Kerri Nelen

CBI gathered industry professionals in early February for two Philadelphia events: the 5th Annual Patient Awareness, Recruitment and Retention for Clinical Trials Conference and the 3rd Annual Clinical Trial Forecasting and Budgeting Conference. Both meetings, which drew a crowd of about 150, ran the same two days inside the downtown Marriott where all talk centered on how to improve the way things are currently done.

For recruitment that means taking a step back and rethinking the process of site selection, a process most attendees easily agreed could use tweaking. "Relooking at things will help you figure things out," advised Atul Mahableshwarkar, MD, Senior Director at Takeda Pharmaceuticals, who added that "this is a team effort, not science and operations being separated."

As such, sponsors must work with their CROs closely and early on to capture the kind of data that can inform selection decisions. "CRO/internal feedback is critical," said Rajesh Menon, MS, MBA, Manager, Research and Development, at Takeda. "They have day to day interaction with centers. They intimately understand the personnel as well." 

This type of qualitative feedback paired with quantitative data, such as site resources, failure rates, data query resolution capabilities, accomplishes what Conference Co-chair Christine Pierre, President and Chief Executive Officer of RxTrials, described as the key to the entire process: tying together art and science to predict site enrollment. 

And it's in this direction-using qualitative and quantitative data-that industry is moving for a more in-depth evaluation, says Gary Lubin, President and Chief Executive Officer of Centerphase. "Predictability is key," he said, and achieved through thorough protocol review and the right partners. Technology like EHRs can help says Lubin, "but it's only as good as the underlying data. It has to be part of the process and not relied upon." 

: These can be developed internally and contain ratings on such soft metrics as whether the site staff were motivated. This knowledge, says Menon, is then later applied to "fit" sites for future studies. Scorecards might also prove useful to sites, suggested one attendee, as they can see where they need to improve. 

: Although avoiding sites that won't perform is ultimately the goal, there must be a process in place to cut dead sites and fast. Whether it's 30 days or 60 days, sites should be informed upfront before the study begins of the cut off date and dealt with accordingly. For Lubin, that also means duly compensating the sites that do perform. 

: There are certain characteristics you want in an investigator, says Arthur Lazarus, MD, Senior Director of Clinical Development at AstraZeneca. Those include: self-motivated, analytical, team player, and excellent record keeper. Avoid over-promisers and doctors who view research as a side business, warned Lazarus, who advised, "You want a PI who understands the budget and timelines and has a track record of completing on time."

In today's economy industry has no choice but to become more efficient, Rama K. Rao stressed during the first presentation of the Forecasting and Budgeting Conference. Rao, Executive Director, U.S. R&D Finance, for Novartis, described the perfect storm battling industry: soaring drug development costs ($1.2 billion +), a decreasing ROI, and higher trial costs. In this context, "we need to go from tactical skills to strategic," said Rao, who listed innovation, process improvement, alliances, and outsourcing as the four key areas that should be part of every strategy.

 Conference Co-chair Deirdre BeVard, Vice President, Clinical Operations and Data Management, Endo Pharmaceuticals, backed the idea of alliances, pointing out the value in a match of equals. "If we would see CROs as an equally critical partner, like GM looks at brake manufacturers," she said, "we might be able to make better strides." Because when both sides have skin in the game-a popular phrase used throughout the conference-responsibility is shared, which spreads accountability.

Something else that needs to be shared is information. This requires a sledgehammer and some muscle. "Smash silos to plan study budgets," said Kelly Larrabee, RN, MBA, Director, Clinical Services, ClearTrial. In particular, this means breaking down the walls between the clinical operations side and the financial side. Without input from both, it's harder to plan costs and schedules. By involving all teams, sponsors can tighten budget variation.

