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FEATURE | Drug Safety eClinical Technologies Remedies for Medidata: Integrating Safer Drugs >> Infrastructure First Base for Clinical Good Days and Bad in 2011 >> Trials >> c CONTENTS | January 2012

FEATURE 46 Drug Safety Remedies for Safer Drugs >> UP FRONT 8 Drug Discovery H3 Biomedicine: Health, Hope and Heaps of Japanese Funding >> 12 Data Visualization Picture This: Molecular Maya Puts Life in Life Science Animations >> 18 Genome Informatics Assembly Required: Assemblathon I Tackles Complex Genomes >> 24 High Performance Computing Products, Deployments, and News from Supercomputing 11 >> 26 News Briefs >> 28 INSIDE THE BOX The Unstable Equilibrium of the Bioinformatics Org Chart >> 32 THE BUSH DOCTRINE The Pharmaceutical Safety Data Problem >>

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ARTICLES 36 eClinical Technologies Medidata: Integrating Infrastructure for Clinical Trials >> 42 Diagnostics A QuantuMDx Leap for Handheld DNA Sequencing >> 44 Informatics Tools Accelrys’ Cheminformatics Solution in the Cloud >> KNOWLEDGE CENTER 54 New Products >> 56 Free Trials and Downloads >> 58 Upcoming Events >> 60 Complimentary Resources >> IN EVERY ISSUE 6 FIRST BASE Good Days and Bad in 2011 >> 66 RUSSELL TRANSCRIPT What is (Quantitative) Systems Pharmacology? >> 64 On Deck | 64 Contact Us | 65 Company/Advertiser Index >>

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Medidata-Solutions-Bio-IT-World-05JAN2012.indd 1 1/5/2012 12:31:01 PM First Base c Good Days and Bad in 2011

By Kevin Davies enthusiasm, that is, I fear, just slightly beyond

CONTENTS our scope. t must be so much fun being a physicist right In 2011, Bio•IT World hosted Stephen Wol- now. Scientists have discovered two mon- fram and a record attendance at the Bio-IT ster black holes—the largest on record—with World Expo, and convened its first Cloud masses several billion times that of the Sun. Computing conference, reflecting the rapidly And in the Goldilocks Zone of a nearby gal- growing capacity to spin up supercomputing Iaxy, a planet known as Kepler 22b orbits with a tasks as well as the expanding acceptance of balmy atmosphere of 72° F, a prime candidate the potential of infrastructure-as-a-service. We for life off earth. also enjoyed covering the potential of new tech- At the other end of the matter scale, sci- nologies in the form of “wellness chips” (see, entists have caught their first glimpse of the “Turning Blood into Gold,” Bio•IT World, July Higgs boson, the so-called “God particle.” And 2011) and “SNP-doctors,” (see, “Powering Pre- we are still waiting with baited breath for con- ventative Medicine,” Bio•IT World, September firmation that neutrinos can travel faster than 2011) as well as the creation of the New York the speed of light, as hinted a few months ago. Genome Center (see, “Genome Center for Go- In reflecting on the past year in life sciences tham,” Bio•IT World, November 2011). Some and IT, however, such notable feats are some- of our New Year’s well wishes go to its founders what harder to find. A list of the top ten science in strengthening what must be at times a tem- stories of 2011 in the Guardian, compiled by pestuous alliance of Big Apple egos. veteran science correspondent Robin McKie, includes three of the physical sciences stand- Cancer Connections outs above, but only a couple of items in con- A story that did not receive as much media at- temporary biology. tention as it should was the approval by the One was the rather sad exit of biotechnol- Food and Drug Administration in August ogy pioneer Geron from the human embryonic 2011 of a pair of targeted cancer drugs and stem cell field it helped to create. The other, their companion diagnostics. One was Pfizer’s more cheerily, was the imaging study of a fe- Xalkori, which treats a small percentage of male brain experiencing orgasm, but while im- patients with advanced non-small-cell lung aging is an important technology we cover with cancer (NSCLC) harboring mutations in a gene

6 JANUARY 2012 Visit Us at www.Bio-ITWorld.com called ALK. (A diagnostic test from Abbott question: what did the doctors find in his Molecular reveals the mutation.) The other DNA? While for obvious reasons, Washington c was the melanoma drug Zelboraf (Plexxikon), University could not comment on Hitchens’ which is accompanied by a BRAF mutation prognosis, at a conference last October, Mar- test. dis presented an intriguing case study of a pa- While on the topic of cancer, two papers tient with a long history of tobacco and alcohol published this year by the team of Rick Wilson, abuse, referred to simply as “ESC1” (esopha-

Elaine Mardis, Timothy Ley and colleagues at geal cancer patient #1). CONTENTS Washington University in St Louis, illustrated ESC1’s tumor, it turned out, carried muta- the potential of individual genome sequencing tions in a gene called DDR2. A quick PubMed in revealing molecular aberrations in cancer search reveals a couple of interesting facts: patients, even if the ensuing targeted treat- first, DDR2 mutations have been associated ments don’t always prevail or arrive in time. with several metastatic cancers. Second, the Ironically, two of the most famous cancer protein encoded by this gene is a potent target patients to pass away in 2011—Steve Jobs and of Gleevec and related tyrosine kinase inhibi- Christopher Hitchens—both underwent ge- tors. So one can see the rationale for switching nome sequencing. According to Walter Isaa- this patient to Gleevec. ESC1 responded well cson’s best-selling at first, but Mardis stressed that her colleagues biography, Jobs were not managing the patient’s care and did had his genome se- not have up-to-date information. quenced by research- Hitchens, who said cancer was like a “malig- ers from Stanford, nant alien” in his body, died from pneumonia Johns Hopkins, Har- in December at the M.D. Anderson Cancer vard and the Broad Center in Houston, writing columns and meet- Institute. Hitchens, ing deadlines to the end. His death hit me following a recom- harder than Jobs’, I suppose because we had mendation from a COMMONS LICENSE ANDREW RUSK/CREATIVE a few things in common: scotch-loving British person the Daily Christopher Hitchens journalists and authors, both graduates of Ox- Mail headline called an “evangelical Christian ford University. Of course, there the compari- doctor”—perhaps better known as NIH direc- son ends. tor Francis Collins—was sequenced by the St In one of his last interviews, Hitchens told Louis group in early 2011 as he battled stage IV the BBC: “Whatever day came that the news- (metastasized) esophageal cancer. papers came out and I wasn’t there to read Hitchens himself revealed that as a result of them, I’ve always thought that would be a bad the sequencing, he was now taking Gleevec, day—at least for me.” the Novartis drug for leukemia, begging the And us, Christopher. Cheers. •

Visit Us at www.Bio-ITWorld.com JANUARY 2012 7 UP FRONT | News c H3 Biomedicine: Health, Hope and Heaps of Japanese Funding [ Drug Discovery ] With a $200 million commitment from Eisai Co., cancer drug start-up has clear path ahead. CONTENTS

BY KEVIN DAVIES name Haruo to be included in that. ‘Human, CAMBRIDGE, Mass.—The ‘H3’ in the name of health…’ I definitely believed ‘Haruo’ comes the new oncology drug company H3 Biomedi- last. But it is ‘hope’—a great disappointment!” cine stands for “Human. Health. Hope.” he joked. It might also stand for the heaps of Japa- Eisai is not just writing a handsome check nese investment—up to $200 million—that it but providing ready access to its drug discov- is receiving from Eisai Co., Japan’s fourth larg- ery and development resources. Several Eisai est pharma company. It is an interesting and chemists have already moved to the U.S. to join possibly unique funding model that spares the H3 Biomedicine’s 30 or so current employees in company the travails of seeking venture finance the gleaming new laboratories (see “Lab Life”). or short-term licensing deals, says co-founder H3’s philosophy marries expertise in can- Stuart Schreiber, professor of organic chemistry cer genomics—the forte of co-founder Todd at Harvard University and the Broad Institute. Golub—with discovery-oriented organic syn- One year after H3 Biomedicine’s official thesis, a field in which his Broad Institute col- launch in December 2010, it formally dedicated leagues Stu Schreiber is an authority. its pristine research laboratories in the heart of Kendall Square, Cambridge, with a ribbon- Clean Slate cutting ceremony held in a swanky new res- “This is an exciting time in cancer research,” taurant—fittingly named Catalyst—in the same said H3’s CEO Markus Warmuth, a German building. Joining president and CEO Markus oncologist. “15 years ago, our knowledge was Warmuth were dignitaries from Massachusetts limited to a few genes. Today, we have data on state and local government, as well as Haruo hundreds of cancer genomes, and it is increas- Naito, president and CEO of Eisai. ing super-exponentially on a daily basis.” “When I first heard of this company’s name, “We have a clean slate, we can look at what H3 Biomedicine, I asked what the abbreviation we learned from cancer genomes, and try to de- stands for,” said Naito. “I was expecting my velop drugs for patients from here. That’s why I decided to join H3 Biomedicine,” Warmuth

8 JANUARY 2012 Visit Us at www.Bio-ITWorld.com c CONTENTS

Stuart Schreiber, Haruo Naito, Markus Warmuth and Todd Golub toast the launch of H3 Biomedicine. continued. the pressure and enable us to take a long-term “We’re trying to be very focused; we’re not [approach] at a time that many other companies opportunistic, it’s not a random walk in the are trimming down their research budgets.” park,” he said. “We’re trying to combine new Warmuth noted that the company’s two insights into the pathogenesis of cancer, de- co-founders conveniently had their offices at rived from actual patients’ cancer genomes, to the Broad Institute, just two minutes walk from bring new small molecules to patients in need… H3’s location. Schreiber is a renowned chemical We have to be very patient to be successful in biologist who is the co-founder of Vertex, Ariad, developing drugs.” and Infinity Pharmaceuticals. Todd Golub is Warmuth said that H3’s success would be the founding associate director of the Broad greatly aided by having “investor pressures” Institute and also the co-founder of Foundation off its back, “so we can focus on real scientific Medicine, among others. questions and move forward developing drugs,” H3 will be tackling cancer in general, not fo- he said. “We’re very happy to have the investor cusing on any specific therapeutic areas. “We’re [Eisai] in the background, who has given us a looking at the cancer genome, no matter if its tremendous amount of money to really alleviate lung cancer or breast cancer or liver cancer. We’re looking for the best opportunities— >>

Visit Us at www.Bio-ITWorld.com JANUARY 2012 9 UP FRONT | News

<< we’re not trying to just make lung cancer try professor and colleague of Schreiber’s. c drugs or breast cancer drugs. Let’s look at what The pharmaceutical prowess of Kishi and the cancer genome actually tells us.” colleagues was demonstrated in the synthesis Eisai CEO Haruo Naito noted that his com- of Halaven, approved by FDA in late 2010 for pany has long-standing roots in the Boston area, late-stage metastatic breast cancer. “It is the having established the Eisai Research Insti- first time a drug is proven to extend life of such tute in 1988 in Andover, Mass. Two of the four late-stage cancer patients,” said Naito.

CONTENTS founding scientists are still present, under the The development of Halaven took 16 years leadership of Yoshito Kishi, a Harvard chemis- from early discovery. The compound is found

Lab Life

Construction of the first phase of H3’s lab mizing safety while minimizing energy expen- space was completed last July, with 48,000 ditures. Evaporation equipment is housed in square feet currently, including spotless labs ventilation hoods, with circulating ethylene for synthetic chemistry, bacterial, and tissue glycol to cool reactions. culture, and genome analysis. The design of- Every chemist is equipped with a lab lap- fers a hybrid between open office space with top providing access to electronic literature glass frontage and respect for scientists’ priva- and Eisai databases and resources. They also cy. “I think it’s important that sometimes you have access to a walk-up mass spectrometer can shut the door and think about a problem,” and a 400-MHz Bruker NMR machine in a said Warmuth. specially vaulted room. “It’s really a privilege The common room/coffee break area is to have a piece of equipment like this,” said surrounded by four modern seminar rooms, Reynolds. each named hope in a different language: Es- “We want to take advantage of modern peranza, Amal, Hope and Kibou. A planned synthetic methods to generate proprietary expansion will include a brainstorming room chemical libraries that take us into chemi- with no projection capabilities, just wall-to- cal space not occupied by anyone else,” said wall white boards and music. Reynolds. The emphasis is on quality, not “It’s absolutely terrific to work in an en- quantity, with the goal of generating chemi- vironment like this,” said chemist Dominic cal libraries containing a relatively modest Reynolds, who trained at Cambridge Uni- 15,000 or so novel compounds a year. versity with Steven Ley. The fume hoods are “We’re embracing old combinatorial surprisingly quiet and split into two, so maxi- methods, but we’re not in an Arqule-style,

10 JANUARY 2012 Visit Us at www.Bio-ITWorld.com in an “ugly black sea sponge” that lives off the take 16 years!” joked Naito. “‘H3’ means three coast near Tokyo. Scientists collected 600 kg of years!” The most important ingredient in H3’s c the sponge to produce 1 mg of anti-tumor agent. ultimate success, he said, would be “the fighting Kishi’s group synthesized the highly compli- challenging spirit to do something new.” cated structure in a tour-de-force 61-step syn- “We want to be very fast and focused,” War- thesis (accommodating 19 chiral carbon atoms muth concluded. “I’d be perfectly OK if we only that resulted in more than 500,000 potential ever work on three projects, if they are all suc- compounds). cessful and produce good drugs.” • CONTENTS “I hope, Markus, in your case, it won’t

300,000-compounds-a-year mode,” he said. Assays will include protein levels and phos- “We’re looking for privileged novel scaffolds phorylation, DNA manipulation and trans- that we can decorate and access and screen formation, and tissue culture—creating cell quickly.” lines with different genetic backgrounds to One of the key differentiators of the new help understand which patients will respond company, Reynolds explained, is that H3 is to various drugs. performing chemical syntheses in solution “We’ll take different levels of genetic in- phase, in contrast to programs at say Infinty formation and mutation status, and we’ll look Pharmaceuticals (another biopharma that for fusions of genes and epigenetic changes. has featured Schreiber’s diversity-oriented We’re not just focusing on one particular ab- synthesis expertise) or the Broad Institute, erration but building the importance of those which run polymer-supported chemistry to genetic aberrations to find the right target,” facilitate the generation of massive numbers said Smith. of compounds. “Here, the chemistry is much Smith said the goal is essentially to define more tailored to each core, hence the smaller the experiment on day one, to understand numbers… so it’s all solution based and HPLC- what needs to be done in the patient and rep- purified at the end, which is really important licate that through enzymology, cell biology, for the medicinal chemists,” said Reynolds. animal models, and ultimately into the pa- Liverpudlian Peter Smith, previously at tient. “Knowing the question at the outset the Dana Farber and Millennium, said he helps us prosecute efficiently, so we should get had a blank slate to buy the right equipment the answer quickly when we go into clinical “to prosecute the biology side of the project.” studies,” he said. •

Visit Us at www.Bio-ITWorld.com JANUARY 2012 11 UP FRONT | News c Picture This: Molecular Maya Puts Life in Life Science Animations [ Data Visualization ] Based on the Autodesk platform, Digizyme plug-in proves aesthetic and educational effectiveness. CONTENTS

