Oncology: Pathways to Progress

Cancer is a disease of endless reinvention, one that is increasingly understood as a collection of rare—and mostly treatable—conditions rather than the impregnable, death-dealing monolith portrayed in popular culture. Advances in our knowledge of the biology behind cancer are leading to new options for treatment, the most important of which is precision targeting of therapies tagged to the genetic profiles of individual patients. The array of new tools presents an enormous opportunity, but there is also the burden of complexity: to find and then transform all this new science into technologies that deliver clinical results to patients, demonstrate value to payers, and lead to the broad public health outcomes that society expects. To help address this challenge, Pharm Exec recently convened a cross-section of industry experts to review current and pending efforts to turn great science into good practice. The sum of the discussion, presented in the following Q&A: Not just courage but coordination, with a heavy dose of cooperation, is required to defeat the proliferating ethos of the cancer cell—biology's ultimate non-conformist. —William Looney, Editor-in-Chief

Managing complexity: the pathways prescriptive

William Looney, Pharm Exec: Numerous surveys find that oncology is the therapeutic segment where it is most difficult to demonstrate value to payers. Several of our participants today—including McKesson Specialty Health and the National Comprehensive Cancer Care Network [NCCN]—are working closely with providers, payers, and other stakeholders to improve the transparency of these relationships and strengthen standards for evidence-based, high quality care. Can we review quickly what initiatives are underway and determine their strengths and weaknesses in shaping institutional behavior?

Kevin Coker, McKesson Specialty Health: The treatment of cancer is highly dependent on innovation. The drive to leverage personalized medicine, investigate the increasing number of potential therapeutic agents, and better utilize technology has led to significant cost increases in care management. The annual cost of cancer care is now $150 billion in the United States alone, and it continues to rise. Drugs account for a highly visible share of the total, which can leave our industry exposed. However, we are also part of the solution, by contributing to the efficient, affordable use of resources in a way that leads to the best outcomes. The value we bring has to be grounded in evidence, observed and measured in real time, under active clinical practice. You cannot do that without keeping the focus squarely on the individual patient: if medicine is now personalized medicine, then the therapies we offer must be targeted therapies.

Participants

This is good for the patient—but it comes at a cost. Targeted therapy is representative of a new, much more complex business model, where the imperative is to conduct more and more clinical studies around a precisely differentiated patient base that adds to the recruitment burden, making trials more expensive and challenging to conduct. In working with the industry to bring 43 anti-cancer agents to market over the past few years, we know that the overarching priority is to find better ways to screen these patients efficiently. US Oncology Research is investing heavily in technology to help find these narrower patient populations. We use a model that allows research sites to open where those patients are actually receiving treatment, so we can leverage the scale of the 900 experienced physicians affiliated with us. Investments in companion diagnostics that match patients with the right drug are also critical when we are making the case to payers.

There is a larger dimension too, in moving the research forward to help patients and providers make better choices—to build in greater clinical precision, relevance and value—at the actual point of care. We have done that to date through Level I Pathways, and in the future will be continuing this effort through our new Value Pathways powered by the National Comprehensive Cancer Care Network [NCCN], the output of our recently announced collaboration with them. Level I Pathways are a series of refined guidelines, developed by physicians and clinicians from our US Oncology Network, to help oncology practices assess the most effective and least toxic care options for patients using standardized, evidence-based software analytics. Physician specialists lead the initiative, with additional input from the clinical pharmacy community. The pathways represent a careful balancing of the science—including efficacy and toxicity—with a broader value assessment that incorporates cost and leaves room for consideration of factors unique to the individual patient. We refer to this latter element as the 80/20 rule, with the 20 percent being the weight each pathway gives to the physician's judgment after weighing all the scientific evidence. The absence of a "one size fits all" mandate is one reason why physicians have really bought in to the process. They see us as one of their own.

