Change Broker

lenty has been said about the problems of the pharmaceutical industry and the need to reinvigorate the model. But how do you go about it? What changes can be made that will have notable improvement without risking the core competency of the company?

In my 17 years in the industry, I've witnessed many major transformations. My company, GlaxoSmithKline, had been working on change since long before I was appointed chief strategist of research and development in August 2008. In fact, the entire pharmaceutical industry is in tremendous flux, in all aspects of its operation; whether it's understanding the pathology of disease, the introduction of novel technologies, or adapting the business model to meet renewed financial and societal expectations, adaptation is the norm. The frequent shake-ups that all companies experience are always expensive, invariably painful, and sometimes not fully effective, but they are definitely necessary.

It's now my job to help continue the reshaping of GSK's research and development (R&D) structure, to empower scientists and leaders to create change that makes sense and that provides them with a sense of accomplishment.

In this task I draw on many life experiences. Reforming the research and development structure of a major company wasn't exactly on the list of things I wanted to do when I was growing up, but in many ways the challenges feel familiar to me. My mother is from Ghana and my father is English, and although I was born in the United Kingdom, we lived in Ghana for most of my childhood. Even after we moved back to the United Kingdom, we'd return for many vacations.

As I grew up, I watched Ghana change dramatically, and began to notice the difference between effective leaders and ineffective ones. My mother set up an educational institute for adult literacy that helped Ghanaians get jobs and educate their families, empowering them to change their lives. In contrast, I watched how ineffective leadership and multiple coups brought the country, which was relatively prosperous in the late 50s, to near poverty in the 70s. Even though the scale of the problems that my mother tackled were very different to those of the governing body, I could see the wide impact that passionate individuals, like my mother, could have on a multitude of others.

From the earliest time I can remember, I wanted to be a doctor. When I was about seven or eight years old, my parents took me on a sojourn to see one of their friends who ran a clinic in Ghana. I spent the day with Dr. May, as she met patients, listened to their symptoms, and prescribed a course of treatment. I remember studying the faces of the patients. They came in distracted and worried and left her office comforted, feeling taken care of.

In due course, I applied and went to school for medicine, earning my MD at the University of Leeds, and began practicing in obstetrics and gynecology within the UK National Health Service. Having seen Ghana change so drastically, I wanted to feel like my work could impact more than the hundred or so patients I would see in a year. My route was to enroll in an MBA program at INSEAD in France. There, I was surrounded by people from many nations and all walks of life—from politicians and bankers to engineers, and even an Israeli fighter pilot. One of the participants in the executive MBA program was head of the Medical Division at Glaxo. He talked about the challenges and rewards of developing drugs. I was quite taken by the promise of developing medicines that had the potential to help hundreds of thousands of patients, and joined the company in 1992.

My first project was to help bring an unheralded new medicine to market. The drug, called Zofran, was for cancer patients. It certainly didn't have the high profile of a new chemotherapeutic agent—all it did was help prevent vomiting. Yet the impact it had on patients was astounding. I'd receive letters from people undergoing chemotherapy who couldn't tolerate the treatment because of their nausea. When they took the medicine I helped develop, they felt not only relief from the symptoms, but also hope about their ability to fight the cancer. That had a huge impact on me.

With the 2001 merger of Glaxo Wellcome and Smith Kline Beecham to form GlaxoSmithKline (GSK), I experienced my second major pharma shake-up (my first was the merger of Glaxo and Wellcome). I understood the reasoning behind it: We really had little choice but to change since neither Glaxo Wellcome nor Smith Kline Beecham were achieving a satisfactory level of research productivity. I led the transition team that brought the two companies' medical affairs divisions together. The merger was an important transition for me not only because I took on new responsibilities, but also because I gained first-hand experience of the major changes in R&D structure that J.P. Garnier instituted when he came on as CEO.

