Oncology outsourced: An emerging research model

In spite of advances in biology and medicine, cancer remainsa major unmet clinical need. In the pharmaceutical and biotechnology worlds,cancer research is focused primarily on diagnostic tool development andtarget-based drug discovery. Diagnostic tests play an important role in patientstratification for treatment and for monitoring therapeutic benefit. Thereductionist target-based drug discovery approach enables a more effective,personalized approach to clinical treatment.

Fortunately for us, the chances for meaningful advances inthese areas are never higher than today. Over the past decade, we havewitnessed the dawn of the 'omics era and the advent of Big Data. Emergingtechnologies like next-generation sequencing and innovative analytical toolssuch as network analysis have improved our understanding of basic cancerpathophysiology. What remains is translating this knowledge from the bench tothe bedside.

Although academic and government research institutions and,increasingly, nonprofit research foundations, contribute to the search for newdiagnostics and therapeutics, the bulk of cancer research is carried out by thepharmaceutical industry. In the past few years, however, multiple factorsincluding decreased productivity, higher costs and the ongoing patent cliff havemade drug research in the pharmaceutical industry unsustainable in its currentformat. As a consequence, newer models of science and business are replacingthe fully integrated pharmaceutical company (FIPCO) model that is quicklybecoming a relic of the past. Evolving technology has allowed and even driventhis shift. The name of the game for drug research today is outsourcing.

Outsourcing of drug research

Pharmaceutical companies are adapting to the changingbusiness dynamics by moving away from a vertically integrated model wherecompany scientists do all of the research in company laboratories. Outsourcinghas become the key to not only efficient technology development, but also theentire drug research process. This is true for all disciplines, but is nowheremore evident than in oncology, drug discovery and diagnostics, where thepharmaceutical industry has established relationships with thousands ofexternal research partners. These days, many companies have become fullyintegrated pharmaceutical networks (FIPNets) comprised of company scientistsworking hand in hand with outside experts.

What are the benefits of this networked research approach? Forone, it makes it easier to access research capabilities and experts on demand,thereby empowering cancer researchers. Other benefits include dramaticallyreduced costs, shortened development times, higher quality and improvedproductivity.

External research partnerships

Pharmaceutical companies have established three types ofexternal research partnerships, each with its own unique benefits:

1. Pharmaceutical companies have long used the publishedfruits of academic research to help them in drug research. Today,pharmaceutical companies are actively partnering with universities. Thesecompanies get access to cutting-edge tools and technologies and an innovationmindset. The academics benefit from research funding and the ability totranslate their basic research into clinical studies.

2. Pharmaceutical companies are turning to small and mid-sizedbiotechnology companies to access new technologies and fill their dwindlingdrug pipelines. Smaller companies are often nimble and more efficient thantheir larger cousins. These partnerships generate revenue for the small companyand often lead to its outright purchase, such as the acquisition of MedImmuneby AstraZeneca in 2007.

3. Pharmaceutical companies have established partnershipswith tens of thousands of research vendors, including contract researchorganizations (CROs), contract manufacturing organizations (CMOs),non-governmental organizations (NGOs) and patient-advocacy groups. Therelationships can be quite diverse, ranging from one-week, fee-for-servicepartnerships to multiyear, billion-dollar deals. As an example of the latter, afew years ago, Eli Lilly & Co. outsourced its drug safety research, in itsentirety, to a single CRO.

Of the three types of partnerships, easy access to CROs ishaving the biggest impact on the pharmaceutical research landscape. Havingthousands of external research providers eager to custom create researchservices, products or tools is game-changing for the pharmaceutical industry.This approach has enabled AstraZeneca to keep just 40 of 800 scientists in itsneuroscience division and shut down most internal neuroscience laboratories,but still run the same number of neuroscience drug research programs.

Pharmaceutical companies fall into two research outsourcingcamps. One camp prefers to outsource services to preferred vendors that are preselectedin each research area, which means they routinely work with hundreds of smalland large vendors at the same time.

The other camp prefers to outsource all or most services toa single large CRO, a so-called "full-service model." With thousands of newresearch tools being created every year at an ever-accelerating pace, however,it will become increasingly difficult for a single CRO, no matter how big, tooffer every research tool required to run multiple drug research programs. Evencompanies that embrace the full-service model today will be forced to access arange of CROs if they want access to the most innovative and cutting-edgeresearch technologies.

