Welcome to Pharm Exec's 10th annual Emerging Pharma Leaders feature! This year, we received many nominations and narrowed them down based on the submission comments, internal review, and input from our Editorial Advisory Board. We chose to highlight 11 individuals to go along with our theme, a play on the movie Ocean’s Eleven.

I encourage you, as you read their stories in the pages ahead, to think of individuals you would nominate for next year’s group. 

In these 11 executives, you will find their experiences of how they got to be where they are; 

what challenges they face; as well as advice they can offer to others looking to rise the ranks in the pharma industry. 

You will also find common themes of wanting to help patients; influencing others to grow; and a knowledge that their mentors greatly impacted their careers by believing in them.

It is an honor for us to showcase these individuals, the future leaders of pharma. 

Carsten Brunn, Head of Pharmaceuticals, Americas Region, Bayer

	Carsten Brunn’s entry into the pharmaceutical industry is somewhat unique-his PhD in chemistry from the University of Hamburg in Germany was funded by a scholarship from Eli Lilly. That connection gave him access to an industry lab at Lilly, but in the end, it wasn’t the lab where Brunn would find his true passion.  

	“While I was interested in research from the beginning and was later offered a job in that area, I became very interested in the commercial side of the business,” says Brunn, who is now head of pharmaceuticals for 

the Americas at Bayer.  “So, I made that transition, and it was my time at Lilly ‘carrying the bag’ and then in a number of sales and marketing management positions in the US, when I really became passionate about meeting the needs of patients and customers. What I think I value most about my career path is the broad range of experiences I gained across different types and sizes of organizations and in different geographies.”

	In addition to big pharma, Brunn worked in a startup environment with Basilea Pharma and at Bausch & Lomb during a period when the company had been taken over by private equity firm Warburg Pincus. He’s had the opportunity to work in the US, Europe, and the Asian markets of Singapore, China, and Japan-the latter two with Bayer. The experience has given Brunn an “incredibly helpful perspective” of working across different cultures and market dynamics. It’s also given him an intimate view of how the industry has changed over the years. 

	“It’s much more complex than when I came in,” he says. “Back then, the model was a single brand approach; you’d develop a drug in-house, market it, or perhaps do a co-market, and then sell. Now, there are many more factors at play. R&D is much more expensive and developing drugs through partnerships is a norm. The markets are value-driven and market access is an essential and central part of the strategy. And we see smaller, more niche sales forces.” 

	Arguably the most noticeable change has been that in the area of innovation-the discovery of the genome, development of biologics, immunotherapies, gene editing. Add to that, emerging dynamics like the increased involvement of patients in the development process, more data, etc., and you need a whole different set of skills than you did 20 years ago. 

	“All of these factors now require a different, more holistic view of the market,” says Brunn. “Companies must adopt a more data-driven approach, using the technologies that are now available to do predictive analytics. This lets you be more flexible with strategic decisions, but it also requires different skill sets. The use of such data, though, can help with decision-making across the healthcare ecosystem and actually lower the cost of medicines while at the same time enhancing clinical outcomes. Thinking and working in this way is indicative of the fundamental changes that have taken place in our industry in recent years.”

	The ability to adapt and understand these new challenges facing the pharma industry is what helps shape a good leader, as does being authentic with the people you are working with. 

	“You have to encourage continued learning, risk-taking, and experimentation,” says Brunn. “I have let the team in the US know that I am a firm believer in challenging yourself and the status quo and doing things differently, but also working hard and playing hard. It may be cliché, but it’s true that our people are our greatest and most important asset. You need to be much more flexible and in touch in leading people in this complex environment.” 

	Working and playing hard also comes with balance. 

	“I think it’s important for people to really find an outlet that allows you to clear the mind, and to a degree feel relaxed,” says Brunn, adding that for him, that outlet is cooking. “There’s something to be said for cooking a great meal, from the prep work to the final product that can make you feel quite accomplished. I also work out often, and have been passionate about martial arts for many years. That’s an important release.”

	Brunn led Bayer’s pharma business in Japan for four years, during which time the company went from 18th in the country to the top 10. 

	“That was the first time in many years the company had been ranked that high, and I’m proud of that,” he says. “Also, we built a very diverse management team, including one of the first woman CEOs. We successfully launched several life-saving medicines and successfully set up one of the first open innovation centers in Japan, based in Osaka. As part of the center, we established a comprehensive research collaboration with the prestigious Kyoto University.”

	That collaboration played a key role in Bayer’s joint venture with Versant Ventures to launch Blue Rock Therapeutics, a regenerative medicine company that plans to develop best-in-class induced pluripotent stem cell (iPSC) therapies in efforts to cure a range of diseases using an industry-leading platform. The basis for the overall approach is iPSC intellectual property invented by Nobel Prize winner Dr. Shinya Yamanaka of Kyoto University and licensed from iPS Academia Japan Inc., which manages iPSC IP. This foundational IP will allow the company to create iPSCs, which will be an important cell source.

	Brunn has some simple, yet practical advice for future pharma leaders. “Don’t be afraid to ask for help,” he says. “Vulnerability is a strength. Things are a lot easier if you ask for help. Also, on the functional side, it used to be that everyone said you needed sales experience to advance on the commercial side. Now I think it’s imperative to have market access experience.”

Specialty Sales & Key Accounts, Takeda Pharmaceuticals

	The pharmaceutical industry is full of bright, intelligent, successful individuals, but you rarely meet one that has known early on that they wanted to work in pharma. Most take a roundabout route that involves business or medicine, and then an opportunity to work in the industry comes up and turns out to be the winning ticket. And that’s exactly what happened with Heather Dean’s…babysitter. 

	Dean, head of specialty sales and key accounts for Takeda Pharmaceuticals, says when she was young, she

 looked up to her babysitter, a neighbor, who was smart, athletic, and very well-liked. She left their small town of 2,000 people in Illinois to become a brain surgeon. Later, in seventh grade, Dean’s babysitter visited her hometown, not as a surgeon, but as a pharma representative. 