Garnier's vision was decentralization. He reorganized the R&D efforts into six Centers of Excellence for Drug Discovery, or CEDDs. Rather than have an R&D biology department and a pan-R&D chemistry department, and so on, each CEDD would have the scientists and experts it required from diverse fields working around a single therapeutic area. At the time, this was a radical change to the traditional structure of R&D in the industry, but other companies soon followed suit.

We've come a long way in six years. At the time of the merger, we had 12 New Chemical Entities (NCEs) in development and our pipeline was ranked number seven in the industry. By the end of 2008, we had 20 NCEs and our pipeline was ranked number one by analysts. A lot of the success of those years can be credited to the CEDD structure. The CEDD concept was considered extremely successful because it recognized the need to integrate functions and focus on delivery of medicines in defined areas. There were other contributing factors, too, including successful licensing of products developed outside the company, a more realistic and integrated assessment of risk, and a major focus on creating smaller, more accountable teams.

When I started as the senior vice president of one of GSK's Medicine Development Centers (MDCs), I was tasked with building the pipeline of medicines for inflammatory, gastrointestinal, musculoskeletal, and urogenital diseases. The MDCs took over where the research teams within the CEDDs completed their work. Their discoveries were passed off to us for development into the drugs that would ultimately make it into humans.

While development isn't given as much attention as discovery, a lot of the value of a medicine is created through thoughtful clinical trial design, and by exploring the profile and potential of a drug in a clinical setting. One of the things I've always felt very strongly about was making sure we consulted—where possible —with patients and physicians as we designed a trial, since they are the ultimate end-users of the medicine. In one recent case, we were developing an injectable medicine for pediatric patients. The parents we talked to told us they had reservations about frequently injecting their child with medicine. Their input meant that we reviewed better ways of giving the medicine, which will ultimately create a more "user-friendly" drug.

When J.P. Garnier retired and was replaced by Andrew Witty, in April 2008, the R&D organization at GSK was moving full steam ahead with its plans to enhance its strategy.

The first part of the effort was an extensive review of our 17 therapeutic areas within the CEDDs, with the aim of identifying those areas with the greatest scientific promise. As part of that process, we consolidated some therapeutic areas and made the decision not to pursue other areas. The final eight therapeutic areas now include: biopharmaceuticals, immuno-inflammation, infectious diseases, metabolic pathways, neuroscience, oncology, ophthalmology, and respiratory disease, each within the CEDD structure.

The structure of the CEDDs made sense, but we saw room for improvement such as fostering the competitive spirit and incentive that really drive the scientists at biotech companies and academic research labs. The original model was still too safe. We decided to subdivide the CEDDs into lab-sized groups ranging from five to 60 people per unit. These discovery performance units (DPUs) are responsible for developing their own projects and drugs and for proving their effectiveness with preclinical trials.

These DPUs are held to the discipline of having to write their own business plans and defend them. They also have the freedom to go outside the company to build deals and partnerships with academia and other biotechnology companies. Creating a more entrepreneurial environment for scientists is the overriding goal. On the basis of their business plans, the DPUs receive funding for three years, at which time their projects are reviewed and a decision made whether to terminate or continue. These groups control their own budgets, which can be spent internally or externally, to deliver the best possible pipeline. The CEDDs provide the overarching leadership and guidance for DPUs across the therapeutic areas. As of April 1, 2009, we had 35 DPUs.

To ensure that we are producing drugs that patients want, that the market supports, and that governments and insurance companies are willing to pay for, the DPU's funding applications are reviewed not only by senior GSK R&D executives, but also by the newly formed Discovery Investment Board (DIB) that includes experts from venture capital companies and biotech CEOs. This board evaluates the research plans and funding, but will also assess the capabilities of the DPU management teams. We realized that as insiders we are not always the best people to assign value to the things we produce. There are times when an outsider's perspective is helpful in revealing faults in our thinking.

My role when I was hired as the chief of R&D strategy in August was to help build a small diverse group of experts with science, business, and accounting expertise. This group's role is to ensure the plan—which looks great on paper—is implemented effectively on the ground. This means that we will be defining our metrics for progress much more stringently and communicating with team leaders as they establish and define their goals and plans.