BY KEVIN DAVIES In 2010, a reporter sat in a Life Technologies hotel suite admiring a promotional video il- lustrating one of the company’s latest research projects—a single-molecule sequencing system featuring enzymes tethered to fluorescing quantum dots. The video was impressive not merely for pushing the boundaries of sequencing technology, but equally for showcasing some powerful production qualities in 3D animation and rendering that, until recently, would have seemed the provenance of a Pixar movie. That video was produced by a Boston com- A mitochondrial molecular landscape depicting sig- pany called Digizyme (www.digizyme.com), naling proteins in apoptosis (created by Digizyme founded in 1999 by Gaël McGill as a side busi- for Cell Signaling Technology).” ness while he worked on his Ph.D. at Harvard museums, and public television stations. Medical School. Since then, Digizyme has be- After a hiatus to run the company full time come a respected source for educational and after his postdoctoral fellowship, McGill joined promotional animations, simulations and vid- the Harvard Medical School faculty five years eos for many diverse life science applications. ago in the Center for Molecular and Cellular “The visual communication of science— Dynamics, where his research focuses on how that’s where my passion is,” says McGill. He rec- visualization impacts research and education. ognized early on that graphic design, animation He is also creating a new graduate program to and visualization tools were needed by several train students in biovisualization approaches. industries, not least his fellow scientists. Clients Most companies offering animation tools include academics as well as biotech, pharma, are staffed by visual specialists or animators medical device companies, along with science with a strong artistic background collaborating

12 JANUARY 2012 Visit Us at www.Bio-ITWorld.com with scientists. “There are some great companies ware suites, such as Maya.” in this space, but what sets us apart is that we’re McGill says that current bioscience research c scientists,” says McGill. “Everyone at Digizyme features “an incredible richness of datasets that is dually-trained as a scientist-animator, scien- is just overwhelming. We see visualization as tist-artist, or scientist-programmer. As a result, the key to knowledge integration—it offers a our visualizations are directly informed by the powerful and flexible platform to import and primary literature and based on raw data.” synthesize data from various fields—data that

At Digizyme, McGill recruits twin-threat would not otherwise interact.” CONTENTS staff with a science graduate degree as well as One example would be to create an intracel- strong artistic talent. The com- lular landscape using cryoEM tomography data pany has created stereoscopic to map the location of proteins in a cell. This movies for science museums, map could be populated with atomic resolution custom projects for pharma protein structures, and then set in motion and clients including Amgen, J&J, simulated using various algorithms including Novartis, Life Technologies, Brownian dynamics. “This begs the question: and Genentech, as well as What software do I use for this sort of thing? It completed work for several doesn’t currently exist, but it’s something that major hospitals, research in- interests many scientists. Our approach is to stitutes, and universities. Mc- modify and adapt existing animation tools from Gill is also the Digital Media Hollywood—platforms like Autodesk Maya—to Director and a collaborating advance toward that goal.” author for E.O. Wilson’s ‘Life McGill’s team built a new layer of code to on Earth’ digital biology textbook. make Autodesk’s Maya more biologically relevant, resulting in a plug-in toolkit called Mo- Going Hollywood lecular Maya (mMaya). (see, “A Better World”) The software that powers the Digizyme plat- Molecular Maya focuses the modeling, ani- form is Maya, a suite developed by Autodesk, mation, rendering, and simulation capabilities which is a modeling, animation, simulation, of Maya in the context of biological animations and rendering application widely used in media and structures. For example, instead of model- and entertainment circles to create video game ing DNA from scratch, it provides a direct link characters and environments and special effects to a scientific database that downloads data for feature films. Of course, such software was directly into Maya and automatically creates never intended to display life sciences data. the 3D model. McGill and his team are also de- “What are we doing with Hollywood soft- veloping tools in mMaya to rig macromolecules ware?” says McGill. “There’s been billions of to facilitate biophysically-accurate animations dollars invested in films to create powerful soft- as well as to build molecular environments. >>

Visit Us at www.Bio-ITWorld.com JANUARY 2012 13 UP FRONT | News

<< Molecular Maya is written in languages with renowned structural biologist Stephen c (including Python and MEL—Maya Embed- Harrison, who specializes in proteins on the ded Language) that allow other researchers to surface of HIV, McGill created an animation extend its capabilities. “We’ve created a series that depicts how a viral surface protein—gp41— of free, open-source scripts that lets anybody spears the target cell membrane and refolds on type in a protein ID, say, and with a click, have itself to drive membrane fusion and facilitate this directly connect to the Protein Data

CONTENTS Bank so they can model, manipulate and animate a protein within seconds,” says McGill. This accessibility came to light in the recent IGEM (International Genetically http://www. Engineered Machine) world jamboree, where student teams from around the molecularmovies.com/ world used synthetic biology principles to design novel cellular circuits and hybrid movies/mcgilliwasa_ proteins. “For a student team trying to design something in a forward engineer- reovirus.html ing approach, the design piece is not just making a pretty picture, it can be an in- tegral part of the conceptualization and Digizyme models the cellular entry of a reovirus. experimental approach,” says McGill. For the past few years, he has been involved with viral infection. Proteins aren’t static, they’re this competition by hosting seminars and offer- shape shifters,” says McGill. “gp41’s conforma- ing workshops to help students use Maya and tional change cannot be depicted with the typi- Molecular Maya. (Autodesk has also sponsored cal linear interpolation morphing techniques. IGEM the past three years.) It undergoes a helical transition and refolds completely.” And trying to communicate such a Not Just Pretty Pictures critical and unusual conformational change in a McGill underscores the critical role that visual- standard research paper was next to impossible. izations can play in experimental research. “I’ve McGill’s group helped Harrison visualize worked with colleagues at Harvard Medical gp41’s unique conformational change and, in the School where the process of creating a visual- process, communicate the mechanism in a way ization can change one’s understanding of the that hopefully facilitates drug discovery. “Un- protein,” says McGill. derstanding the specific mechanism of how gp41 In one project carried out in collaboration refolds may drive better approaches to drug >>

14 JANUARY 2012 Visit Us at www.Bio-ITWorld.com A Better World c

The life sciences community might appear a velop visualization tools for their industries. little staid next to some of Autodesk’s other We want to extend and enable that.” marquee clients, including James Cameron, One of the keys to Maya’s popularity is Frank Gehry, Disney, and not just the modeling, texturing and ren-

Boeing. Not so, insists Patrick dering capability, but its extensible nature. CONTENTS Byrne, director of business de- Users can write their own plug in, which can velopment for the Californian be complex or very simple. For students and company that celebrates its academic users, Autodesk offers free access 30th anniversary in 2012. to the software for three years in a termed- “Our mission is helping free license (http://students.autodesk. customers imagine, design com/). “As you’re perfecting your skill, let’s and create a better world,” make sure you have access to the tools to says Byrne. The principal cus- perfect your craft,” says Byrne. tomers are in architecture/en- Byrne sees three prime opportunities for gineering, manufacturing and Maya in the life sciences: first, as a platform media/entertainment. Within for innovative tools; second, use in science the latter group, Autodesk education curricula; and third, helping sci- has been building a product entists in industry visualize and communi- development group to extend Maya into life cate research to a wider marketplace. sciences. “It sits in our media and entertain- There is some strong competition in ment team, because Maya was developed for the marketplace, including an open-source media professionals,” says Byrne. product called Blender, and its derivative But why life sciences? “When we look at Bio-Blender, but Byrne sees the market the range of industries we’re in, the concept expanding. of design workflows is transparent across all Support of the IGEM competition, for industries. Whether you’re in one of those example, puts Maya in the hands of a global industries, our tools enable you to be more student body eager to harness the software efficient, more iterative and more creative. in various synthetic biology applications. And when we look at academic research, we Byrne says he is proud of the MIT group, see an interesting place,” says Byrne. “With- which won the 2011 IGEM prize in the out much ado from us, people like Gael have health/medicine category, enabling cells to taken Maya and used it as a platform to de- autonomously regenerate. •

Visit Us at www.Bio-ITWorld.com JANUARY 2012 15 UP FRONT | News

<< discovery or vaccine development,” he says. c Another example is Shawn Douglas (Wyss Center, Harvard Medical School), a former visualization student of McGill’s and now a leading figure in the field of DNA Origami—designing novel DNA molecules to fold in vitro to create biologically useful entities. Douglas’ Maya

CONTENTS plug-in, Cadnano (http://cadnano.org), greatly simplifies DNA origami projects and brings the power and ease of use of typical modeling tools in Maya to this rapidly growing field. “We’re now collaborating to have both plug-ins—mMaya and Cadnano—work together 3D visualization techniques prove a valuable tool inside Maya,” says McGill. “Cadnano figures for teaching molecular biology. out how to create the genetic sequences that, when mixed in a test tube, fold into the shape of collaborators tested students before and after an object modeled in Maya. It’s magic—a great viewing these animations as well as monitored example of how a design tool can transform a their reactions using eye-tracking methods. process that previously took weeks or months “Typical medical animations often impart deci- to navigate.” sion-making properties to molecular entities—as Visualization research isn’t just about mak- if molecules know where they are going. This ing movies but also about understanding how couldn’t be further from the truth!” says McGill. to design the most effective movie to impact a He acknowledges that creating animations that target audience. Says McGill: “We’re very inter- depict both the stochastic nature of the molecu- ested in understanding how design choices— lar world while keeping students’ attention on how we represent or animate a process—can the mechanism and specificity of an interaction have an impact on the effectiveness of a movie, is quite a design and technical challenge. especially in the context of educational anima- McGill has created an educational web site tions. We strive to create animations and inter- called molecularmovies.com. It has three sec- actives that have a high pedagogical impact on tions: one is a Showcase of some of the best on- students, not just animations that are engaging line cell and molecular animations, organized and aesthetically pleasing.” by scientific topic. A Learning section contains In one recent project, hundreds of students McGill’s teaching curriculum at Harvard Medi- assessed four different styles of animating a cal School, available free. And third is the Tool- simple molecular interaction: a hormone bind- kit section, where researchers can download ing to a cell surface receptor. McGill and his Molecular Maya. •

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Drug Discovery Research arrangements. They were designed for HEOS – A SaaS Based Solution and Externalization scientists who were employees with mostly Design to Facilitate Externalized free to access the data and for IP that was Discovery Research For most pharmaceutical and biotech com- all owned within the company, but in col- panies, discovery research has become an laboration networks, each partner is likely HEOS is a SaaS based system designed externalized process across networks of authorized to only see part of the data, and from the ground up to address the data in-house, academic and research institute the IP ownership may be with the commis- management issues within externalized collaborators and CROs where synthesis, sioning company or across the partners. drug discovery projects, securing the IP of assay development and execution, safety each party and providing real time sharing assessment and other aspects of the How Do Companies Solve and access to project data to maximize the process may all be conducted by different the Problems Today? projects efficiency and drive forward innova- organizations. tion. By using HEOS, project teams across Recently there has been a change from one- Most companies today solve the problem all organizations can have instant access to to-one relationships between a pharma/ in one of two ways, each of which has information that they are authorized to see biotech and a CRO to dynamic networks significant drawbacks. about their projectsand securely share the data that they are responsible for generating in which several partners collaborate on 1. Exchange of files. Data is traded in files with the rest of the team. HEOS provides a single discovery project,and are added over email, via FTP or in E-rooms which upload, storage and search of all types of or removedaccording to specific skills. • has the potential to be insecure complex data critical for drug discovery Whilst early collaborations focused on • makes it hard to keep track of IP own- projects including biology, chemistry, safety cost-reduction with fee-for-service rela- ership as files move around and pharmacokinetics for example. tionships, now partners are sought for • is not real time advanced technology and expertise, and • can be error prone or lead to ambiguity For the organization commissioning the IP is discovered jointly. in interpretation research it has the benefit that this col- • is costly and time consuming laboration happens in the cloud and there Challenges for • is impossibly complex as the number is a clear delineation between their collabo- informatics Systems of collaborators on a single project ration system and their in-house systems grows and data. As a SaaS based solution it is These new arrangements bring significant easy for a new collaboration to be spun up data management challenges: 2. CRO/Collaborator access to internal quickly and then shut-off just as quickly at systems. The lead company opens up the end of the engagement with the data • Each participant needs to share their access to their internal systems allow- from that partner secured in the system. data with the commissioning company ing the CRO to access or deposit data and appropriate partners directly into those systems. Most in- • Each partner needs real-time access to house systems provide row-level security To learn more join the web the data from other partners that they to allow data access to be controlled but require to complete their work symposium on January 19th: were designed with the assumption that • Dynamic collaborations must be spun up most data can be shared and that those Enhancing Productivity of and down as fast as the collaboration accessing the IP are company employ- network changes Internal and Externalized ees. There is a risk involved in opening IT departments struggle to support the up these systems and an IT cost to Research through Integrated partnerships with in-house data manage- ensure that the systems are secured Cheminformatics Systems ment systems not designed for external for external access and monitored UP FRONT | News c Assembly Required: Assemblathon I Tackles Complex Genomes [ Genome Informatics ] The genome assembly competition challenged entrants to assemble a synthetic, ‘human-ish’ genome. CONTENTS

BY KEVIN DAVIES From familiar but repeat-laden plant species to obscure vertebrates, more and more genomes are being sequenced that require de novo assembly without alignment to a reference sequence. “Every genome has its own story in terms of repeats,” says Ian Korf, associate director of bioinformatics at the University of California Davis Genome Center. Korf is one of the principal organizers of a genome assembly challenge known as the Assemblathon—a competition to identify best practices in the de novo assembly of complex plant and animal genomes. Results of the first phase of the Assemblathon were recently published in Genome Research. Korf discussed some of the Assemblathon results and, more broadly, the inherent challenges in genome assembly in a recent webinar vertebrate genomes. Clearly, in order to se- hosted by the community forum NGS Leaders. quence and assemble 10,000 genomes, it is cru- “Sequence analysis starts after genome assem- cial to know what is the best sequencing and as- bly—you can’t do much beforehand... Every sembly technology for the money. “It definitely genome is a complex genome—even the sim- becomes a cost-benefit ratio looking at 10,000 pler ones are pretty complex. There’s no easy genomes,” says Korf. genome,” says Korf. Joseph DeRisi (Berkeley), David Haussler The Assemblathon grew out of the G10K (UCSC), and Illumina helped launch the As- project, which is an effort to sequence 10,000 semblathon idea. The original goal was to make

18 JANUARY 2012 Visit Us at www.Bio-ITWorld.com two targets: one was a real genome (snake), the reads together. “Because we knew the answer, other a synthetic genome, to enable participants we could evaluate each one of the assemblers,” c to determine how well they performed. In the says Korf. event, the snake data weren’t ready, so Assemb- lathon I, which took place in early 2011, utilized Results Are In just the synthetic genome. Commenting on the results, Korf said: “A lot To create the synthetic genome, the organiz- did a pretty good job, but it’s more difficult to ers took a copy of human chromosome 13, and assemble regions with more mutations, so the CONTENTS artificially evolved the sequence using Evolver coding regions were assembled better than non- coding regions.” (The contest did not test the growing number of commercial assembly pack- ages, from the likes of CLC bio, DNAStar, Gene Codes and others.) The assemblies were ranked by various criteria, including contig and scaffold paths, structural and copy number errors, and so on. In the final rankings, the top five were: • Broad Institute (ALLPATHS-LG) • BGI (SOAPdenovo) • Wellcome Trust Sanger Institute (SGA) • DOE Joint Genome Institute (Meraculous) • Cold Spring Harbor Lab (Quake, Celera, Bambus2) Several useful tools emerged, says Korf, but experience in using the tools makes a big difference. “We found that sometimes two groups will use the same assembler, but the group that Ian Korf says assembly can’t be a stepwise process; knows a bit more about the assembler might do it starts as far upstream as library preparation. a slightly better job. It’s something of an art at software, which introduced mutations in differ- this point,” said Korf. ent regions (coding/non-coding) and at differ- Korf says that wisely choosing the many dif- ent rates. “The sequences were human-ish, but ferent parameters involved in de novo genome after 200 million years of evolution, didn’t look assembly is difficult and “probably shouldn’t that human,” says Korf. be attempted by amateurs.” He advises inex- The Assemblathon participants—17 groups perienced users to “contact one of the major in all—were then challenged to put the synthetic sequencing centers and get them to help you. >>

Visit Us at www.Bio-ITWorld.com JANUARY 2012 19 UP FRONT | News

c Reads and Errors

These two paragraphs illustrate the different type of reading errors associated with Illumina and PacBio data, according to UC Davis’ Ian Korf. Illumina sequencing data are made up of very short reads with few errors. Pacific Biosciences technology has a higher (10-15%) error rate, but the sentences (reads) are long enough that they can

CONTENTS largely be interpreted.