	“She talked to me about her job and she loved that she was working in business, but she was also helping patients and was speaking to doctors every day,” remembers Dean. “I wanted to be a nurse, but I wasn’t sure I could detach myself emotionally from patients. From that point on, I knew I wanted to be a pharmaceutical rep.” 

	Dean wrote a paper about what she wanted to be when she grew up for English class, and hasn’t wavered since.

	Dean says she views her career to date in thirds. The first third was traditional, as a pharmaceutical sales rep; the next third, in a home office-based role in marketing, and the last third, which brought all her experiences together for an enterprise view in her current role. Dean joined Takeda in 2004 in that second-third, where she led the pre-launch, launch, and post-launch phases of the metabolic commercial program and eventually, GI Marketing, then onto area sales vice president, leading half of the General Medicine commercial sales organization before taking on the third-third, her current position, in October 2016. 

	She is most proud of embracing opportunities that have come her way, and points to two pivotal moments that influenced her 14-year career at Takeda. 

	The first, Dean explained that she had started in marketing at the lowest entry-level position and ultimately was one of the few people left on a brand team that had been built and dismantled a few times because of regulatory hurdles. When the brand director left to pursue another opportunity, Dean knew there were two paths for her, and one was brand director. “There was a big part of me that thought ‘it would be really disappointing if I have to teach somebody everything I already know and not get the job,’ and on the other hand, ‘well, clearly they couldn’t give me the job; I’m not ready for this.’” But her management said they had faith in her and that she was ready for it. 

	“I jumped in with both feet and loved every second of it,” says Dean. 

	The next pivot ended her marketing tenure. “The leaders at Takeda said we think you need to move over and get sales leadership experience. I hadn’t been a district manager or regional director but our culture here very much embraces diversity of thought and experience, and an enterprise leadership concept,” says Dean. “Initially, I was concerned because I felt that marketing was so dynamic and difficult and interesting that I was worried it wouldn’t be as challenging in sales. But I learned that I could take my experiences about how the home office worked and operated and share those insights with the field. We could align better on the strategy because I could give them that “why” of what the leadership wanted. I was also an earpiece for the field because I could tell the home office that some processes they did were not easy for those in the field, and if they made a few simple changes, it would make a world of difference.”

	Dean was selected to participate in Takeda’s elite global development program for high potential leaders in 2013 and is now designated as a Global Enterprise Leader. Takeda has a clear chain for developing talent, and Dean says the company is focused on four principles: Enterprise thinking; focus; elevating capabilities; and inspiring others. These principles carry over into the culture of Takeda, of which she says values diversity, values communication, and allows all employees the opportunity to have their ideas heard. 

	For the next thirds of her career, Dean would like to continue expanding her scope of commercial leadership responsibilities either in Europe or the US. “In the long term, I would like to have a business unit leadership role,” she says. “Again, I feel that enterprise leadership is so important and I think I have many good experiences over the years that will give me that big picture view, but I can also give that “why” to people in slightly larger settings such as in a business unit.” Ramona Sequeira, president of Takeda US, is confident of Dean’s skills and says, “I would love to see her in my role.” Sequeira, in charge of the changes to Takeda’s business unit structures, says, “Heather is a unique leader that can lead from the front and behind. People want to work with her, and she gets right in the trenches, connecting with people and their concerns.”

	As for Dean, she enjoys time with her husband and two young boys, family, friends, running, and mentoring activities. “I feel like I’ve hit the jackpot, with this industry and the roles I have had, and finding my home here at Takeda. It has been a pretty incredible opportunity.”

Mohamed Hamada, Country Portfolio Lead, Women’s Health, Pfizer

	There are a lot of books that executives can read about leadership, how to succeed in business, and how to lead a corporate team through a tough time. But, for Mohamed Hamada, he gains his leadership style from a unique place-horses.

	Hamada is the country portfolio lead for women’s health, Egypt and Sudan, for Pfizer Essential Health, Egypt, but he is also a professional polo player who in addition to working in the pharmaceutical industry all 

over the world, has also competed in the sport of polo all over the world. His experience with horses has helped him learn to stay calm in high-pressure situations-a common occurrence in a volatile industry such as pharma. 

	When playing polo, a person has to juggle multiple competing interests at the same time-ride a horse at high speeds with competitors charging at you, while swinging a mallet to get the ball in the goal. But, more importantly, as Hamada explained it, you have to control your emotions and stay even-tempered as to not upset the horse. Focus and fast decision-making is also very important as hesitation will cause you to be left behind during the game or, worse, you or your horse could get a serious injury. 

	Not easy skills to master, but definitely positive qualities that transfer to high-pressure business situations. 

	Another key element to success in polo, that is just as important in business, is strategic communication. “You have to use emotional intelligence in every situation that you are presented with,” says Hamada. “Have a plan about what you are going to do, and communicate it with people regularly.”  

	The pharma industry is changing at a fast pace, and being able to quickly adapt to those changes and welcome them with excitement is something Hamada believes makes a good leader in his field. “A good leader now in the industry is a transformative and a change agile leader,” he says. “Being a transformative leader helps because you’re agile enough to respond and deliver results, and teach others how to do that, too.”

	Being a good leader also means cultivating a  positive team spirit and knowing how to work in a team environment, which may sound easier than it is. 

	“Like in polo, you have to have a good team spirit and have to learn the team dynamics if you want to win, and it’s the same thing in business,” says Hamada. “A winning team has a good team spirit. You have the best players and the best equipment. You each have clear roles and responsibilities, and a clear strategy of what you are expected to do.” 

	While having all of these team elements is important, the team’s execution is also critical; however, it doesn’t always have to be perfect. 

	“You have to learn from mistakes,” says Hamada. “You have to let them [your team] make mistakes, because they will learn from them. You cannot be afraid to make mistakes in business.” 

	Hamada’s career has allowed him to gain experience in different areas of the pharma industry. A pharmacist by schooling, he tried out a variety of different areas within the industry, but learned he liked the commercial marketing side best. He also has a strong academic background in business, holding a master’s degree in pharmaceutical marketing from the European School of Business in Paris and an executive MBA from the Mediterranean School of Business in Tunis, majoring in mergers and acquisitions in the pharma industry.