We are pledged to leave the decisions to the people who are best informed and therefore best able to make the judgment. We want to challenge our teams, empowering them to take ownership for the success or failure of a project, creating a structure where our scientists feel their input is a key component of that equation. Another part is ensuring that every person on a team is responsible not only for the job functions listed on their resume, but for the overall success of the team. Ultimately, the success of any great plan is the flexibility to modify it when we identify aspects that aren't working as we had envisioned.

Rethinking R&D has to go beyond simply changing the structure to enhance research and development productivity. We can work on fostering sleeker research teams within our own company, but we don't believe that we have a monopoly on great talent and scientific expertise. In fact we know there are expert research teams outside our company's walls that could greatly contribute to our research and development goals. We have been aggressively increasing our outside collaborations, and we believe that as much of 50% of our drug discoveries could be obtained from outside the company.

One way we've started doing this is to create our own venture capital fund to seek out and invest in innovative start-up companies that are working on some of the disease areas that we are focusing on. While this fund isn't managed by R&D, these early-stage investments give us the chance to watch technologies develop so we have a better sense of hot areas as they mature.

Last year GSK launched a new concept to tap into the highest quality thinking in academia to optimize the early clinical development of new medicines in a model of shared risk and reward. Academic Incubators have been formed in which leading clinicians and scientists at carefully selected academic institutions partner with GSK drug developers to design and conduct experimental studies to investigate the efficacy and safety of novel drugs originating from GSK or from academia. Incubator projects are now in place at the University of Cambridge, United Kingdom. Our agreement with these labs gives them access to clinical research and imaging facilities at GSK, while the university bears the cost for some the development of therapeutics for obesity and addictive disorders. If their studies prove successful, GSK will pick up the development costs.

We understand that the major currency of the academic researcher is counted in quality and number of publications, thus we encourage researchers to publish all of their findings at a much earlier stage than ever before.

Another exciting partnership with academia is the 5-year, $25 million–plus collaborative agreement that GSK signed with the Harvard Stem Cell Institute (HSCI) to build a unique alliance in stem cell science. The collaboration will integrate HSCI's world-class stem cell expertise with GSK's pharmaceutical capabilities to drive advances in drug discovery research. This will include, for example, a staff exchange program where HSCI and GSK researchers will spend up to several months in each other's laboratories.

In addition to opening our doors to academics for collaborative projects, our R&D business strategy makes it easier for academic researchers to access tool compounds. These are drugs that GSK has decided not to develop but that can be used in experimental models. These compounds can be used to further basic research in many areas and can be explored for therapeutic purposes that we may have missed.

While the goal of our strategy is to imbue our company with entrepreneurial spirit, we have to wait and watch for aspects we may have missed. We've guided our DPUs as much as we can; now it's time to take off the training wheels and see how well these groups do on their own. It's a big step forward.

These are exciting times. We will maintain the services that only a large pharmaceutical company can provide but have driven further than ever in developing an entrepreneurial atmosphere within the company R&D structure and a new openness to the outstanding research being done outside our walls.

Yvonne Greenstreet is the Senior Vice President and Chief of Strategy for Research and Development at GlaxoSmithKline.

GSK simply buys its science. This has been evident by its acquisition of Sirtis and now the stem cell deal with Harvard. Internally, they don't have much going on thus they layoff their employees and hope that can get back to being a leader with this strategy.

A business strategy by all means. A science strategy?????

Re: Relying on former employees for opinion statements is full of trap doors - axes to grind from a limited perspective of the entire enterprise.

I would think that the company would want to hear from former employees, who have worked in the environment. The present employees sometimes can't give a straight, honest opinion simply because of fear of retribution. The more known, the better. It's then up to them to decide whether the statements are allegations or the truth.

Regardless, I also think that a VP of Strategy with such a meager publication record won't really be respected, especially in light of the planned collaborations with academia.