ILLUMINA: PACBIO: e pro opria e acc plays erial ng. T in so ks is ll In the past, genome prbjects moved rather in case meter lete s is gene a cr s tas ining slowly, and the tricqle of data meant lhay plete the s s are ay, s g the nome gene a gen parameters could be estimjqeg before tfs f amo most geno uracy ainin prope s cou genome wns coq that parameterg iould be inder es so dant. mate the f and t ckly, st im qstimgted before the genome was completej can iven ole b ous t ckle more and m ing a Today, saqwencing and assemblm are so ripid ene s mong es ar any f e of rmini proj he fi that genomes cag appear well in advazce cy s rel leav on pl ar we ng ma ly. T hout st im nh a gene finder depebds on many facrors. ather ortan genes a la , and find firs n pro Chief agong these is proper graining. Training appea . Giv equen ts pr be e ical ermin e ann a gene finder can ie a laborbous task. In the ably. ensiv plete lete. raini le be f its es ar past, genome ckly, one meant pends t imp ture ore t appe task. se it assem apid

<< Doing it on your own is pretty much guaran- “It’s really garbage in, garbage out,” says Korf. teed to give you a sub-optimal assembly… Don’t “So much is dependent on having high quality jump into genome assembly thinking it’s just sequence and making your libraries correctly.” like any other bioinformatics problem you can Indeed, some Assemblathon participants be- hack with some Perl scripts.” lieve there should be a library construction It starts as far upstream as DNA library competition, because that’s more important in preparation. “You don’t want to choose the as- some ways. sembler as the last thing you do,” says Korf. “It Another wise move, says Korf, is to perform must be in conjunction with the sequencing a pilot project “to explore what your genome technology, how are the libraries made, the full looks like” and gauge the overall repeat con- equation. You can’t do it stepwise.” tent of the genome in question. For example, Library preparation is a non-trivial step. in a recent project to sequence the gigantic >>

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<< pine genome (22 billion bases, three times Korf says UC Davis was one of the first cen- c larger than the human genome), his group ters to receive a commercial PacBio machine, al- was surprised by the extent though it is currently being to which the DNA repeats used for studies of genome were diverged. The most t’s really garbage in, biology (centromere struc- common repeat only made ‘I ture, fragile X repeats) than up 3% of the genome, mak- garbage out. So much assembly. “There are cer-

CONTENTS ing it easier than expected is dependent on having tain things that PacBio can to assemble. “You should high quality sequence do that nobody else can do. do a little homework ahead We like those things! Yes, of time to get an idea of GC and making your there are errors, but better content and other factors,” libraries correctly.” to ask the question with a says Korf. few errors and have to do a —IAN KORF, University of California Davis Genome Center little harder analysis than Longer Lengths not be able to do it at all.” The availability of longer Korf believes the NGS read lengths, such as those produced by the Pa- community—“super smart people, full of com- cific Biosciences platform, should complement petitive spirit”—will figure out how to use these existing short read systems and prove a boost 3rd-generation technologies. “Right now, they for genome assemblies. “The long reads are haven’t had enough time to figure out how to fantastic, but the error rate is a bit of an issue,” put it all together, but they will pretty soon,” he said Mario Caccamo, head of bioinformatics at says. “What you’ll get three years from now will The Genome Analysis Centre in the UK and a be a lot better than today.” co-author of the Assemblathon I report. For the second round of the Assemblathon, But Korf says the PacBio reads can prove which concluded at the end of 2011, participants very useful in integrating with short read data: have belatedly tackled the snake genome, along “Genome assembly with longer reads will get with the bird and fish. “The disadvantage is that much, much easier. The game will be com- we don’t know the answer in the end,” said Korf. pletely changed with reads on the order of 10 Those results will be announced later in 2012. • kilobases.” FURTHER READING: Earl, D.A. et al. “Assemblathon I: A As an analogy, he offered two paragraphs, competitive assessment of de novo short read assembly representing the shorter Illumina reads and methods.” Genome Research 21, 2224-2241 (2011) the PacBio read lengths (see, “Reads and Er- The NGS LEADERS webinar, “De Novo Assembly of Com- rors”), pointing out that despite the errors in the plex Plant and Animal Genomes,” featuring Mario Cac- PacBio segment, it was still possible to interpret camo (TGAC), Ian Korf (UC Davis) and Jeffrey Rosenfeld the text. (UMDNJ), is available on demand.

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12bpn_bioitworld_010412.indd 1 1/4/12 5:46:35 PM UP FRONT | News c Products, Deployments, and News in Supercomputing [ High Performance Computing ] The atmosphere at SC11 was big data-focused and full of new tools. CONTENTS

BY BIO-IT WORLD STAFF simple, GPU-vendor-neutral, full of functions, SEATTLE—November’s Supercomputing 11 and free for most users.” (SC11) conference* in Seattle was full of news Jason Stowe (of Cycle Computing) was and product announcements across the indus- working the Amazon Web Services booth. try. Here’s a sampling of what caught Bio•IT AWS theorized a bit on the cloud’s role in high World’s ear. performance computing in a blog post mid- Top500 announced their newest list. The week, and announced a new type of instance— Top 10 order didn’t change, but the space be- CC2, or Cluster Compute Eight Extra Large—at tween systems did. Japan’s “K Computer”, at the event. the number one spot, completed a build out Cycle Computing offered $10,000 worth to make it four times as powerful as China’s of free CycleCloud time plus technical support Tianhe-1A system in the number two position. (at SC11 Amazon kicked in their own $2,500) to The Cornell Center for Advanced Com- help a research group address an “un-askable puting received an HPC Innovation Excellence question” as part of its BigScience Challenge. Award from the International Data Corpora- The finalists named at SC11 were Alan Aspuru- tion for enabling hepatitis C virus research on Guzik and Johannes Hachmann from the Har- a remote experimental MATLAB computing vard Clean Energy Project; Jesus Izaguirre from resource located at Cornell University. the University of Notre Dame; Soumya Ray from AccelerEyes launched ArrayFire, a freely- Harvard Medical School; Victor Ruotti from available GPU software library supporting Morgridge Institute for Research; and Martin CUDA and OpenCL devices. “ArrayFire is our Steinegger from TU Munich ROSTLAB. best software yet and anyone considering GPU Bright Computing is a company worth computing can benefit,” said James Malcolm, watching for their cluster management capabili- VP Engineering, in a press release. “It is fast, ties in the cloud and new status as an Amazon Web Services Solution Provider. Bright just * International Conference for High Performance Comput- ing, Networking, Storage and Analysis, Nov 12-18, 2011, announced comprehensive support for cloud Seattle, Washington bursting: with a few mouse clicks, customers

24 JANUARY 2012 Visit Us at www.Bio-ITWorld.com can either create new clusters in the cloud or The United Kingdom’s National Grid Service add cloud-based nodes to existing clusters that has adopted Globus Online as the preferred data c Bright manages like part of the local cluster. movement method for its users. Convey Computer announced a part- NETLIST introduced its new 32GB Virtual nership with Nimbix (link to PDF) to deliver Dual Rank HyperCloud Planar-X RDIMM, en- Convey’s unique hybridcore architecture and abling up to 768GB in a standard two-processor bioinformatics personalities as a cloud-based server, and demonstrated 1333 MT/s (mega

HPC solution, and a doubling of its Graph500 transfers per second) on a standard server. CONTENTS performance (link to PDF). Oak Ridge National Laboratory, Myr- Cray won a University of Illinois’ National icom, and Juniper Networks demonstrated Center for Supercomputing Applications con- “wide-area” 100 Gigabit Ethernet (100 GbE) be- tract, and will provide a Cray XE6 system and a tween the ORNL and Juniper Networks booths. future upgrade of the recently-announced Cray Juniper Networks and Myricom are providing XK6 supercomputer with GPU computing ca- ORNL the infrastructure required to connect to pability for National Science Foundation’s Blue DOE’s Advanced Networking Initiative (ANI) Waters project. Once fully deployed, the system 100G testbed, which links several national is expected to have a sustained performance of laboratories. more than one petaflops. Cray also announced ScaleMP pushed virtualization with the the Sonexion 1300 system, an integrated file newest version of its server virtualization for ag- system, software and storage product. gregation software platform, vSMP Foundation Along with Cray, NVIDIA announced a 4.0, and showcased the product line with part- parallel-programming standard—OpenACC— ners HP, IBM, AMD, and AdvancedHPC. with the Portland Group (PGI) and CAPS SGI hosted an impressive booth and intro- enterprise. OpenACC allows parallel program- duced their Next-Generation ICE X Scale-Out mers to provide simple hints—“directives”—to Bladed HPC Cluster. The SGI-Cloudera part- the compiler, identifying which areas of code to nership is also worth watching. SGI will now accelerate, without requiring programmers to distribute Cloudera software pre-installed on modify or adapt the underlying code itself. SGI Hadoop Clusters. The DataDirect Networks booth was Platform Computing made a big splash, busy as the company released new storage of- as they always do. Since being acquired by IBM ferings tied to its Storage Fusion product line. in mid-October, Platform’s offerings could get The company’s Storage Fusion Architecture was even more interesting. chosen by Munich-based Leibniz Supercomput- Bull had a solid presence and launched a ing Center to power its SuperMUC HPC system. new generation of ultra-dense petascale super- Globus Online celebrated its first birthday computers, though it’s not yet clear how much at SC11, and is doing effective large file transfer. that will affect life sciences. •

Visit Us at www.Bio-ITWorld.com JANUARY 2012 25 UP FRONT | News Briefs c Elsevier Acquires should help researchers more Ariadne Genomics easily visualize important relationships among chemical com- Dutch publishing giant, Elsevier, has acquired pounds to aid in drug discovery Ariadne Genomics, a software provider of path- and support advanced cancer way analysis tools and semantic technologies research. The data was extracted from patents for life science researchers, based in Rockville, and journal abstracts using the IBM business

CONTENTS MD. “Ariadne Genomics’ pathway analysis tools analytics and optimization strategic IP insight and semantic platform (SIIP, www.ibm.com/gbs/bao/siip), technologies a combination of data and analytics delivered integrate research findings from across mul- via the IBM SmartCloud, and developed by IBM tiple content sources providing a deeper un- Research in collaboration with several major derstanding of biological pathways and disease life sciences organizations. The platform uses progression,” commented Alexander van Boet- automated image analysis and enhanced optical zelaer, managing director of Elsevier Corporate recognition of chemical images and symbols to Markets. “Ariadne’s products improve research extract information from patents and literature productivity and outcomes for life science re- upon publication. searchers by delivering new insights for potential interventions, therapies and cures.” The NHGRI Pledges $416m to Ariadne acquisition delivers “an information Sequencing, Software offering in the biology domain and a passionate and dedicated team of life science profession- The National Human Genome Research Insti- als,” van Boetzelaer continued. “Ariadne’s team tute (NHGRI) has announced the latest iteration and offerings are a powerful complement to our of its flagship genome sequencing funding pro- chemistry, pre-clinical and clinical workflow gram—worth $416 million over four years—that solutions.” features new initiatives in the search for the underly- IBM, Pharma Donate ing causes of rare inher- Chemical Database ited diseases and acceler- ates the use of genome IBM, Bristol-Myers Squibb, DuPont, and Pfizer sequence information in are providing the National Institutes of Health the clinical arena. “Our with a database of more than 2.4 million chemi- goal is to empower all Eric Green cal compounds extracted from about 4.7 mil- types of researchers and health care profession- lion patents and 11 million biomedical journal als to use genomic information in their research abstracts from 1976 to 2000. The chemical data and eventually in patient care,” said NHGRI

26 JANUARY 2012 Visit Us at www.Bio-ITWorld.com director Eric Green in a press briefing. The bulk The moveAnnual will Report accommodate 2008 of the funding—$86 million in the first year of significant growth over the past c the plan—will be divided among the three prin- few years. “This move marks a cipal genome centers in the United States—the key stage in ChemAxon’s evolu- Broad Institute ($35.9 million), Washington tion,” commented Alex Drijver, University, St Louis ($28.4 million) and Baylor CEO, ChemAxon. “Our new headquarters will College of Medicine ($21.3 million), under the enable us to serve our customers better and direction of Eric Lander, Richard Wilson and continue our growth across all aspects of the CONTENTS Richard Gibbs, respectively. business.”

Thomson Reuters Receives MMRCMultiple Speeding Myeloma Up Research Consortium Parkinson’s Grant Cancer Trials Thomson Reuters has received a grant from The The Multiple Myeloma Research Consortium Michael J. Fox Foundation for Parkinson’s Re- (MMRC) has been able to accelerate the clinical search (MJFF) to create and publish the world’s trials process by making improvements to trial most comprehensive source of biological maps start-up and enrollment as well as patient ac- crual for oncology clinical trials run through the Consortium. MMRC presented the data in an oral presentation at the American Society of Hematology (ASH) Annual Meeting. Oncology for Parkinson’s disease (PD). The project aims trials are notoriously difficult to set up, enroll, to identify possible causes of Parkinson’s disease and complete, by mapping biological mutations of the Leucine- often taking as rich repeat kinase 2 (LRRK2) protein, the most long as two common genetic contributor to the disease dis- years from de- covered to date. The maps trace the disease’s bi- sign to activation. Between May 2006 and July ological pathways to pinpoint relevant biomark- 2011, 25 multiple myeloma trials were conduct- ers, which are biological molecules that signal an ed with MMRC project management resources. abnormal process or disease. They also support Trials conducted from June 2006 to September the drug discovery process for treating PD. 2008 made up a set of baseline trials, with the subsequent trials serving as test cases for the ChemAxon Moves to Budapest MMRC’s model to accelerate drug discovery. They found that the more recent trials opened ChemAxon is moving its European headquar- 28% faster than baseline trials and enrolled 10% ters to expanded offices in Budapest, Hungary. more patients. •

Visit Us at www.Bio-ITWorld.com JANUARY 2012 27 UP FRONT | Inside the Box c The Unstable Equilibrium of the Bioinformatics Org Chart CONTENTS By Aaron Kitzmiller A genome center can afford to have key technical teams of optimal size (between 5 and 9) n most organizations, the human resources that are given relatively focused tasks. These of bioinformatics are a regular source of ten- groups are not plagued with the single point of sion. Unless you’re particularly lucky, you failure and turnover risks of smaller teams and can be plagued by politics, illogical decision can afford some intra-team specialization (e.g. making, disappointment, and low produc- UI-oriented developer). Itivity. While you can have these problems in a At the other end of the scale, a single, skilled properly-balanced organization, there are cer- individual—more often ‘home grown’ than re- tain org charts in which they are endemic. cruited— works directly for a lab, with either Before discussing the bad organizations, let’s no other management, or a very weak link to a briefly enumerate the good ones. While there line manager. This individual can directly solve may have been much groping for solutions most data analysis problems through a com- early on, modern genome centers and large bination of small databases, workgroup tools, core facilities consider a dedicated software analysis web sites, and downloadable software. staff as a given. This full-time, in-house group Communication difficulties are drastically re- works exclusively on the software and IT re- duced because there is no development /analy- quirements of generating and translating large sis team and understanding lab personnel amounts of sequence data from the instrument and processes quickly becomes internalized. into a usable result. Organizational questions Problems can arise down the road, however, about reporting structure, strategic direction, since the individual rarely leaves enough docu- and customer relations are mostly non-exis- mentation for his or her replacement. While tent due to consensus about the nature and these individuals will need to draw on external scope of the task. The group may be part of a resources to accomplish certain tasks from larger informatics organization that provides time to time, with the correct mix of friends, external services and software, but the team is consultants, and software vendors, the lab can dedicated. usually solve a wide range of problems. The reason these two organizational struc-