 "Too often it's a hand off," explained Mike Sherman, Chief Financial Officer, Endocyte, referring to the divide between finance and clinical operations. Sherman, a member of the panel that discussed points of view from the small-to-medium sized pharma or biotech, has seen what happens when both sides share a relationship and accountability. Take, for example, when a problem arises with patient recruitment. "[The] first reaction is not: This is a clinical issue," said Sherman. "They are immediately together to figure out consequences of the situation."

 Granted, this type of intimacy is easier to come by in a smaller operation, where teams are 50 people strong. But while it might prove harder and require more effort in a larger company, Sherman believes it is possible. In fact, when it comes to budgeting and forecasting,  larger organizations could benefit from  applying the same kind of hands-on approach employed by smaller companies, where the numbers and timelines are assessed  at least weekly. Again, that might be impossible, the panelists agreed, but in today's challenging times it doesn't hurt to rethink strategy.

 and CBI are owned by Advanstar Communications.

Articles

CBI Tackles Recruitment and Budgets

Like many industries, clinical research is no stranger to the allure of the global world. Its advantages are plenty, and for most, read like a memorized shopping list: lower costs, shorter timelines, more patients. But unlike other industries, going global with clinical trials raises red flags in many circles.    

"Pretty much everything out there is negative," says Todd Clark, referring to press covering the global expansion of trials. To get beyond this, what it calls anecdotal reporting, the Association of Clinical Research Organization (ACRO) commissioned Clark to do some research. The result is the white paper, The Case for Globalization: Ethical and Business Considerations in Clinical Research. 

When asked if any of the findings in the midsummer report surprised him, ACRO's Executive Director Doug Peddicord said there were two: the small size of the marketplace emerging countries currently constitute and how some act stricter than U.S. and EU bodies. 

Clark likened this strictness to paternal protection. "In Latin America, especially in Brazil," he said, "it is virtually impossible to do a placebo controlled trial...they think it's sort of excessive experimentation to some degree. And in India, you cannot do as a foreign sponsor a Phase I first-in-human trial." 

India also provides an example of what the white paper says may prove an additional layer of oversight in less developed countries: close relations. It cites one study in which 92% of Indian patients said they consulted with family or friends before enrolling in a trial, compared with just 62% of the Americans. 

Positive findings like this are heavily sprinkled throughout the 39-page pro-global report to support its thesis that "emerging countries play a vital role in the advancement of medical science." With them, it finds, years can be shaved off Phase III cancer trials via shorter enrollment times. Which means drugs get to patients, get to market faster—"In truth," notes the report, "the largest benefit of globalized trials." 

None of that matters, of course, if the quality isn't there. Which is a common criticism. How can a country with little experience ensure good clinical quality? The answer: with some help, which has come from industry and CROs. It seems the consensus view is that their growing global presence over the past 10 to 15 years has created a wider knowledge base. 

Both groups are at the forefront of education, says FDA Senior Advisor for Clinical Science David Lepay, MD, PhD. He told 

 that "It is rare for FDA to approach a country about capacity building without them talking about industry training programs taking place in their country." 

Clark credits sponsors for central Europe's rise to nearly being on par with western Europe. Their trials and financial investments in the region are behind its improvement, he says, and better global health care. 

Exposing developing countries to clinical research exposes their medical professionals to new equipment, new approaches, new patients. Clark describes it as a "technology transfer and knowledge transfer that improves the level of health services in these countries." 

Take Poland for example. According to Clark, 30% of cancer care in its hospitals come from clinical trials. What good would it do, he asks hypothetically, to take away this care because Poland is still an emerging country? That might make sense to globalization skeptics, but it doesn't to Clark. "It's really a case of letting the perfect be the enemy of the good," he says.—

Recent white paper from ACRO emphasizes the need for global trials.

Globalization Gets An A+

DIA officially commenced its 45th Annual DIA Meeting early Monday morning in sunny San Diego with the always well-attended plenary session. This year proved no exception, as the packed auditorium seemed to attract a majority of the nearly 8000 attendees present.