Re: "The researchers who live at the bench and in the teams focus on the critical scientific up-front aspects. Nothing happens without them." That is very correct and that is the foundation upon which a successful pharmaceutical company used to be built upon. Now GSK appears to be trying to get to the front by buying and acquiring rights/companies/etc. because their own science is not up to snuff and their gatekeepers lack the critical knowledge to know how to determine what NCE has the best chance to successfully transition from a cell model to a preclinical model to a patient because they lack basic knowledge in physiology and pathology. Thus their pipeline may be ranked #1 but what actually is approved by the FDA is very disappointing. The author is an MD with a business-degree and it certainly shows.

These things happen at all companies, not just GSK by any stretch of the imagination. Relying on former employees for opinion statements is full of trap doors - axes to grind from a limited perspective of the entire enterprise.

The reality: Data driven science, in a perfect world, should lead to prioritization and success through development into the marketplace. But Pharma strategies aren't solely data driven - they are by necessity much more complex. There are multiple considerations including, but not limited to marketing forces, clinical issues (how do you demonstrate efficacy in a reliably diagnosed patient cohort?), bio- and surrogate marker-based translation from preclinic to clinic, regulatory issues in a changing regulatory environment, governmental-political-economic issues also in an ever-changing environment, landscape analysis relative to estimated competition launch dates (is the investment in the project cost-effective if it succeeds on schedule?), risk analysis of success potential vs. disease impact, etc.

The researchers who live at the bench and in the teams focus on the critical scientific up-front aspects. Nothing happens without them. But it needs to be recognized that the corporate strategies must account for much more than the science alone. And the corporate officers are accountable to the shareholders. This all requires the judgement of many individuals who, naturally, are influenced by the people they value who surround them. So every company has its more and less influential insiders. This should surprise no one.

The best and most successful data-driven project may result in glorious publications, but never be able to reach the physician whose hands touch the patients for reasons related to any one or more of those hurdles. A corporate decision to down-prioritize or eliminate such a project will be terribly unpopular for many reasons, but it may be the right decision for reasons beyond the science, certainly with a downstream impact on the personal lives of the people who work(ed) on the project. It's a bloody shame, but a reality nonetheless.

An NCE that makes it to the market is an absolutely incredible accomplishment that requires the best efforts of a whole raft of disciplines, not all of which are best served by a world-class well-published scientist. Some corporations are led by such individuals, but it's not necessarily a prerequisite for success at that level. There are many roles to fill in such an endeavor that require world-class capabilities and intuition in many disciplines.

The struggles that have been raised at GSK between science and management "would" appear to impact product quality and new products development. This discussion is intriguing. It has a sense of revellations a few years back at the Food & Drug Administration, where, there were scientists loyal to science and health, and then scientists loyal to their own interests who had no problem compromising science to appease higher-ups who were cozy with industry lobby groups.

In lieu of revellations of enumerable abuses at prestigious U.S. financial and other institutions, it is fathomable that GSK too was compromised by higher-ups seeking "quick profit and opportunity" to the detriment of the organization, shareholders, and customers.

Clearly, these stakeholders would be most interested in hearing more from former GSK scientists as to how management compromised the company and its products for their own personal gain. This story would no doubt be of great interest to a number of major publications. Find someone you trust and would be willing to work with.

The author has published 2 reviews and a 1 pager in Lancet. I agree with the earlier posters! How can any of her present subordinates respect her track record as a scientist without verified credentials.

Personnel issues are certainly an issue at GSK. Science is given a "nosebleed" seat. Gatekeepers putting favorite projects with their "pets" ahead of science-driven, data-based alternative projects. Letting "quick & dirty" one-on pilot projects dominate a portfolio. Unwillingness to let projects that have been unproductive for prolonged periods of time lapse. Hiring experts and not letting them have access to resources. This is just the tip of the iceberg.

Based on some of the comments on this article, one cannot wonder if personnel issues might be affecting product development and quality at GSK?

