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Pharmaceutical Executive Digital Edition - July 2011

Despite its prominent role in the growth strategies of Big Pharma, India is the ultimate frustration for business planners. Its size, diversity, and freewheeling politics make the country an endless moving target that complicates the accurate and timely assessment of potential opportunities. This is why the release last month of India's latest population census—the seventh since independence in 1947—provides some useful context in helping pharma investors decide where to put their resources, and to what end. 

The results of the census will carry weight as the government intends to use it to chart a more strategic approach to investment in areas critical to pharmaceuticals, such as information and communication technologies; healthcare services, especially in under-resourced rural areas; energy and manufacturing infrastructure; and higher education. The document is particularly strong in analyzing India's huge demographic dividend, which predicts that millions of citizens are primed to join the middle class over the next few years, stoking the demand for better healthcare and access to medicines— nearly all of which is currently paid for out-of-pocket.  

The results also provide some subtle hints about continuing sources of risk, not the least of which is the potential for confrontation along the key religious fault line between the majority Hindu and minority Muslim populations. The proportion of the Hindu population is slated to fall below the 80 percent mark for the first time in over a century, revealing a significant divergence between Hindu and Muslim growth rates. This could serve as a drag on social progress because for many indicators the Muslim population tends to rank below the national average—literacy among the Muslim cohort currently stands at slightly under 60 percent, compared to more than two-thirds for the Hindu majority. "Religious demographics" is important as an indicator of future political stability, to an extent not seen in other markets.  

Another divisive factor is the sex ratio, where the gap in births of boys versus girls has widened significantly since the last census in 2001. That data comes as a surprise, given the many laws enacted to prevent female feticide along with schemes to encourage families to have a girl. The results have sparked a political debate focused on the fact that, in the opinion of many leading health advocacy groups, and after a decade of strong economic growth, India remains a hostile place for girls—status among the sexes is still highly unequal.  

Nevertheless, what the census shows in stark relief is just how big the country is today. Total population stands at 1.21 billion people, a figure nearly equal to the combined populations of the US, Indonesia, Brazil, Pakistan, and Bangladesh. One of every six people in the world is an Indian citizen. Between the last census in 2001 and this current one, India added nearly as many people as there are in Brazil.  

More important, the population boom has not yet played itself out. The fertility rate is slated to continue at 2.8 percent, or slightly higher than replacement. The Health Ministry has pushed back the timeline for achieving population stabilization to 2070, from the 2045 target set via the previous census. Practically, this means that India is slated to overtake China as the world's most populous country within the decade.  

The census carries important new information on the state of heath and the potential for sector-led growth. Demand for healthcare services in India is growing at a compound growth rate of 16 percent. The healthcare industry accounted for 5.2 percent of India's GDP in 2002, but the census says this will rise to somewhere between 6.2 and 7.5 percent by 2012, or $47 billion annually. 

However, the public sector accounts for a mere 20 percent to 25 percent of total health spending, with the country's public outlays among the lowest in the world. Large parts of the country continue to have no access to basic medical facilities. Expensive healthcare adversely impacts the economic condition of the poor, leading to a vicious cycle that further reduces their standard of living.  

For the first time ever, mental illness was extensively mapped in the census as part of a major effort to track the level of disability. Besides mental retardation, people were asked if they have a family member suffering from depression or anxiety. According to one estimate, two out of every five Indians suffer from depression, creating an enormous wellspring of unmet medical need involving a target treatment population in excess of 200 million. Other questions on disability covered topics such as schizophrenia and anxiety disorder.  

Another area of inquiry focused on lifestyle diseases, especially non-communicable conditions such as cardiovascular disease and diabetes. "The WHO says that between 2005 and 2015, the cumulative economic impact of noncommunicable diseases on India will surpass $237 billion," S.L. Narayanan, chief financial officer at Max Healthcare, a specialty hospital chain, told 

The country has a huge 'population to hospital bed ratio' gap. "Almost everyone in the government is aware of, and talks about, the importance of building a world-class nationwide medical ecosystem, from primary healthcare centers to diagnostics to high-end tertiary care. We also hear that much of the investment ought to come from the private sector. But it is baffling that no action has been forthcoming despite years of seeking 'preferential infrastructure' status for the healthcare sector. Hospitals need to be created with a sense of urgency, given our abysmally low ratios compared to the global benchmarks of beds per 1,000 citizens,'' Narayanan said. 

Conversely, India is showing better results around some basic preventive initiatives. The data indicates that maternal mortality linked to childbirth has dropped sharply, while average life expectancy for both male and females has doubled since independence in 1947.  

Yet India continues to fare poorly in comparison with global averages. On the broad social indicator scale, India is ranked a mediocre 119 out of 169 countries on the United Nations Development Program's (UNDP) Global Human Development Index 2010. 

In fact, if India is compared against other emerging countries, it is way behind China. Government expenditure on healthcare in China is nearly five times that in India. Though China has a larger population and a higher per capita income than India, the Chinese government spends nearly 2 percent of GDP on healthcare, while in India it is only slightly above 1 percent. 

In a report on "Quality of Life" between the two Asian nations, Amartya Sen, the Nobel Prize winner in Economics in 1998, cited the 2011 census data in noting that life expectancy at birth in China is 73.5 years, while in India it is 64.4 years. Infant mortality rate is 50 per 1,000 births in India, as compared with just 17 in 1,000 births in China. The mortality rate for children under five years of age is 66 per 1,000 for Indians and 19 in 1,000 for the Chinese. Sen also noted that only 66 percent of Indian children are immunized with triple vaccine (diphtheria/pertussis/tetanus), as opposed to 97% percent in China. 

Though more than a third of the population in India is still too poor to be able to afford an adequate diet, the overall poverty rate has been cut by around 10 percentage points since 2000, largely as a consequence of an underlying GDP growth rate that averaged more than 7 percent a year during this same period.  

What is also new is data covering household amenities and assets, as a surrogate way of tracing advances in living standards, in addition to income. With specific reference to employment, a new category was brought in to identify those who have worked for less than three months in the past year. This will provide the government with more accurate information on the actual level of underemployment. 

As part of the census exercise, the government is launching its first national health survey in which information on blood pressure, blood grouping, sugar levels and other basic primary care indicators are to be collected, to help identify predisposing disease factors. This data will be collected directly at the community and even neighborhood level, with the aim of close targeting of healthcare policies relevant to affected populations as well as gaining guidance in deciding Union Budget priorities. Pharmaceutical companies should watch this exercise closely as it will shape the coming debate on expanding government investments in a basic healthcare system linked to a commitment to universal coverage. 

India Invests in Identity Cards for All Citizens 			

There were other positives as well. Literacy has jumped, with the effective literacy rate rising to 74.04 percent, up from 64.83 percent in 2001. The male literacy rate, at 82.14 percent was ahead of the female literacy rate of 65.46 percent. India's Planning Commission has set up a target to further reduce this gap to 10 percentage points by 2012. 

Progress has also been posted in basic health indicators such as sanitation. An interesting tidbit revealed at the last census was that India had more households owning television sets than those with bathrooms. Likewise, while the 2001 census found that 68 percent of the population had access to clean drinking water, today 94 percent of rural dwellers and 91 percent of urban residents have it.  

Nevertheless, some 37.7 million Indians are affected by waterborne diseases annually, 1.5 million children are estimated to die of diarrhea, and 73 million working days are lost due to waterborne disease each year. Treating these diseases costs the strained public health system in excess of $600 million per year, which could be ameliorated by new investments in health infrastructure.  

The census exercise has been useful in helping drive awareness that India needs to invest more in health. Whether it will do this successfully depends on political factors that are hard to assess at the present time.  