Annual Meeting Program Chair Nancy Smith, PhD, former director, office of Training and Communications at FDA's CDER, expressed delight at such a high level of attendance during these challenging economic times, which also includes over 1000 speakers and 520 companies that are manning over 835 booths.

Over the next three days, 350 sessions will provide attendees with what Smith described as the most important part of the meeting: the chance to meet colleagues from around the globe. "So, talk to the person sitting next to you, make a new friend every day," she advised. 

Communication was also at the heart of the key note speaker's address, specifically responsible medical communication. In a world where information seems to travel at the speed of light thanks to the Internet, Nancy Snyderman, MD, chief medical editor at NBC News, says it is our responsibility-industry, academia, global governments, and the press-to tell the story correctly.
 
 "So what is our role?" she asked. "To figure out what the message is and move it forward." According to Snyderman, that means making sure the medical information out there is credible and can help the average person, and having a free press that is an ally and not an enemy and who acts as a cautious watchdog.       
 
 The dangers of telling the wrong story or telling the story wrong, Snyderman said, can undermine the health and well-being of the populace. She gave the example of what happened in the early 1980s with HIV as proof, when uninformed doctors and an uninformed press created a lot of bad information, leading to unintelligent health policies.
 
"Never before has this world been so small," she said, "and never before has the responsibility been to communication with transparency, so the people who rely on us know we can be trusted."

 


This year's plenary also played host to farewells and awards. Marie Dray, MBA, addressed the audience for the last time as DIA president. Dray, who is handing over the reigns to 

, MD, FACP, of IDM Pharma (Irvine, CA), warned that "adherence to [the] status quo will not propel our industry forward." To that end, she said, DIA must embrace healthy change-the only certainty in 2009-while maintaining the agency's core values.

In addition, Dray awarded DIA's Outstanding Service Award to none other than 

' columnist Kenneth Getz, who is a senior research fellow at Tufts CSDD and Chairman of CISCRP. Such a recognition comes as no surprise to those who know the passion Getz has for the clinical research enterprise. Congratulations Ken!

Don't miss interviews with both Ken Getz and Nancy Smith. You can find them 

San Diego Convention Center welcomes a packed house, as U.S. meeting gets underway with California casualness.

Annual Meeting Rises with the Sun and Shines

It might be 20 years younger than its U.S. counterpart, but DIA’s 21st Annual EuroMeeting proved to be a mature gathering of over 3500 professionals from over 50 countries. And for the second time since 1994, the city of Berlin played host to the three-day event, which ran from March 23-25.

Outside the spaceship-like Internationales Congress Centrum where inside hustle and bustle was the norm, Germany’s capital city celebrated with no noticeable fanfare the 20th anniversary of the Berlin Wall’s collapse. A fact brought to the attention of the audience that gathered for the plenary that officially kicked off the beginning of the meeting.

Inside the packed auditorium, DIA’s president of the Board of Directors Marie Dray-president of Dray Regulatory Associates-reflected on the similarity between the historic event and the 45-year-old association. What both share in common, she said, is the theme of unification. “DIA’s members have long understood the value of working together,” she said. “Berlin’s successful unification is a good example of DIA, of redefining itself.”

And it will continue to, according to Dray. She explained that the meetings of tomorrow will look nothing like the DIA meetings of today. With the exception of the U.S. and European annual meetings and those in areas with a growing DIA presence like China, India, Latin and South America, Africa, and the Middle East, a large portion of activities, including training and education, will move online.

”It’s really not DIA making that decision,” explained William Brassington, acting DIA worldwide executive director, “it’s what the market wants from us.”

The want is influenced by the global nature of industry today-reflected by the fact that for the first time in its history DIA’s two candidates for president live outside the United States-and by the current economic environment. Just as financial pressures are changing the face of R&D, they are also at the forefront of change at DIA.

“DIA is facing economic pressures it has never faced,” said Dray, “We will focus on our legacy as a neutral forum as we reexamine methods to bring members together."