28 JANUARY 2012 Visit Us at www.Bio-ITWorld.com tures are successful is that many of the vari- The Bioinformatics Core: In this setup, some ables associated with bioinformatics service are mix of informatics analysts and developers are c set to a constant. The intra-team communica- put together under a common organization tion and informatician-customer communica- that then distributes their time to affiliated tion issues are set to “1” for the dedicated indi- laboratories. This makes sense in companies vidual. While the genome center support staff where line management tends to be skill- must communicate well internally, their cus- oriented and is a natural analog to the wet lab tomers and tasks are fairly constant. Far more core facilities that are commonly established in CONTENTS common are the tense organizations where companies and universities. customer, task, and team are But this never works the allowed to float. way people expect it to. Infor- nless you’re matics does not fit the core fa- Informatics Issues U cility mold. One could imagine Lab scientist with added bio- particularly lucky, a disciplined core with a menu informatics responsibilities: you can be plagued of options and strict time In some smaller laboratories, by politics, illogical frames for them (R scripts or those venturing into higher for gene expression analysis: throughput sequencing or decision making, 1 month maximum; SOLiD arrays, a lab scientist with a disappointment, and RNA-Seq analysis: 2 month predilection for technology low productivity. maximum). Coupled with can begin to take on the au- a charge-back system, labs tomation of data processing would make careful, focused and analysis that is overrunning spreadsheets. decisions on narrowly scoped, time-limited This quickly becomes a demanding task that tasks. The tasks, at least, would be set to a con- competes with lab responsibilities. This was far stant. (Un)fortunately, software development more prevalent 10-15 years ago when the idea and analysis is so broad that it can be applied that lab would need software/IT support was to a number of tasks in any given lab. Robot- novel. The individuals that I’ve known in this ics, LIMS, algorithm development, specialized category usually become unhappy because of analysis, statistics, visualization are just of few the variability and uncertainty in day-to-day of the varied dimensions in the bioinformatics tasks. This position either decays into a dedi- universe. A good sized group of 5-10 can cover cated informatics resource, reverts back to any of these and more. And charge-back sys- pure lab work when another solution is found; tems are rare, so core staff members are usu- or the individual leaves for a pure lab or pure ally “free” resources for the affiliated lab. informatics job. The fungible nature of software and analysis and the “free”-ness of the resources com- >>

Visit Us at www.Bio-ITWorld.com JANUARY 2012 29 UP FRONT | Inside the Box

<< bine to drive decisions toward politics, in- c formatics staff interest, and “relevance”. There is nothing inherently wrong with an economy G etting the organizational driven by favors, but it does not scale. The lab structure around that brain with the largest mindshare and political weight usually gets the lion’s share of attention, lead- right can be the difference ing to competition to be associated with the between years of productivity CONTENTS more important projects. Other requests get and constant politics, served in such a way as not to tie down resources for long periods. You can get the core to reorganization and lost value. build a web application to run a custom script, but you can’t get the core to do something as general as “improve efficiency by automat- where the “skilled, dedicated individual” de- ing critical tasks.” As priorities are vague, staff scribed above is part of a larger bioinformatics interest will start to drive decisions as well. organization can work. However it assumes Vaguely optimistic assignments like “prototype that the bioinformatics management is pretty cloud-enabled algorithms,” will always win out hands off, doing little more than communicat- over critical but unglamorous tasks like “mi- ing best practices among the group helping grate all legacy data into the new LIMS.” to screen new applicants. Without a capable A centrally-managed bioinformatics orga- leader, though, the temptation to absorb the nization can function under different models dedicated resources into the lab is very strong. than the “Core” described above, but organi- Again, we decay into the “skilled, dedicated in- zational fear often prevents adoption. A core dividual” system. with a small menu of well defined services, Informatics support is an increasingly neces- charge-backs for disk and CPU usage, and a sary part of laboratories of all sizes. The pace of team of scientific consultants can be highly ef- change has so far prevented the establishment fective. Affiliated labs know well ahead of time of shrink-wrapped solutions and necessitated what they can expect and what they will have the application of the immensely powerful to do for themselves. They also know that the human brain. Getting the organizational struc- consultant’s time is not free. However, as most ture around that brain right can be the differ- managers can see, this is a prime outsourcing ence between years of productivity and con- target. No matter how cost effective and cus- stant politics, reorganization and lost value. • tomer friendly the group, some executive looking to have impact will eventually replace this Aaron Kitzmiller is a senior scientific consul- organization with an external company. tant with the BioTeam. He can be reached at The loosely coupled local expert model [email protected].

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8861 BIO12_AD BLUE_BITW.indd 1 1/3/12 3:33 PM UP FRONT | The Bush Doctrine c The Pharmaceutical Safety Data Problem CONTENTS By Ernie Bush Nearly all major pharma companies have three separate divisions that are responsible doubt most people fully appreciate the size for some aspect of safety data generation and and scope of the pharmaceutical safety maintenance: Research (discovery and early informatics space. I consider myself an development), Development (clinical trials avowed information systems advocate with and regulatory submissions) and Marketing decades of pharma R&D experience, but I (post launch surveillance and pharmacovigi- Idid not begin to get a handle on this issue until lance). These usually report up to the CEO the last few years. through separate VPs and have different goals, What we in the industry call “safety data” milestones, and bonus/reward structures. No covers everything from discovery-oriented in wonder their informatics systems tend to be vitro or cell based studies (e.g. cytochrome disparate and lacking good mechanisms to P450 drug-drug interaction results) to exten- share knowledge or be easily mined across the sive and regulated GLP toxicology study data, enterprise. voluminous clinical study records, and finally The solution is probably similar to the one to the complex and extensive post-marketing/ implemented for financial-based issues within pharmacovigilance systems. It leads one to the enterprise: have one individual that is ac- wonder: does anyone have informatics systems countable for all financial aspects of the busi- that allow safety investigators across the phar- ness, the Chief Financial Officer. A Chief Safety ma enterprise to effectively mine this ocean Officer with the mandate and authority to drive of information? In my experience the answer an integrated safety organization would un- is clearly no, or at best only on a very limited doubtedly also help drive a more thorough and scale. This may be a major missed opportunity. robust safety informatics strategy. As with many aspects of pharma R&D issues But the problem is much deeper than just there is both a corporate (or human) aspect lack of alignment. Perhaps the biggest issue is and a technology (or systems) aspect. Of these, that neither toxicologists nor clinicians want I have always found the corporate to be the to open up their data to those “unblessed” most difficult to address. members of the company whom they believe

32 JANUARY 2012 Visit Us at www.Bio-ITWorld.com unqualified to interpret the safety assessment. And from a results. There is a fear that in- traditional “observational” based c dividuals without the proper I f we mine the safety assessment point of view, training and background will entire safety that seems logical. somehow abuse the informa- But increasingly, safety assess- tion and the professionals would space across ment is moving to a biochemi- like to limit access to only those the enterprise, cal- and mechanism-based ap- they believe will treat the data would it make proach. And here, all three legs CONTENTS appropriately. That sense of of the safety informatics space proprietary ownership between a difference? really carry an equal amount of different groups within the same the insights. After all, it is in the company (sometimes within the preclinical area where we devel- same building) is very difficult to address, but op the best understanding of the mechanisms will have to change if we are to truly leverage of adverse effects. For example, currently our safety investment to the maximum. most companies screen against 800 to 1,000 off-target receptors in order to get a feeling for The Technology Is Here what kinds of adverse events could be seen in The problems associated with disparate safety the clinic. This is very valuable data, yet how information systems are, in fact, smaller now many post-marketing surveillance organiza- than five years ago and much, much smaller tions can explore whether there was an activ- than ten years ago. And, at least from a tech- ity at an off target receptor that might help nology perspective, it should only get better. manage an adverse event in a new population? The new systems for clinical safety data man- Actually, a few do and the list will grow more, agement and pharmacovigilance are merg- which proves the point. ing (or at least becoming more aware of each An enterprise-wide safety assessment infor- other) and the tools for accessing data from matics solution is the optimal tool for fully le- multiple legacy systems have blossomed. veraging the investment in generating and col- Ultimately, however, the big question re- lecting this data—especially to achieve a mains: If we truly could mine the entire safety mechanism-based understanding of what is space across the enterprise, would it make behind the safety issues. This in turn greatly a difference? Traditionally the answer was improves the ability to manage or mitigate believed to be no, or at least not very much. these adverse effects. • There has always been a sense that the clinical study data “trumps” the other data and there- Ernie Bush is VP and Scientific Director of fore other data—especially preclinical—does Cambridge Healthtech Associates. Email. not add a lot to late stage or post-marketing [email protected]

Visit Us at www.Bio-ITWorld.com JANUARY 2012 33 Cambridge Healthtech Institut e’s Eleventh Annual

CONFERENCE & EXPO ’12

Enabling Technology. Leveraging Data. Transforming Medicine.

Platinum Sponsors: CONCURRENT TRACKS: KEYNOTE PRESENTATIONS BY: 1 IT Infrastructure – Hardware 2 IT Infrastructure – Software Eric D. Perakslis, Ph.D., CIO and Chief Scientist of 3 Cloud Computing Informatics, U.S. Food and 4 Bioinformatics Drug Administration 5 Next-Generation Sequencing Informatics Martin Leach, Ph.D., 6 Systems and Multiscale Biology CIO, Broad Institute of MIT and Harvard 7 eClinical Solutions 8 eHealth and HIT Solutions for Jill P. Mesirov, Ph.D., Personalized Medicine Associate Director and Chief 9 Drug Discovery Informatics Informatics Offi cer; Director, Computational Biology 10 Molecular Diagnostics Informatics NEW! and Bioinformatics, Broad Institute of MIT and Harvard 11 Open Source Solutions NEW! 12 Cancer Informatics NEW! KEYNOTE PANEL: A special plenary session featuring trends EVENT FEATURES: and challenges in cancer research:  Access All 12 Tracks for One Price Julian Adams, Ph.D., Vice President, Business and Offi cial Publication:  Network with 2,000+ Global Attendees Corporate Development, Infi nity Pharmaceuticals, Inc. Jose Baselga, M.D., Ph.D., Chief and Bruce A. Chabner  Hear 125+ Technology and Scientifi c Presentations Chair, Division of Hematology/Oncology, Massachusetts  Connect with Attendees Using CHI’s Intro-Net General Hospital; Associate Director, Massachusetts  Choose from 16 Pre-Conference Workshops General Hospital Cancer Center; Professor of Medicine, Register by Harvard Medical School  See the Winners of the following 2012 Awards: Benjamin Franklin, Best of Show, and Best Practices John Quackenbush, Ph.D., Professor, Biostatistics and January 27 Computational Biology, Cancer Biology Center for Cancer  View Novel Technologies and Solutions Computational Biology, Dana-Farber Cancer Institute and Save in the Expansive Exhibit Hall  And Much More! up to $500!

Please mention keycode U02 when registering! Organized by: Cambridge Healthtech Institute Bio-ITWorldExpo.com Featured Speakers Featured Topics Pankaj Agarwal, Ph.D., Dir Computational Biology & Bioinformatics, GlaxoSmithKline Collaborative Drug Discovery Dimitris Agrafi otis, Vice President, Informatics, Johnson & Johnson PRD Drug Repositioning Garen Avetissyan, Senior Manager, Clinical Business Systems, Biogen Idec Health Informatics Networks in Clinical Decision Support Toby Bloom, Ph.D., Director, Informatics, Genome Sequencing, Broad Institute HIT & Personalized Medicine & Health: Real World Use of EHR Data Professor Sir John Burn, M.D., Fellow of the Academy of Medical Sciences, Professor of Using Data Visualization to Improve the Effi ciency and Quality of Clinical Trial Monitoring Clinical Genetics, Newcastle University Overcoming Challenges in Integrating Systems (EDC, IVRS, CTMS) and Clinical Michael Cantor, M.D., Senior Director, Biomedical Informatics Services, Pfi zer; Assistant Operations Data Professor of Medicine, NYU Medical Center Moving Beyond the Mean: The Role of Variation in Determining Phenotype Chris Dagdigian, Founding Partner and Director of Technology, BioTeam, Inc. Tying Individual Molecules to Phenotype David Dooling, Ph.D., Assistant Director, The Genome Center, Washington University, St. Louis Technologies and Infrastructure for Acquiring, Storing, and Sharing Data Ramesh Durvasula, Ph.D., Director, Molecular Sciences & Candidate Optimization HPC on the Cloud – Implementation Issues Informatics, Bristol-Myers Squibb Open Source Platforms and Collaborative Technologies Christine Gibson, Associate Director, Clinical Business Systems, Biogen Idec Data Modeling and Computational Integrative Tools Stephen Granite, Director of Database and Software Development , Center for Translating Genomic Data and Research into Clinical Practice Cardiovascular Bioinformatics and Modeling , Institute for Computational Medicine , The Johns Hopkins University IT Infrastructure on the Cloud Andrew Kasarskis, Ph.D., Vice Chairman, Department of Genetics and Genomic Sciences; Hybrid Strategies for Biomedical Research Data Management Co-Director, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine Clinical Application of Molecular Diagnostics Isaac Samuel Kohane, M.D., Ph.D., Director, Children’s Hospital Informatics Program, Multiplex Assay Accuracy and Test Result Interpretation Henderson Professor of Pediatrics and Health Sciences and Technology, Harvard Medical School Kevin Krenitsky, M.D., Chief Operating Offi cer, Foundation Medicine Anthony Leotta, Bioinformatics Manager, Cold Spring Harbor Laboratory Pre-Conference Workshops Roger (Rangjiao) Liu, Ph.D., Research Manager, Bioinformatics, Life Science Morning Workshops Development, Corning Beyond the Cloud Subha Madhavan, Ph.D., Director, Clinical Research Informatics, Lombardi Comprehensive Cancer Center; Director, Biomedical Informatics, Georgetown-Howard Leveraging Saas for Next-Gen Sequencing Universities CTSA, Georgetown University Medical Center Utilization of EHRs/EMRs for Protocol Design Keith Perry, Associate Vice President & Deputy CIO, University of Texas MD Anderson Building and Using an Ontological Framework Cancer Center Clinical Genomics John Quackenbush, Ph.D., Professor, Biostatistics and Computational Biology, Cancer Collaborative Innovation and Open Source Deals Biology Center for Cancer Computational Biology, Dana-Farber Cancer Institute Vishal Rosha, Senior Scientist, Bioprocess Research & Development, Novartis Pharma Ag Marketing and Sales: Science Training 101 Anthony Rowe, Ph.D., Principle Scientist - External Innovation, R&D IT, Janssen Best of Breed Informatics Sandeep Singhal, Bioinformatician, Breast Cancer Translational Research Laboratory J.C. Afternoon Workshops Heuson (BCTL), Jules Bordet Institute Data Visualization in Biology Vas Vasiliadis, Director, Products, Computation Institute, University of Chicago Microscopy Imaging Analysis Xiaoming Wang, Ph.D. Fellow, Computation Institute, University of Chicago and Argonne National Laboratory Cloud Computing Zheng Yang, Ph.D., Associate Director, IS Business Partnering Research, Boehringer Enhancing R&D Effectiveness through Global ELN Deployment Ingelheim Pharmaceuticals, Inc. Finding eHealth Savings Alexander Wait Zaranek, Ph.D., Director, Informatics, Harvard Personal Genome Project, Seeking Precise Knowledge Genetics, Harvard Medical School Social Media Analytics For a complete list of speakers and topics, and Scientists: Business Training 101 to register, visit www.bio-itworldexpo.com [ eClinical Technologies ] c Integrating Infrastructure for Clinical Trials Medidata on the cloud, ‘omics, and

CONTENTS personalized medicine.