India-based reporter Mangesh Sai can be reached at 

Features

What India's latest census tells us about current and future pharma opportunities.

What the 2011 Census of India Reveals for Pharma

If you want to know what the Vatican is thinking, a pontifical high mass is a good place to start. If you want to know what the European pharmaceutical industry is thinking, you can do worse than attend its equivalent—the annual meeting of Europe's main drug industry association, the European Federation of Pharmaceutical Industries and Associations (EFPIA). 

This year's ceremony, in mid-June, offered some fashionable displays of ecumenism: a desire to bridge divisions, to collaborate, to work together. "Europe's public health challenges can be solved only through sustainable partnership," EFPIA trumpeted, even before its meeting had gotten under way. 

The federation's president, Glaxo SmithKline CEO Andrew Witty, pledged to "continue listening to patients, customers, and other stakeholders and work in partnership with them to find solutions to the challenges facing Europe." The declarations of a firm purpose of amendment from the European industry's high priest were backed up, as outward signs of inward grace, with a volley of leadership statements on ethics and trust, and with a tightening up of the industry's own limitations on samples for healthcare professionals and funding for patient associations.  

Other virtues that the industry paraded included joint actions with European regulatory authorities on everything from new pricing methodologies to seeking innovative responses to the challenges of an ageing society. The new definitions of saintliness envisage new approaches to drug development: "We have to rethink our business model in the way we operate," says Witty, "a different relationship which does not try to force-fit the same model, the same economic structure." It is important now, says EFPIA, that the industry works closely with the authorities in Brussels and across the member states. "New thinking, new mindsets, and new partnerships will be essential," added EFPIA's new director-general, Richard Bergström. 

John Dalli, Europe's health commissioner, was a willing concelebrant of the service: "Let me stress that I consider the pharmaceutical industry to be a crucial partner in providing European patients with access to safe and effective medicines," he intoned in a speech to EFPIA members.  "We need to work closely together to face the many challenges that lie ahead and to prepare the groundwork for a successful and sustainable future," his litany continued; it is critical, he says, speaking of new partnerships, "that all voices are heard and taken into account." 

The pharma industry's Damascene conversion to cooperation may in part be pure altruism, but there are some strong practical incentives for the European drug industry to start singing from a different hymn book too. Over recent months the debate on healthcare among European governments has become increasingly focused on keeping a tight rein on expenditures—with frequent evocations of the growing burden of medicine costs. In the face of this irresistible force (since national authorities continue to control the purse-strings of drug spending in Europe), the drug industry is recognizing that it can no longer rely on what it has for years regarded as a clinching argument in its dealings with governments: that industry research imperatives require decent prices for drugs. Such an approach has for years been the immoveable element in pharmaceutical companies' strategic approach to the organizations that decide what industry can charge. But times have changed, public spending constraints are much tougher, and the industry knows there is no point in advancing its chin to meet the outstretched fist of national pricing and reimbursement authorities.  

The June council of European Union health ministers ended with a tirade against overpriced drugs, unleashed by the current council president. Miklós Réthelyi, Hungarian minister for national resources, who chaired the meeting, highlighted the importance of "cost-efficient use of medicines." It will be necessary, he says, "to impose controls on expenditure on medicines." He insisted that contracts will have to be signed on prices and volumes, and prescriptions will have to be regulated. The meeting took note of actions by member states that "include the regulation of the pharmaceutical sector." This angle of attack is becoming the norm in the EU, as a followup to extensive council debates last year on healthcare that produced highly critical reports on the cost of medicines. 

As a consequence, industry is shifting its arguments away from the need for drug sales to fund the research cycle, and is putting its faith in a more comprehensive view of the overall healthcare scene. It is trying to build a new niche for itself in this broader context, profiling itself as a generator of savings in the total healthcare budget through its delivery of products that prevent disease, reduce hospitalization, or that offer cheaper alternatives to surgery and other therapy options. Success in this revised strategy depends on winning friends not just among the authorities that handle drug budgets, but among the authorities that handle the entire healthcare budget. Hence the surge of enthusiasm for new partnerships. 

Nonetheless, obscured though they may be behind clouds of incense, or muffled by the outbreak of harmonious chorusing, some stubborn vestiges of the old industry dogma still lurk. At its most innocent, the pre-reformation doctrine emerges in messages such as the mild cautionary observation about the risks of excessive government cost-cutting: "The key is to avoid actions that have unintended consequences—too strong a focus on cost, rather than value, will undermine valuable innovation and therefore reduce patient benefit," EFPIA points out.  

EFPIA claims that its members "have shown their commitment to work with governments to bridge funding gaps," and it invites any government "to talk to us about their needs"—because, it goes on, "EFPIA is committed to finding solutions that work short-term without having international knock-on effects and without hurting valuable innovation."

The tone sharpened perceptibly with warnings from Bergström that while major innovations are within the reach of industry, "there are significant challenges in delivering these to patients in an equitable way." And Witty upped the ante by pointing an accusing finger directly at politicians who are "not geared up" to thinking about effective ways of tackling healthcare problems, because they have "too short-term a horizon." Healthcare authorities lack the information systems that would allow them to understand what drives their overall costs and to identify accurately how to make real savings, he alleged, and the industry suffers from the "schizophrenia" that affects Europe's governments. Depicting his own industry in a way that conjured up images of a choirboy punished for stepping out of line, Witty remarked: "We have been taken behind the woodshed and given our treatment by the governments and everybody else."  

Like a disappointed missionary who finds his message rejected by unsympathetic pagans, Witty inveighed against widespread resistance to arguments linked to overall healthcare expenditure: "People only care about what is in their silo. Nobody really believes they will have to worry about the consequences," he says. On top of that, he even attacked the very foundation of the institution he claimed to be seeking an understanding with: any progress in Europe is impeded, he suggested, by "the division of the member state and European competencies for this agenda."  As a result, "we have duplication at several levels and an increase in bureaucratic barriers." 

The overwhelming impression left by the EFPIA meeting is that although the industry says it has embraced a new vision, and claims to be a born-again believer in cooperation, little has changed in its inner soul. The same old determination appears to persist, to be devout only in a clear quid pro quo bargain where virtue is to be rewarded by guaranteed salvation. "We will make our medicines better, and it is up to member states to make provision for paying for them," says Witty. And he warned that "governments must not drive the pendulum too far in one direction—balance is their responsibility too." It is hard to resist the conclusion that the industry's odor of sanctity is tainted with a more earthy scent of the pursuit of wordly goods—that business model is still in place. 

's anonymous columnist, a commentator so close to the action in Europe that his identity must remain a secret

Columns

While Europe's EFPIA preaches about embracing change, much remains to be done to prove the adjustment in philosophy

Holy Surge of Enthusiasm!

Similar to the old quotation about war and truth, it seems that "the first casualty of marketing is often common sense." In the heat of a marketing battle, when choices must be made and decisions are filled with risk (career, political, and otherwise), it's common wisdom that often prevails, a product of corporate culture, groupthink, and the we've-always-done-it-this-way syndrome.   

 Unfortunately, the result of corporate politics, decisions-by-committee, and reliance on past experience means good-old common sense isn’t called upon nearly enough.  

The problem is, as you know, common wisdom is often dead wrong. From assertions that violent movies lead to violent acts (not so, says a study by the National Bureau of Economic Research) or that advertising is dead (let's hope not), the fact is that just because you think it's so doesn't mean it is.  