	Hamada has been with Pfizer for 11 years and explained that he enjoys the multitasking his job requires. 

	“You get to do a little bit of everything,” he says. “Analysis, planning the execution of a marketing campaign, following up with sales, manufacturing, regulatory-you never get bored.” 

	In his current role, Hamada is responsible for all aspects of the company’s women’s health marketing in Egypt. This includes planning the strategic and tactical marketing of the products and overseeing the execution.   

	Some products provide more challenges than others, and requires different strategies, which is why being able to adapt to various situations is extremely important in Hamada’s point-of-view. For example, marketing a product that touches hundreds of thousands of patients is different than a personalized medicine that might touch 100 patients. Both have their pros and cons, and knowing how to tackle each one takes time and patience. 

	When asked about what he is most proud of during his career, Hamada quickly responds, “a lot of things, one of them is my experience in France. I studied and worked there for more than two years, it was a huge challenge for me-new language, new culture, tough curriculum in one of the top global business schools. I had to stretch my capabilities in different directions at the same time to succeed, which gave me a strong reserve of resilience that helps me a lot since.” 

	Maybe what contributes most to Hamada’s success is his answer to this question, “What keeps you up at night?” 

	“I don’t ever let anything keep me up at night,” he responds. “I believe everything will be solved in the morning.” 

	That calm, level-headed approach to business shouldn’t be underestimated. Hamada’s determination is what has gotten him to where he is today. It’s also something he encourages future pharma leaders to embrace. 

	His advice: “Read everything you can, be persistent, and don’t be afraid to take a risk.”

Todd Horich, VP of Marketing, Supernus Pharmaceuticals

	While beginning at the bench as a pharmacologist, earning a PhD in pharmaceutical sciences at the University of Maryland, Todd Horich always envisioned himself on the business side of the industry. Entrepreneurialism is in his genes, having come from a family of business builders and owners. This industriousness was evident during his days as a graduate student, where Horich completed his MBA in parallel with receiving his PhD. 

	Post-graduate, Horich worked for a time at the NIH’s National Institute of Neurological Disorders and Stroke,

 before joining Novartis’s neurology group as a market researcher, eventually moving onto the company’s Trileptal brand team. Getting into pharma via market research “allowed me to use the skill set I developed as a scientist, while learning the business of pharmaceutical marketing,” says Horich, noting it was “a perfect blend of science and business.” Nearly every day, he still uses the tools he learned in market research.

	As he progressed with Novartis, Horich kept an eye on his bigger goals. Following the advice of one of his mentors, Randi Roberts, he formed his own “mini board of directors, four or five people who I could bounce ideas off.” Under their guidance, he made the leap from Novartis to a small startup of less than 40 employees (Vanda Pharmaceuticals) in 2006; it was a risky move, but, as his advisers told him, “you need to take the risk while you’re young and can still recover from it.” A few years later, this outlook led him to Supernus Pharmaceuticals, a young commercial startup company focused on treating CNS disorders. At the time (2010), he was Supernus’s first commercial employee; by the end of 2013, Supernus had launched Trokendi XR® and Oxtellar XR®. “At first, neurologists couldn’t even spell Supernus,” says Horich, “but of the 10 anti-epileptic drugs launched in the last decade, Trokendi XR and Oxtellar XR have been among the most successful. And this is from a startup, building every department and process from zero, which had budgets (and still do) many magnitudes smaller than most other companies in the field.” 

	As Supernus’s vice president of marketing and new products marketing, Horich thrives on being involved in almost every function in the organization. 

	“From day one, I was at the table in clinical meetings, R&D meetings, and supply meetings, in addition to every commercial function,” he says. “We make decisions very quickly as a unified team; there’s not a lot of red tape.” He highlights his “incredible partnership” of mutual respect with Taylor Raiford (VP of sales) in building the organization together, and notes that Supernus has “some very tenured folks-it’s a misnomer about startups just having junior employees. The mentorship from veterans such as Jack Khattar, Victor Vaughn, and Stefan Antonsson has been invaluable to my continued professional growth.”

	Helping to build the commercial organization at Supernus “with no safety net” (“Building the plane as we were flying it!”) was “incredibly scary, but also incredibly empowering,” says Horich. “Employees and their families rely on you to help lead the organization to profitability.” His background helped to ensconce him in the company culture. “Some startups transitioning to commercialization can look at the commercial people like they’re from another planet,” he laughs. “But with my skill set, I could speak the language of everyone here.” Horich has since honed a leadership style focused not just on “getting people to do the things they need to do to be successful, but having them want to do the things they need to do.” He adds: “We try to instill the feeling in all employees that this is their company, not just a company they work for. I have such a great team; never in my career have I seen such a small group accomplish such great things.” 

	If Horich has any fear nowadays, it is one of an organization that grows extremely fast on its success, and staying focused on the fundamentals that got them there. The challenge for Supernus is maintaining its ethos as it grows larger. “Deloitte’s 2015 Technology Fast 500 recognized us number one in biotechnology, and number three in 2016,” he says. “We need to make sure we keep that up, but also protect our unique culture at all costs.”

	In a way, Horich’s career has come full circle. He’s back in his home state, Maryland, where he studied and began his career. But there’s no danger of him sitting back. He is now looking to take Supernus “from a small- to mid-level organization to a larger organization with multiple business units.” 

	With two psychiatry products in late-stage development, the company is “back to 2013, so to speak,”  says Horich. “Psychiatrists don’t know us yet; we need to build up a new franchise. We’re now looking to achieve in psychiatry what we’re achieving in neurology.”

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Pharm Exec’s 10th annual list of rising leaders highlights 11 pharma managers who are poised to help chart the industry’s path forward. 


Pharm Exec's Emerging Pharma Leaders 2017

	In recent years, with the Affordable Care Act and consensus on the “triple aim” (better outcomes and patient experience at lower cost), payers and providers have been moving toward a value-based healthcare system. But the pace has been slow, and other than a few paradigm shifts, which have been positive (accountable care ogrganizations, medical homes, growing use of telehealth, and self-insurers), there has not been significant changes in care delivery. 

