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The Evolving Dynamics of Collaboration In Global Clinical ResearchAs sponsors of clinical trials become more discerning about the strengths of individual contract research o rgan iza t ions (CROs ) , strategic alliances between CROs offer access to shared efficiencies in new geographic areas

C a t o R e s e a r c h ’ s H e s c h i Rotmensch, M.D., regards the decision to partner with another CRO on the same trial as fairly natural and logical. "For the last 15 years, we have realized that we are a mid-sized company relative to the big multinational CROs," he says. "If we want to play in the ground of mid- and large-sized companies, then we need to have collaborative services." Rotmensch is Cato’s senior vice president of drug development; chief project officer; and he manages all research activities outside the U.S. The company, he says, uses caution as well as a gradual and careful approach to be sure his firm and a prospective partner CRO

can work smoothly together. The company selects partners in countries or geographic areas w h e r e i t h a s n o e x i s t i n g infrastructure. "We collaborate based on mutual chemistry, vendor audits and lengthy discussions to s e e i f c o n c e p t u a l l y a n d philosophically there is a fit,” Rotmensch says. “We have started always with small steps, giving a small piece of work, and then expand on that. That has worked pretty well for us." Cato tends to retain standard clinical trial activities such as project management. Other assignments (regulatory affairs, perhaps) are shared with other firms that have the necessary

A White Paper

RETHINKING CRO ALLIANCESON

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specialized knowledge or expertise in a particular corner of the globe. Rotmensch says that sharing research-related projects may require a certain well-established confidence at both CROs, which must believe that a valued client can be shared but not lost to a competitor. "If you look at it narrowly, concerned and afraid about exposing yourself—that someone will steal your client or your processes—that is not a good start for a collaboration," he says. Most sponsors are now sufficiently sophisticated to understand that CROs have areas of particular strength and unusual competence, and slightly weaker areas that may be augmented by other organizations. Cato partners with Target Health and with other CROs. For its projects around the globe, Cato has ongoing collaborations with eight additional CROs on a nonexclusive basis. “The experience with Target Health has been quite smooth,” Rotmensch says. He and his colleagues have appreciated the unusually speedy responses from the Target Health electronic data capture system programming wizards when the inevitable minor glitches arise during any project. Rotmensch believes both organizations have had mutual benefits from the projects they have collaborated upon. "We are working closely together for many years,” he says. “We have not had any major disruptions between the two organizations. Target Health has come up with innovative concepts. We have added our experience to whatever they had. We have contributed improvements to their software."

Michael Harte of the Harte Group oversees a network of 140 different clinical trial serv ice and technology providers. Cumulatively, the companies in his network have 16,000 employees. Harte doesn't work directly with Target Health, but

suspects its technology may help to provide a standard foundation, unifying people and processes on far-flung research projects around the globe. Harte's firm is generally hired by sponsors to partner with a few well-vetted, seasoned small firms to toil on a trial together. Harte functions like a general contractor, providing vendor oversight and central project management. That

allows him to help select the right clinical development partners and avoid some of the contorted processes that can plague any big project or any large organization. Often, Harte reports, his firm is retained to rescue trials—only to discover that some sponsors have not identified the most efficient ways to manage external providers against missed timelines or bal looning budgets. From a b u s i n e s s p e r s p e c t i v e , Harte and his h a n d - p i c k e d niche providers generally try to impart a greater sense of urgency than what they first encounter. Based on his own projects, Harte believes there are potentially large financial and time savings from CROs working together. Many large, publicly traded CROs are struggling to reconcile the concerns of stakeholders in the sponsor community with those of their own investors. As an example, the use of esource and risk-based monitoring might trim trial budgets and timelines. Sponsors would approve. But CROs adopting such techniques could face revenue shortfalls that would alarm their own investors. More usage of technology at large CROs, likewise, should provide sponsors with actionable insights into study progress. But those same tools could also require major realignments of both human resources and revenue streams inside CROs. Small, private CROs have none of these constraints. In projects managed by Harte's network, there is an eagerness to take advantage of all of the time- and cost-savings that close teamwork and well-chosen clinical trial software can provide. "What it boils down to is having like-minded individuals and niche providers," Harte says. "We propose our own teams and systems. And we take ownership of them." If the trial is on track, all participating firms share in performance incentives. And if not? Harte is blunt about the need to manage clinical trials in a hawklike manner, like any other modern, complex business process. "We own the contract," Harte says. "We manage the accountability. If they don't perform, then we provide a replacement." Like his own hand-picked teams on trials, Harte says, Target Health and similar

The experience with Target has been quite smooth—Heschi Rotmensch, Cato Research

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strategic CRO-CRO alliances may be able to sing from the same hymn book to a degree that other larger firms cannot yet match.