As noted, this year we are launching an expansion of the pathway initiative with the NCCN. The US Oncology Network and NCCN are jointly developing a "Value Pathways Powered by NCCN" program of peer-reviewed disease management protocols for 19 tumor types, with additional plans to support cancer detection, diagnosis, biomarkers recommendations, treatment, and supportive care. Each will build on existing NCCN Guidelines—the gold standard for clinical practice in oncology—to add the value-based metrics, including cost evaluations, developed previously for our Level I Pathways. In addition, the Value Pathways Powered by NCCN can be accessed through software designed to be integrated with the electronic health record and other data workflows of practices or hospitals, creating a new standard for content and technology, and helping providers focus on the best way to enhance outcomes for their patients. Most important, the Value Pathways will rely on the timely input and expertise of 2,000 practicing oncologists and researchers affiliated with the NCCN Guidelines Panels as well as some 1,000 community physicians active in the US Oncology Network.

Lyn Fitzgerald, National Comprehensive Cancer Care Network: This collaboration addresses a need that state oncology societies have identified relative to our guidelines, which is helping the oncologist community use the guidelines effectively. What is particularly useful about the McKesson collaboration is the power of the technology and the Value Pathways Powered by NCCN, both of which supplements the content of the NCCN Guidelines, thus providing the necessary tools and information that meet the increasing evidence requirements of the payer. The technology will empower them with the evidence based information to interpret, act and do what's right for each patient, all at the point of care and within normal work flow.

Neelima Denduluri, Lead Investigator, McKesson US Oncology Research

Dr. Neelima Denduluri, Virginia Cancer Specialists: I am a practicing oncologist and member of The US Oncology Network Pathways Taskforce and Breast Research Committee. The Value Pathways project advances the idea that scientifically-based standards of care actually increase the autonomy of the physician and safeguard the interests of the patient. When members contract with payers, we do so with the capacity to demonstrate that having more options and flexibility in treatment is actually a cost saver because it leads to better outcomes. The standards are there, but are not so rigid as to allow payers or other stakeholders to dictate the terms of engagement. We can show that when physicians are allowed to police themselves, excess and waste—crazy things—don't take place.

From pathways to practice

Looney:The Value Pathways are a reflection of how rapidly the financing and delivery model in oncology is changing, uprooting the traditional relationship between a passive payer, segmented providers and powerless, information-poor patients. Is the industry ready and prepared to help facilitate application of the Pathway model? What "influencers" might be missing to ensure this new tool is used most effectively?

Steven Stein, Novartis

Dr. Steven Stein, Novartis: The objective of a treatment guideline is to try to change physician behavior. You can apply the carrot, or the stick. I'm interested in how these pathways promote practitioner compliance with the standardized parts of the package—what you refer to as the 80 percent of the pathway that is prescribed decision support. Physicians clearly prefer being autonomous and acting on their own discretion, so is there any "punishment" for not staying compliant within that 80 percent?

Denduluri: We don't believe in negative incentives like penalties. The pathways are structured to advance excellence in patient care first and foremost as well as build confidence and foster a spirit of partnership between providers and payers. Involvement of the NCCN and incorporation of its extensive information base is crucial to this process. To the payers, we can show that the standards we set are sufficiently stringent because they are based on hard evidence drawn from the literature and actual clinical experience. We can furnish data on just where the pathways have yielded lower costs and similar or better outcomes. This in turn allows us to tell the network physicians that compliance with the standards means that payers will be more willing to negotiate higher payments. It's positioned so that both sides see a benefit in upholding their core interests.

Coker: Internal peer pressure also keeps the practice community aligned. One of our network practices, Rocky Mountain Cancer Center, monitors performance of its oncologists around the pathways and requires physicians with variations against the norm to answer to the other physicians in the group why that is the case. There is no sanction against the physicians' judgment, bar the fact that they must explain to their peers why their performance is out of range. The transparency keeps people honest and encourages predictable, fiscally responsible behavior.

Dr. Faisal Mehmud, GlaxoSmithKline: How will you position these new Value Pathways in tandem with the different evidence based guidelines, based on the US Oncology Network Level I Pathways, and especially the relevant NCCN Guidelines?