Which may be why relying on common wisdom at product launch time can lead you right down a path to disaster. According to Mintel research, a company that tracks many industries, of the 250,000 new products launched each year, 85 percent to 95 percent of them fail. Many of them are from reputable companies like yours, launched by smart people like you. And many are failures, despite growing industry sectors such as Hewlett-Packard's recent smartphone line, the iPAQ. Last year 

 reported that in a market that is exploding, Q1 2010 sales of iPAQ were down $57 million from the year before. 

So what goes wrong exactly? While there are a million books on the subject and many companies offering to analyze failure for a fee, I suggest the reason is much simpler: We often abandon common sense for common wisdom. Unwritten rules, past experience, unrealistic enthusiasm, and political compromise can dominate corporate decision making. So step by step, meeting by meeting, the simple proposition of launching a product that fills an unmet need gets lost. 

Keeping common sense at the forefront of planning can help brand teams ask the right questions, challenge prevailing assumptions, and have the courage, in the case of a potential failure, to call the baby ugly before the marketplace does. And how does that happen? Putting your plan to the following test is a good place to start.   

While both groups are working toward corporate goals, it can seem like senior management and the marketing/commercialization teams are motivated by opposing forces: short-term commitments to shareholders versus long-term brand building. The result can be a disparity in expectations and disappointment on both sides. A perfectly solid product can be branded an instant loser if expectations are unrealistic or not aligned.  

So put on your common-sense hat and take a realistic look at your market, your product, your label, your customer, your sales force, and your marketing budget. Then work with senior management to set goals you can hit.  

2) Have you found the "moments of truth" in your target customer's decision process? 

As a physician or healthcare professional considers a protocol or algorithm in approaching their patient's issues, a marketer should find where in that protocol lies their brand's "moments of truth." At what point can you influence that script, that purchasing contract, or that patient request? Common wisdom may hold that efficacy data is the critical driver of a new script ... until research reveals that cost has become a barrier. That's a different moment of truth for the prescriber requiring a different set of strategies from you.  

Deliver the right message at the right time and you multiply the value of your brand. Leave it to chance and you waste an opportunity.  

Our agency creative brief requires us to answer the question, "What customer problem are we trying to solve?" We ask, because we know that if your brand isn't addressing an unmet need or creating an opportunity, you're the one with the problem.  

Common sense helps you solve the right problem. After years of R&D, product development, and clinical research, the corporate pressure to go forward with a brand launch is enormous. But before that critical decision is made, make sure there's pressure from your marketplace as well. Make sure, after all that work and investment, your brand still offers something your customers want and cannot get elsewhere.  

But what if your customers don't know they have a problem? In an industry that deals with human lives, caution and familiarity create significant barriers to change. You may be offering a better approach or an improved outcome, but a healthcare professional may see limited value unless you create a compelling need. Can it be done? Of course—with the right combination of education, peer influence, and time.   

We see this one over and over again. Brand and medical teams fall in love with their data and are sure their customers will feel the same once it gets into a sales aid. But remember, not all endpoints are created equal, and 

 significance. If you're lucky enough to have input into trial design, make sure endpoints are meaningful and reflect clinical practice. Talk to all the prescribing clinicians, not just KOLs who may be a bit removed from daily practice. Feedback from trial investigators (if you can get it) is invaluable in terms of learning exactly how your brand performed in your target patient population.  

5) Have you made your target uncomfortable enough with their current brands to try yours? 

Someone once said, "Change will come when the pain of staying the same is worse than the pain of change." Now, that may sound a bit dramatic, but it makes sense: Discomfort is what drives change. And in an industry where patients' lives are at stake, it can take a lot of discomfort for healthcare professionals to try something new.  

So, seeds of doubt about current practice must be planted before your brand hits the market. Make customers feel that whatever they're using now isn't strong enough, fast enough, or easy enough—so a switch to your brand makes sense.  

6) Will your plan be able to pass the authenticity test?   

Does your plan have the ring of truth and clarity? Will your hardened sales veterans see that you have understood the realties they face each day and accounted for them in the plan? Are your positioning and claims credible? Will patients believe your product will improve their condition?  

Yes, if your brand is authentic. Interestingly, as skeptical as they can seem, physicians want to believe you've got a great product that will help patients. Sales reps want to believe the new addition to their bag will help them hit their goals. But if you've got data gaps you don't own up to, or product performance problems you're not addressing, or back orders you keep promising to fill, your brand's (and company's) authenticity goes right out the window. Your sales rep ends up all alone in front of the customer unable to answer some very tough questions. And you find your brand trashed all over the Internet.  

7) Your tactics are driven by strategies, aren't they?  

It worked on the last launch ... The sales force likes it this way ... The competition has one ... We did one last year ... My boss thinks it's cool ...

 No joke, these are actual rationales we've heard over the years for different tactics.  

For example, every company wants to put an Apple iPad in their reps' hands. Yes, the technology is brilliant and seemingly limitless at this point. But before you follow suit, make sure it makes sense for your brand. If your brand is in third position with not much new to say, a leave-behind flashcard may be the better tactic because your strategy is to deliver quick, bite-sized messages for the brand.  

But sometimes excitement, the desire for immediate results, and politics win over well-thought-out tactics and targeting. So demand a common-sense reason for every idea, or your team will end up with a bunch of tactics searching for a strategy. 

8) Is your plan focused and aligned? Or are you about to jump on your horse and ride off in all directions? 

In today's market of limited time and budgets, it's doubtful that you can address every challenge your brand faces equally. Maximizing impact takes a plan that's focused on meeting specific objectives, strategies, and tactics that are prioritized. Otherwise you'll be everywhere and nowhere at the same time. It sounds obvious, but often the fear of not covering every base and including every suggestion makes a plan tough to execute. Focus requires choice and sacrifice. And common sense.  

9) Is your team justifying their emotional prejudices with apparent logic? 

Frankly, while we would all like to think that planning and marketing is based on solid information and objective judgment, unless you can remove human beings from the planning process, the subjective will always find its way in. And so our detailed rationales, decision trees, and comparative assessments of alternatives all contain shreds of emotional prejudices and apparent logic.  

The aim for any marketing team is to be able to talk openly, think clearly, and view a situation from all sides. And a heavy dose of common sense never hurts either.  

Which is why you need to stop from time to time, stand up in a meeting, and ask, "Does this make sense? Or, "Are we rationalizing our way into the plan we want, rather than creating the plan we need?"   

Case in point: A brand team sees broad use (and big sales dollars) for its new product. They see it used as monotherapy and, adjunctively, potentially as a core therapy for every patient. The market, which operates with its own common sense, disagrees. Uptake is slower and more selective as physicians struggle to figure out where it fits in their armamentarium, and reps are unprepared to help them. With expectations too high and a plan that's too broad, the launch falls short even though the product eventually finds its place in the market. 

So what went wrong? The team's focus, justified with research and logic that supported their belief, made them blind to some of the realities of the practicing physician.  

10) Can you see how your plan will drive transactions? 

In the end, marketing is all about the transaction. The script has to be written, the product needs to be on formulary, and your customers' behavior has to change. It's not about a great sales meeting, or impressing the sales force, or loading the distributor's pipeline. Somewhere, somehow, something has to get sold. 

Sounds obvious, of course. Common sense, sure. Forgotten, rarely. But clearly targeted by the launch plan? Maybe not. Take a look at some of the products that haven't made it in the market, and with the wisdom of hindsight, you can often see that somehow, the ultimate transaction got buried in the process.   

The customer and their needs must be present in every discussion to keep the transaction top of mind. How will a treatment protocol influence the transaction? How will sales tools help the sales force change their customers' behavior? How can we ensure patient access? 