 
 A not necessarily “new” but better way of operating was the focus of this year’s plenary. During the three hour debate-which was pleasantly interrupted with a performance by the Berlin Children’s Choir-moderators probed the minds of the eight member panel with questions on topics such as the state of the European Regulatory Agency, transparency, generics, and the impact of drugs on the environment.       

. Thomas Lonngren, EMEA's executive director, summed up the walk-away message when he told the audience: “We have a robust system for 14 years. I don’t think we should change it in a major way, [but] fine tune it.”

According to Lonngren, one area that needs fine-tuning is clinical trials. A more centralized approach to them, he said, would benefit the EU and also make it more competitive.

But as for any talk of moving toward a single, centralized regulatory agency like the U.S. FDA, Lonngren made it clear that is not the desired outcome of the EU, whose success, he told the audience, has nothing to do with a centralized system. "It doesn't work that way," he said, "You build on what you've already achieved."

Moving forward, other areas where he'd like to see improvements made include transparency and science. In the science arena, Lonngren expressed satisfaction with the Committee on Advanced Therapies (CAT), but acknowledged the EU's need to increase its capacity to work with others to meet today's scientific challenges.

What seemed like refreshing insight came from panelist Christine Akerman, director general, medical products agency, Sweden. Her suggestions for a better governance system [the plenary's theme] included: increase work sharing among the European Network of experts; better collaboration between the national authorities and EMEA [a sentiment echoed]; and reduce travel by replacing one-third of it with virtual video meetings, which would provide an opportunity for all member states to attend and share in. 

Akerman did acknowledge the importance of continued face-to-face meetings among EU experts and stressed the need "to develop a system where 

scientific assessment of new drugs will not be repeated." Her idea: Start a pilot project whereby agencies offer joint scientific advice to prevent or lessen repeat work.   

. Generics seem to be a hot topic in the EU. Pricing and reimbursement was brought up, with consensus that member states stay responsible for final decisions but that the Commission could play a role as a "coordinator" to improve communication among member states and help set ideas into motion. 

"We can be quite an important player in this area," announced Martin Terberger, head of unit, European Commission, and Enterprise and Industry DG Pharmaceutical Unit, EU.

Criticism came by way of Georg Stark, joint managing director at Alfred E. Tiefenbacher, an API business that provides generic pipeline services. In addition to speaking of the need for a generic pricing policy, with pricing automatically given upon market authorization, he complained that "regulations are blocking generic products and are giving access to early generic products away."

As for what's at the heart of the generics debate in the EU, Alastair Kent, director of genetic interest group and president of EGAN, shed some light. "We need to strike a balance," he said, "between access to generics and sustainability of programs to develop innovative medicines." One got the feeling a verbal game of chicken or the egg was taking place on stage between the pharma and generic industries, with Stark declaring: "There will be no innovative medicines without generics being available."

Nonetheless, generic talk wrapped up with audience laughter over the friendly banter between both sides: Stark on the one and Eddie Gray, president pharmaceuticals Europe for GSK, on the other.   

 The question was posed: Will environmental requirements decrease the availability of new medications? It did for the veterinary industry, said Lonngren, who explained it made it tougher for that group to get approvals. "I think it's extremely important we know more about it," he said, indicating a need for further research on the impact of drugs on the environment.

This was the one topic that nearly all panelists addressed. Their thoughts on the issue: 
 • "It's about how to meet the needs of the present generation without jeopardizing future."-Akerman
 • "I guess [the] challenge is one of scientific demonstration and proportionality."-Gray
 • "We could learn lessons from veterinary, especially for proportionality, there is some example already."-Terberger
 • "It shouldn't, but I suspect what will happen is interpretation [in direct response to the question if eco requirements will decrease new drug availability]."-Kent
 • "Maybe price of products will go up."-Floortje van Nooten, senior research associate, UBS, Belgium
 • “Should look at [a] more global scale."-Stark

. What's a European meeting without talk of the directive? It's still got a reputation for "driving clinical trials out of the EU and academic research," said Terberger. "We'll look at this and bring life to criticism, and if necessary we'll make legal proposals."