Denduluri: The two information streams actually complement each other. The Value Pathways built from the previous Level I Pathways include a focus on economic issues pertinent to providers and payers. The NCCN Guidelines continue to provide a panel of evidence-based treatment options, but do not assess costs to patients and payers and lack a "how-to-do" framework on the actual administration of care. McKesson Specialty Health, which supports The US Oncology Network, has a useful electronic health record, iKnowMed, which integrates these different strands of evidence. Between iKnowMed and the new quality support tools in development with NCCN, we can put changes immediately into effect throughout the community practices.

Jorge Puente, Pfizer

Dr. Jorge Puente, Pfizer: I am curious how your pathways address the situation—quite common in the oncology space—where there is absent or unconvincing clinical data to weigh against the high cost of a particular therapy. On what basis then do you determine what might be the recommended or most cost effective treatment option?

Denduluri: If there is no evidence of real clinical benefit from trial data and the cost of the drug is in the six figure range, then we do not include it on the pathway, and usually dissuade any prescribing of that treatment; exceptions are made on a selective basis, and we make sure the drug payments are pre-authorized.

Dr. Mark Rutstein, ImClone Systems: If the evidence is built around the patient, do you provide specific metrics to evaluate his/her quality of life? More specifically, are patient reported outcomes part of your assessment?

Denduluri: Yes. We are looking at many aspects of this important issue, such as trying to measure the relationship between proper drug utilization and patient quality of life. Since this is a physician-driven effort, we recognize that costs have to be evaluated in a broader context that gives credence to when a patient is able to carry out normal functions and maintain the lifestyle to which he or she is accustomed.

Don Creighton, PriceSpective

Don Creighton, PriceSpective: I believe the drug industry would be supportive of building clear metrics around the linkage between the cost and effectiveness of treatments, as payers and health technology agencies are interpreting this relationship to render important judgments about market access. Right now, decisions are being made that make companies very anxious about whether approved treatments will actually be obtainable by patients in the clinical setting.

Stein: The larger issue here is reconciling the concept of a practice guideline —which by definition relies on a population-based metric—with the move toward individualized treatment, now being facilitated by the progress in understanding genetic variations in tumor growth and in the application of diagnostics. It's a dichotomy we struggle with throughout the compound development process; payers too are trying to find the right way to be fair in deciding what treatments are reimbursed.

Fitzgerald: NCCN Guidelines must tackle this dichotomy if they are to maintain status as the standard of care in oncology. We have just launched a biomarker compendium and, as the technology and understanding of tumor heterogeneity advances, our NCCN Guidelines will need to incorporate this evidence. There is no choice: the market dictates. When the NCCN compendium was formally recognized in 2008 by United Healthcare and CMS, coverage decisions for millions of patients were now driven by the compendium. Today, however, insurers are contracting separately with multiple for-profit pathway companies that have the effect of limiting provider choices in applying our guidelines. This is one reason why NCCN is contracting with McKesson on the Value Pathways Powered by NCCN and the decision assist tool based on the NCCN Guidelines. The fact that it is devised and managed directly by physicians for physicians gives the profession an alternative to just accepting what the payers are putting forward.

Mehmud: From my perspective, guidelines are only a starting point. While they work well for a large proportion of patients, where there is an existing good base of evidence that can be applied, what is necessary is more definitive and precise guidance on how to use them in the clinical setting, including more subjective factors like patient satisfaction and quality of life as well as cost effectiveness. There must be clarity and transparency in the methodology used in making the transition from the evidence-based guidelines of NCCN to the point-of-care issues that are covered in Level I Pathways. We don't want a situation where it all comes down to direct costs [e.g., drug acquisition], which can be very misleading and leads to frustration for providers and their patients. Clarity in the process will allow pharmaceutical companies to ensure that they generate the right evidence to support appropriate positioning and inclusion of their medicines in Level I pathways.

Dan Paterson, Verastem

Dan Paterson, Verastem: A physician-driven standard that enforces compliance through peer pressure is a good way to engage around these issues. If you succeed in convincing payers at the macro level that your practicing physicians are providing good care that is also cost effective, then you avoid a whole host of problems. One is that there will be less demand for prior authorizations, where access to a medicine can appear to be determined arbitrarily, and impacted by things like a patient's particular benefit plan or his/her home zip code.