How to put some common sense back into your marketing program 

You may start by tearing this article out and asking your team (and yourself) the above questions. Delete some, add more. Keep them on hand during your planning process. The objective is to create a culture that challenges the team to think clearly, talk openly, and look at a situation from several points of view. And, most importantly, to learn to rely not on common wisdom, but rather on their own common sense.  

 is president of Topin Associates, a full-service medical marketing communications company, and a member of 

 Editorial Advisory Board. He can be reached at 

EAB Member Al Topin delivers 10 questions that should drive your brand-building marketing program.

10 Emergency Brand Building Questions

Despite a significant transformation in pharmaceutical marketing over the last several years, in response to new models of care, expanded access to online physician and patient data, and new regulations on detailing and DTC, marketing research has remained more or less consistent. But as pharmaceutical marketing has grown more complex, it's time for new approaches to answering questions fundamental to sound marketing strategy in several key areas: 

How can your organization be a better advocate for patients? How can you understand their needs if they don't even discuss them with their physicians? How can you help physicians address those needs? 

2) Communicating effectively through intermediaries. 

 How can you more effectively and efficiently communicate with physicians? What channels, messaging, and materials provide the greatest value and help improve the patient-physician dialogue about your brand and the condition it treats?   

3) Diagnosing physicians' prescribing behavior.

 What factors keep physicians from prescribing your brand to qualified patients at various points in the product lifecycle (e.g., dearth of long-term evidence, formulary tier, competitors' messaging) and what can you do to quickly overcome those hurdles?  

These important questions can be addressed through new approaches to market research. These approaches include new methods and/or use of new technologies to dive deeper into the issues to help brand teams extend their reach, while facilitating the exchange of valuable information between sales forces, physicians, and patients.  

No matter the health condition, brand marketers benefit from knowing how patients regard their health, their symptoms, your brand, and your competitors' brands. Uncovering these attitudes and behaviors can be even more challenging when the condition is of a personal nature. The solution lies in providing a safe environment that allows patients to share attitudes and behaviors they might not even admit to their doctors or spouses. The key to such an approach is to create an ongoing, intimate, but "anonymous" relationship with patient respondents. Short-term online communities (groups of similar customers sharing ideas through online bulletin boards) foster a high degree of candid and insight-rich communication, especially when used to study stigmatized, highly personal conditions, to generate a richer understanding of patient needs and their true concerns. 

Case in point: A pharmaceutical company sought to expand usage of an existing drug to a new treatment category for an STD. To develop an effective marketing strategy, it was crucial to fully understand the patient experience and barriers to getting treatment. As any brand manager would expect, the most revealing questions would be impossible to ask in a traditional focus group. 

The research objectives for this study included:  

» Gain an in-depth understanding of the patient experience, particularly how the condition affects lifestyle, attitudes, and behaviors;

» Examine patient attitudes, behaviors, and motivations related to diagnosis, physician interactions, and treatments; and 			

» Identify marketing and messaging opportunities for DTC communications, physician detailing, and patient-physician interactions. 

The short-term online community included patients from across the US and involved individual private blog assignments and group message boards over the course of three weeks. All participants remained highly engaged throughout, providing thoughtful, detailed, and unrestrained perspectives, and participating in free-flowing dialogue with one another. Many expressed gratitude for the opportunity to participate and commented on the benefits of the study's unique environment.  

Having overcome some of the hurdles of traditional research on such a sensitive topic, the brand team was able to deliver valuable insights that are directly impacting the company's marketing strategies within this new category. 

Communicating Effectively Through Intermediaries 

In an industry that relies on intermediaries to convey finely tuned product messages, the distance between the brand team and the actual patient conversation can seem like a million miles. Such is the case with a physician and patient, where the conversation about symptoms and treatment options is critical to what brand—if any—is prescribed for treatment. 

The ideal way to learn how a physician communicates with his or her patients about a specific therapy or condition would be to observe the actual conversation as it happens organically in the doctor's office. Of course, the private and confidential nature of those conversations typically prohibits such an observational approach, so brand teams often conduct separate research with patients and physicians, relying on perceptions and recollections of how those conversations went. 

When the research goal is to understand the complexities, challenges, and opportunities that occur during these important conversations, a simulated conversation—known as a "dyad"—is an incredibly effective substitute. A carefully researched and strategically designed dyad between a physician and a patient (though not actually that physician's patient) can reveal startlingly real representations of actual conversations to reveal a genuine dialogue. Those representations deliver actionable insights to empower and educate marketing and sales teams to better target and communicate both directly with physicians and, ultimately, to patients through better communications and materials. 

Through this observation, researchers can identify language that is effective—both from the physician's and patient's perspectives. And by having a bird's eye view of these conversations, companies can gain valuable strategic insights around major messages and issues. 

 Sometimes a marketing research study uncovers issues that beg new questions. For example, as part of a physician survey last year, one pharmaceutical company identified a cohort of physicians who had been detailed on a particular drug, but who had not yet prescribed the drug to any of their patients. This revelation begged the question, "Why?" 

The brand team needed quick insights into this challenging group of physicians. To that end researchers deployed a quick and cost-effective series of deep-dive interviews to learn how to increase prescribing rates among this niche group of detailed non-prescribers. Our client needed to understand what key issues were preventing three particular groups of physicians from prescribing the new brand: 

» Those who had been detailed but would not consider prescribing; 

» Those who had been detailed, who would consider prescribing and, in fact, planned to prescribe; and			

» Those who had been detailed, aren't completely opposed to prescribing the medicine, but have no plans to prescribe it. 

Our client wanted to learn more about physician reactions to the detailing experience, and whether it was the detail or another factor that was getting in the way of prescribing. Researchers had conversations with physicians from each of the three groups to determine what additional information and/or messaging a sales representative could use to reach physicians more effectively, or whether the problem was something other than the detail itself. 

Researchers created a fast turnaround strategy for reconnecting with those physicians through highly specific, in-depth phone interviews (IDIs) with trained moderators. Because the IDIs were limited to 15 minutes, physicians easily fit the interview into their busy schedules, and researchers got them to quickly address the compelling issues with the brand. 

In very little time and with modest cost—a fraction of traditional, full-scale qualitative research projects—researchers dug deeper to reveal detailed information about the decision-making behavior of these key physicians. The physicians provided an abundance of important and specific insights that are being used to revamp the tools and approach that detailers will use with similar physicians in the future. 

Using these approaches, you can help answer key strategic marketing questions, and by doing so shed light on areas that traditional methods simply cannot reach. By understanding the 

 story, the reasoning, and emotions buried within decision-making processes, marketers can more effectively influence outcomes and find new messages that resonate with, and address the needs, of target audiences. 

 are Qualitative Research Managers at CMI. They can be reached at 

If you can learn to understand patient and physician behavior, you are well on your way to strengthening the position of your product

New Ways to Gain New Brand Insights

This sponsored supplement was produced by Focus Reports.  

Nicolas Carayon; James Waddell; Manuel Mendoza

For exclusive interviews and more info, please log onto 

Stretching across the heart of continental Europe, Poland is a massive bridge that links east and west, old and new, and which epitomizes a changing continent. At one time an enigmatic behemoth cast behind an iron curtain, Poland's accession to the European Union in 2004 has injected its economy with new levels of competition and investment. A population of 38 million citizens, in turn, offers an enticing market for companies looking to expand east. The country's leaders proudly boast that Poland was the only EU economy to grow in 2009—the nadir of the financial crisis—and last year Poland surpassed the Netherlands as Europe's sixth-largest economy. Today the pharmaceutical industry looks to Poland for a skilled pool of human resources, an eastern platform for competitive manufacturing, and high-quality clinical trials. Yet there is still much work ahead, and in order to fully embrace the future the industry must overcome certain communication barriers stemming from the country's long, closed-market past. Greater room for innovation and increased dialogue between business and government are necessary steps to truly awake Europe's sleeping giant.  