Sure,"It's the height of academic arrogance that a scientist is judged by the number of Pubmed citations." but you forgot 1 word "solely". Yes, "There are scientists whose jobs do not require publishing" but certainly a VP in Strategy in Big Pharma would have a track-record as verified by peer-reviews publications some time (earlier) in their career. I agree that some "well-published scientists would be unqualified to lead a strategic position in Pharma." Success will float all boats - within the industry, within academia, and ultimately for the patients...that's a no-brainer

It's the height of academic arrogance that a scientist is judged by the number of Pubmed citations. There are scientists whose jobs do not require publishing, and well-published scientists who would be unqualified to lead a strategic position in Pharma. Not all disciplines can be judged by the same criteria. There are many problems within the pharmaceutical industry, not the least of which center around sustainability. I applaud the GSK initiatives and wish for their success, even if the initiatives are not entirely novel. Success will float all boats - within the industry, within academia, and ultimately for the patients.

GSK has been spinning their wheels for years. In their recent layoffs, there have been no winners except a few executives who took their gold parachutes. Many of the people, who got laid-off are still unemployed while the people who are still there simply view themselves as survivors without a supportive "critical" mass.

Avandia and Paroxetine are just examples of drugs, which have received black-box warnings from the FDA that GSK has produced and made money selling.

Perhaps their pipeline hit a septic tank!

I appreciate all of the comments made from the various posters on this website about this particular article. I invite the author to contact me to discuss the problems that GSK (in particular, since I have worked there) and some other big pharmaceutical companies have encountered.

My perspective will not only be as a former scientist/manager, who worked within big pharma but as a former academic researcher and tenured faculty member, who collaborated with different drug companies and a former member of numerous federal study sections and non-profit agencies.

Sincerely,

Thomas W. Balon, Ph.D.

Dr. Yvonne Greenstreet,a Senior Vice President and Chief of Strategy for Research and Development at GlaxoSmithKline poses as a Scientist and pens the article entitled "GlaxoSmithKline is overhauling the drug discovery and development process, one more time. The crucial difference: putting big decisions in the hands of our scientists."

If I had only 3 articles listed in PubMed, as Dr. Greenstreet does, I would never have the audacity (the ability to publish bold-faced lies?) to claim to be a Scientist and submit such a ridiculous article claiming that important decisions will be placed in the hands of Scientists.

Until recently, I had worked at Pfizer and I am surprised thatDr. Greenstreet is not a Pfizer Alum, as she preaches Pfizer Management's Mantra.

I don't know how the internal politics is like inside GSK, but, political conflicts among the big egos heading different departments usually contribute much to the ineffectiveness of a large institution such as GSK. No matter what different approach is introduced, if there is poor cooperation to follow it, then poor results will naturally follow.

When I was at GSK, managers and associates were urged to attend similar sessions but the gatekeepers of research direction (department chairs, VPs) simply kept to their own self-serving agendas. A number of them (both good and bad) are no longer there. GSK needs a lot of help in many different ways

It would seem based on comments here that today's large R&D organizations, GSK no exception, face substantial bureaucratic and communications challenges. I have a suggestion. Try some group drumming teambuilding & communications exercises to help rebuild the "team" in your organization and setting.

All you need is some simple hand percussion, silver ware, or stuff around the lab. Try and communicate thru this early language. It teaches you to be attentive, to listen to others around you, and how to better brainstorm as a team. Every team member is on the same level. Seniority and intimidation out the window. It reveals who is full of HOT AIR.

I've been facilitating and writing on rhythm and communication for several years, plus still write on AI and neuroscience topics. I've worked in the imaging dept's of over 50 hospitals, placed and hired employees, worked in research settings, and have done mgt consulting.

There's a 10 minute power point presentation on my web site that details how group drumming works, with instructions on exercises to try.

Stephen Dolle
a.k.a. MacGyver/The Professor
Dolle Communications
LINK

Likewise, I worked for GSK. They are not receptive or supportive to ideas or suggestions even within the company. I am glad that I do not work there anymore

OK. Good comments above. But, at the end of the day, companies and R&D must develop novel products that match the specific needs of patients. Since suffering a brain injury and permanent CNS shunt placement in 1992, out of survival I became an expert in CNS shunts, headache, cognition, and sensory integration complaints. Prior to this, I worked in nuclear medicine, consulting, and some research settings.