Looney: Much of what we have been discussing so far relates to uptake—translating the evidence so that it is "cooked in" to the pathways and then pushing this out to shape decisions taken at the bedside. Are the conditions ripe for widespread acceptance of pathways as a benchmarking tool that will produce consensus in making patient welfare the focal point of treatment? Oncology does seem to be one of the few therapy areas where pathways and guidelines are actually making a difference in resolving distortions in practice patterns.

Fitzgerald: In the case of cancer care, I think we are indeed ahead of the curve. The McKesson decision support technology is going to accelerate our progress. Where I see danger is the complexities of the US health reform agenda may lead to more efforts to "reinvent the wheel." We already have a guidelines/pathway redundancy issue in this country.

Puente: I've heard several times today that the NCCN Guidelines and the collaborative Value Pathways with NCCN will never put cost over efficacy. That's a guarantee certain to be tested over time, as we all know that for oncology drugs it's a steep hurdle to gauge overall survival benefits. Efficacy alone can be an ambiguous metric. A drug might post a spectacular improvement against existing therapy in a small number of patients, but because of crossover effects performance in a larger trial set is muted. This is evident in the international setting, where there is even less consensus on how a benefit is defined and measured. Drug costs will also continue to rise, particularly in specialty areas like cancer, because of the complexity of the follow up—not only in how drugs are administered, as part of the continuum of increasingly personalized care, but in the post-marketing studies and trials that industry must commit to in responding to regulator concerns about safety.

Fitzgerald: There is a discrepancy too in the fact that diagnostics have a lower burden of proof in making the case for regulatory approval. Yet all our guidelines panels want the same level of evidence, whether it is a drug, a device or a diagnostic. Industry must develop evidence recognizing that stakeholders may require a different value proposition: what the FDA wants is one thing; what the physicians or the payers want may be another.

Gary Geipel, Eli Lilly & Co.: Pressures on innovators are coming from all points. Data that we generate to obtain a market license is not always going to be sufficient to get a product supported on a pathway, while the very existence of a pathway can hinder the generation of the real-world evidence that might lead to additional understanding of effectiveness. It's important to remember that cancer progress almost always has occurred in a step wise incremental manner—often based on insights in the real world of practice.

Robert Martell, Tufts University Medical Center

Dr. Robert Martell, Tufts University Medical Center: It follows that, as personalized medicine takes root, indications for oncology drugs are becoming smaller. This puts significant strain on the process and cost of obtaining regulatory approval. You can build down from an approved indication for ALK positive lung cancer because the eligible patient population is large. But when you have a relatively smaller indication and then seek approval for a still smaller sub-set of that, how do you do it at a cost commensurate to the potential size of the market? You can't be funding 600 trials in such a situation. The system has to adjust: you might have a lower hurdle in winning initial approval, followed by a structured, step-by-step process to better understand how an additional indication might add to the disease fighting armamentarium, perhaps in combination with other therapies. Over 80 percent of oncology drugs are initially approved as single agents, yet clinical exposure tells us that their best use comes as combinations. In fact, the NCCN Guidelines for the top 10 malignancies recommend combinations as primary treatment in most situations.

Fitzgerald: Guidelines have to adapt to a world where the financing and delivery of healthcare is changing. Industry too must do more to understand what the decision-makers driving system reforms really want. Accountable Care Organizations [ACOs], an alternative to traditional fee for service payment, are being incentivized under the new health reform law. In this new structure, the ACO chief financial officer may be the person who is key to assessing evidence and deciding that therapies end up on formulary.

Stein: The mindset of the industry is already moving in this direction. Celebrating approval has shifted to celebrating reimbursement, because that is what gives our medicines access to the market. Our registration work has to begin with an understanding what it will take to obtain a positive nod from the CMS, and quickly, as time to market is a competitive differentiator. The bad news is all the additional tradeoffs we have to invest in to get to this decision. Such tradeoffs must be incorporated into the drafting of guidelines or pathways, because without including the perspective of the payer these texts will not survive in the real world.