Niebianska Parmiec (Celesitial Memory) by Elzbieta Murawska			

The past two decades have brought about sweeping changes and lasting benefits for Poland through its transition to a market-based economy and, more recently, incorporation into the European Union. The Balcerowicz Plan of "shock therapy" undertaken in the early 1990s liberalized trade and privatized former public assets, thereby increasing industrial competition and promoting foreign direct investment. Poland was widely lauded as a success story among transitional economies. Since 2004, EU membership has compounded the positive effect of capitalist reforms by granting the Polish economy access to structural funds. Today the country is the largest beneficiary of EU funds among the 27 member states, receiving approximately 20% of total EU financial support. While GDP per capita in Poland is still below the EU average, it is on par with that of its neighboring Baltic states. With 1.5% GDP growth in 2009, Poland was the best-performing European economy during the global financial crisis. Peter Koetsier, general manager of Bristol-Myers Squibb Poland beams that "the country has gone through a remarkable transition in the past twenty years, if you consider the huge steps forward in terms of infrastructure and the financial and legal systems. I look forward to continued progress in healthcare that will see the people of Poland reach health outcome levels more akin to other EU countries."  

Valued at slightly over €5 billion, Poland is the sixth-largest drug market in Europe, according to classifications by the European Pharmaceutical Market Research Association. The country's pharmaceutical industry is shaped by high generic penetration and government-dictated cost-containment which limits market access to innovation. 

However, compared to similar-size markets such as Spain, Poland has an uncharacteristically high penetration of generics, which account for 85% of volume and 66% of value, according to PZPPF, the leading association for generics companies in Poland. As PZPPF president Cezary Slediewski explains, the dyamics behind high generic rates stem from "a patent system and data exclusivity which allowed Polish companies and importers to introduce generics earlier on in Poland than in Western European countries. There are some molecules in Poland that are already generics, whereas in Western Europe, generics for the very same molecule are not yet in the market."  

Additionally unique to Poland are minimal price spreads between generic and innovative drugs. Pawel Sztwiertnia, general director of INFARMA, the leading association for R&D companies in Poland, notes that "the average price of innovative originator products is one of the lowest in Europe. Subsequently, there are expensive generic products in Poland when compared to the average originator product prices in Europe. This is due to a market structure overpowered by generics. IMS Health data demonstrates that the average generic price is roughly 70% of that of an originator." 

Per capita expenditure on healthcare and pharmaceuticals—less than $100—is one of the lowest in the OECD, three times less than Slovakia and the Czech Republic, and six times less than France and Germany.  

POLAND - market value mln EURO, ex-manufacturer net prices			

As Sztwiertnia explains, "The system in Poland reduces the already very limited window for innovative products. When a company manages to establish its product on the reimbursement list, it can then be prescribed by any doctor and be made available in every pharmacy. Thus, from the government's perspective, there is always the fear that reimbursement costs will skyrocket if a new product is added to the list. Reimbursement costs are very difficult to control; monitoring of prescriptions is practically nonexistent in Poland. There are no specialized categories of drugs that specialists could prescribe under certain conditions. For instance, because many patients need treatment for diabetes or cardiovascular diseases, the government is afraid that costs could grow out of control."  

The federal government notes the necessary limitations on health expenditures in even the most developed countries. "The reasons for this are, among others, constantly growing health needs resulting from the aging of the population, quickly growing costs of medical technologies, and financial expectations of medical staff," cites Ewa Kopacz, Poland's minister of health.  

Despite the prevalence of generics, INFARMA assesses that market growth for innovative drugs is quite sustainable in Poland. Compound annual growth of 8.5% for innovative medicines from 2007 to 2010 exceeds EU-15 markets over the same period, a trend that reflects growth in value more so than volume. 

Like many industries, the Polish pharmaceutical sector has capitalized on the country's inclusion into the EU, and key statistics are positive indicators of investor confidence in an open market. IMS estimates that more than 700 pharmaceutical companies presently operate in Poland, with increasing numbers every year. Similarly, the local market's 3.3% year-on-year revenue growth in 2010 is consistent with the average across all EU pharmaceutical markets over the same time. 

Prior to EU accession, foreign innovative companies were deterred from entering the Polish market due to weak patent legislation. During the communist era local manufacturers were essentially the sole providers of pharmaceutical products. Closed Eastern European markets and prohibitively stringent EU standards turned industry inward favoring a lower cost culture of generics. Companies such as Teva and Sandoz established a strong presence. With today's open borders, product marketing is less of a threat and greater data protection is now implemented.  

Jacek Glinka, President of the Management Board of Polpharma			

Geography and a malleable East/West cultural cohesion is one driver behind an attractive pharmaceutical climate in Poland. "In Polish history, the country has always stood between two great powers: Germany and Russia," says Michael Pilkiewicz country manager of IMS Health Poland. Pilkiewicz assesses that in both market potential and value, Poland is recognized as a big Western European Union country that shares many similarities with other European markets. "At the same time," he adds, "Poland knows the culture of Eastern countries. Poland can easily talk to its partners in Russia, Slovakia, Hungary and the rest of the East. The East of Europe has a completely different culture to that of the West. Polish exporters therefore have a very good starting point in terms of knowing how to operate in these markets." 

A recently liberalized market with a relatively low-cost base in the geographic heart of the continent also makes good economic sense for manufacturing. Innovative companies have invested hundreds of millions of dollars in Poland through the privatization process of state owned companies. GlaxoSmithKline, Sanofi-Aventis, and Novartis operate factories in Poland employing thousands of people and provide a positive stimulus for the local economy.  

Recognizing operational benefits, perennial top-five pharma giant GSK has invested $417 million in modernizations for its manufacturing warehouse in Poznan, 175 miles west of Warsaw, which it deems one of its most strategic plants in Europe. As Big Pharma companies increasingly review global manufacturing sites for cost-saving synergies, "Poznan is definitely one of the key sites in the region where GSK continues to invest," according to Jerzy Toczyski, president of the board and general manager of GSK Pharmaceuticals in Poland. Capitalizing off of Poland's central location, production of one of GSK's R&D-based products is currently being shifted to Poznan. "Poznan is one of the four European multimarket warehouses where we keep the stocks of our products to be distributed to the regional markets," says Toczyski. "Additionally, since we have such good access to qualified personnel, one of GSK's global information technology (IT) hubs is located in Poznan. Indeed, more than 200 highly qualified IT experts work there to support GSK's global network. Apart from regular business operations such as marketing and sales activities, there are three other major areas of investment for the company: production, logistics, and IT." 

The closed market under communist times made it difficult for even generics players to enter Poland, notwithstanding the presence of Teva and Sandoz. Poland is therefore a relatively new market for multinational generics companies such as Canada's Apotex. Having registered several products such as Ranitidine or Verapamil in the early 1990s, it took Apotex nearly seven years to make the full leap into Poland, ultimately launching a range of medicines and employing 20 sales representatives in 1998. Today, managing director Michal Pietraszek says that "Poland is considered by the head office in Canada a very good market for the long run." Primed to take on the competition in a crowded generics market, Apotex is closely tracking patent expirations across Europe to seize potential new market share. "The company's best generic products have been chosen for registration in Poland, and the affiliate will now be focusing on new products," he says. "The group is looking at the patent situation in every European country. In Poland, if a patent expires today, Apotex is ready to enter the market tomorrow."  