One CRO that is judiciously partnering with other firms is George Clinical. Headquartered in Australia, it is one of the top CROs in the region, with a focus on the Asia Pacific region, including India and China. Some of the CRO's personnel overlap with the adjacent nonprofit George Institute. Maria Ali, M.B.B.S., M.B.A., head of medical safety and scientific liaison at George Clinical, believes that in some CRO alliances, subtle corporate cultural nuances may not receive sufficient attention early in the assessment of any proposed alliance. Those issues should loom as large as matching standard operating processes (SOP) and more technical matters. "Just working together does not mean that you are collaborating," notes Ali. "Collaborating is working together with respect for the key strengths that each organization is bringing and allowing them to maximally input those strengths into the project." It doesn’t hurt to surprise the other partner in a favorable way. On one endeavor, a Phase III project, Ali was surprised that the aggressive timelines for the project presented no difficulties for Target Health. "The project had a very quick startup phase," she says. "The timelines were quite challenging." In other industry projects, she acknowledges ruefully, it is possible for the implementation of competing clinical trial technologies

to delay the start of the study. Al i i s par t icu larly intrigued by the paperless, e-source technologies of Target Health. Says Ali: "That is the kind of thing that makes them stand out. Everyone is talking about

buzzwords. Target Health has actually done something, submitted NDAs based on e-source." Of particular interest to her company: the Target Health program to handle trial master files electronically. The two CROs have embarked on a limited number of projects to date, but with high expectations for more jointly shared trials. Ali says the relationship is expected to be mutually auspicious for both companies.

"They could use our expertise in Asia-Pac," she says. "We could use their software. It is a natural synergy." A l i s a y s t h a t George Clinical does not always have the ability to choose its CRO partner. "We are o f t en to ld by the sponsor who their preferred provider is in the U.S. and European region," she says.

At TechnoSTAT, a contract research organization in Israel, Yael Shtrit is department manager of clinical data management. She says TechnoSTAT and Target Health are working on "quite a few" trials. "We use the Target Health platform and they assist us with any additional programs,” says Shtrit. TechnoSTAT has no in-house electronic data capture system. She says the EDC solution from Target Health works beautifully. And the people at Target also prove easy to collaborate with. "It is very easy to work with them," Shtrit says. "We have not had any problems. We are not working with paper CRFs anymore," she notes. "We are changing our way of working, as we have Target Health.” Just as Southwest Airlines uses a single type of jetliner for more efficient training and repairs, TechnoSTAT uses the Target Health technology exclusively. Says Shtrit: “It saves something if you put all your eggs in the same basket." One of the dynamics of projects in the Middle East, Shtrit observes, is that even well-funded biotechnology sponsors in the region are price-conscious. Microsoft Excel remains a common tool for clinical data collection. Needless to say, some large, well-known EDC suppliers are simply not under consideration because of the 6- or 7-digit cost of those systems. Says Shtrit: "Prices are a big issue for them." The pricing of Target Health's system, in contrast, allows TechnoSTAT to share the project without jeopardizing its financial return. When bidding on new projects, TechnoSTAT CEO Tal Zucker says, neither of the CROs feels at risk or threatened by the other: "Target on their end are doing their best to let us win each of the projects we are trying to achieve. We get a good chance to win most of the cases. We really appreciate the collaboration."

Prices are a big issue—Maria Ali,George Clinical

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TechnoSTAT did explore working with a few other firms, she says, but has been fairly impressed by the Target-enabled transition away from paper case report forms. “We are now almost stopping to do paper CRFs,” Zucker says.

Working with other CROs is nothing new for Young Jack Lee of LSK Global, the company's founder and president. The Korean company has completed 700 projects since its start in 2000. Its forte is local knowledge, says Lee. "If Korean authorities ask something relat ively simple about the design, global CROs or local affiliates have to go back to their headquarters,” he says. “They don't have the expertise in statistics. Headquarters has to think about it and get back to the affiliate. That takes time. We can answer much better and faster." Early in his career, while working for a large global CRO, Lee got a question about a trial from the Korean government. He could have answered it in minutes. But that approach would have violated his then-employer’s policy. Under its approved process, the answer slowly passed through multiple levels of the CRO in Korea, the United Kingdom, the U.S.—and back down the chain of command to Korea. The process took three months, Lee notes ruefully. Lee says some big multinational CROs trying to operate all over the world can become a bit rigid, insisting on finely-honed processes without ever compromising. That can make it hard for his project teams in particular locales to operate in the most efficient manner available. Target Health, he says, is more flexible: "Target Health is very willing to accommodate us or accommodate the study, whatever particularities we may have." In Korea, Lee reports, Target Health doesn't have a large number of strong competitors. "Target Health is sort of the standard of practice for EDC in Korea," Lee says, partly because there is no doubt it is battle-tested to meet global and U.S. regulatory standards, a claim small locally-developed Korean EDC systems usually cannot