One panelist who brought to life some of his own criticism was Kent, who blamed the directive for the increased regulatory burden in academia. His vision for an improved research arena involves patients, who would help determine trial risk and end points. "Patients are not content that decisions are made by others," he said. "Patients want to see a more flexible approach by regulators." 

On a positive note, Akerman let it be known that harmonization of the directive is a priority for member states. She again suggested video and Web-based meetings, expressing an optimistic cup-is-half-full view. "I see room in clinical trials directive for harmonization," she said, "and no need for a new one."      


 Keeping in line with the global theme of the meeting was the down-to-earth session on conducting international trials. What made it so were the speakers, who didn't glamorize what it's like to undertake studies in emerging areas like China, India, and Latin America. 

They covered the good and the not so good. But also made it perfectly clear that these trials need to be done and that there's no turning back. Already, participation by these regions in clinical trials has increased dramatically over the past three years-as much as 74.5% in China, 27.4% in India, and 30.7% in Latin America [with the largest market in Brazil], according to figures presented.

As for what's driving this globalization, Graciela Racaro, senior director of Latin American operations at Parexel, credits:
 • FDA's acceptance of foreign data
 • Faster enrollment rates because of global outreach
 • Cost reductions due to lower salaries [but the one-time huge gap for investigator grants is closing up]
 • Market potential for Brazil, Russia, India, and China, or BRIC. 

Her key message: "Think globally but execute locally."

Even then though, expect challenges. Which is what Per Nilsson, head of strategic clinical development, and his colleagues at Switzerland-based Actelion Pharmaceuticals found themselves up against after launching trials in China and India. 

Nilsson described the experience as “maze-like,” revealing that it took about two years for the Chinese study to officially get underway. One reason for the delay: Eventually-and not right away-a large portion of the intended study population was deemed “off limits” by regulators because they were of childbearing age. Nilsson indicated that such a decision would not have been sprung on the sponsor like that in the United States or Europe.

Meanwhile in India, during the course of the study two sites that had been recognized as credible by the company early on were eventually closed by authorities without an explanation.   

As for advice when undertaking studies in developing countries:
 • Do not rely on email and fax for initial communication with investigators. The best way to get an understanding of their capabilities and limitations is in a telephone conversation.
 • Consider the standard of care in the country because it might be different than what you’re used to. For the best insight, check with key opinion leaders in the region before making a decision.
 • Arm yourself with as much information as you can by conducting a feasibility study.

“Make your decisions based on data and experience,” advised Racaro.” Amen.

March Memories from Berlin

As a light on the gray horizon, so shines the upcoming Biotechnology Industry Organization (BIO) International Convention, otherwise known as BIO 2009. 

A little dramatic? Perhaps, but when most biotech stories today—outside of the recent $46.8 billion Roche/Genentech acquisition—tell tales of woe and depleted company bank accounts, an opportunity like the one in mid-May in Atlanta offers hope. It's a rare chance for thousands of professionals from around the world (BIO looks to match last year's 20,000) to meet up face-to-face and together figure out a positive way forward. 

"I think the networking, the discussions, and the meetings that will happen will all be around: What's the new business model? How are they [companies] finding funding? What are they looking for?" says Robbi Lycett, vice president of conventions and conferences for Washington, DC-based BIO. "I think that will be the focus in every discussion regardless of the session." 

That includes those related to clinical trials as well. Although the questions will be different, the theme will be the same: What's the best business model moving forward? To this end, many sessions will highlight ways to improve efficiency and decrease costs—whether discussing subject recruitment or global outsourcing. 