Glen de Vries thought he would be teaching biology or chemistry in college, but somewhere en route to a satisfying career in academic research, he got distracted. He became exposed to clinical research while working on a molecular Medidata co-founder Glen de Vries biology project at the Columbia Presbyterian We found someone who thought it would be a Medical Center. Together with a friend and great idea for a clinical trial he was running. We medical resident in the same lab, he ended up wound up taking the bed out of my one-bedroom quitting to pursue Medidata Solutions World- apartment and converting it into a studio apart- wide full-time. De Vries is currently president of ment with an office, and that’s how the company Medidata Solutions, a provider of clinical tech- was born! The sponsor of the trial, when they nology solutions that believes in “optimizing heard that our systems were being run out of a clinical trials from concept to conclusion.” He closet, said that makes no sense. We’ve got to was the original architect of the Medidata Rave be serious about creating an infrastructure that electronic data capture (EDC) and clinical data people would trust. That was in 1997. management system (CDMS). By 1999, we had all our ducks in a row and Bio•IT World chief editor Kevin Davies really opened the doors on Medidata. At that spoke to de Vries about the progress of Medi- point, we met Tarek Sherif, the other co-founder data and the state of e-clinical technology in [and chairman/CEO]. Culturally, it’s still use- general. ful to think [the way we thought back then]—a combination of thinking about basic science, Bio•IT World: Glen, what was the origi- practical aspects of providing health care, being nal goal of Medidata? a clinical trial site and a sponsor, and a healthy de Vries: Medidata was founded because dose of business realities. We’re not just a tech- we’d been talking over ideas about taking data nology vendor but one working in the world of management during a clinical trial to the Web. services that get outsourced.

36 JANUARY 2012 Visit Us at www.Bio-ITWorld.com Would you call yourselves a CRO (con- modate as many of our customers’ needs today. tract research organization)? If you look at Rave, which is one of our core We are not a CRO. In its most extracted pure solutions, there’s an interesting illustration of form, we’re trying to provide a platform—the that idea. We never bought into the idea that an technology infrastructure—that pharma, bio- EDC system that handles the data in a CRF [case c tech, and medical devices will need in the fu- report form] should be separate from a clinical ture. I’d stress that we’re trying to build for the data management system that integrates CRF future state. data with lab data and with randomization data. Over the last 15 years, most people have ap- We thought that should be one system, and proached clinical trial technology infrastructure that’s what we built. We’ve gotten people in the by taking individual paper processes and auto- industry to change their expectations around CONTENTS mating them. Sometimes you can make it more that. It used to be that people said, “Those efficient, but nobody has really tried to take an things used to be two things. I can’t manage all approach similar to the ERP (Enterprise Re- that data.” Well, it is 2011. I think you can man- source Planning) industry. If you look outside age that way! life sciences, companies would have different Our customers who are doing this are cre- departments to manage individual processes ating much more efficient processes, getting (manufacturing, sales, customer support etc.), visibility into their data earlier. And we hope to then companies like SAP developed platforms deliver for them a real competitive advantage. that fall under ERP—bringing all the functions When we think of a technology stack or a in a company together in one central software business process… we see ourselves as the bot- base (e.g. ordering a custom computer over the tom tier of a stack of layers focused on running Internet). There hasn’t been an ERP-like plat- the most efficient clinical trial today and in the form in clinical development. future. We try to support our sponsors and CRO We see that as an opportunity—instead of partners by getting their people on top of that replacing individual systems, many of which platform. are 30 years old, we’re trying to think about how to connect all the different people, from the How much have you been able to in- executive in charge of an entire drug program tegrate into your platform and where or research portfolio to the patients who volun- are some of the remaining holes or teer to be the subjects in a clinical trial. Can we opportunities? create much more modern, efficient business We don’t see any finish line where we’ll be done processes in a clinical trial that demonstrates with our platform. The idea is to always think of safety and efficacy, present it to a regulator, and what people will need in the future and to invest get permission to bring it to the marketplace? in things that will be useful for those clinical trial processes. If you look at companies in a How does that translate into your core similar position to us, you’d see something like mission now? five percent revenue being put back into R&D. We’re trying to build that platform to accom- We put more than 15 percent revenue back >>

Visit Us at www.Bio-ITWorld.com JANUARY 2012 37 << into R&D. We see so much change coming in managing the clinical development process that we want to make sure we stay on top of those ‘I nstead of replacing future requirements. individual systems,... we’re c How far have we come? With Rave, we started to deliver EDC and CDMS in a new, trying to think about how to hopefully better, way. To categorize some of the connect all the different system types, we’ve added randomization and people, from the executive... drug logistics [IVRS]. We’ve recently added capabilities in CTMS (clinical trial management to the patient.

CONTENTS system). We think we’re defining a category that didn’t exist in terms of structured protocol It must be something that provides value in the design—leveraging a database system to ensure platform context. Each individual part needs to you’re designing the best protocol possible, and add value if used alone, because it’s a great EDC using that structured design to inform other system or investigator payment administration activities, like budgeting the clinical trial and system, but, when used in conjunction with the managing the way you deal with site grants. other parts of our platform, it has to be part of We’re constantly looking for opportunities a seamless flow of data between the pieces of to integrate technologies we don’t have. We talk the platform. We’re big believers in open inter- about ‘new, different, and better’—it’s our job to faces, so when we build or integrate an acquired show it’s better. technology, the way we connect them is with the same set of tools we provide to partners and ef- Do you typically build new capabilities fectively the general public. We have a website internally or acquire new technologies called Developer Central, where anyone can get as you need them? access to all our documents and APIs. Those are We build a lot, and building technologies is one the same tools that our internal developers are of our core competencies. We think software using… That openness is key. How can we make development is an art form and we’re proud of any new system part of our platform in a very the way we do it. But we will, and just did, make holistic way? a tuck-in acquisition, if we find something com- patible philosophically with the technologies we Any other significant new acquisitions have to date. we should be aware of? We just acquired a company called Clini- Clinical Force has put us into the CTMS space. cal Force, which has capabilities in the CTMS The way CTMS has been implemented by category. There’s a philosophy we have—that many sponsors, it’s often provided on top of a we applied to Clinical Force and Fast Track heavyweight, legacy on-premise system, often Systems, another company we acquired—that highly customized, very costly to upgrade. A we’re not interested in just assembling a suite lot of people are talking about a better business of software that meets industry requirements. process to attack trial management activities,

38 JANUARY 2012 Visit Us at www.Bio-ITWorld.com requiring a change to the CTMS. But the sys- various contexts in marketing and other agen- tems people think it would be too expensive or das. We think today the cloud is business as time-consuming to upgrade their CTMS. My usual for us, as it has been for 12 years. We thought is, isn’t the technology supposed to be think the way the entire world of IT is going there to make it easier to implement a better is based on the same concept. The end user c business process? We think, “Great, here’s an shouldn’t have to worry about the infrastruc- opportunity.” ture being used to deliver the functionality you We’re firm believers in software-as-a- need; you should just be able to consume that service—not just hosting the application for functionality. customers, but making it so they don’t have to Here’s an analogy: Income tax software worry about implementing the application. We started with a paper process. You’d have to sit CONTENTS try to make everything as self-service as pos- down with your receipts and transcribe onto sible. Our approach to CTMS is to provide it in paper, just like a CRF. So what happened? a similar fashion—consume the modules you People sold you software to transcribe your data need, when you need them, easily over the web. into a computer… Now, you don’t even have to If you’re using them with other systems, use a buy a CD anymore—you just go to the web and set of open interfaces. purchase the functionality you need and enter your data. That’s become a cloud service. Put- What is your stance on cloud comput- ting your information into these sites means the ing? Are clinical data incompatible software you’re interacting with can give you with the cloud? real-time feedback on how well you’re doing… If you’re looking at the world of clinical develop- It’s leveraging a much larger body of data. ment—I wouldn’t just place Medidata into this This is not so different from how we think category—we are the cloud for clinical data. In clinical data should be managed. We started the very first days of Medidata Solutions, when with paper, people started building heavy cli- we first started doing EDC, the vast majority ent software, it moved to the web… We’ve been of sponsors and CROs had no infrastructure to showing demonstrations on how to load data run an over-the-firewall e-commerce applica- from electronic health record systems into the tion. Their networks were buttoned up because Medidata platform, effectively bypassing the they were used to running in a very conservative EDC data entry process entirely. What better pharma-IT environment. way to collect clinical data than to have it hap- From the first days, we were in the business pen that way?! of hosting EDC, then other systems, for our customers. They just access them over the web. It’s fair to say that big pharma’s pro- The [clinical] sites’ doctors and nurses access ductivity has been pretty mediocre for the software over the web, then via the web they the past several years. What is your download the data. That is effectively the cloud view on the potential impact and ap- business model. plication of new technology, including The term cloud is thrown around a lot in ‘omics technology, on improving >>

Visit Us at www.Bio-ITWorld.com JANUARY 2012 39 << clinical research through things tive. Then we’ll have the ability to put more and such as biomarker discovery and pa- more data through the clinical research pipeline tient stratification? and answer more sophisticated questions. Let’s start with the availability of real integrated c platforms such as ours—this will help people But what about personalizing medi- get much more effective at the general people- cine through new technologies and based processes of designing and managing strategies? clinical trials. There is just a spectacular oppor- From the perspective of a patient getting better tunity for making this not just more efficient but medical care, personalized medicine is inher- more effective. ently a great idea. As the industry takes the

CONTENTS When ERP came around, the next thing words personalized and medicine though, the that happened was everybody started trying to two ideas don’t scale very well in their current design new business processes based on the new state. Now we’re trying to put them together, we capabilities provided by these new technology know we need to do that, but it won’t be possible platforms. Then they realized they needed to ef- until we really wrap our minds around how to fectively measure how well those new processes leverage technology. were working. A whole industry of business If we do that, there’s an exciting, healthy intelligence was born, based on that end user future for personalized medicine and leverag- requirement. People wanted to have the right ing new genomic data. If you look back at the dashboards and predictive capabilities to man- Human Genome Project, there was a somewhat age their businesses much more aggressively. naïve view in the general public that all of a sud- Right now I think we’re living through the den, we could understand and cure a lot more same transformation in clinical trials. If you diseases. The reality is a lot more complicated. look at the huge amounts of incremental data Just having access to a ton more data doesn’t that we think will help life sciences get new make the data more useful. The relationship be- drugs approved, or new combinations, we can’t tween genotypic data and phenotypic data and just throw resources at the problem and expect the vast range of combinations for any given it to work. We’re talking about an exponentially patient mean this is a really different class of increasing amount of data we need to wrap problem. I think we’ll be able to equip people to our minds around and associate with labeling tackle those data but we need to start with basic claims we want regulatory agencies to approve. blocking and tackling. There is no way to add that capacity at our current level of efficiency. Is the ROI Medidata provides principal- We need to use more sophisticated transac- ly saving sponsors money, increasing tional capabilities. We need to layer on the right efficiency, expediting trials, or failing analytics—we feel passionately about bench- ineffective drugs sooner? marking as the key to analytics—so companies We see ROI coming from two main angles. First, can look at their own performance, compare if you’re spending money on Medidata technol- their performance to peers and get more effec- ogy, you should be able to save money in the

40 JANUARY 2012 Visit Us at www.Bio-ITWorld.com operational component of your clinical trial. scale up commercially doing hybrid Phase II/ For every dollar spent on technology in a clinical III studies if I’ve taken a traditional view of how trial, there’s more than 25 spent on the opera- clinical trial systems work. So we think a key tions and supplies required (manufacturing test ROI with Medidata is—by putting your opera- drug, distribution, monitoring, compensation tion on top of our platform, we’re there to help c etc.). Our premise is, if we can help redesign make sure you’re ready for the future state. And your processes so steps can be automated, or we look to our customers to help us make sure change other business processes, there’s defi- we know what that future state is going to be. nitely the financial ROI. But if you think about changing business Any final thoughts that we haven’t processes, eliminating or automating steps, touched on? CONTENTS another key ROI is the speed by which you’ll be Yes. There’s an interesting dynamic in what’s able to access and leverage the happening in higher echelons in information you’ve collected. clinical trial management that You’ll be able to do an interim sit above Medidata right now. analysis that much faster, or ‘The reality is... We think about the technology identify safety or efficacy clinical just having access infrastructure. If you look at data earlier to figure out where to a ton more what’s happening in the spon- you might have a problem or sor/CRO world, there’s interest whether to change course. From data doesn’t in more and more outsourcing, an operational perspective, how make the data so CROs are getting more ag- quickly can I identify sites that more useful. gressive about distinguishing are giving me high-quality data their offerings. Can a CRO pro- and other sites giving me low- vide value beyond just executing quality data that I might want to on traditional requirements of spend more time on? data management or clinical monitoring? I think The third piece of ROI is harder to measure that’s a really exciting thing in our industry, be- in a tangible time or dollar sense, but it’s being cause when you shift responsibilities between ready for what is going to be the future state of two parties, it creates an environment where clinical trials. If you look to the forefront of the people are looking for new ways to provide that commercial and academic worlds, they are not service. That’s dynamic and we think that’s great just thought leaders but they are designing and for our business. running studies that are incredibly progressive Hopefully the result is sponsors getting in terms of finding combinations of therapies their trials done more efficiently, running their that are most effective, looking for ways to ex- programs faster. CROs are building healthy pose as few patients as necessary to harmful businesses and looking to distinguish them- doses, etc. These are studies that are difficult selves. When you get to the bottom of this, there or impossible to execute if you don’t have the are companies like us benefiting from people right kind of integrated infrastructure. I cannot demanding more and better functionality. •

Visit Us at www.Bio-ITWorld.com JANUARY 2012 41 [ Diagnostics ] c A QuantuMDx Leap for Handheld DNA Sequencing From pharmacegenomic testing to handheld sequencing within 5-7 years?