	While some see the provider community as the primary player in meeting the triple aim, I believe the payer will lead the way, because it is the group that holds the purse strings. While providers want to meet the aim, fee-for-service financial incentives don’t support their efforts. Ultimately, financial incentives will motivate providers to change practice patterns, and financial incentives are driven by decisions of payers (both public and private). 

	Payers are strongly indicating that value-based reimbursements are the future of healthcare, with the new Medicare financial incentives via the Medicare Access and CHIP Reauthorization Act (MACRA) legislation and a growing use of risk-based and capitated contracts in the private sector. Payers are also behind the increase in use of telehealth as a means of lowering costs and improving patient convenience.

	So where does the pharmaceutical and clinical research community fit in this new paradigm? 

	As value-based payments for pharmaceuticals become more common, pharma companies will be engaging more directly with payers and providers. They will need to gather data to prove value and will need to engage with patients to improve adherence to treatments (and by extension, outcomes).

	But beyond this financial necessity of greater involvement, there is an opportunity to accelerate value-based care through a stronger partnership between payer, provider, and pharmas. All three, along with patients, can benefit from this partnership, with pharmas offering two important opportunities to payers and providers, both involving data exchange.

	For providers, pharmas offer the opportunity to gain value, in the form of insights to guide treatment decisions, from the enormous volume of electronic patient data they house. This data, of course, has to be appropriately anonymized to protect patient privacy, and pharmas will need to be specific about how and why the data will be used. R&D uses should be clearly separated from marketing and sales uses, and patient consent must be gained for using anything other than anonymous data.

	Pharmas need the anonymous data to speed up drug research and development through better understanding of target patient populations, their most desired target outcomes, likely responders, non-responders or adverse responders, to a new drug or for repurposing existing approved therapies. Access, linkage, and analytics of this data in an integrated research platform can enable pharmas to test hypotheses before risking time and money in clinical trials. The data could also help predict which kinds of patients are good candidates for trials, and which are not, based on their clinical markers and patterns of adherence to treatment. Pharmas and contract research organizations (CROs) have the budget to support this spend on patient selection/recruitment, as it would significantly reduce their overall costs.  

	In addition to helping discover new treatments and lower the cost of research, providers and payers could benefit from the insights learned to help better match patients with existing treatments.  

	On the other side of the drug delivery process, lies an opportunity for payers to contract for reduced-cost pharmaceuticals in exchange for referrals from payers to their in-network provider communities, provided that the drug offers positive outcomes comparable to the results from published trials. To show evidence of efficacy takes real-world data, and pharmas need to collect information on responders, semi-responders, and non-responders to the medication. 

	All of this information will be needed to retain or renegotiate contracts with the payer community, and will require significant exchange of information between providers and payers and pharmas. Pharmas will need to link clinical, claims, and pharmacy information to identify responders from non-responders, positive from negative outcomes, adverse reactions, and correlation of outcomes to medication adherence patterns.

	It is in this exchange that we should add a fourth partner to the community, and that partner will be a systems integrator. Payers have claims data, providers have electronic health record (EHR) systems, and pharmas have enterprise resource planning (ERP) and laboratory systems. Adding to the complexity, software designers tailor their products to narrow-use cases within a specific market, resulting in a vast array of disparate applications. Payers can have two systems for care management and customer service, with a third for mobile interactions. Providers can have outreach systems different from the EHR and also multiple, yet related, portals. And in the pharma community, the number of application systems is staggering and growing. 

	None of these systems are designed to interact easily with each other or share data with outside platforms, including those that are cloud-based and platform as a service (PaaS). To combine data from these systems 

requires massive systems integration. The interim step has been the sometimes-elusive, all-encompassing data lake to hold everything from every system, from structured to unstructured data, from which data can be drawn for all purposes. While this approach has benefits, positive use cases inside of a division or function, and should sit at the core of a corporation, sharing the information across the payer, provider, and pharma partnership brings numerous challenges in data and system integration, causing the continued use of calls, faxes, and flat files.  

	 A supportive application to each organization’s core data layer is a platform that can accept, organize, and analyze data from multiple sources and platforms, and within the patient-centric perspective, that would be the customer relationship management system (CRM). It’s a platform that has been adopted by all three communities (mostly salesforce.com). Payers are starting to twist it toward care management, as it offers a way to organize, analyze, and use non-clinical data that is critical in population health management. A West Coast hospital system, for instance, has over 70 apps on the salesforce.com platform that sits on top of its EHR to ease the entry and view of information for individual roles, from the nurses to the staff to the patients themselves. Pharma has gone all in, with the top 200 globally adopting Veeva for sales and marketing activity (Veeva is built on the salesforce.com platform).

	Imagine the scenario of a pharma and CRO looking to accelerate enrollment in a trial and paying for provider clinical data to organize and analyze its search (providers earning new revenue streams) and during the trials identify those that actively adhere and those that don’t. This data could be used to create a persona that can be shared with payers once they begin to correlate actual users of the drug and outcomes. Once a treatment is approved and prescribed, the provider can follow up with patients via salesforce.com apps and telehealth capabilities and allow pharmas and payers to use the community feature to mine the feedback, understand the experiences, and even get in front of any adverse effects or complaints.

	Imagine if a patient has a complaint and shares it online, not in Twitter or Facebook, as most people do now, but

 in a secure, collaborative community forum. Users of the platform would be other people with the same condition and using the same drug, as well as stakeholders from the provider, health plan, and life science communities.

	Instead of venting frustration, as many patients do now, a collaborative platform offers the opportunity for the healthcare insurer’s care manager to inquire as to how the patient is feeling and suggest follow-up with the doctor. Or the care manager could facilitate a conversation with the pharmaceutical manufacturer to understand if the patient is experiencing a known or new side effect. The care manager also could provide valuable interaction information based on other drugs the patient might be taking and provide a significantly higher level of information about the drug than the primary care physician. 

	I don’t know about you, but I’d like to live in a world where my health plan texts me, my prescription drug company (whose company name I probably don’t even know) offers me a discount or to pay for a follow-up visit, and my doctor has more information about what is happening with users of the therapy and the real-world efficacy of its outcomes.

