ProSanos Talks Safety Tools, Predicts New Controversy

Forget, for a moment, the media hyperbole and legal stakes surrounding drug safety. The related scientific paradox is even more discouraging. Profoundly so.

On the one hand, virtually every seasoned participant in or observer of clinical trials understands that such research will never predict many serious adverse events. These only become apparent once a drug is approved by the FDA and sold in every Walgreens in the country.

On the other hand, sound approaches to analyze a drug's safety profile after its commercial launch remain clinically and mathematically controversial – techniques of art as much as science. When the FDA proposed research to fix this, Congress emitted a bored sigh.

So pharma is stuck with immaculate data from clinical trials – results surprisingly free of noise and confounding factors like other medications. And yet after a decade or more, when a drug emerges from clinical trials and reaches national distribution, the data become filthy, ambiguous, and unsuitable for the same precise analysis that persuaded the FDA to approve the stuff in the first place.

Is there a way forward?

Jonathan Morris thinks so. He's the president, chairman, and CEO of ProSanos, a 30-employee firm out of La Jolla, Calif. He spoke at the Bio-IT World Expo this year, and we chatted with him recently. ProSanos specializes in the analysis of drug safety data. It is helping pharma and biotech companies listen for subtle signals in the data available after a drug has reached the market.

The services, data sources, and software that ProSanos provides are varied. The company may clean your data, design your case report forms, or blend data from your trials and the real world. The math and the IT underlying the company's judgments are cutting-edge, but the company doesn't get mired in arcane theoretical or statistical issues. In some cases, Morris says, ProSanos may have an answer to a drug-safety question in 48 hours.

Morris predicts another Vioxx is on the horizon. "Absolutely," he says. "It's coming." He notes cardiologist Eric Topol of the Cleveland Clinic was not the only person to detect the Vioxx safety signal in 2001, years before the lawyers began circling. "We saw that," Morris says.

His chief concern now? The industry is simply not as sophisticated as it should be in studying the links between drugs and adverse events that arise after a drug has been approved. "We have to be able to understand the associations, the relationships," he says, between drugs and problems allegedly caused by drugs.

Take the all-too-common problem of news reports linking a particular drug and a particular side effect. Such reports typically trigger more reports – copycat patients. It can be complex to discern the genuinely ill from the worried well. "If you see an event being reported for a given diseases or product, is it due to the drug?" says Morris. "We've got analytic technology that helps subtract out the bystander effect."

He's blunt about the predictive limits of many clinical trials. "Today, in 2005, the best-designed prospective Phase III studies will not pick up all of the potential safety problems that will occur when the product is being used," says Morris. "Once a product is launched, you have to be able to follow it over time. That's where the unexpected things begin to occur."

Of all the Phase IV studies that sponsors are obliged to conduct, Morris notes, just 27 percent are actually completed. "Many companies do not fulfill their obligations," he notes. "If only a quarter of all the committed studies are done, it's hard to say anyone is holding up the gauntlet for good behavior."

New thinking and new tools are needed. "Conventional statistics and conventional approaches – the way you approach Phase III data – cannot be applied to the association data," Morris argues. "How do you deal with the association between the drug and the event? That we don't have a handle on."

Some customers, he says, want to go deeper. "There is a need, once you integrate the trial data you have, to go to other collections and see if the things you're seeing are there as well." That could mean data from a pharmacy benefit manager. It could mean health insurance claim data, or even reports from emergency rooms.

Believe it or not, Morris is optimistic. As electronic data capture becomes more common, as paper stops gumming up the process, the industry might actually get better at keeping safe drugs on the market and pulling bad ones faster.

XML and the Clinical Data Interchange Standards Consortium (CDISC), he says, will slowly make a difference. "If the companies are required to fill in and report their data in a marked-up way, now you can build automation and tools that can look against what's expected in the trials vs. observed in the world. It's going to take time. But those things are coming."

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Patient Recruitment Technologies from Acurian

Recruitment is the eternal issue – the intractable problem. Who can say how many dollars, companies, people, projects, and ideas have been thrown at finding more patients? And yet delays continue to plague most trials.

Acurian, out of Horsham, Penn., serves as a matchmaker for investigators, patients, and trials. The company has 40,000 investigator names and six million patients in its databases.