CONTENTS BY KEVIN DAVIES proof of principle, according to Burn, showed MONTREAL—Speaking for the first time in his that changes of impedance in silicon nanowires life as a commercial consultant rather than a could record the arrival of a biomolecule. Re public servant, Sir John Burn, a highly respect cently, QMDx announced the exclusive license ed clinical geneticist in the of intellectual property from United Kingdom, provided Lieber’s company, Nano the first glimpse at a nano sys, of the diagnostic and wire technology for rapid sequencing applications of DNA genotyping that could nanowires and nanotubes. eventually mature into the (The arrangement succeeds world’s first handheld DNA a non-exclusive IP deal pre sequencer. Burn previewed viously announced in 2009.) a potentially disruptive ge QMDx operations and nome diagnostic technol manufacturing are current ogy in a presentation on the ly headquartered in New closing day of the Interna castle, U.K.. The company tional Congress of Human Sir John Burn unveiled nanowire sequenc- has built a prototype DNA Genetics in Montreal*. ing technology from QuantuMDx. sequencer, which Burn ad One day a week, Burn, mitted didn’t exactly con professor of clinical genetics at Newcastle Uni form to handheld dimensions just yet. (The versity, serves as medical director for Quan company is working on a sequencing device tuMDx (QMDx), a British start-up co-founded called Q-Seq, but Burn did not dwell on that.) by molecular biologist Jonathan O’Halloran and health care executive Elaine Warburton. Pass the Q-Poc The potential of nanowires was demonstrat The first goal is a handheld point-of-care instru ed in a 2001 Science paper authored by Harvard ment that is dubbed Q-Poc, which Burn likened University’s Charles Lieber and colleagues. That to “a big fat iPhone.” Possible applications range * 12th International Congress of Human Genetics, October from companion diagnostics and genetic testing 11-15, 2011, Montreal to DNA forensics. The QMDx technology uses

42 JANUARY 2012 Visit Us at www.Bio-ITWorld.com peptide nucleic acids (PNAs) to tether DNA QMDx is targeting. The first is the pharmacoge sequencing templates to a nanowire. As the nu nomic polymorphism that controls sensitivity cleotides arrive at the template, their negative to the blood thinner warfarin. Today, Burn said, charge influences the nanowire and changes its “We give all [patients] the same dose; the ones impedance. The process would use a reversible- that nearly bleed to death, we bring them back c terminating technology that is able to read to hospital and transfuse them and put them on through repetitive stretches of DNA. the right dose. It would be nice if we could do Burn acknowledged that the electrical dif the genetic analysis and predict the right dose ferences could only be detected for a range of instead.” Using an algorithm developed by his about 100 Angstroms (10 nanometers), equiva Newcastle colleague Ann Daley, Burn wants to lent to about 50 bases of DNA in any one stretch. use warfarin testing as “a proof of principle for CONTENTS But down the road, an idea was to lay a longer the use of this as a point-of-care test in clinics DNA template, say 10 kilobases, and interrogate and GP surgeries.” at multiple points along the molecule. Another application is in the field of bowel The manufacturing process relies on an cancer, a long-time research interest of Burn’s. etching technique featuring a silicon nanowire The detection of key microsatellite (MSI) risk about 120 nm in diameter, and about one mil markers should be identified at the point-of- lion features on the chip, roughly the size of a care, said Burn. “We’ll be moving into the pa microscope slide. “It’s a highly reproducible thology lab and doing genetic testing of MSIs, system for mass manufacture,” says Burn. even as samples come out of the clinic or even To place the DNA templates onto the wire, surgery.” Burn even suggested the possibility of QMDx has invented several methods to rapidly using the technology during live surgeries, as the prepare and PCR DNA. A DNA extractor uses process should only take some 15-20 minutes. a nanoparticle filter to capture and elute the In short the goal is to carry genomics into starting DNA. A microfluidic cartridge performs the world, Burn said. The 20-minute test should PCR (polymerase chain reaction) not by heating prove valuable for pharmacies and hospitals. and cooling the liquid, but by passing it through The device would be priced in the $300-400 heat zones created in the microfluidic device. range, with the disposable cartridges about $20. “There are up to 32 silos of passage across The company plans to begin clinical trials for the heat plates,” Burn explained. “We can do HIV testing in South Africa in the next 1-2 years. PCR in 6 minutes through this device—10 min “I’m convinced—and obviously hope—the utes from sample arrival to PCR product coming nanowire idea is coming to a clinic near you,” onto the nanowire.” said Burn. “We’re limited more by our imagina Eventually the sample prep segments will tion than anything else.” Burn’s QMDx col be combined to produce a disposable chip with league, chief science officer Jonathan on-board chemistry that is inserted into the ma O’Halloran, goes even further. “I predict that chine. The results can be read locally or trans we’ll be able to sequence a genome on a hand- mitted to a remote reader. held device within 5-7 years,” he writes on his Burn listed several early applications that LinkedIn page. •

Visit Us at www.Bio-ITWorld.com JANUARY 2012 43 [ Informatics Tools ] c Cheminformatics in the Cloud Accelrys launches next-generation informatics suite and cloud portal.

BY KEVIN DAVIES change direction. Tests can be done quickly, Accelrys announced its next-generation infor- but the informatics systems can’t deliver matics suite at its European user group meet- information.”

CONTENTS ing in Athens last year. The suite consists of some updated existing products and some new Something New components, explains Accelrys’ senior director The Accelrys Cheminformatics Suite is designed for life science marketing, Rob Brown. Those to gather data more efficiently, leading to bet- features include a chemical registration system, ter informed decisions early on while designing a chemical data cartridge, and a cloud-based compounds, says Brown. product called HEOS, in partnership with Complementing existing commodities such SCYNEXIS, for externalizing research. as Isentris are new features such as a chemical “We’re building on the joint heritage of Ac- registration system—the first new cheminfor- celrys, MDL and Symyx—more than 25 years,” matics product developed since the merger be- says Brown. “This is the first time there’s been tween Accelrys and Symyx. “It lets the medici- a coherent suite to cover all capabilities that nal chemists register their molecules into the scientists need to cover daily workflows,” estab- corporate database. It’s a modern, Web-based lished through a combination of in-house devel- product that should be very seamless for the opment with acquisitions and partnerships. chemists to use,” notes Brown. “Data gathering steps can be very time- Accelrys has also upgraded the companion consuming,” says Brown. “Scientists should biological registration system. “By having both be spending time doing innovation.” During registration systems on the same architecture, a recent case study, Brown says a big pharma as we go forward, we can think how to handle partner plotted the time taken by its scientific those situations when you’re registering an teams during various phases of drug develop- entity with attributes of both a biological and a ment. “What alarmed the pharma was that a small molecule,” Brown says. particular compound was made very early, but Additional updates have been made to the a lot of results were locked up in labs doing vari- Accelrys chemical cartridge, which allows users ous tests. The informatics systems not sufficient to store data in an Oracle database. “Now we to get results back to the team,” says Brown. can handle patent structures and chemically Meanwhile, many other compounds have modified biologics,” says Brown. been screened and tested, which could amount A key question is how to represent a chemi- to wasted effort. “Now they have to go back and cal entity in software so it’s a faithful reproduc-

44 JANUARY 2012 Visit Us at www.Bio-ITWorld.com tion of the structure. “Many companies offer car- says Brown. “They built this system to handle tridges to handle regular small molecules… We all types of data.” The closest competition, as he now have single representation not just for small sees it, is from Collaborative Drug Discovery. molecules but reactions, patent structures, and Users will subscribe to a software-as-a- chemically-modified biologics. So it’s a much service model. “We spin up a big sandbox for c broader representation.” And Brown points out, the operation and partition areas for each of the there are tens of thousands of users already. CROs,” says Brown. “The commissioning company decides who gets to see what. Importantly, Holy HEOS it’s all a real-time upload, making data available Perhaps the most exciting element of the new to the people who need to see it.” suite is the integration of HEOS, a cloud-based Brown says the value of HEOS has already CONTENTS platform developed by SCYNEXIS, a drug dis- been demonstrated in the neglected disease covery and development company based community on multi-continent projects. in North Carolina. The CRO has passed audits for As the pharma ecosystem large pharma, including an ethi- evolves, partner networks cal hacking audit. (Security sometimes include many features of HEOS include a discovery partners, aca- state-of-the-art data cen- demic groups for safe- ter with physical security ty, and CROs. “Partners features and 48 hours of come and go quickly,” power autonomy; off-site says Brown. “I might use encrypted data backup six partners, but only and geographically sepa- 2-3 are active at any given rated disaster recovery; a time. We might need to spin host of web/software secu- a partner up or down very rity measures, firewalls, and quickly. IT in pharma is not de- restrictions on incoming IP.) signed to that very quickly.” Accelrys will license seats for The cloud offers an attractive HEOS is a cloud-based HEOS and/or the registration. “Some solution in principle, and Brown platform to manage start-ups might say HEOS is their in- notes that attitudes to the cloud are partners and projects. ternal system, and just license seats changing: “Fears of data security to that,” says Brown. As for the new are diminishing. It also fits the operating ex- suite, users can pick and choose their desired pense model. The budget comes from business, elements. “In most companies, pieces of the not IT.” [Accelrys] suite will already exist,” says Brown. Accelrys has signed a partnership with “We can’t always replace everything—we have SCYNEXIS for its HEOS software, which is to offer say our chemical registration, but the hosted in a data center managed by the CRO. user continues to use someone else’s assay data “They wanted to add value for large pharma,” management tool, for example.” •

Visit Us at www.Bio-ITWorld.com JANUARY 2012 45 Feature c Remedies for CONTENTS SAFER

] New solutions to seek signals, organize DEBORAH data,BORFITZ BY DRUGS[ Drug Safety train interpreters, expedite reporting, and find better biomarkers.

harmacovigilance experts have an trial participants, patients, and the reputation abundance of signal detection tools of recall-weary drug developers. But drug safety to sift through large quantities of specialists can’t be sure which technology or data seeking causal relation- signal detection method is best. ships between adverse events Drugs today aren’t as safe as they could be (AEs) and experimental drugs. for several big reasons, including failure to see They also have an assortment of the big picture, says Steve Jolley, principal of data mining tools capable of find- SJ Pharma Consulting. “It took years to figure ing statistical associations suggestive out Vioxx was killing… 2-3 patients per thou- of problems regarding approved drugs. All sand due to heart attacks and strokes because this technology is intended to safeguard clinical the people taking it were likely to die of [those

46 JANUARY 2012 Visit Us at www.Bio-ITWorld.com causes] anyway.” blood and urine tests. The expanding field of Software tools by themselves are of little pharmacogenetics has also identified genetic consequence without professionals medically differences in patients with AE susceptibility. interpreting the signals to determine which ones are legitimate product safety concerns, Signal Detection c says Sally Van Doren, president and CEO of the Signal detection of common AEs is best accom- drug safety consultancy BioSoteria. But there is plished in a controlled clinical trial setting where Remedies for a shortage of trained drug safety practitioners the sponsor can collect details of reported AEs evaluating product safety signal detection, she and calculate actual incidence. Safety problems says. “There’s a huge training need in this area. are more likely to be detected as data accumu-

Pharmacovigilance, risk management, and lates and clinical development progresses, >> CONTENTS signal detection training—including certificate

programs offered by organizations like BioSo- 409,608 teria and the Drug Information Association— Rising Volume of are a good start but not completely sufficient,” Unexpected SAEs because certification confirms only class attendance. No competency testing is presently avail- Reported SAFER 330,476 able or required for those actually entrusted (Approved Drugs) with drug safety surveillance. The proficiency of plumbers and accountants is better defined! Post-marketing regulatory inspections pro- Unexpected Serious 275,421 Adverse Events ] New solutions to seek signals, organize data, vide some benchmarks about how well product BY DEBORAH BORFITZ safety signals are detected, evaluated, and acted 230,919 [ Drug Safety 219,956 DRUGS 213,324 upon by pharmaceutical companies, she says. train interpreters, expedite reporting, and find better biomarkers. For example, the UK Medicines and Healthcare Products Regulatory Agency’s latest metric re-

port of key pharmacovigilance inspection find- 162,007 ings notes limited safety signal detection sys- 144,271 tems in about 13 percent of pharma inspections. 128,680 Heightened recognition of the importance 114,693 of safety signal detection and evaluation has 94,931 improved therapeutic risk management. Drug makers can ill afford suboptimal patient outcomes and the expense of legal damages as a result of shortcutting safety monitoring. So if preclinical or early-stage clinical studies suggest an experimental drug might be associated with kidney or liver damage, additional biomarker 2000 01 02 03 04 05 06 07 08 09 10 measures get monitored in addition to standard SOURCE: FDA

Visit Us at www.Bio-ITWorld.com JANUARY 2012 47 << often with thousands of patients with the tar- ing different safety information. Today, with geted disease, says Van Doren. Even in blinded electronic data capture (EDC) systems, spon- studies, a data safety monitoring board often sors may interface the clinical data with a safety reviews incoming safety data for imbalances in database, making “real time” SAEs and patient c the drug’s safety profile compared to placebo or data available for analysis. Most sponsors also marketed therapy. utilize alert systems triggered from clinical da- Still, safety is a hard endpoint to evaluate tabases and sent to the safety monitor when in- relative to efficacy, says Cynthia Uber, former dividual patients experience predefined thresh- VP medical services at Eisai. “Safety requires olds of certain AEs or abnormal laboratory exposure to broader populations than are uti- values, Van Doren says (see “FDA Final Rule”).

CONTENTS lized in clinical trials and can therefore be more costly and time consuming to confirm. It is also The Weaknesses of AERS subject to a labyrinth of reporting requirements FDA currently accepts only post-marketing that can become labor intensive,” she says. safety reports in its Adverse Events Report- “Safety centers are typically not revenue gener- ing System (AERS). But the agency anticipates ating for pharmaceutical companies.” electronic transmission of—and presumably an One challenge for safety departments in electronic repository for—IND safety reports on past years was that those evaluating and report- experimental products. In Europe, expedited ing serious adverse event (SAE) data often had safety reports of serious unexpected adverse little access to the full clinical data set during reactions are amassed in the EudraVigilance a clinical trial, with separate databases hous- database for both investigational products and

FDA Final Rule Effective March 2011, the FDA’s Final Rule on gregate safety analyses for investigators and IND Safety Reporting required study spon- IRBs to fully interpret. If patient-level safety sors of drugs and biologics to look periodi- information is going to be of practical value, cally at individual and aggregate safety data it should be organized in an accessible elec- from all sources. If any safety finding indi- tronic data repository by the sponsor. cates a significant risk to patients, FDA and “Just staring at raw individual patient participating investigators must be alerted safety data, without analysis, is no way for the expeditiously. sponsor, investigator, or IRB to protect pa- In past years, clinical trial investigators tients,” says Van Doren. Building a real-time and institutional review boards (IRBs) were central repository for integrated safety data inundated with reports from sponsors of across multiple trials of a drug will require unexpected SAEs, says Sally Van Doren. But “savvy” individuals to design the database, the accumulation of such individual patient ensure data collection consistency and deter- reports lacked cumulative experience and ag- mine data outputs, she says. •

48 JANUARY 2012 Visit Us at www.Bio-ITWorld.com post-authorization (marketed) products. Although many AEs are detected by spontaneous reporting systems, these systems have limitations that hamper signal c detection, says Van Doren. Beyond the study setting, only a small fraction of post- marketing AEs—even the most severe tox- Just staring at raw icities—are reported to drug manufactur- individual patient safety ers or regulators. Improving the ability of data, without analysis, is no way health care professionals to recognize and

‘ CONTENTS report AEs will undoubtedly be a focus of for the sponsor, investigator, or IRB future technology. Applications for the to protect patients.BioSoteria iPad and similar devices will allow health care professionals and patients to send AE — SALLY VAN DOREN, ’ information directly to FDA. Drug manufactur- create a national electronic system for track- ers typically have product-specific or corporate ing reports of AEs linked to FDA-regulated websites or call centers for reporting of AEs, products. The idea is to query diverse health although as Van Doren notes, that information care data holders—including electronic medi- is often re-entered into a corporate safety data- cal record (EMR) systems, administrative and base again when it gets reported to regulators. insurance claims databases, and registries—to Paper-based reporting systems are so resource- quickly evaluate potential safety issues. Data intensive that drug manufacturers and regula- owners are tasked with mining for answers to tors not using electronic AE capture systems FDA-posed questions and submitting summary have a backlog of hundreds to thousands of results. However, it may be a few years before cases awaiting manual entry at any one time. the Sentinel Initiative “comes good,” cautions Another concern with AERS, according to Jolley. As of December 2011, progress had Uber, is that it gathers information from multi- been made on EMR querying methods but “not ple sources, potentially “over-representing” in- many” new safety issued had been identified. formation. A physician could conceivably report The FDA has been instructed by Congress a SAE to both FDA and the drug manufacturer, to mine at least 100 million EMRs—about one- while the same event could be reported by an third of the U.S. population—for signs of safety attorney without necessarily being flagged as a problems with drugs, says Paul Watkins, direc- duplicate. “To look at data at the aggregate level tor of the Hamner-University of North Carolina and not the individual case level can lead to the (UNC) Institute for Drug Sciences. But without wrong conclusions,” she says. “It all comes back any validated tools to do this, “most safety sig- to the accuracy and quality of the source data.” nals that pop out will probably be false ones,” The FDA’s remedy to under-use of its Med- he says. In the absence of randomization to Watch AE reporting system is the Sentinel treatments and placebo controls, interpreting Initiative. Launched in May 2008, this aims to the data is “extremely challenging.” The Ob- >>

