios can be seen at:
http://innovationwell.net/comty_conferences
 
Or you can download a copy of the program as a pdf here:

Download InnovationWell-BM09-90812

 

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).

Dear Michael, Thanks, Respects and Inspiration to you (Michael Jackson)

Thanks Michael for all those great music videos in the 80's.  You were a leader, an innovator, doing completely new and great things back then.  You entertained us when we took a break from our studies in college in the early 80s, and tried out this new MTV experience at the time.  (It was much more interesting back then!)  You were a Thriller!

Respects to you Michael, we played and danced to your songs last night, and were not alone.

Inspiration Michael, if we can take inspiration from your tragedy and Childhood legacy you could not shake off, it is that we should take some more time to reach out to our family, friends and contacts.  Even if it is that business partner, don't just always email them, get on the Skype with them, talk and get some understanding, build some shared meaning, reach out and support. As you said:

You are not alone, I am here with you
Though you're far away, I am here to stay
You are not alone, I am here with you
Though we're far apart, You're always in my heart

And if you want to collaborate folks in this flatter world don't be alone and far away. Reach out!

The Ferryman

Collaboration in Drug Discovery and Development

I am co-chairing with Peter Gates (Johnson & Johnson) a forum session on Collaboration in Drug Discovery and Development which will take place on October 12-13 to kick-off the InnovationWell 2009 Community of Practice Meeting, which will be hosted at Bryn Mawr College (near Philadelphia) the week of October 12-16, 2009.

The specific goals of the forum are to discuss developments in collaboration support including:

- the challenges and requirement complexities across time, function and organizational spaces
- key ingredients for combined collaboration and innovation success
- promising practices, models, and solutions for collaboration
- service requirements for flexibility, evolution, and learning characteristics
- accounting for structural and business model changes in the healthcare industry environment
- key requirements and directions for collaboration infrastructure
- potential and actions for collaborative approaches to collaboration infrastructure development

Research is by its nature a set of disciplines that are undergoing constant change. Development in contrast, largely due to safety considerations, is a set of disciplines that are looking for stability, reliability and consistency. We must add to this the scale in terms of resources and duration of the pharmaceutical research and development process.

These factors combine to create formidable challenges in the creation of effective collaborative strategies. We will discuss specifically the need to build support for collaboration where change and adaptability are requirements that must be specifically engineered into our collaborative solutions.

The goal of the forum is to bring together a variety of perspectives to discuss the opportunities, challenges, practices and solutions required for successful collaboration in advancing drug discovery and development goals in an increasingly collaborative virtualized environment. We call on participants to consider a diversity of perspectives to include technical, business, scientific, medical, intellectual property, culture, and knowledge management viewpoints.

A Knowledge Café involving all forum participants will be used to have an extensive discussion of experiences and opinions.

Speakers can also submit a perspective manuscript before the meeting for refereed publication in a special focus issue to be published by the Future Science Group in Future Medicinal Chemistry in early 2010, for which Peter and I as chairs will also act as guest editors for, and to which we also intend to provide a group industry perspective as an outcome from the forum to.

Please contact Peter and I if interested in proposing a perspective to seed the discussions.

Barry Hardy

Email: barry.hardy -(at)- douglasconnect.com

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

InnovationWell 2009 - Call for Contributions

We will return to Bryn Mawr for our fifth InnovationWell community of practice meeting which will take place 13 - 16 October 2009 at Bryn Mawr College, Philadelphia.

We invite contributed papers from members of academic, government research and commercial organizations on areas of new research and innovation relevant to innovation and knowledge management in the life sciences. The work presented should involve innovative new method development or application in the areas of systems biology, translational medicine, knowledge management, computational biology, metabolomics, predictive ADME, predictive toxicology or bioinformatics. Studies including experimental work in medicinal chemistry, screening, novel in vitro assay development, pre-clinical evaluation, and translational medicine are welcome.

Abstracts (300-500 words) should be submitted to innovationwell -[at]- douglasconnect.com by 31 March 2009, and be accompanied by a short biography of the presenting author (300-500 words). Abstracts approved by the scientific organizing committee will be selected for scheduling on the conference program and in meeting poster sessions. Authors will be notified of acceptance as soon as a review of submitted materials takes place and at the latest by 15 April 2009.

The conference organising group includes Peter Gates (Johnson & Johnson PR&D), Barry Hardy (Douglas Connect, Switzerland), Frank Tobin (Tobin Consulting), Richard Judson (US EPA), Vladimir Poirokov (Russian Academy of Sciences, Russia), Romeo Cecchelli (Université d'Artois, France), Jimmy Chen (DOV Pharmaceutical), and Peter Elkin (Mount Sinai Medical Center).

Schedule for InnovationWell and eCheminfo Autumn 2008 Community of Practice Meeting

I provide below a schedule for the upcoming InnovationWell and eCheminfo Community of Practice meetings at Bryn Mawr.

I also include a location map here which may be useful upon arrival:

Download bryn_mawr_campus_map_douglas_connect_meeting.pdf

[Please follow continuation here to view schedule.]