Pawel Sztwiertnia, President of INFARMA			

The rising tide of EU accession certainly benefitted Popharma, the No. 1 generics company in Poland. With drastic, industry-wide changes occuring in Poland following EU membership companies were requested to upgrade their documentation for existing products to conform to European standards, which, as Jacek Glinka, president of the Polpharma's management board tells, "practically meant for most of them that 100% of the product portfolio had to be invested in or redeveloped." While EU requirements were originally only on the development side, uniform standards also triggered major investments in manufacturing facilities. "Everything had to be upgraded to some extent," Glinka adds.  "The result is that Polpharma has today one of the most modern facilities in Europe, completed over five to 10 years ago and based on state-of-the-art technologies. In a way, the company has been forced to build a more competitive platform to grow its generics business in Poland." Enhanced manufacturing facilities add to Polpharma's dominant market presence. With 13% of the market and 18% in value, Polpharma is both a mature and constantly growing company in Polish generics. 

As a signal of the market's bursting potential in the eyes of many multinational affiliates, Poland is often included in the discussion as the "next" or "sixth" country for multinational affiliates invested in Europe after the big five of England, France, Germany, Spain, and the United Kingdom. "The country can be considered as a 'sleeping giant,' when looking at the overall population, the economic growth, and the fact that it is now an EU member," asserts Bednarz Bartosz, general manager of AstraZeneca Poland, one of the fastest-growing pharma companies in Poland in 2010. "Given its size and population, one could expect that Poland should somehow get closer to Spain in terms of the size of the pharmaceutical market," he adds.  

However, the juxtaposition between a geographically massive, well-populated, and economically liberalizing market that is cautious about creating the financial access for innovation has convinced many industry executives that pharmaceutical industry development is still very much an ongoing process. "Naturally, the primary objective of the pharma industry is to continue its mission to improve health standards and sustain profitability, whereas the primary objective of the national healthcare system is to introduce more and more control over its spending, especially in the area of reimbursement," opines Anna Gajec, general manager of French consulting house Cegedim's Polish business. Peter Koetsier, general manager of Bristol-Myers Squibb Poland concurs, stating that "the transition to a free open market and a world of innovation will continue to be an evolution." Drawing a more figurative analogy, Koetsier likens the healthcare system in Poland to an adolescent. "It has its adult moments mixed with moments of being quite underdeveloped, and sometime a constant movement between the two."  

Within this context, a better dialogue is called for between various stakeholders of the healthcare sector, including local authorities and the pharmaceutical industry in order to reach a common goal—better health outcomes for Polish patients—and to move Poland from "next" to "now."  

Peter Koetsier, General Manager of BMS			

Poland's accession to the EU has, of course, stimulated the competitive landscape and pushed local industry to align with European standards and regulations. Consequently, the benefits that have come with joining Europe's exclusive club have also fueled an appetite for further reforms and at a faster pace. Commenting on this two-fold effect, Michal Bichta, managing director of Germany's Merck Group, which is present in Poland through both pharmaceuticals and chemicals, notes that "the socio-economic situation has dramatically changed in Poland in the last 10 years, partly due to the fact that Poland became a member of the European Union (EU), but also due to the evolution of the national economic situation. Poland is gradually applying more and more European directives, yet at the same time, some existing regulations from the communist period still remain. Since Poland is part of the EU, Polish people have started to look around and compare what is available in neighboring countries. This awareness creates more pressure on healthcare services in Poland, as the population expects the country to be catching up much faster than the current pace." 

The rapid pace of reforms, however, is countered by a government that is keen to control spending. The result has been what Cegedim's Anna Gajec describes as idiosyncrasies in the Polish regulatory and reimbursement systems. She notes, for example, that Poland negotiated a 15-year transition period before implementing the EU's harmonized 8+2+1 data-exclusivity standard. The regulatory environment is therefore typically characterized by long delays for reimbursement approval.  

Jacek Barlinski, General Manager of Nycomed			

However, as Health Minister Ewa Kopacz posits, due to limited funds at the National Health Fund's disposal, "The existence of waiting lists cannot be avoided. It is important to provide equal access to services, taking into account, among others, health status and acceptable waiting time for a given patient to receive service. In Poland, depending on health status, a patient is granted urgent or stable status, which means that the order of patients is not only established on the basis of the date of reporting to a doctor, but also on the basis of medical indications." 

Strong economic conditions of the Polish healthcare sector will indirectly influence the security of funds for reimbursement in a positive way. Numerous discussions within government circles are taking place regarding potential changes to the healthcare system and medicinal reimbursement. Minister Kopacz says that "the draft legislation on the reimbursement of medicines, food for particular nutritional uses, and medical devices has provided for the total reimbursement budget indicator at the level no higher than 17% of expenditures on total healthcare, which guarantees that access to reimbursed products will be gradually wider, along with increased the budget for total healthcare."  

But according to Gajec, draft legislation is not so clear-cut. With complexities in proposed scenarios varying significantly from one to the other, building up long-term strategies in a capricious and ambiguous environment can be real challenge. "As a consequence of these characteristics I would say that Poland is highly different to some others markets in the region and that every single general manager in Poland must find a good, sometimes very specific, operational way to conduct business," she adds.  

Fully concurrent, Merck's Bichta notes that in Poland, "business is driven by change; planning years in advance seems almost impossible in our country." However, adaption to local market specificities and the adoption of different cultures—in this case, the demand for reform and the need for patient planning—is of second nature to Merck Serono. Having assisted in the corporate integration of Merck and Serono in 2007, Bichta attests to the experience as an "alignment of mindsets and culture." He recalls that "whereas the Serono legacy was customer-oriented, highly specialized, and focused on short-term results, Merck's legacy was more focused on the general practitioners market and with emphasis on long-term growth and lifecycle management." Very applicable to the disparities in the Polish market, "Merck Serono is today benefiting from both mindsets and cultures, which have a very positive impact on the performance on both sites—pharmaceuticals and chemicals—in real terms." Merck in Poland is a market leader in treatments for highly prevalent social diseases such as oncology, cardiovascular, and neurodegenerative disorders and, according to IMS data, was the fastest-growing top-40 pharma company through the first three quarters of 2010. Underscoring flexibility and diversity as a key to success in Poland, Bichta states, "It is important to be close to people who understand the market from different angles, who show their expertise in certain areas. General knowledge is definitely not enough; companies should be specialized."  

Michal Pietraszek, General Manager of Apotex Poland			

A country that bridges East and West, old and new-while boasting a growing economy in Europe-is being looked to for its pool of talented industry resources

Poland: A Sleeping Giant

The only area of agreement about developing and regulating follow-on biotech therapies is that the process is more complex and more costly than for conventional generic drugs, and that the Food and Drug Administration (FDA) will require more testing to label a product biosimilar or interchangeable. Developing a biosimilar will cost $75 million to $250 million and take seven to eight years, according to those experienced in the field.  

Even so, the growth prospects for biopharmaceuticals makes follow-on development increasingly attractive to diverse players. The worldwide market for biosimilars is projected to grow to $3.7 billion by 2015, up from about $250 million last year, reports Datamonitor. As more biotech patents expire and regulatory authorities clarify the rules, development of copycat therapies is slated to soar. Payers talk of biosimilars offering discounts of 25 percent to 30 percent off brands, but reimbursement experts say that prices that are just 10 percent lower will be able to gain market share, particularly for therapies with high price tags to begin with (see sidebar). 

FDA officials are under pressure from Congress, government agencies, and payers to develop an abbreviated regulatory pathway for approving biosimilars, as authorized by the Biologics Price Competition and Innovation Act (BPCIA), part of the Affordable Care Act of 2010. The legislation aims to reduce spending on pharmaceuticals by bringing "highly similar" versions of biotech therapies to market based on less extensive preclinical and clinical testing than was required to approve the original reference product.  