One session that will focus on this theme is Adaptive Research in Practice, led by Michael Rosenberg, MD, president and chief executive officer of Durham, NC-based Health Decisions. Dr. Rosenberg, a third-time presenter and passionate proponent of the adaptive approach, says his session aims to equip attendees with valuable practical insight.  

"I hope they'll come away realizing there is a faster, less expensive way of developing drugs than what they're used to," he said, attributing adaptive approaches with reducing trial times and expenses by 10% to 25%. 

For the second year, the conference will include a Clinical Trials Pavilion—one of 70, and the second largest with 28 exhibitors. In terms of growth, Eric Misic, conventions and conferences, BIO, estimates an approximate 20% increase in square-footage over 2008. 

The Pavilion is part of the "Clinical Trials Zone" (there are 11 different Product Focus Zones) and will host a range of companies that fall under the clinical research umbrella, including CROs, subject recruitment firms, data management providers, manufacturers, and imaging labs. 

The idea for a pavilion came about after attendee feedback revealed that locating companies on the bustling show floor sometimes proved difficult. So, "instead of searching for a needle in a haystack, they're able to find exactly where these companies are," said Misic. 

Hopefully with the same ease, answers to the challenges facing industry will also be found during the convention. That would certainly meet BIO's expectations for this year's event. According to Lycett, the goal is that "the industry comes away from this meeting with ideas and business deals...that will help our industry get through the rest of the year and 2010." 

For more information on the upcoming 2009 BIO International Convention in Atlanta, GA, May 18-21, visit 

May convention provides golden opportunity for industry to collaborate and to strategize for a better future.

BIO Breeds Hope

Roy Vagelos, retired chief executive officer and chairman of Merck, took audience members through his illustrious and exciting career at the pharma giant. His objective was to shed light on lessons industry can learn from the golden age of pharma-and in doing so, made one lament the fact they hadn’t the chance to be a research scientist in the early 1980s.     
  
  What an interesting time. Hope for the next cure seemed as high as motivation. So, what can we learn from those glory days of R&D? A few things.
  
  

            
  For starters, breakthroughs mustn't be considered the only path to success. Plus, "no breakthrough is ever perfect," says Vagelos. Which leaves room for other success routes. In Merck's case, it was a second-generation antihypertensive drug that had real advantages over the first generation-the biggest advantage being no loss of taste, thus no black box.
  
  Vagelos also touched upon the impact of company culture. He learned of its power firsthand after a drug the company had developed to kill deadly worms in horses and dogs had been successfully tested in treating river blindness in sub Sahara Africa. After a few major setbacks, including no financial backers, the "magical drug" (as the 

 dubbed it), received approval and Merck decided that it would provide the drug itself. 
  
  "[That] had a terrific effect on people at Merck. We lived what we said; we were there to make important drugs," said Vagelos. "That set a culture for the company, which is one of the reasons the company had such success."
  
  Another reason is expertise. For Merck, in-house expertise led to the first recombinant vaccine in the world. And outside expertise led to the company's first bisphosphonate. But if not for the expert eye of one Merck employee, who noted the work being done by a small company in Italy, that compound never would have been brought in, said Vagelos.
  
  "No matter how much you outsource," he warned, "you better have somebody with great expertise."
  
  


  As for what we can expect moving forward, it was no big surprise to hear Vagelos predict big pharma will take a back seat to small pharma when it comes to discovery. They're the ones working hard to attract bright, young professionals, as the bigger folks slim down their R&D workforce.
  
  The result, according to Vagelos: "Many companies will outsource more and more of their discovery because there's more going on outside." 

Inside industry, meanwhile, he described a great revolution taking place, where the science is making strides with the help of genomics and proteomics. In the eyes of Vagelos, the post golden age of pharma isn't tarnished, it's alive and well, and will continue to thrive. "People will live better because of what is accomplished in this great industry," he said.-

Notes from IIR's Clinical Trials Congress 2009 held this past February in Philadelphia.