Looney: Is it time for the industry to embrace a multi-stage approach to registration, what the European Medicines Agency [EMA] calls "adaptive licensing," that requires a medicine to demonstrate its value in the clinical setting, after the initial licensing authorization?

Stein: Novartis is intrigued by the idea. If you can get a product on to the market earlier, and then accumulate evidence that we can agree on to demonstrate the creation of value for the health system, it has the potential to be a "win win" for us and for the regulator. It is certainly a trend that is building, so we will need to consider it seriously.

Creighton: I am concerned about the impact that adaptive licensing might have on the integrity of the physician-patient relationship, which is at the center of the pathways model we are discussing today. Industry is likely to have little control over what a regulatory authority sets as ground rules for re-examining the status of an approved medicine. What would the criteria be for deciding if a therapy is effective, especially relative to other medicines? What would be the comparator? I think that for any system to be personalized around the patient, the physician must manage the process. This is what the pathways are for. Why do we need the regulator to come in once again and make a judgment about value? The market will decide.

Geipel: The Affordable Care Act [ACA] poses a challenge to patient access in its own right. The new insurance exchanges and the delineation of "essential health benefits" may mean that enrollees will have little discretion in obtaining services not prescribed in a plan or the list of benefits. It could make this discussion of physician-led pathways an academic exercise.

Drivers of discovery

Looney: Despite the challenges of high development costs, payers' willingness to reimburse, and sharp variations in patient access, the science of cancer continues to improve. What are the most important advances that will enhance treatment options for patients?

Paterson: The application of anti-cancer stem cell therapy to treat metastatic cancer is a field that is evolving rapidly. Bob Weinberg of MIT, one of the founders of my company, has developed a process for identifying a stable population of cancer stem cells that in turn makes it possible to test a large number of drugs to find the few with sufficient potency and selectivity to limit the cancer stem cells' capacity to reproduce the cancer through the body. These drugs focus on fighting the cancerous stem cells rather than the bulk of the tumor itself. By mid-2013 we will have three clinical test programs underway—one is for mesothelioma—that will try to pair these drugs with conventional chemotherapeutic treatment regimens designed to attack the tumor. The interaction between cancer stem cells and tumor cells is fascinating and hopefully this work will guide our understanding of how these two lines interact in pulling the trigger on metastases. This is important to cancer survival rates, as most of the progress in cancer treatment to date has been in eliminating cancer at the early stage; once a tumor becomes metastatic, we are not so good at stopping it.

Martell: The success rate for oncology drug development has been stuck for years at about five percent. A contributing factor may be lack of predictability of pre-clinical efficacy models. For example, we rely on killing tumors in animal populations, which may not be the best predictors of outcomes in humans. So finding novel ways of screening drugs that don't depend on tumor shrinkage may improve the odds, even though the naysayers will tell you that there is almost no example of an approved drug that did not show this kind of effect.

Puente: Researchers are often bound by rigid definitions. I recall a case of a test drug for liver cancer in which the tumor was actually decreasing but due to necrosis within the liver and inflammation in surrounding tissue, it looked as if the tumor was progressing. Investigators had to pull the patients and ultimately the project because it was hard to identify the clean result sought by regulators. When you confront real life problems like these, it's hard to chart a path forward to Phase III and registration, which is of course what the drug company wants.

Stein: Novartis is looking closely at changes to the structure and execution of the clinical trials we fund. Why is it that in adult oncology we get only a three to five percent enrollment rate, while pediatric medicine typically gets 80 percent? One thing we have found is there is a huge harvest of data to be found in the molecular screening work conducted outside of the industry and academic networks, mostly by private companies who specialize in testing. That information can certainly be useful in framing our trial protocols around the most recruitment ready patients, regardless of location. Typically, we will have to pay to access this information, as payers are reluctant to share the cost, but this will be less of a factor as the cost of screening goes down—at some point in the near future, it will be more expensive to store the data than to pay for the test.