	But the answer is not in simply procuring a platform; it’s all in the integration and the awareness of the real-world business of quality care across the payer, provider, and pharmaceutical ecosystem. And that is where the fourth partner, the systems integrator, brings tremendous value. 

is Chief Operating Officer, Life Sciences, at NTT DATA Services. He can be reached at Adam.Nelson@nttdata.com

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Today’s model requires a fourth partner-the systems integrator

How Pharmas, Payers, and Providers Can Meet the ‘Triple Aim’

	The recent FDA approval of the first chimeric antigen receptor T cell (CAR-T) therapy to treat young patients with a serious form of leukemia reignited charges that high drug prices limit patient access to life-saving medicines. Novartis announced that it would charge $475,000 for treatment with Kymriah-less than most analysts anticipated, but a flash-point for advocates seeking to control pharmaceutical outlays.

	FDA always emphasizes that it does not consider price directly in drug regulatory decisions. But agency officials do see potential savings from several regulatory initiatives and transparency proposals. Commissioner Scott Gottlieb recently announced actions to streamline research policies to reduce the risk of failure in costly development programs. This complements agency efforts to promote competition by speeding more generic drugs to market and to challenge branded firms that “game our rules.” Payers and patients, says Gottlieb, thus should “capture those savings in the form of lower prices.” 

	The savings may be considerable, particularly for cutting-edge therapies that benefit from FDA accelerated and breakthrough regulatory policies. A recent study claims that it costs only $648 million on average to develop a new cancer treatment, challenging the generally accepted $2.7 billion cost for developing a new drug, including the cost of failures and of capital as calculated by the Tufts Center for the Study of Drug Development. Even if the new analysis (published in 

last month) is skewed by limited data and sketchy assumptions, it undermines the conventional wisdom that high pharma prices are needed to finance important research. 

	In fact, it’s now well-accepted that drug prices reflect “what the market will bear” based on current and prospective competition and have little correlation to R&D outlays. Even so, policymakers expect that less costly preclinical and clinical testing and speedier approval and regulatory processes, as described in FDA’s “Medical Innovation Access Plan,” should lead to savings and improve public access to medicines. The agency thus seeks to modernize clinical data collection and encourage more informative clinical testing methods that provide useful data faster and more efficiently. FDA encourages sponsors to utilize “seamless” clinical trials, master protocols, model-informed development, and study enrichment strategies that help predict which patients will respond to treatment and those likely to suffer adverse effects. 

	A high-profile initiative seeks greater use of real-world evidence to support decisions on product safety and efficacy. Both the 21st Century Cures Act and the newly authorized prescription drug user fee agreement expand FDA regulatory decision-making based on patient data from healthcare systems and observational 

studies, an approach that FDA and stakeholders are examining further in several public workshops. The aim is to use data from health plans and registries to answer questions about treatment effects and outcomes for broader patient populations than possible in a specialized research environment.

	FDA proposals for accelerating clinical research are not new, but sponsors have been reluctant to rely on them without clear assurance that the regulators will accept the data. Agency reviewers also look to expand their use of advanced computing tools and statistical and computational methodologies to evaluate more efficiently the sophisticated data submitted in applications. 

	FDA acceptance of more real-world evidence on how well a drug treats a disease should bolster medical product value assessments that link drug prices and reimbursement to patient benefits, as Novartis has proposed for Kymriah. Under an innovative outcomes-based reimbursement arrangement, the Centers for Medicare & Medicaid Services (CMS) will pay Novartis for the drug only if patients respond after a month of treatment. 

	The deal raises many questions about what constitutes “success,” who measures it, and why a one-month period was selected for measuring patient response. But the plan also is stimulating greater interest in

 outcomes-based reimbursement policies. These adjust reimbursement to treatment success, with payment higher when individuals see improvement in health, and lower if patients fail to respond. There has been a trickle of such agreements between pharma companies and health plans, but progress has been hampered by limited consensus on how to measure health improvements and other outcomes, and payers have seen little or no savings so far.

	Analysts acknowledge that even six-digit price tags on gene therapies may be justified if the medicine cures deadly cancer or reverses blindness. And such equations may be bolstered by comparing drug costs and outcomes to the enormous outlays involved in treating a cancer patient with bone-marrow transplants and other procedures for years. 

	Long-term benefits, though, raise questions about who should pay the initial cost of drug treatment. Health plans with millions of enrollees can spread outlays for a very expensive therapy across broader populations, especially when treatment is highly targeted; the equation changes, though, when many individuals seek access to a new drug. One idea is that an insurer pay for initial coverage, followed by regular reimbursement if a drug continues to provide positive effects; another insurer would pick up the tab if the patient changes coverage. 

	Strategies for reducing uncertainty in the regulatory process, and drug pricing schemes that reflect value and effectiveness, should be more palatable to marketers than public formularies, price controls, liberal drug import policies, and curbs on patent and exclusivity protections. Greater transparency in practices and prices may be inevitable, though, as payers demand more details on rebates and costs and FDA champions greater disclosure of drug safety issues and regulatory decisions that deny or delay approval of a new drug. 

’s Washington Correspondent. She can be reached at 

FDA seeks to de-risk research and promote competition to achieve savings for patients and plans.

Can Streamlined R&D Reduce Drug Prices?

	Obscured beneath bigger-and grimmer-news in a world overcrowded with events, an annual European Union policy event in mid-September might have seemed irrelevant to pharmaceutical executives. But the 2017 State of the Union address by the President of the European Commission contained more than a few nuggets that drug industry strategists are now starting to take seriously-aided by a few injections of real money too.

	There was only one direct reference to health in Jean-Claude Juncker’s 6,000-word speech. Just a paragraph on equality. But that was powerful enough to jar a few preconceptions about Juncker’s attachment to health.

	“In a Union of equals, there can be no second-class citizens,” he said, denouncing as “unacceptable” that in 2017 there are still children dying of diseases that should long have been eradicated in Europe. “Children in Romania or Italy must have the same access to measles vaccines as other children right across Europe. No ifs, no buts,” he said.

	Juncker underlined that the Commission is working with all member states to support national vaccination efforts. “Avoidable deaths must not occur in Europe,” he said. And he announced his intention to come forward with a joint action plan on national vaccination policies.