Much of the disappointment we see today in health care products I believe is due to an ongoing "disconnect" between industry and patient users (customers) and the complaints and quality of life they face as a result of medical disorders and disease, and the tradeoffs most will accept in undergoing treatment via drug therapy, invasive procedures, or other methods. It would seem that if patient user needs are not that well understood, researchers and R&D would face even more confusion in crafting solutions that might meet their needs.

In 1997, in response to ongoing confusion and poor diagnostics in the use of CNS shunts (4 revisions at the juncture), I created a diagnostic program that I used to direct my much needed shunt revision. Today, this DiaCeph Test could run as a software app on a mobile phone. In 2006, I spoke to GSK about integrating neuro and headache software apps into phones and PDAs. At the time, GSK only offered a paper diary. It is critical that you monitor patient headache markers and triggers to minimize sequela. I envision this going the way of software, ideally as mobile phone apps.

Outside of software apps, I see an increasing role of alternative or mind-body medicine in health care. I have particularly found drum rhythms and group drumming to help with sensory integration, headache, cognition, and coordination and gait complaints, and have written up many findings. There are also some clever ways applied kineseology (AK) can be used diagnostically in the clinical and home settings.

Stephen Dolle
Patient User & Scientist
CEO, DOLLE COMMUNICATIONS
Southern California

For someone who has only 3 citations in Pubmed, I wonder from what limited perspective is the author viewing research. Having been a Ph.D. educated researcher in both an academic, private research institute and most recently an industrial setting (GlaxoSmithKline[GSK])for more than 25 years, it is my opinion that that this reorganization that is referred to is just a dog and pony show. GSK has had a strong pipeline for years but produces relatively little for its size. Its problem is that it is not nibble and can't even be a "fast-follower". The decision-makers in the preclinical areas are not at the cutting-edge nor do they understand basic physiology which can translate to meaningful clinical progression. Novelty.... Pharmaceutical companies have long been noted for sponsorship of academic projects and programs. The only novelty is that GSK is attempting to solicit a big-name institution in an area that is now more accepted by the government.

I wonder though if all of this outside collaboration doesn't increase conflicts of interest among academic scientists as they become associated with the pharma company. I think collaboration is great, but Pharma funding causes problems, and perceived conflicts of interest are slowly eroding medicine's reputation in the general public.

I know that GSK is technically pharma, but there are biotech companies (5000+ employees)that have already been functioning with this scheme in mind. Out of all of the ideas mentioned above, one particular company does all but one of them. In its locations, it has buildings separated by therapeutic area and then thereapeutic areas separated into labs. The project managers apply for these "grants" mentioned here and they drive the research with regular reviews from upper management. Furthermore, it even has small incubators as mentioned above that it will then buy up if they are doing well. The only collaboration missing is something huge with academia like the HSCI, though there are several smaller collaborations. Maybe The Scientist should look at its own story from a few weeks ago about Nature/Science hyping research that is not so novel. Nevertheless, this is an insightful view as to the current structure of many biotechs.

Dr Greenstreet and GSK are to be commended for their collective strategic approach to drug development. For too many decades scientists and commercial development professionals within life science companies have been hindered by disciplinary silos and a striking lack of information sharing, problem solving, knowledge creation, innovation, and value. Duplication of effort, lemming-like organizations, and pursuit of products and clinical relationships that demonstrated equivalence more than superiority have collectively bloated the pipeline with marginal products, diverted resources, and hindered real clinical breakthroughs.

Hearing how small teams at GSK are charged with discovery, creation, and the reinforcement of value is not only refreshing...it is essential if the true value of the life sciences is to be realized globally. No one has a monopoly on ideas. Everyone has a responsibility to cultivate them.

Neil H. Gray
Managing Partner
Healthcare Trends & Strategies, LLC
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