match. Lee notes that some sponsors do occasionally ask him to support other major EDC solutions. When a sponsor asks LSK Global to use a different EDC system, Lee says, he pushes back. He is especially uninterested in risking a project on a small, in-house clinical system that has been developed in Korea. For Lee, the operational and regulatory risks to sponsors (and his company’s reputation) are too great. "We say no," he says. "Quality is more important. We simply refuse to work with the locally developed system.”

In Korea, Lee notes, the paper case report form is heading to the same extinction territory as the do-do bird. " T h e p a p e r C R F i s disappearing," he says flatly. "But there are sponsors that like to use paper. We can use Target Health for paper data entry." The Target system has supported trials using the Chinese, Japanese and Spanish languages in addition to English. At this point, inside Korea,

Lee feels that his firm is uniquely positioned to match the capabilities of a big multinational firm. "We can do everything global CROs can do," he says. His assessment of Target Health is that the functionality of its EDC system is equivalent to any firm in the niche. Even with a large observational study that collects only a small quantity of data about each patient, he says, the systems from Target are perfectly attuned. Says Lee: "Target Health is very flexible. We could even build a pharmacovigilance program based on Target Health. On other EDC systems, you cannot do that. Target Health is not a one size fits all kind of service. They are flexible and they try to accommodate."

The president of New York-based Target Health, Jules Mitchel, Ph.D, M.B.A., actively seeks out alliances with other CROs. He believes the contracts can be mutually beneficial. His company is a traditional CRO with a major clinical software development emphasis. After supporting over 400 clinical trials over the years, Target Health is genuinely global, recently launching an electronic informed consent module in English, Japanese and Spanish. Mitchel says that in an optimal alliance, each potential partner should understand its

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strong suit. Ideal candidates for partnering, needless to say, have different domains of special expertise. A few elements of some trials are more standard. And either firm in the partnership can capably handle those tasks. But Mitchel doesn't lose a great deal of sleep over jockeying for a particular contract if the relationship, over time, seems to work for both CROs. " O n e o f t h e companies that we work with got some business that we could have done," he notes. "We got some business from them that maybe they could have done. What you can't do is court the client that you got introduced to in order to get more business for yourself." Why are so many disparate CROs in the U.S., Korea, Israel and other countries eager to partner with Target Health? The firm's technology is a draw. "We do have features the other electronic data capture companies do not have," says Mitchel. "We have an e-source solution. You can enter data in real time. That is available to all of our collaborators." The technology has been used in more than 20 trials. Also, Target Health prices for data management and electronic data capture (EDC) are hyper-competitive in an era in which some suppliers of EDC are taking advantage of higher pricing due to a smaller pool of providers. Target’s fee structure is often a simple annual license, with a cost per study and hosting fees—not a bewildering compendium of hundreds of charges for each discrete change order or system modification. In some cases, Mitchel says, a CRO alliance requires a discussion about which company’s process

to use in a particular aspect of the trial. “The biggest issue for CROs is optimizing their processes,” he says. “But there are no conflicts." CROs of all sizes, he believes, are starting to explore less paper-intensive processes—and how such processes could fit within strategic alliances and evolving business models. “The size of the company is not the key issue,” he says.

“What matters is having a n o p e n - m i n d e d a p p r o a c h t o h o w technology can help in clinical development.” CROs outside the U.S. are being strongly

pressured on price, and don't possess in-house EDC solutions. In such cases, it makes sense to partner with a company like Target Health. It's not a secret to the industry that trials are complex. And in some cases, Mitchel believes, the sponsor community still does not judge the top EDC solutions to have all of the optimal and necessary functionality to support what sponsors desire. "Clinical trials are not simple," Mitchel observes. "All of a sudden, in the middle of a study ... can you do this? Can you do an interim database lock? You need both the database and the electronic data capture—and knowledge of pharmaceutical data management. That is what is wrong with some of the systems. They are too simplistic.” In the complex world of modern trials, he says, it can be helpful to have an experienced partner. Mitchel has a philosophical outlook on the division of tasks between allied CROs. With the best alliances, everything seems to even out in the end. "I don't have to win the whole program," Mitchel says. "We are willing to share. To us, relationships are very, very important."

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The paper CRF is disappearingYoung Jack Lee, LSK Global