	 In itself, this determination provides an illuminating gloss to Juncker’s thinking, since he has in the past tended to duck health issues, and has provoked concerns in Europe’s healthcare community about neglect and even abandonment in future Commission planning.

	But the bulk of Juncker’s remarks also offered some glimpses of an approach that could equally play to the interests of the drug industry. The emphasis that Juncker has frequently put on boosting Europe’s ability to compete in the world market was even more evident in his outline of how he sees the future for the EU. Among the top priorities he spelled out were strengthening Europe’s trade agenda, making its industry stronger, and deepening the single market so that it maximized support for innovation.

	Trade, he said, “is about jobs, and creating new opportunities for Europe’s businesses big and small,” expressing satisfaction with the trade agreement with Canada that is now entering into force, with agreements reached with Japan, Singapore, and Vietnam on new economic partnerships, and with the prospect of doing the same with Mexico and South American countries by the end of the year and opening trade negotiations with Australia and New Zealand. The EU’s trade ambitions have been strongly supported by most of Europe’s pharma sector, as opening up market opportunities and enhancing, in some cases, intellectual property protection beyond Europe.

	On strengthening industry and the internal market, there was still more music to the ears of pharma executives pursuing investment and innovation. Europe’s global leadership in high value-added and sophisticated products and services has been built on a large single market with 500 million consumers, strong value chains, a skilled and talented workforce, and a world-class science base, Juncker acknowledged. But adjustments are needed or a new industrial age, he warned: the future of Europe’s industry-and of its workforce of 32 million people-will depend on continuous adaption and innovation, “by investing in new technologies and embracing changes brought on by increased digitization.”

	Accompanying his speech, the Commission released a new industrial policy strategy, offering “a new boost for jobs, growth, and investment initiatives to be launched and/or completed by end 2018.” This will respond to deficiencies that Juncker admits to in Europe’s “enabling environment,” and will “ensure that its risk-bearing disruptive innovations will create new markets and industrial leadership in Europe rather than outside.” Action is also needed, he said, to accelerate and improve the uptake of technologies, particularly among smaller firms.

	 He also highlighted the need for flexibility in regulatory frameworks that will allow innovation to develop. “We must learn to consider the perspective of innovators,” Juncker said, committing the Commission to take into account the impact on research and innovation in developing regulation in all policy areas. Carried through into the current debates on adaptive pathways for new medicines authorizations, that sort of thinking may well help to counter resistance among regulators to evolution. And within the Horizon 2020 program, that already funds the Innovative Medicines Initiative, he is creating a $3 billion Innovation Pilot scheme “to more effectively support projects focused on market-creating innovation,” with a focus on “highly promising but also potentially risky innovations.”

	Juncker’s words coincided with some deeds that offer some tangible confirmation of intentions. The EU has just announced a series of investments in companies conducting innovative medical research, through its European Fund for Strategic Investments-the so-called “Juncker plan” introduced in 2015 to boost  competitiveness in the European economy.

	One of the agreements, a $90 million loan to Evotec of Germany, breaks new ground in risk-sharing finance.  This unsecured loan facility is the first contingent investment guaranteed by the fund, meaning that the fund shares the risk of Evotec’s research and development success. It is also the first large equity-type investment by the fund in any industry anywhere in Europe. The money is being provided as long-term financing “to finance drug discovery and the development of new treatments for serious illnesses and diseases,” said the Commission at the signing ceremony for the deal. The demand for new therapies “requires innovation in drug discovery in a capital-efficient manner as well as through innovative financing models.”

The Commission highlighted the potential of Evotec’s drug discovery, such as its integrated patient-derived induced pluripotent stem cells platform, and innovative collaboration models such as its BRIDGE initiatives from Academia to Pharma.  “Since 2010, Evotec has built a pipeline of over 80 partnered product opportunities through such partnerships, spin-offs, or equity investments,” the Commission said.

	Just days earlier, an agreement was finalized with German medical device company MagForce to develop new treatments for brain cancer. MagForce has developed NanoTherm therapy for local treatment of solid tumors by introducing magnetic nanoparticles and heating them in an alternating magnetic field. The financing, which permits the company to borrow up to $45 million over the coming three years subject to achieving a set of agreed performance criteria, will support NanoTherm’s Europe-wide rollout for brain cancer treatment, and European and global approval for prostate cancer.

	 Austrian Apeiron Biologics is also to receive financing of $30 million to support its work in immuno-oncology, particularly in rare pediatric cancer treatments. Dinutuximab beta, its product for neuroblastoma, was recently granted marketing approval in the EU. The company is developing additional cancer immunotherapy projects based on targeted, tumor-specific approaches and on stimulation of the immune system via novel modes of action, such as unique checkpoint blockade mechanisms.

	In his speech, Juncker took credit for the plan, which has triggered $275 billion worth of investment so far across European industry, through loans to over 445,000 small firms and more than 270 infrastructure projects. And there is more to come. On the eve of his speech, the European Parliament and EU member states reached an agreement in principle on EFSI 2.0, extending and reinforcing the plan. The intention now is to win swift adoption of this expanded version, which will widen still further access to financing, particularly for smaller firms. EFSI’s timeline is to be extended to 2020 and the target for triggering investment is increased from $400 billion to more than $600 trillion.

	Of itself, the Juncker speech does not resolve all of European pharma’s problems. But it does hold out some hope of a more constructive attitude to innovation and investment-and offers a welcome counterbalance to the pervasive atmosphere of gloom induced by a daily diet of North Korean threats, Russian meddling, and Brexit.

European Commission talks drug industry investment, health issues during State of the Union. 

Glimmers of Hope for Innovation Support in Europe

	In the pharmaceutical industry, there exist fundamental variations between clinical trials and the real-life utilization of medicines. Such variations create treatment and safety gaps that undermine the significant investments made by drug manufacturers.

	When certain medicines are exposed to “real-world settings” and experience safety issues and reduced effectiveness, this seriously limits the success of the marketed medicine, especially when compared to the results projected at the clinical trial stage. On top of this, the gap between what is estimated during clinical trials and the reality of a given drug usually necessitates an increase in resources.