Most of its revenues, of course, are derived from sponsors of clinical trials. The company's position is that its services, expertise, and software, seamlessly tied to call centers, offer a better window into which trials are on track to meet recruiting goals.

In May, the company announced a new CEO, Rick Malcolm, who was most recently VP of business development at contract research organization (CRO) ICON Research.

Acurian's tools, Malcolm says, include software called Recruitment Manager. It brings together patient, call center, and clinical site information; the effectiveness of advertising campaigns can also be factored into the mix. It's possible to see that the mass-transit ads in Chicago worked, while the TV spots in Miami flopped. "Recruitment Manager will allow them to see at an aggregate level and a detailed level the performance of individual patient recruitment tactics," Malcolm notes.

Recalling his experience in the CRO trade, Malcolm says most in the industry (especially with electronically collected data) use software once patients are enrolled. But Acurian is trying to educate sponsors that there is additional data about the clinical sites, marketing campaigns, and call centers that starts to pile up long before the first patient is officially signed up.

Some sponsors are not aware that this pre-enrollment data can be accessible, Malcolm notes. Acurian's prospective, forward-looking analytics can predict what will happen before a trial begins. He says Acurian can offer a high degree of granularity: it's possible to click on a research site, a call center, or a single patient. Sponsors can see real-time data about what's working, and which regions or nations are on target. Says Malcolm: "That data just was not there in the past. This will wind up changing the way a lot of sponsors look at enrollment."

Early facts gathered from a few clinical sites, he speculates, may be funneled back into the design process. Perhaps an age criterion is a problem, excluding too many patients. "Maybe we should increase the upper age limit by five years," Malcolm says. "People have the opportunity to see the data and make the on-the-fly decisions that have not been available in the past."

Acurian's chief technology officer, Roger Smith, says the company offers a speedier integration of data than may always be possible in trials that are being run by the seat of one's pants. "The speed of the integration of all the data is key," says Smith. "In most cases, by the time the data can be analyzed, the money is spent. This puts the sponsor in the driver's seat."

Smith says customers are encouraged not to request custom reports. Acurian has spent a fair amount of time working out the most useful, potent ways to slice and dice the data; the company believes it has identified perhaps 10 essential reports that are critical to understanding the recruitment of any trial.

Says Smith: "I don't think anyone questions the fact that the pharma industry is sitting on a sea of data. Recruitment Manager has taken the time to say, what are the 10 views you should look at to make a decision? This is what you should be looking at – the metrics that should tell you the health of your trial, and that doesn't come with most electronic data capture systems."

New Tools from Target Health

Target Health is a double role model. It is showing where both leading technology vendors and fearless contract research organizations (CROs) need to migrate.

As a small, focused, service-oriented CRO, the company knows how to take care of customers ranging from mid-tier biotechs to large pharmas that claim to be standardizing around other technology vendors.

But Target Health is itself a technology company, giving its own software an unusual amount of internal resources and attention. The company takes a release of its core application as seriously as any electronic data capture (EDC) concern. As with much larger EDC innovators, Target Health is exploring both e-source – paperless or almost-paperless data entry – and integration with hospital and physician-office IT systems.

The Manhattan company has just released version 3 of Target e*CRF, a suite of tools for setting up and running clinical trials digitally. The origins of Target e*CRF lie in its own experiences serving sponsors and gathering data. Denmark's Ferring Pharmaceuticals has already had two NDAs approved with earlier versions of Target's tools. Ferring says it locks its databases a single day after the last patient visit.

Target Health's president, Jules Mitchel, is not a fan of software for the sake of software. "Drug development and device development are our business," says Mitchel. "We make presentations to companies without demonstrating our software. We say, 'This is what we have done.' Customers want someone who can help them solve problems, not just make software." Within e*CRF there is a WYSIWYG editor to create case report forms, and the SAS programming language for edit checks.

The key thing for sponsors, Mitchel says, is that no additional proficiencies will be required by a clinical research associate (CRA) or statistician using the tools. Says Mitchel: "For companies to use our software, they do not need to change the current skill sets employed by the company. The skill sets of a good CRA or SAS programmer are the fundamental skills needed to run our system."