Visit Us at www.Bio-ITWorld.com JANUARY 2012 49 << servational Medical Outcomes Partnership that one of its trial participants had been hos- had mixed results trying to find EMR evidence pitalized with a heart problem, because the of known drug troubles during beta testing of reporting investigator used the wrong fax num- the Sentinel system, he notes. ber. The SAE was entered into the EDC system, c Watkins predicts the most immediate effect Jolley notes, but the information wasn’t passed of the Sentinel Initiative will be to make FDA on to the safety team, so unsuspecting patients reviewers—already spooked by the recent Vioxx continued being enrolled. and Avandia disasters—“more cautious.” In the Debate continues about how useful com- long term, once reliable approaches have been puters are for linking AEs to drugs, because developed to screen EMRs for AEs, the Sentinel statistically suggestive causalities ultimately

CONTENTS Initiative might allow a graded approval of cer- require a “prepared mind” to prove, says Jolley. tain drugs. One possible scenario is a new drug Data mining tools are designed for use in the approved for use in health care networks where post-marketing environment, where both the EMR data get mined in real time, allowing for numerator (drug-associated AEs) and denomi- rapid, real-world safety assessments. nator (the drug’s universe of users) are largely unknown. The software thus seeks clues either Corporate Due Diligence in public databases such as AERS or the World Based on audits of 50 pharma firms on three Health Organization’s VigiBase or in propri- continents, SJ Pharma Consulting says there etary big pharma databases. The denominator is a lot drug makers can do themselves to beef is approximated by comparing the number of up product safety. Jolley developed a 50-page AEs reported for a drug to the average number checklist of safety-related questions, best prac- of drug-event combinations reported for other tices and regulatory guidances to help compa- drugs. nies tease out deficiencies. Safety data exchange Corporate desire to ensure drugs are ap- agreements with partners and subcontractors, proved, especially among small companies, may for example, may be weak or absent entirely. also be compromising the clinical trial enter- Participants in a U.S. clinical trial were recently prise, says Jolley. Sponsors tend not to use sig- put at risk when a Japanese drug licensor failed nal detection techniques to proactively identify to inform the sponsor of a label change indi- problems. The good news is that the European cating potential liver toxicity. The obligation Medicines Agency now compels companies to to report any drug risk was never written into annually submit a Development Safety Update the safety data exchange agreement by the U.S. Report (DSUR) of therapies under develop- licensee, whom the FDA holds responsible for ment, much as they do for marketed drugs. maintaining the integrity of the “supply chain of FDA plans to do likewise. DSUR contains ten safety information,” says Jolley. elements not in the IND annual report used in Companies also sometimes struggle to the U.S., including cumulative summary tabula- report unexpected SAEs within 15 days, as tions of all AEs of special interest and an over- required by FDA. Last November, it took one all safety assessment. “This should encourage sponsor’s safety group three months to learn companies to take a more holistic view of the >>

50 JANUARY 2012 Visit Us at www.Bio-ITWorld.com The 2012 Bio•IT World Best Practices competition has released its call for entries. Since 2003, Bio•IT World’s Best Practices Deadline competition has been recognizing outstanding Extended! examples of technology and strategic innovation initiatives across the drug discovery enterprise. February 15, The awards attract an elite group of 2012 life science professionals: executives, entrepreneurs, innovators, researchers and clinicians responsible for developing and implementing innovative solutions for streamlining the drug development and clinical trial process. Bio•IT World’s distinguished peer- review panel of judges has reviewed more than 400 entries in the program’s history. Entries will be accepted in six categories: Clinical & Health-IT; IT infrastructure/HPC; Informatics; Knowledge Management; Research & Drug Discovery; and Personalized & Translational Medicine. The 2012 winners will receive a unique crystal award to be presented at the Bio-IT World Conference & Expo in Boston, April 24-26, 2012. Winners and entrants will also be featured in Bio•IT World.

For more information on the program and to download the entry form, please visit www.bio-itworld.com/bestpractices.

Deadline for Entry: Extended to February 15, 2012 << safety of drugs in development,” Jolley says. Advanced Research Projects Agency recently Hiring out safety surveillance functions to committed over $70 million to developing a less well-qualified employees of offshore con- “human on a chip” that can assess the safety tract safety organizations is another growing of medical counter measures to a biological at- c problem, says Jolley. For sponsors, this is an tack when there is no time for animal studies. issue of control that can be mediated by better Pre-clinical animal models are time-consuming contractual language and perhaps higher allow- and expensive, not to mention relatively poor able fees for the advanced level of medical deci- predictors of results in humans. In fact, safety- sion making required. related issues—and more specifically, actual or Outsourcing of safety surveillance is be- feared liver toxicity—are the main reason drugs

CONTENTS coming more common for drug makers, says fail, contends Watkins. Uber. With limited real-world data in the early Cardiac arrhythmia disturbances, as evi- post-approval phase, companies are obliged denced by a prolonged QT interval, were until to employ the FDA’s risk evaluation and miti- recently the most frequent culprit in drug re- gation strategies (REMS) that might include calls. But early-phase EKG testing on healthy restricted product distribution or creation of volunteers has become standard practice, mak- patient registries. Based on the sentiment of ing liver meltdown the major unresolved safety 28 organizations recently surveyed by the Tufts issue. In the absence of a regulatory path for University Center for the Study of Drug De- drug-induced liver injury (DILI), FDA some- velopment, REMS may not be packing much times requires expanded clinical trials to im- punch: only 22% think the REMS system has prove the odds of detecting a latent liver issue. improved safety. As products mature, compa- The “disaster” is not just the time and costs of nies can learn more from safety signaling tools. these extended trials, but potentially billions of But the technology often yields a large volume dollars for the years of lost patent life “we all end of potential signals that may or may not be caus- up paying for.” ally related to a drug, and can require extensive Watkins is chairman of the steering com- resources to investigate, says Uber. mittee for the NIH-funded Drug-Induced Liver Injury Network, which since 2004 has been en- Informed Dosing deavoring to genetically characterize people who Both FDA and National Institutes of Health experience uncommonly severe liver reactions (NIH) are clearly interested in improving the to a drug. Separately, the Hamner-UNC Institute science behind the assessment of drug risks, has been attempting to create a computer model and support research in priority areas of regu- of DILI to make animal models more predictive latory science such as adaptive trial design. The —and ultimately help eliminate animals from regulatory science program has recently focused drug development entirely. The European Union on novel approaches for testing drug efficacy is taking the lead in this arena with its Innova- and safety prior to clinical trials, notably in vitro tive Medicines Initiative (IMI) that has set aside cell-based technologies that can mimic how 2 billion euros ($2.6b) for matching grants going human tissues respond to drugs. The Defense to pharma companies engaged in regulatory sci-

52 JANUARY 2012 Visit Us at www.Bio-ITWorld.com ence research. The IMI’s goal, says Watkins, is to “make Europe the worldwide home for pharmaceutical research.” Meanwhile, the Hamner-UNC Institute is about to launch a DILI-sim initiative with c partners AstraZeneca, GlaxoSmithKline, Novartis, and other pharma companies, says Watkins. The goal is to model signifi- Better biomarkers of cant inter-species differences and suscepti- bilities to liver toxicity, to help inform first- organ toxicities would be in-man dosing. Watkins argues that part CONTENTS a huge— PAUL advance WATKINS, Hamner-UNCfor trial safety. of the problem in achieving efficacy is the Institute for Drug Sciences failure to administer a sufficiently high dose. Currently, drugs are typically given in doses “at least ten times lower than what causes liver toxicity in animals,” he says. als,” says Watkins. “If they do, there’s no stan- Corporate partners are providing financial dard way to handle them and link [the samples] and in-kind resources as well as data from com- to patient data.” Watkins is leading the push to pounds that looked promising in animals but create a standardized safety database linked to subsequently fail in humans. The FDA, which a biospecimen repository. In the cardiovascular intends to apply lessons from DILI-sim in regu- arena, FDA already prescribes how EKGs should latory decisions, is also supportive. The first be performed and the data warehoused. The iteration of the computer model will be distrib- mandate helped spur formation of the Cardiac uted to partners early in 2012. Safety Research Consortium for ongoing evalu- Previous research from the Hamner-UNC ation of medical products. Watkins would like to Institute suggests a simple urine test could pre- launch a similar consortium, initially focused on dict which clinical trial participants are at risk liver safety, at the Hamner-UNC Institute. for DILI, based on specific metabolite patterns However, increasingly robust patient pri- predictive of mild liver damage associated with vacy requirements could make creation of a acetaminophen. Better biomarkers of organ biospecimen repository problematic, warns toxicities would be a huge advance for trial safe- Uber. “If a study sponsor retains samples, it has ty, says Watkins. The four blood tests currently to inform study participants. And if a sponsor available for detecting liver problems have been doesn’t know how those samples may eventu- in use for 50 years, produce false-positive really be analyzed and evaluated, they will need to sults, and miss sudden-death liver injury that obtain permission for ‘research not yet speci- can inexplicably arise weeks or months after fied.’ Language that provides the sponsor un- ingestion of a drug. limited future access to retained biological “Companies do not routinely collect and specimens is a permission patients are likely to keep blood and urine samples from clinical tri- question, and may be reluctant to grant.” •

Visit Us at www.Bio-ITWorld.com JANUARY 2012 53 KNOWLEDGE CENTER | New Products c CONTENTS

Stability Trial Software Gene Design in Open Language Two Fold Software is adding a user-friendly DNA2.0 has announced the integration of the Stability Trials software module to Version 1.1 Synthetic Biology Open Language (SBOL) into of the company’s innovative Qualoupe LIMS the company’s groundbreaking gene design software. The new Stability Trials software has and assembly tool, Gene Designer. SBOL is a been specially tailored for organizations that synthetic biology standard exchange format need to run stability trials over any given pe- that allows scientists to share, store, explore riod of time and different storage conditions. and publish genetic elements created through Using the software the user can create proto- computer design. SBOL is the first standard- cols for parameters such as sampling regimes, ized information exchange framework created detailing storage conditions, sampling fre- specifically for bioengineering. This newly- quency and time units. When running a trial released language forms the basis for Gene the user can select the protocol which would Designer’s integration of genetic parts from then create the scheduled samples for the trial. BIOFAB and enables a new feature in the ap- The material on trial would associate the meth- plication called Diagram. Diagram provides ods to be performed on the samples. Trials can a clean visualization interface of designed se- be associated with studies and projects. The quences and eases scientific collaboration by Stability Trials software also enables the LIMS enabling graphic exports of sequences. to provide prompts for sample pull schedules Product: Diagram visualization interface for and the storage location. Gene Designer Product: Stability Trials module for Qualoupe Company: DNA2.0 LIMS For more information: www.DNA20.com Company: Two Fold Software For more information: www.twofold-software.com

54 JANUARY 2012 Visit Us at www.Bio-ITWorld.com Kinase Services c Caliper Life Sciences has launched In-Cell KinaseScreen, a new services offering based on a panel of cellular assays that measure the effects of drug candidates on the functional activity of kinases involved in critical cell- signaling pathways. The technology platform and initial panel of nine assays were developed CONTENTS in collaboration with Pfizer. The service is im- Expanding Genomics Suite mediately available for compound screening, Partek has released two new products: Partek profiling, and custom assay development ser- Flow and Partek Pathway. Bookending the vices for Caliper Discovery Alliances and Ser- Partek Genomics Suite, Partek Flow provides vices’ (CDAS) clients, ranging from academia upstream alignment, QA/QC and quantifica- to pharmaceutical companies. tion of next generation sequencing (NGS) data, Product: In-Cell KinaseScreen and can be installed on a desktop, cluster, or Company: Caliper Life Sciences cloud environment. Partek Pathway provides For more information: contextualization of the gene relationships www.caliperLS.com/CDAS identified within Partek Genomics Suite, allowing users to study gene-gene and gene-protein relationships with the ability to identify Next Gen Analysis Server and display significantly affected pathways, Biomatters has released version 1.5 of Ge- search for specific pathways and genes, and neious Server, an NGS analysis product that color code them based on their p-values and connects biologists to powerful Linux-only fold changes. Together, the tools offer a com- software algorithms and high-performance prehensive start-to-finish solution for NGS hardware resources such as clusters. Geneious data analysis providing alignment, QA/QC, ex- Server 1.5 includes the ability to connect to ploratory analysis, statistical analysis, interac- clusters using MOAB/Torque in addition to tive visualization, genomic integration, and bi- Oracle’s SGE and Platform Computing’s LSF, ological interpretation. They support raw data adds support for Queue Licenses and features from all major commercial NGS and microar- TopHat for mapping millions of RNA-Seq ray technologies and the five core assays: RNA, reads against a reference genome in minutes. DNA, microRNA, ChIP, and Methylation. Product: Geneious Server v.1.5 Company: Biomatters Products: Flow and Pathway For more information: Company: Partek www.geneious.com For more information: www.partek.com

Visit Us at www.Bio-ITWorld.com JANUARY 2012 55 KNOWLEDGE CENTER | Free Trials & Downloads DATASHEET c accelrys draw

accelrys draw enables scientists to draw and edit complex molecules and chemical reactions with ease, facilitating the collaborative searching, viewing, communicating and archiving of scientific information. CONTENTS

Faster and more eFFicient • Easily create structures with Rgroups for queries or enumerations Company: Textco BioSoftware Accelrys Draw has the same look-and-feel as ISIS/ Product: Gene Construction Kit (GCK) Company:Draw, but ARX brings additional speed and efficiency to • Annotate reaction schemes with text, color and Description: Download GCK to see for yourself Product:chemical CoSign structure Digital drawing: Signatures a variety of arrow styles how this flexible plasmid mapping tool makes Description: CoSign is the most widely- • Continuously draw bonds, pull out rings and • Easily create publication-quality structures for analyzing and annotating DNA cloning proj- deployedadd digital atoms using signature all-purpose solution drawing tool in the Life inclusion in Microsoft Office documents and ects faster and easier—making your lab more Sciences industry, employed by over 20,000 presentations productive. FDA-regulated• Drag-and-drop organizations. commonly-used structures and chemical abbreviations onto the toolbar for reuse Try if for free: http://bit.ly/FreeTextco Try it for Free: http://bit.ly/FreeARX • Right-click for atom, bond, fragment properties easy to integrate and query options and conFigure • Quickly retrace steps using Multiple Undo/Redo As an enterprise software application, Accelrys Draw offers flexible integration with custom Java® and .NET applications as well as integration with Accelrys Isentris® and ISIS applications. Use XML to configure the chemical drawing look-and-feel according to the organization’s needs.