Why is real-world evidence increasingly important?

	In this modern, competitive healthcare marketplace, pharmaceutical and medical device companies are increasingly required to provide evidence on real-world outcomes in order to differentiate, and justify, their products. In fact, in 2016, the FDA released a draft guidance document on how real-world data should be used when making both premarket and postmarket decisions for devices. This guidance has been created in order to develop a system that “would build on, and leverage, the vast amounts of data and information collected during the treatment and management of patients.”

	Data generated from real-world settings can help to provide significant insights into how a drug, or class of drugs, performs or is used in a real-world setting. For this reason, it is important to continuously generate evidence-based information to attain optimum effectiveness and safety for the stakeholders involved.

RCTs versus real-world observational studies

	Randomized controlled trials (RCTs), considered the “gold standard for clinical research,” are not without disadvantages and drawbacks. They offer proof of efficacy only under very controlled conditions. Normally, Phase I, II, and III studies represent a niche pocket of the population with specific characteristics, and, therefore, under-represent the greater patient populations. For this reason, RCTs might only be providing short-term outcomes. 

	It is for reasons such as these that some sources argue large-scale observational trials might reflect the “real clinical world” much better than an RCT performed in a specific, uniform subgroup of patients.

	Late-phase and real-world evidence studies demonstrate and help drug and device companies to understand the real picture of patients through the entire patient journey. Since there are demands for ongoing investigations, it helps in generating and detecting the rarest safety signals by capturing data (structured and unstructured) from large populations and over prolonged periods of exposure. 

	Studies with a large number of patients from the real-world setting have an advantage over trials conducted under controlled environments. Real-world studies provide the flexibility to monitor a number of parameters in order to determine the performance of a marketed product. Some of these parameters are:

		Will the product provide an equal, or greater, benefit when compared to other marketed drugs?

		Will the product be more cost-effective than the existing options?

		Will the product’s safety profile be equal to, or better than, the alternatives in a real-world setting?

		Does the product facilitate better compliance?

		Are there differences among individuals in terms of response rates?

		What are the differences in dosing and pharmacokinetic/pharmacodynamic modeling?

		How does the product react in combination therapies?

		What changes are needed in treatment patterns?

	Late phase and real-world evidence studies have varied styles and designs, and Phase IV clinical studies are designed to  collect information from the real-world setting to assess the treatment effectiveness for specific patient subgroups, or enriched populations, under the controlled protocol. 

	Patient databases, chart audit/reviews, and registries expedite access to retrospective studies with sizable amounts of patients and data. These studies are ideal for the validation or generation of hypotheses for future studies, thereby feeding into research and development plans. The correct style and approach depend on the target, the required outcomes, and other limitations, like time and information.

	In recent times, retrospective data has been a source to determine various patterns that are not visible in a controlled clinical study setting. The ability to determine the right patient populations for a particular drug in order to arrive at the best outcomes is an input that real-world data always provides to R&D teams. Through big data and predictive modeling, the existing real-world data determines:

Patient personas for improved outcomes by determining: 

		Patients who demonstrate better outcomes

		Patients who need support to be compliant

		Existing beneficial programs/interventions

		Comorbidities that change treatment outcomes

		Patients more likely to switch due to a lack of results

		Most practical frequency and methods to monitor in chronic diseases

		Benefits of population-based programs for screening 

	Given the importance of late-phase and real-world evidence studies, and the potential implications of the results, it is clear that these studies should be designed and conducted with the identical scientific rigor we afford to RCTs. Though there are multiple operational barriers, which can be overcome with structured approaches, scientific rigor can increase the credibility within the scientific forum and with the policymakers. 

	The timing of late-phase or real-world evidence studies are becoming increasingly important, as the market access landscape continues evolving and adapting to the variations occurring in the healthcare landscape. Pharma and device companies are facing challenges during the post-launch phase in order to get a product to the right audience to influence greater adoption. These companies are taking the help of post-launch market studies, which hold the capacity to spawn insights from a wealth of information available from different channels. This is in order to help pharma companies unveil trends and patterns about patient adherence, switching, adoption, physician sentiments, key opinion leaders, and sales force competency in a cost-effective way to create competitive advantage.

	Life sciences firms must concentrate on these studies and appraise them from time to time to attain business goals. “The more you know, the better for the patients” is the motto that must drive companies in order to attain the ultimate goal of patient benefit. 

	Sensing the same, the pharma world is experiencing a transformation. But, there is still some ground to cover, which can be done with appropriate awareness by disseminating sensible information on these studies. The idea is to showcase the outcomes of these studies so that actual proof can encourage more companies to delve deeper and utilize the advantages of such studies. 

	Healthcare research and consulting firms have been striving to unearth the potential of real-world evidence studies, and some stake claims to have dug deeper than many on the impacts and implications of these studies. 

	Conducting observational studies, both prospective and retrospective, enables us to uncover hidden gems in the form of real-world data. Using these studies, the diverse concerns of stakeholders, such as the generalization of results, healthcare professional interests, the quality of data collected, and the level of accuracy involved in such studies, can be anticipated.

	Studies with a sound scientific design, standard operating procedures (SOPs) specific to real-world studies, creating owners among clinicians in publishing results derived from these studies, leveraging technology for remote monitoring, reducing time between reports by ensuring e-capture of data on intuitive systems with smart checks, etc., are a few ways to ensure the robustness of data. 

	Real-world studies are here to stay, and their usefulness and full-potential are only just being unraveled. There are various facets that are yet to be uncovered and tapped. The involvement of artificial intelligence (AI) and machine learning in the drug development phase has put us on the threshold of faster drug discovery cycles, reducing the importance of expensive and drawn-out phase trials. However, monitoring these interventions in the real-world setting becomes more important as they need more intricate scrutiny. 

	Real-world data has always been around, but its significance has not been realized to its full potential. However, the relatively easy access to it, technology interventions to capture quality data and make sensible decisions out of them, AI and machine learning to look at data in novel ways and decipher more meaning from them, big data capabilities to harness huge amounts of data over long durations of time and sift for quality information, and the economic sense of obtaining the desired results make this data source all the more interesting. 

is a Clinical Project Manager and Clinical Research Professional at phamax

Pharma companies today must increasingly provide evidence on real-world outcomes to differentiate and justify their products. But what is the true potential of real-world evidence studies and what are the right questions to ask in determining product performance in the marketplace?