Puente: Getting the right patient into the right trial is an elusive goal in cancer. The field is increasingly being looked at as a collection of rare diseases, each with different evidence requirements. It follows that we have a big problem in convincing the registration authorities to act on the basis of a very small data sample, where you often find many inconsistencies. This is why, in my view, it can be productive to jump start the process by working in close concert with the authorities. Pfizer experienced this recently when we were approached by a consortium of Canadian academics to participate in a biomarker testing program for 10 rare diseases, in which we would supply the drugs while they funded the trial network of investigators. Initially, we balked because of the regulatory hurdles, but then Health Canada entered the picture and together we defined a protocol that set a 30 percent positive response rate as the benchmark for allowing Pfizer to obtain commercialization rights for the discoveries. So we were able to share the cost, define our regulatory risk exposure, and create a potentially remunerative business opportunity.

Looney: Are there other "rogue theories" about cancer discovery that could revolutionize treatment?

Stein: There is resurgent interest in immunotherapy, influenced by the pace of discovery against HIV. Companies are finally starting to invest significant resources in this area.

Puente: Interesting work is underway in viral vectors of cancer, using disabled forms of the AIDS virus. It suggests further progress toward an eventual cure for some forms of leukemia.

Rutstein: Cytotoxic chemotherapy, a traditional form of treatment, is being updated and improved. One trend we see is cytotoxics being reengineered to have a better safety profile.

Mehmud: We should expect many more small molecule targeted therapies. Precision medicine will be key to realizing their true potential. We have to keep the momentum around generating evidence with biomarkers and companion diagnostics, persuading more companies to take the up-front risk and invest there, even with currently available therapies.

Big (b)ounce of prevention

Looney: What progress can industry point to on the topic of cancer prevention? What advances are taking place in screening and early detection? Is industry committed to investing more in this area?

Paterson: We are slowly beginning to see genetic tests as a practical alternative to invasive screening procedures, at least for some cancers. Questions about cost effectiveness continue to plague screening for breast and prostate cancer, where the benefits can be outweighed by the morbidity associated with false positives. Nevertheless, more test options will lead to greater accuracy in determining who needs a biopsy. There is an incentive question in opening the door to new screening approaches, since specialist physicians often rely on invasive procedures for a disproportionate share of their incomes.

Stein: For Big pharma companies, prevention is all about the target—precisely, what do we go after? Our understanding of the viral etiology of cancer—the hepatitis and human papiloma viruses come to mind—has led to some very important vaccines to slow the progression of liver and cervical cancer. But defining those endpoints is a complex task. In addition, the regulatory hurdle in getting a drug approved as a preventive is very high. We must demonstrate close to zero toxicity in this setting.

Puente: Early detection has seen some real advances. I saw recently in Canada two such instances, using state of the art technology: an exhaling device that can pick up traces of cancer cells in the lungs, and a circulating antigen test that can detect cancer cells in the bloodstream. This technology is exciting because it could allow scaled-down treatment over a long-term, with the aim of preventing a cancer from expanding.

Creighton: Patient information is a critical factor in prevention, yet in all but a few countries the industry is barred from communicating with this audience. That has to change if we are to move the needle on early detection.

Geipel: Lilly started a policy outreach effort called PACE [Patient Access to Cancer care Excellence] that surveyed the public in six countries. The findings show there are some fundamental misconceptions about cancer as a disease. For example, fully half of all the respondents believe that cancer is one disease—the implication being that it might be tackled with one cure. This is fundamentally wrong. On the encouraging side, another finding is that the public expresses a great willingness to participate in clinical trials, which at least challenges the notion that cancer patients are hard to recruit for clinical trials.

Speaking truth to power: agenda for progress

Looney: As a conclusion, can each of you identify the one message to decision-makers outside the industry that will do the most to maintain the momentum of progress against cancer?

Mehmud: More transparency from regulators and especially payers is critical. This is the only way that industry can generate the right evidence at the right time and not be put in the position of having to play catch up post Phase III.