• Create custom add-ins to enhance the scientist’s drawing experience • Integrate with existing desktop applications • Leverage Web applications for query and browsing Figure 1: Drawing a synthesis suitable for high-quality printing is Company:simple with Accelrys Accelrys Draw. The product name displayed below the structure was generated automatically using the included structure- Company: Accelrys Product:to-name Draw generator. Product: DS Visualizer Description: Accelrys Draw enables scien- Description: DS Visualizer is a commercial- tists to draw and edit complex molecules and grade graphics visualization tool for viewing, chemical reactions with ease, facilitating the sharing, and analyzing protein and modeling collaborative searching, viewing, communicat- data. ing and archiving of scientific information. accelrys.com 1 Try it for Free: http://bit.ly/FreeVisualizer Try it for Free: http://bit.ly/FreeAccelrysDraw

56 JANUARY 2011 Visit Us at www.Bio-ITWorld.com Feature Your Free Download To have your free trial or download listed on this page, contact Allison Proffitt, Managing Editor, at [email protected]

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Visit Us at www.Bio-ITWorld.com JANUARY 2011 57 KNOWLEDGE CENTER | Upcoming Events

Strategic Alliance Management Congress c Keep abreast of the variety of educational events May 7-9, 2012 | Philadelphia, PA in the life science industry that will help you with Biomarker World Congress your business and professional needs. To pre- May 21-23, 2012 | Philadelphia, PA view a more in-depth listing of educational offerings, visit the “Events” section of bio-itworld.com. WPCWorld Pharma Congress To list an educational event, contact Lisa Scimemi June 5-7, 2012 | Philadelphia, PA at [email protected]. CONTENTS

CHI Events For more information on these conferences and oth- June 6-8, 2012 | Singapore er CHI events, visit healthtech.com. Visit BarnettInternational.com for detailed infor- Summit for Clinical Operations Executives (SCOPE) mation on Barnett’s live seminars, interactive web February 7-9, 2012 | Miami, FL seminars, on-site training programs, customized Cloud Computing eLearning development services and publications. February 19-20, 2012 | San Francisco, CA Next Generation Pathology Barnett Live Seminars February 19-20, 2012 | San Francisco, CA Auditing Techniques for Clinical Research Professionals February 6-7, 2012 | Boston, MA February 21-23, 2012 | San Francisco, CA Data Management in the Electronic Data Capture Integrated R&D Informatics for Arena Knowledge Management February 6-7, 2012 | Boston, MA February 21-23,2012 2012 | San Francisco, CA Comprehensive Monitoring for Medical Devices Bioinformatics & Cancerinformatics February 7-9, 2012 | Philadelphia, PA February 21-23, 2012 | San Francisco, CA CRA & CRC Beginner February 7-9, 2012 | Philadelphia, PA Clinical Project Management: Advanced March 5-8, 2012 | San Diego, CA February 9-10, 2012 | Boston, MA microRNA in Human Disease and Development Clinical Project Management: Introduction March 12-13, 2012 | Cambridge, MA to Practical Clinical Trial Planning for Project Managers February 14-15, 2012 | Philadelphia, PA Monitoring Clinical Drug Studies: Intermediate April 24-26, 2012 | Boston, MA February 16-17, 2012 | Philadelphia, PA PEGS: the essential protein engineering summit Conducting Clinical Trials Under ICH GCP April 30 - May 4, 2012 | Boston, MA February 16-17, 2012 | San Diego, CA

58 JANUARY 2011 Visit Us at www.Bio-ITWorld.com Regulatory Intelligence Comparing FDA and Health Canada Regulations: February 17, 2012 | San Diego, CA Using an ICH GCP Framework c Monitoring Clinical Drug Studies: Beginner January 26, 2012 February 20-22, 2012 | Philadelphia, PA Critical Decision Points in Design & Adverse Events: Managing and Reporting for Conduct of Patient Registries Medical Devices January 26, 2012 February 23-24, 2012 | Philadelphia, PA New FDA Guideline to Informed Consent Advanced Good Clinical Practice January 27, 2012 February 23-24, 2012 | Philadelphia, PA March 2011 Compliance Program Guidance CONTENTS Medical Device Approval Process Manual (CPGM) Update: Recommendations for February 27-28, 2012 | San Diego, CA the Inspection of Sponsors, CROs, and Monitors January 30, 2012 The Highly Effective CRA February 27-28, 2012 | San Diego, CA RECIST 1.0 and 1.1: Overview and Data Challenges in Oncology Clinical Trials Developing Clinical Study Budgets January 30, 2012 March 1, 2012 | San Diego, CA Train-the-Trainer: Successful Web-Based Good Clinical Practice for Laboratory Scientist Training Strategies March 1, 2012 | San Diego, CA January 31, 2012 Pharmacovigilance Audit NEW! Investigator Selection Criteria and March 1, 2012 | San Diego, CA Strategies for Investigator Qualification Adverse Events: Managing and Reporting for January 31, 2012 Pharmaceuticals March 1-2, 2012 | Philadelphia, PA Clinical Project Management: Intermediate March 1-2, 2012 | Philadelphia, PA Conducting Clinical Trials in Resource Limited Settings March 1-2, 2012 | Boston, MA Patient Recruitment and Retention March 1-2, 2012 | Boston, MA Introduction to FDA March 8-9, 2012 | Philadelphia, PA

Barnett Web Seminars Corrective Action Plans: Essential Documentation of a Site’s Response to GCP Deficiencies January 23, 2012 For more details on this newly published report, visit Adverse Events for Medical Devices InsightPharmaReports.com January 23, 2012

Visit Us at www.Bio-ITWorld.com JANUARY 2011 59 KNOWLEDGE CENTER | Complimentary Resources

stored. Learn how Radiology Ltd. has utilized the c Visit bio-itworld.com to browse our extensive Dell Compellent SAN to improve the performance list of complimentary Life Science white papers, and scalability of its data center, while gaining critical podcasts and webcasts. transparent reporting to help enable better patient To learn more about developing a multimedia care. lead generating solution, contact Lisa Scimemi at Presenter: Colin Schmugge, Data Center Manager [email protected] at Radiology, Ltd. Moderator: Dr. Kevin Davies, Editor-in-Chief,

CONTENTS Bio-IT World Whitepaper Download Now Accelerating Decision Making Podcast Processes in Life Sciences R&D Meeting Today’s Challenges Sponsored by HP and Microsoft in Clinical Trial Supply Management Life sciences organizations Sponsored by: Medidata need an easy way to access Solutions Worldwide and share information to make timely R&D decisions. Read Setting up and managing the this white paper to learn: clinical trial involves many com- • How IT and business chal- plex procedures. Among the lenges complicate decision-making efforts most challenging are planning and executing the • How to avoid missed opportunities, duplicate logistics of the trial’s clinical supplies. This podcast work, and inefficient use of time focuses in depth on the following topics which trace • How a jointly developed HP and Microsoft busi- current practices and future evolution of this crucial ness intelligence appliance provides a way for life aspect of clinical trials: sciences researchers and managers to accelerate • Current practices in clinical trial logistics their analysis and decision-making work. • Comparing advances in clinical supply practices to other aspects of clinical trials Download Today • Where current practices fall short of meeting the challenges Webcast • Trends and evolving improvements that may Meeting Compliance Needs through change the way logistics are conducted Enhanced Management of Patient Data Listen Now Sponsored by: Dell Compellent Healthcare providers under- Web Symposium stand the pressure to keep Whole Genome Sequencing (WGS): The Next the data center highly- Diagnostics Platform available at all times. These April 3, 2012 organizations consistently try to manage rapidly growing digital patient data, while adhering to regula- healthtech.com/zmdsq tory compliance that dictates how long it must be

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• Data Orchestration: How IDBS is deploying workflow solutions and electronic lab notebooks to aid data management and advance translational medicine. For advertising and sponsorship opportunities in this exciting issue contact: • Is IT a Cloud? In a further sign of growing acceptance Accounts A–K of cloud computing, a biopharma consulting Alan El Faye firm describes how and why it put its entire IT (213) 300-3886 infrastructure into the cloud. [email protected] Accounts L–Z • Plus: One big pharma’s approach to medical Tim McLucas imaging, supercomputing prediction of adverse (781) 972-1342 [email protected] events, and a round-up of news and trends in ELNs.

EDITOR-IN-CHIEF VP BUSINESS DEVELOPMENT CORPORATE MARKETING Contributing Editors Cambridge Healthtech Institute COMMUNICATIONS DIRECTOR Kevin Davies (781) 972-1341 Angela Parsons PRESIDENT Lisa Scimemi Michael Goldman, Karen [email protected] (781) 972-5467 Hopkin, Deborah Janssen, Phillips Kuhl [email protected] (781) 972-5446 MANAGING EDITOR John Russell, Salvatore [email protected] Contact Us: Allison Proffitt VP SALES — ACCOUNTS A–K Salamone, Deborah Borfitz, [email protected] (617) 233-8280 Alan El Faye WEB ADVERTISING OPERATIONS Ann Neuer, Tracy Smith [email protected] (213) 300-3886 MANAGER Schmidt 250 First Avenue, Suite 300 [email protected] Franscena Schandelmayer- Needham, MA 02494 ART DIRECTOR Davis Advisory Board Mark Gabrenya ACCOUNT MANAGER — (781) 972-1351 Jeffrey Augen, Mark Boguski, CONNECT WITH US! (781) 972-1349 ACCOUNTS L–Z [email protected] Tim McLucas Steve Dickman, Kenneth [email protected] Getz, Jim Golden, Andrew (781) 972-1342 ADVERTISING OPERATIONS Hopkins, Caroline Kovac, [email protected] COORDINATOR Stephanie Cline Mark Murcko, John Reynders, (781) 972-5465 Bernard P. Wess Jr. [email protected]

62 JANUARY 2011 Visit Us at www.Bio-ITWorld.com Companies in This Issue

AccelerEyes...... 24 Convey Computer. . . . . 25 Johns Hopkins...... 7 QuantuMDx...... 42 Accelrys...... 44, 56 Cray...... 25 Joint Genome Institute . . . 19 Real Time Genomics. . . . 57 c AdvancedHPC...... 25 Cycle Computing...... 24 Juniper Networks...... 25 ScaleMP...... 25 Amazon Web Services. . . .24 DataDirect Networks. . . . 25 Life Technologies...... 13 SCYNEXIS...... 45 AMD...... 25 Denodo Technologies . . . .57 Medidata Solutions. . . . .36 SGI...... 25 Amgen...... 13 Digizyme...... 12 Morgridge Institute for SJ Pharma Consulting. . . .46 Ariadne Genomics. . . . . 26 DNA2.0...... 54 Research ...... 24 Stanford University. . . . . 7 ARX...... 56 DNAStar...... 19 Multiple Myeloma Research Textco BioSoftware. . . . .56 AstraZeneca...... 53 DuPont...... 26 Consortium...... 27 Thomson Reuters . . . . . 27 CONTENTS Berkeley...... 18 Eisai...... 8, 48 Myricom...... 25 Tufts University ...... 52 BGI...... 19 Elsevier...... 26 Nanosys...... 42 Two Fold Software. . . . . 54 Biomatters ...... 55 Gene Codes...... 19 National Human Genome University of California, BioSoteria...... 47 Genentech ...... 13 Research Institute. . . . .26 Santa Cruz...... 18 Brainloop...... 57 GlaxoSmithKline...... 53 NETLIST...... 25 University of California, Bright Computing . . . . . 24 Globus Online...... 25 Newcastle University. . . . 42 Davis ...... 18 Bristol-Myers Squibb. . . . 26 H3 Biomedicine ...... 8 New York Genome Center. . .6 University of Illinois. . . . .25 Broad Institute . . . . 7, 8, 19 Harvard Medical School. . , 24 Novartis ...... 7, 13, 53 University of North Bull...... 25 Harvard University. . . . .7, 8 NVIDIA...... 25 Carolina...... 49 Caliper Life Sciences. . . . 55 HP ...... 25 Oracle...... 55 University of Notre Dame. . .24 ChemAxon ...... 27 IBM...... 25, 26 Pacific Biosciences. . . . .22 Washington University in CLC bio...... 19, 57 Illumina ...... 18, 22, 57 Partek...... 55 St Louis...... 7 Cold Spring Harbor Lab. . . 19 Infinty Pharmaceuticals. . . 11 Pfizer...... 6, 26, 55 Wellcome Trust Sanger Complete Genomics. . . . 57 Johnson & Johnson. . . . .13 Platform Computing . . . . 25 Institute ...... 19

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Visit Us at www.Bio-ITWorld.com JANUARY 2011 63 The Russell Transcript c What is (Quantitative) Systems Pharmacology? CONTENTS By John Russell and successful drugs as well as others—work in the body? What are the detailed mechanisms? ust a few days apart in the middle of Oc- How are they influenced by various ‘omics? tober, Harvard Medical School (HMS) How do they vary by tissue? etc. This is a great announced a broad initiative in systems idea, which is not to say such activities weren’t pharmacology and NIH released a like- part of the broad the systems biology world. minded white paper, Quantitative and The practical implications of such a com- SystemsJ Pharmacology in the Post-genomic pound-centric approach are exciting: new Era: New Approaches to Discovering Drugs targets, new screens, new markers, new under- and Understanding Therapeutic Mechanisms. standing of drug failure mechanisms. Indeed That’s a fair amount of attention from two very sophisticated drug failure analysis may be one big guns on a topic that may ring both familiar of SP’s most promising goals and eventually and unfamiliar. most rewarding contributions. (FDA should Actually systems pharmacology has been open its treasure trove of information for these loosely percolating for some time. While not ex- efforts, but that’s another matter). It’s a fairly actly a splinter from the systems biology world, firm rule-of-thumb that the biopharmaceutical systems pharmacology shares much of systems industry doesn’t spend a lot of time or resourc- biology’s methodology and conceptual frame- es investigating why drugs fail. work. Indeed, the Harvard Medical School sys- Helping launch, promote and develop systems pharmacology initiative is being launched tems pharmacology as well as delivering from its systems biology department and one of concrete SP results are the main goals of the the NIH paper’s lead authors (Peter Sorger) is a Harvard initiative. It is being led by William member of the department. Chin, executive dean for research at HMS; Nuanced definitional wrangling aside (sure Marc Kirschner, chairman of the HMS Depart- to be fun), what distinguishes systems pharma- ment of Systems Biology; Peter Sorger; and cology is its laser-like focus on compounds and Tim Mitchison, deputy chair of the depart- how they perturb biological systems and path- ment. The ambitious plan calls for adding ways. How specifically do compounds—failed

64 JANUARY 2012 Visit Us at www.Bio-ITWorld.com faculty (10), tackling research, establishing pharmacology is an applied science, “I’m not new research infrastructure, and collaborative a big believer in distinguishing at least in the c outreach to biopharma, other academia, and early stage applied from fundamental. People biomedical communities. were trying to understand how to make steam engines more efficient and we ended up with SP in Practice thermodynamics. [Y]our goal may be to make According to the Harvard SP announce- nylon but you end up having to figure out all ment, “The initiative will support both new physics and chemistry surrounding polymers CONTENTS approaches in translational science, such as and how they assemble and interact. [That] failure analysis on unsuccessful drugs and gets to be very fundamental.” use of chemical biology to develop probes of Biopharma’s response has been positive, biological pathways. It will also include a new Kirschner says. Industry execs he’s talked to educational program, one that develops a believe SP can have practical benefits. They new generation of students, postdoctoral fel- also agree the effort is best led by academia, lows and physician-scientists, the future lead- given that economic pressures are prompting ers in academic and even the biggest drug makers to downscale re- industrial efforts in search, especially basic research. It’s also more systems pharmacol- difficult for biopharma to attract the multi-dis- ogy and therapeutic cipline talent required to pursue SP properly, discovery.” says Kirschner. Obviously every- One question is how to measure SP prog- thing won’t happen at ress and impact. Broadly speaking, “[It] can once, but Kirschner be looked at in two different ways,” says and colleagues are Marc Kirschner Kirschner. “If the goal was to achieve some charting the path forward. “One project al- specific target for a specific disease, I think the ready going on in our place and at MGH likelihood of that happening quickly is small. (Massachusetts General Hospital) is a study On the other hand if the goal is to achieve sig- of the drug Taxol,” he says. “It delivers nice nificant information and tools useful for the understandable effects in some cell cultures development of targets in some disease, that but the effect on human xenograph tumors in likelihood is quite high.” the mouse, when viewed by intravital imag- In the end, he says, systems pharmacology is ing, shows the drug acts in a very different way an open-ended exercise and biopharma will there. We have a lot to understand about drug have access to the results. Systems pharmacol- action not only in cells but also in more com- ogy and framing it as a compound-driven exer- plex environments.” cise is great idea. Let’s see where it leads. • Kirschner resists the notion that systems

Visit Us at www.Bio-ITWorld.com JANUARY 2012 65

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