The challenge for FDA is to establish science-based standards for documenting biosimilar safety, purity, and potency that acknowledges reference drug data and market experience. FDA held a public meeting in November 2010 to launch the process for establishing a biosimilar testing process to ensure there are no "clinically meaningful differences" between the new biologic and the reference product; the new drug has to use the same mechanism of action and have the same route of administration, dosage form, and strength. Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER), recently indicated that general guidance should appear this year, and that its requirements for human testing will vary according to how well a biosimilar can document sameness to the innovator product. Although biosimilars generally will need additional clinical studies to document equivalent efficacy in at least one approved indication, even innovator firms acknowledge that the biosimilar pathway will involve less animal toxicity testing and probably no dose finding or Phase II clinical studies.  

Another key step is to set a user fee schedule for biosimilars. The agency has proposed application fees similar to those for innovator drugs and biologics, but with a new approach to help finance FDA involvement in steering sponsors through the development process. The plan is for companies to pay a product development fee of $150,000 when it submits an investigational new drug application and annually thereafter; those upfront payments then will be subtracted from the eventual application fee.  

Even without final guidance, FDA officials say they're ready to evaluate biosimilar applications on an individual basis. "We were open for business a year ago," said Steven Kozlowski, director of CDER's Office of Biotechnology Products, at a May biosimilars conference, jointly sponsored by the Drug Information Association (DIA) and the Food and Drug Law Institute (FDLI). So far no manufacturers have attempted the 351(k) approval route authorized by the BPCIA, but many are talking to FDA and considering their options. 

Meanwhile, FDA is tackling some very basic issues, such as which products fall under the new regulatory program. The BPCIA redefines most proteins as biologics, beginning in March 2020. FDA thus has to set new policies for manufacturers of proteins long regulated as drugs and address the nine-year transition period.  

Another thorny topic is whether FDA can approve a biosimilar based on a reference product that is approved overseas, but not in the US. The BPCIA says that reference products have to be licensed by FDA, but biosimilar makers want flexibility to permit comparison to a biologic licensed by a foreign regulatory body. This is important for global biosimilar development programs, pointed out John Pakulski, head of US biopharmaceutical regulatory affairs at Sandoz, at the DIA/FDLI conference. He and others propose to permit the use of foreign reference products that are made by a US manufacturer or in a facility inspected by FDA; licensed in  highly regulated markets such as Europe or Japan; or present sufficient postmarketing history to confirm safety, purity, and potency. Additional scientific data could be required on a case-by-case basis to establish comparability between a US and foreign-sourced reference product.  

Also contentious is whether biosimilar sponsors can extrapolate data from a clinical study to other indications of the reference product. European regulatory authorities permit this if the added indication involves the same mechanism of action and same receptor, and if extrapolation of immunogenicity data applies to a lower-risk population or route of administration. Biosimilar sponsors want a similar approach from FDA, probably with support from open-label safety studies for each indication.   

Equally challenging for FDA is to define interchangeability testing requirements and whether clinical switching studies will be required to meet that standard. An interchangeable designation is important because the first follow-on biologic so deemed by FDA enjoys a year of market exclusivity, during which FDA may not approve another similar interchangeable product.  

Biosimilar makers note that switching studies are not required for innovator manufacturers to document comparability following post-approval changes. Yet, innovators maintain that clinical studies in multiple populations are necessary to ensure safety and efficacy with product switching. Amgen vice president Anthony Mire-Sluis pointed out that head-to-head studies are needed to compare immunogenicity between reference and follow-on products, and that product labels should explicitly state approved indications and whether the biosimilar is interchangeable for that indication.  

Although the BPCI authorized 12 years' exclusivity for innovator biologics, that has not ended the exclusivity debate. In addition to the 12 years when FDA cannot approve another product based on innovator data, biosimilars sponsors have to wait four years after BLA licensing to even submit a 351(k) application. Innovators claim these protections are needed to spur investment in R&D, but critics claim that 12 years is too long. The Obama administration recently proposed reducing exclusivity to seven years, largely to cut spending, but also to prevent patent "evergreening." Biosimilars makers fear that innovators will seek to extend protections by modifying a reference product's safety, purity, or potency sufficiently to make it "new." The change has to be significant, says Kozlowski of CDER: "I don't think that 'slightly better purity' is enough to extend exclusivity," he observed at the DIA/FDLI conference.  

As with conventional generics, everyone is bracing for extensive legal maneuvering over patent and exclusivity issues. The BPCIA took FDA out of the patent-listing arena, but set up an even more complex process for dealing with patent disputes: Biosimilars makers have to provide the reference product sponsor with a full dossier on its process and product so that the innovator can determine which patents it feels may be infringed. This "hokey-pokey process," explained Sidley Austin attorney Jeffrey Kushan, was designed to promote early agreement on which patents are worth fighting about, but appears likely to create a highly competitive legal environment. Biosimilars makers fear that too many parties will gain access to their confidential filings, while BLA-holders stand to lose protection if they miss a deadline.  

If the biosimilars regulatory process appears too complex and costly, it may limit the value of the 351(k) procedure and make the traditional BLA route to market—and its 12 years' exclusivity—the more attractive option for copycat biotech developers. 

's Washington correspondent. She can be reached at 

Sponsors must handle interchangeability, exclusivity, cost and coverage hurdles to win biosimilars game

Battles over Biosimilars

The path to commercializing a breakthrough discovery is rarely a linear process. The orderly rationale of the scientific method is often overtaken by the random artistry of passion, personality, business culture, and sheer luck. Each plays a significant role in handicapping success or failure in that wending transition from bench to bedside. The story behind drug development is thus as interesting as a dime-store novel, except what is fiction in the second case is truth in the first—and always the developer's own dime is at stake.  

Pfizer's crizotinib—a new targeted therapy that blocks progression of a genetic alternation in a subset of patients with non-small-cell lung cancer (NSCLC), extending survival well beyond the current standard of treatment—is revealing on two counts. The compound's extraordinarily fast development timeline shows that improvements in basic science around molecular biology are bringing more order to the process of moving from POC to confirmatory trials that conform to regulatory requirements for an accelerated NDA. At the same time, the path for crizotinib was littered with unforeseen risks, best exemplified by a chancy decision on clinical testing that, instead of yielding a medical breakthrough, could have shut the door on an entire field of investigation and potentially harmed Pfizer's reputation.  

With reference to the speed of the science, several institutional drivers helped pull crizotinib out of the filing cabinet and into active development. First was a seemingly unrelated commitment by Pfizer to expand its research capabilities in Asia to accommodate the region's demand for data relevant to local clinical conditions. Governments like Korea were committing significant funds to facilitate home-grown research, particularly in oncology where the disease profile bore distinctive variations compared to the US. As a result, Pfizer began looking at how various tumor suppressing therapies based on the c-Met mutation that progresses metastasis could be leveraged against additional tumor types, including those prevalent in Asia. 

"Crizotinib was just one of a broad panel of drug candidates we started looking at as a c-Met/HGFR inhibitor, from the same platform of discovery that led to Sutent, our multitargeted agent approved for the treatment of renal cell carcinoma and gastrointestinal stromal tumor," Darrel Cohen, senior director in the Pfizer Oncology Business Unit, tells 

. "During the dose escalation part of the Phase I study of crizotinib in the US and Korea, we observed early responses in patients with advanced NSCLC. At the same time, we came across new academic research from Japan that identified how the anaplastic lymphoma kinase (ALK) fusion protein, normally associated with the growth of anaplastic large cell lymphoma, could be an oncogenic driver in a patient subset of NSCLC as well. Hence we went back and found that what these responding NSCLC patients shared was the presence of the ALK fusion gene. Given our strong local networks, we were able to connect the dots and apply this knowledge quickly to expand the Phase I clinical trial and initiate a Phase II study of crizotinib in ALK-positive NSCLC. And despite the limited test population evidence, we were able to take the risk of expanding the trial to focus on establishing how crizotinib suppresses tumor growth among those patients with advanced NSCLC harboring ALK rearrangements, a group that represents approximately 3 percent to 5 percent of the entire NSCLC patient population." 