The Future of Real-World Studies

	The compliance paradigm in pharma is flawed. My evidence, I confess, is largely anecdotal but as in medicine, a weight of anecdotal evidence does warrant further investigation and these are not simply my own observations. If you provide an opportunity to express frustration with “compliance,” you can hear the problems for yourself. In no particular order and without any claim to being exhaustive, here is a list of some of the things I heard from a mixed medical and commercial group to whom I gave the opportunity to vent. 

	Among other things, compliance was described as:

		A legal exercise to apportion blame when things go wrong

	From a business perspective, one could perhaps reasonably say “so what?” to most of this. So what if compliance is made boring? Lots of jobs are boring. So what if it appears arbitrary and a legal exercise? The company has to cover its responsibilities in law. So what if it is tribal? Medical and commercial functions have differing roles and objectives. By themselves, perhaps these aren’t problems, but they do reflect a compliance paradigm that has negative consequences for our business and society. It is a paradigm in which the central flaw is the belief that rules are the sole protection against immoral behavior and individuals cannot be trusted to reach good decisions.

	Consider for a moment how commercial ideas are developed and progressed. An idea is created by a brand team (a sales aid, a meetings program, or a website) and it is flung with its details at a compliance sieve; what takes place is whatever gets out the other side. Too often that is very little or nothing. The compliance sieve is getting finer and finer as more and more mesh is added, not by regulators, but voluntarily by companies. This is in the mistaken belief that more rules make things clearer and less risky: doing nothing is compliant-surely the fewer things we can do, the more compliant we must be.

	This “do-nothing default” may achieve compliance but it is ethically deficient; if a program of education and communication in a neglected disease area is abandoned because of a small imagined risk, compliance is achieved, but no one is helped and the ethical equation is in the negative. Worse perhaps is that doing nothing is more usually not even a conscious decision; it is simply a consequence of uncertainty about what is allowed and fear of repercussions that leads to inertia and projects ending up in the long grass that has grown around them.

	The obsession with adding internal company compliance rules not only engenders inertia, it also undermines the very thing that most protects the pharma industry: the ethical good sense of the people within it. Every time a new compliance SOP is issued, dictating the actions an individual must take in a particular arena of activity, it restricts further the need for that individual to decide for themselves. That may be the aim, but simultaneously it removes from the individual their accountability to do the right thing. They must comply with a course of action-not decide a course of action. They must learn a rule-not understand how to make a decision.

	None of this is to say compliance regulations within companies is unnecessary; it is only to say it is not a panacea to address the ethical problems the industry gets itself into. We cannot write a rule for every scenario and we should stop trying to. Lay out basic expectations and critical processes to get things done, but let’s stop trying to dictate every action, or identify every possible wrong.

	Just as internal company compliance regulations need to change, so too does compliance education. We need the good people in pharma to think and we must empower them to do so. The pharma industry employs people with well-above-average intellect who in their day-to-day lives have formed views about some of the most complex moral issues humanity has faced, from euthanasia to stem cell research to capital punishment and beyond. These are people we should trust. Compliance education should utilize those natural ethical abilities, making the links between morality and compliance strong and intuitive such that being compliant is not seen as a company hurdle but a personal moral obligation. 

is a consultant and trainer in pharmaceutical ethics and compliance with Makara Health 

Pharma needs a reeducation on what it means to be compliant.

Challenging the Current Compliance Paradigm

	After conducting interviews and editing the stories for this month’s Emerging Pharma Leaders section, I couldn’t help but be inspired. Our 

 shine a positive light for the future of pharma. As I mention in the introduction, many of this year’s alumni share commonalities, including a

 willingness to grow, the ability to listen, learn from their mentors, and an enthusiasm to lead their staff and share the load. The Emerging Eleven inspired me this month to feature the staff of 

 and highlight their unique skills and qualities that make this publication and website the very best it can be. They have great ideas and deserve recognition and a big thank you!

. Let’s start with those who have been with the publication the longest. Julian Upton is our European and Online Editor, who has been with our organization in its previous and current ownership for  12 

 for several years, and is the institutional knowledge resident for the brand. Before 

, he worked on trade/b2b mags focused on the defense industry, public-private finance, and healthcare. 

	Julian is a resident of Leicester, England, and is our go-to expert for anything related to the UK or all of Europe, for that matter. Julian tolerates and/or entertains all our questions about what people think overseas. He has also become the point person for reviewing contributed articles, and continues to interview and write on all aspects of commercial pharma for the magazine.

	Mike Christel is our Senior Managing Editor, managing both 

. Mike has been on the brand for almost four years and is in charge of making sure everything in print goes out with

 all the i’s dotted, t’s crossed, photos in the right places, writing headlines and transitions, and dealing with the staff dragging out deadlines. In between managing all of that, he finds time to interview people and write articles, and help the newer staff members learn our systems and processes. 

	Mike started in journalism at local newspapers, first as a sports writer and eventually heading a newsroom. He then moved on to b2b, working for 

. With his experience, we all count on him for his clinical and commercial knowledge and sense of journalistic ideals.

	Christen Harm is our Associate Editor, joining in March. Christen is becoming the go-to person for...everything. She writes, she interviews, she’s learned our back-end systems quickly and is 

As we again highlight a roster of emerging leaders in pharma, I wanted to recognize Pharm Exec's own unique team behind the scenes.  

Pharmaceutical Executive-10-01-2017

Pharm Exec's Emerging Pharma Leaders 2017

How Pharmas, Payers, and Providers Can Meet the ‘Triple Aim’

Can Streamlined R&D Reduce Drug Prices?

Glimmers of Hope for Innovation Support in Europe

The Future of Real-World Studies

Challenging the Current Compliance Paradigm

Inspiring People, Inspiring Teams

Country Report: Colombia

Pharmaceutical Executive, October 2017 Issue (PDF)