Creighton: Attention within companies has shifted from registration to reimbursement. Companies need to know what the expectations are from payers at a very early stage of the development process. And if governments regard oncology as a public health priority, then it should be reflected in a willingness to help companies secure an appropriate return from their investments in new therapies through predictable, evidence-based access and pricing. In return, companies must do more to educate payers on what is most important to clinicians and the patient about the incremental value of a new medication.

Stein: There is unprecedented opportunity in oncology because of the explosion in our understanding of the molecular roots of the disease. This is reflected in our R&D: most companies today are putting upwards of 30 percent of their development dollar in the oncology space. But this entails a responsibility to be more focused and disciplined in how we spend that money. Society expects that of us, but we all must share in the results.

Fitzgerald: As stakeholders examine how to increase efficiency in the financing and delivery of cancer care, they must begin with an awareness of how much the clinician community has already done to root treatment decisions in evidence-based standards of good practice. We should celebrate the guidelines and pathways that physicians use daily in delivering the best care for their patients. Guidelines act as a barrier against decisions being made arbitrarily, from outside the care community.

Martell: As we develop the potential of personalized medicine in cancer treatment, we need the support of regulators in devising enhanced approval strategies for very small drug indications. A new regulatory pathway is required for drugs appropriate for the micro-sized patient populations we will be able to treat, with a higher probability of success, in the future.

Puente: The industry needs a better return from its investment in cancer. Pfizer has ceded more than $20 billion in revenues from patent expirations over the past five years; the industry itself will lose another $40 billion in the next three. That's a lot of money flowing back into the healthcare system, a saving that should be recognized. Meanwhile, Pfizer is spending about 35 percent of its R&D budget on oncology, even though oncology products currently amount to only three percent of our global sales. So the last thing our management is predisposed to do is give us more money for this market. I actually make a point to seek out investors, and there is a big challenge in getting them to see we have a strong value proposition. Society must understand the consequences: when the value proposition goes away, money for research will stop. In turn, government must know that decline can affect its own legitimacy. Information is boundary less. There is someone in a small village in central China right now who has been diagnosed with lung cancer; he will soon find through the Internet that treatments we have in the West are not going to be available to him, and he will die. This is a latent source of social unrest.

Rutstein: What is needed in oncology is more active cooperation in the development of treatments that are tailored to the clinical profile of each patient. There is great emphasis on the financial and regulatory hurdles to commercialization of new treatments, but it's also important to consider how we can increase collaboration across industry and with regulators on the science. The competitive aspects of drug development can make scientific collaboration difficult, but industry should continue efforts to build consortiums to share biomarker data and learn from each other.

Geipel: Global demographic trends suggest that this is not the time to disinvest in medicines for the diseases of old age, which includes cancer. In an era of scarcity, it is equally true the only viable way to make progress is through collaboration. Lilly's PACE Project is a good example of how to create networks that promote awareness and patient access to care. Building communities able to tackle practical issues—such as the ways in which health technology assessment and cost-effectiveness research shape investment and access to new cancer treatments—is also important.

Denduluri: All the complex strands that bind our work in oncology—from discovery to clinical trials to patient access—have to be brought together. Pathways and guidelines are an ideal instrument to facilitate interaction, but vigilance is required to keep them current and relevant to the practitioner. Redundancies and the inconsistencies that flow from this are a threat as government supervision of the healthcare system increases.

Paterson: Payers hold a great deal of power, so industry has to think more about how they can be compelled to cooperate. We must separate out the negatives like perceptions about pricing and inappropriate marketing and focus on some of the creative approaches to drug benefit design now underway between insurers and companies.

Coker: I second the comments about more cooperation. It surprises me, but there is still resistance in some quarters of industry to working together around a commitment to transparency. Another issue is to ensure that our regulatory and legal framework keeps pace with science and the preferences of clinicians and patients. Regulation should never be a drag on innovation.

William Looney is Pharm Exec's Editor-in-Chief. He can be reached at wlooney@advanstar.com.