Pfizer contends that crizotinib is not only a potential therapeutic leader, but a benchmark in new ways to facilitate development partnerships across regions and markets. "It is an example of multisite codevelopment between East and West at a time when most such partnering has followed established pathways involving the US and Europe," Cohen says. "It speaks to our mindfulness that cancer is a global disease." Pfizer signals the success of this approach is exemplified by its joint simultaneous filing submissions on crizotinib to the FDA and the Japanese Ministry of Health Labor and Welfare in March of this year.  

But there was also real risk in going global. The expanded trial proved more complicated than expected, involving extensive outreach to academic partners and regulatory authorities in Japan and Korea. In both groups there was concern about the generally precarious state of health among the candidate clinical trial population, most of whom were in the late stages of the disease. This was compounded by the cultural and medical practice gaps between the two countries that proved to be a potent challenge in defining and communicating the clinical trial protocol. 

In one instance, Pfizer had to make a wrenching choice, says Oncology Business Unit Regional President for Asia, Jorge Puente. "We had a strong test candidate associated with one of our key academic research partners in Japan. The patient was at that point near death but our assessment was that getting him to the trial center in Korea might possibly prolong his survival and enhance the clinical relevance of the data. So we decided to pull out all the stops in registering the patient, including getting the Korean regulatory officials to accept his entry to the country, obtaining approval of the institutional trial review board, ensuring the patient's informed consent with the government oversight required under Japanese law, and arranging logistics and transport for a subject who by that time was on a respirator." 

Puente notes that there was an acute awareness within Pfizer of the risks involved. "Consider if the patient had died while he was being MedEvac'd from Osaka to Korea. Our Japanese sponsoring professor would have been ostracized for pushing a sick man over the edge on behalf of a foreign commercial enterprise, while the competence of Korean medical research could have been tarnished. Most important, the Asian trial would have collapsed along with the strong test group we had assembled in Korea, which was based on both those countries' advanced understanding of the pharmacokinetics of the ALK rearrangement. By limiting the population to the US and Europe, we decidedly could not have achieved the rich response rate that allowed us to file globally with this early data." From a societal point of view, says Puente, the availability of this type of therapy to patients could have been set back years. 

As it happened, the outcome was different. The 27-year-old patient survived the trip, was administered the drug, and within two days was off the respirator and walking unaided. 

In a world where individual accountability has grown opaque, it is still true in science that reputations and livelihoods can be put on the line, often around statistically assumptive outcomes whose interpretation in the clinical setting can deliver life—or death—to thousands of patients. Says Puente, "Medicines research is not so much about institutions as it is about the passionate individual—the believer. They're the ones who face the biggest risks." That's why he's created a new incentive within Pfizer to recognize what he calls "Courage in Clinical Trials at Work." The first two recipients of the award are the Japanese researcher who discovered the link between ALK fusion genes and NSCLC and ensured that the sick test patient got to Korea, Dr. Hiroyuki Mano of Jichi Medical University; and the Korean researcher who accepted that patient into the Korean trial center, Professor Yung-Jue Bang of Seoul National University. They received the tribute at a ceremony on June 4, coinciding with the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, which heard further confirmation of their work in setting crizotinib as a potential treatment breakthrough. 

Pfizer's crizotinib development program combined organization, art, and science-and a large dose of unforeseen risk

Planning Beyond the Petri Dish

 and the near-universal acceptance of health as a key factor in social development are combining to make the process of decision-making in health less local, and more global. For Big Pharma, the implications work both ways. There is an efficiency bonus and the opportunity to leverage connections fostered through the advantages of cross-geography scale and reach. At the same time, more "bad" ideas on how to manage the healthcare burden are circulating beyond the boundaries of the countries and stakeholders that initiated them, with the best example being the ubiquity of the reference-based pricing model to set the price of new innovative medicines against older alternatives. 

This dynamic is most prominently at play in Europe and of course here in the US, where the debate on high drug prices has revolved around cross-border issues such as why Canada can provide the same treatments to patients, ostensibly at much lower cost—and how US consumers should be empowered to take advantage of the price gap through legislation that authorizes importation of such medicines for personal use. Managing the fallout to preserve a cohesive industry position that works for both countries has become a key focus of trade association work, as evidenced in a series of frank exchanges 

 conducted with PhRMA President John Castellani and Canada Rx&D Director Russell Williams in our March and April issues, respectively.  

In this blossoming database of ideas, some of the best work on behalf of the innovator industry may be found where you least expect it. It pays to scan widely. For example, advocates who retain their faith in market-based solutions to promote medicines innovation might want to look at three recent studies published by the Canadian Patented Medicine Prices Review Board (PMPRB). A federal government-funded bureau whose mandate—to ensure domestic prices of patented drugs are not "excessive"—is widely criticized in the US as a paragon of interventionist bureaucracy, the PMPRB is not seen as a friend of Big Pharma. Yet, consider the findings from these new PMPRB works, published in December 2010: 

Use of the World Health Organization's ATC/DDD (defined daily dose) classification system for tracking trends in drug utilization is being "misapplied" in many European countries as a basis for determining the price and cost of new drugs. The PMPRB report, "The WHO Defined Daily Dose in Canadian Drug Utilization and Cost Analyses," argues forcefully that this should not be done in Canada, noting that "use of the DDD metric to compare costs of different drugs generally produces invalid or questionable results." This, in the PMPRB's view, should not qualify the ATC/DDD system to test or confirm cost-of-illness, cost-effectiveness, or budgetary impact analyses. The report is doubly valuable as an endorsement of the industry position against using the system to fix costs and set prices, since it represents the unbiased finding of an independent third party.   

Another study, "Generic Drugs in Canada: Price Trends and International Price Comparisons," reverses the assumption that Canadian medicines are necessarily cheaper than in the US. This may be true for on-patent drugs, which take up a dwindling share of US scrips, but generic drugs in Canada actually are priced higher—and cost more to payers and consumers—than prices for the same products in 11 other industrialized countries. This includes the US, where average prices for generics are roughly 40 percent lower, on a cross-border purchasing power parity calculation. Overall, among the 11 markets surveyed, foreign prices are only about two thirds of corresponding Canadian prices. The report concludes "these price differences are substantial." 

The third work, "Generic Drugs in Canada: Market Structure," can be used to infer that one factor behind these high prices for generics is a very high level of market concentration in Canada among suppliers. In most therapeutic categories, including those where the volume of prescriptions is highest and thus would be theoretically crowded with competitors seeking market share, only two generic suppliers control upwards of 85 percent of sales. The report does not document a cause, but supportive provincial government policies toward generic medicines has to be factored in.   

Globalization of the information flow is clearly here to stay. Casting the net as widely as we can is a key part of our mandate at 

More bad ideas on how to manage the healthcare burden are circulating beyond the stakeholders that initiated them

Pharmaceutical Executive-07-01-2011

Pharmaceutical Executive Digital Edition - July 2011

What the 2011 Census of India Reveals for Pharma

Holy Surge of Enthusiasm!

10 Emergency Brand Building Questions

New Ways to Gain New Brand Insights

Poland: A Sleeping Giant

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