Mitchel's VP for business development, Bill Johnson, formerly participated in EDC development at Merck. He believes Target Health is something of a new breed of companies, an e-CRO. Target Health's technology is sufficiently flexible, Johnson says, to have two different departments in the same company using his software to design trials in their own preferred ways.

Yes, that might seem ill-advised to senior managers in, say, the financial services industry. But in pharma, it's not top secret that teams dedicated to different diseases or types of trials often have idiosyncratic groups of preferences, standard operating procedures, and even color schemes. All of the above are invariably not shared by colleagues within the same company. Says Johnson of customers: "They can change our system to match their process."

Joon You, Target Health's chief technology officer, adds that the system can store the data in any common format. "The system can archive the data natively in XML and also PDF and SAS datasets. It does all three automatically, and there are other formats you can specify like Excel spreadsheets."

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Upcoming Industry Events The 2005 cancer Biomedical Informatics Grid (caBIG) Industry Partners Meeting – September 30, Bethesda, Maryland The Industry Partners Meeting will be an opportunity for representatives from companies that are not yet involved in caBIG to learn about the initiative, consider the benefits and requirements of caBIGô compatibility, and explore opportunities within the caBIGô program for industry partners. More information, including a detailed description, agenda and pre-registration information can be found at: https://cabig.nci.nih.gov/2005_Industry_Partners/. Bridging Discovery and IT - September 29-30, Philadelphia, PA Bridging Discovery and IT is a unique conference that will highlight novel technologies and strategies that enable organizations to extract knowledge from mountains of heterogeneous data. Drawing on the reputation and expertise of Bio-IT World and Cambridge Healthtech Institute, this conference will feature compelling examples of successful partnerships between IT and biopharma groups and organizations, and insights into cutting-edge information tools and systems. A number of joint presentations from pairs of end users and IT & informatics partners will provide indispensable guidance for surmounting challenges and delivering results. Attendees will gain insights into building a genuine competitive advantage by deriving useful knowledge from data Find out more at http://www.bridgingdiscoveryandit.com/ Project Management for Discovery and Development - Practical Applications and Methodologies to Increase Project Leader Effectiveness September 22 - 23, Arlington, VA http://www.cbinet.com/show_conference.cfm?confCode=HB544  This conference provides concrete examples of business strategies and processes being used today, shows the benefits of building and growing a stronger project leadership program and most importantly, gives practical solutions on how to invest wisely on both people and technology levels in this space. For more information or to register, please contact the Center for Business Intelligence toll   free by phone at 1-800-817-8601 or via e-mail at cbireg@cbinet.com. Genomics, Medicine & the Environment - October 17-19, Hilton Head Island, SC Enjoy science, sun and sand in beautiful Hilton Head, South Carolina. From nature and medicine to technology and pharmaceutical development, advances in genomic science play a critical role in all areas of life and business. Conference attendees hear first about cutting-edge research, participate in in-depth discussions of future innovations in the field, and have the opportunity to network with other researchers and scientists at the forefront of genomic discovery. The conference will feature three days of ground-breaking science covering relevant topics such as environmental and comparative genomics, genomic medicine, intellectual property rights, the future of genomic testing, and advances in genomic sequencing technologies. For more information, visit http://www.venterinstitute.org/gsac/index.php  The 2nd Annual Business of Discovery Conference on Molecular Diagnostics Strategic Business Development and Partnerships to Commercialize New Products - October 20-21,San Francisco, CA  https://www.cbinet.com/show_conference.cfm?confCode=HB592  This conference provides diagnostic and pharmaceutical companies in the molecular diagnostics market space with the latest thinking on issues affecting the development, acceptance and management of genomic based tests for patient care, i.e. assessing the value and clinical utility of tests, patenting of technologies and target molecules, the integration and interpretation of genomic based test results with other tests (imaging, biopsies) for patient care, working with molecular laboratories, pricing and appropriate payment for tests.  Various views and positions on developing and commercializing MDx tests once the genetic discovery work (i.e. biomarker research) has already been done is offered. For more information or to register, please contact the Center for Business Intelligence toll free by phone at 1-800-817-8601 or via e-mail at cbireg@cbinet.com.