The almost 4,000 U.S. preclinical CROs are distributedwidely across the country with CRO clusters in the expected pharma/biotech hotspots. For example, a 2010 study shows almost 150 CROs in the greater San Diegoarea alone that are collaborating with local drug research companies.

Research from virtuallaboratories

Since it is no longer necessary to maintain expensivelaboratories to run a drug research program, groundbreaking drug research is nolonger restricted to the few big, wealthy organizations. Any talentedindividual with a computer and basic knowledge of spreadsheets, biology andstatistics can run a drug research program or develop clinical diagnostictests.

Take the example of Dr. Purvesh Khatri, a computer scientistworking with Dr. Atul Butte at Stanford University. Purvesh accessed publicgenetic data on tumor samples from an online repository and used his knowledgeof statistics and free online software to identify genes that were overexpressedin tumors compared to normal samples (a case/control study). He next used a CROto obtain blood samples from 10 cancer patients and 10 healthy individuals, andthen shipped the blood samples to yet another CRO for testing by ELISA. Usingthis virtual research approach, Purvesh identified biomarkers for threedifferent cancer types within one year—without ever setting foot in alaboratory!

Purvesh's example is an encouraging step forward fordo-it-yourself biologists with limited resources, but an unlimited drive andideas waiting to be tested. As Butte says, "we say, 'outsource everythingexcept the genius.'" Virtual research may represent a paradigm shift enablinghighly efficient use of limited finances and manpower.

Outsourcing makes ourscientific world flat; a citizen scientist with limited resources can now doprojects previously restricted to a large pharmaceutical company with enormousresources.

Empowering citizen scientists

It's been more than 40 years since Richard Nixon first declaredthe "war on cancer." We have made progress, but with more than 7 million peopledying every year from cancer, we still have a long way to go. Althoughtroubling to some, it may be time for scientists to embrace the idea that wealone can't solve this problem fast enough. We may need help from our lesswell-trained brethren: the citizen scientist.

ClicktoCure is an excellent example of citizen scienceattacking the challenge of cancer. Createdby Cancer Research UK, a charity dedicated to the cure of cancer through basicand translational research, ClicktoCure recruits citizen "soldiers" who examinecolored sections of tumor images and analyze data using prompts provided on thewebsite. Automated techniques can generate thousands upon thousands of imagesof tumor biopsies. The bottleneck is not having sufficient researchers toexamine each and every image. The ClicktoCure program leverages the power ofcitizen scientists, asking volunteers to undertake the front line analysis ofthousands of images of biopsy slides. Those that are flagged by volunteers are reviewedby experts. This crowdsourced project makes excellent use of citizen scientistseager to participate in meaningful research with tangible results. CancerResearch UK says it firmly believes it "will change the face of cancer research."

Citizen scientists are also important for the study of rareand orphan diseases, often neglected by the pharmaceutical industry because ofsmall market size and low expected financial returns. Now that it is possiblefor a single highly talented person to use outsourcing to run an entire drugresearch program from a laptop computer, it is likely that there soon will benumerous examples of personalized drug discoveries carried out by patientadvocates or even by patients themselves. With enough basic knowledge andresourcefulness, citizen scientists will be able to leverage outsourcing todevelop specific, more effective drugs and diagnostic tests for rare cancers andother rare diseases.

The way we develop oncology diagnostics and therapeutics ischanging rapidly. Though the shift to an outsourcing research model is beingintensely debated within pharmaceutical and biotechnology companies, it isrevolutionizing how virtual laboratories run by professional or citizenscientists can function. Empowering all scientists and lowering barriers toresearch innovation is the essence of this new research model.

Dr. Kevin Lustig is theco-founder and CEO of Assay Depot, an online marketplace that gives scientiststhe ability to access 8,000 global vendors to any research skill or servicethey need for their drug research project. In 2001, Lustig founded Kalypsys, adrug discovery company that raised more than $170 million in venture capitaland put five drug candidates into human clinical trials. Prior to Kalypsys,Lustig directed lead discovery at Tularik, a biopharmaceutical companypurchased by Amgen in 2004 for $2.5 billion. Kevin has an M.S. degree inbiochemistry from the University of Missouri-Columbia and an A.B. degree inmolecular and cell biology from Cornell University. He carried out postdoctoralwork in cell biology at Harvard Medical School after receiving a Ph.D. degreein biochemistry from the University of California, San Francisco (UCSF). Hisresearch discoveries have been published in Science, Nature and other leadingscientific journals, and he has been awarded eight technology patents.