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In establishing the value of new medicines, old-way theory is yielding to real-world practice - but there are risks in being 'of the moment'.
Economic crisis, the soaring costs of innovation, and a consolidation of the payer base have spawned a new global consensus that all medicines must provide evidence of value—either by lowering the cost of therapy against other medicines and technologies or scoring an improvement in overall patient outcomes. Beneath that basic consensus is a debate now raging on what evidence works best in establishing value. Is it the randomized clinical trial, the familiar “gold standard” for meeting the concerns of regulators? Or is it a metric that eschews the hypothetical test case for less rigid observational studies based on actual use of the product in clinical practice?
With payers in the driver’s seat, the momentum seems directed toward the latter—and Big Pharma is scrambling to meet the challenge of supplementing the clinical trial with what it calls “real world” data (RWD). How one company—Astra Zeneca—is seeking to build the bona fides for that observable data point illustrates the old adage that he who can define the terms of the debate will control the outcome, with enhanced access to the market at a better reimbursement rate the ultimate measure of success.
According to an October 2011 McKinsey & Co. report, the ‘availability of RWD is rapidly advancing, driven by the application of IT at the point of care and in the management of payer data sets. The U.K.’s National Health Service (NHS) General Practice Research Database, for example, now contains data on 11 million patient lives. The Nationella Kvalitetsregister in Sweden, a much smaller country, houses information on 9 million patients. In the U.S., Wellpoint’s HealthCore unit currently tracks 34 million patient lives across 14 states. These aren’t just impressive numbers; in the long term, the report suggests, analysis of RWD will become “a cornerstone of value-based pricing methods that may redefine the basis of competition and access”.
Scoping—and Sharing—the Data Field
Big Pharma, then, is attempting to build the tools, platforms, and organization to enable it to respond to this increasing demand for data. The stakes, of course, are high: “The acute traction point for RWD in the near term is in gaining or defending market access,” says McKinsey. All the top 10 pharma companies surveyed by the company are said to have initiated RWD projects to guide product development and commercial decisions that hinge on a better understanding of disease states and treatment patterns.
A scenario where RWD eventually becomes ‘public property’—that is, made available jointly by payers and providers, using precedents like the U.S. FDA’s Sentinel Initiative, which monitors RWD for product safety signals—is foreseeable. But for the time being, it is pharma-sponsored real-world evidence studies that “will continue to be the primary vehicle for comparative effectiveness research”.
Astra Zeneca’s Step Forward
AstraZeneca has taken an early lead in offering a new menu to slake the payer community’s thirst for new forms of evidence on value. One of its key market access priorities in Europe is to advance the use of real-world evidence based on observational and retrospective studies. A new three-year collaboration agreement with IMS Health, announced in January, allows the drugmaker access to pre-existing, anonymized electronic health records, and will see the two companies jointly develop a customized research and data analysis platform to achieve “a deeper insight” into how medicines that are already on the market are working in real-world settings across Europe.
Speaking to Pharm Exec, Jon Resnick, IMS Health’s vice president of real-world evidence solutions, points out that the collaboration’s first hurdle is in joining the various streams of information out there. The current knowledge fragmentation, he says, is one of the key impediments to moving the real-world evidence discussion along. “Across the healthcare setting, everybody wants information that will help them to do their jobs better,” he says. “Payers are looking for cost effectiveness and value for money; physicians are looking for the best way to manage patients; individual payers are looking at the data that they themselves accumulate. But they’re not seeing the entire picture. Nobody is accessing a robust body of evidence and connecting all the dots on information. But the more information that’s available, the more there is the ability to articulate the value of products not just as a price point but as a larger—and ultimately more meaningful—intervention within the healthcare setting.”
At the macro level, Resnick explains that the premise of the IMS/AZ collaboration is to see pharma as a stakeholder in the broader healthcare setting. The industry’s challenge, of course, is to demonstrate the value it’s providing, but the more information that can be “connected,” believes Resnick, the more the various stakeholders can be aligned, and the more pharma’s value will be known.
Four Steps to a Successful Outcome
Resnick identifies the specific barriers that any evidence-based strategy on access and P&R must surmount as
1) scientific methods (“how do you work with the data?”);
2) stakeholder alignment (the willingness to share data across settings);
3) current market rules on privacy; and
4) building trust.
AZ and IMS aim to overcome some of these by committing to a spirit of openness from the outset. Resnick confirms that there will be active efforts to involve payers and other providers in “an honest set of conversations” about how to work with the information, both during and beyond the collaboration.
“For this to work, you need the buy-in,” he says. “You can’t create real information in a vacuum; you can’t work with a set of databases that are closed to the universe and then hand the information to a payer and say you want to charge 20 percent more.” Whichever data will eventually be made publicly available depends on the type of study it relates to, but Resnick emphasizes that the IMS/AZ research is not just between the two companies. “Opening it up to academics and broader audiences is healthy if we want to maintain credibility. A broader set of participants will be needed to ratify the information.”
Nay to Confidentiality
He adds that the arrangement between IMS and AZ is not an exclusive one. For it to be viable in the medium term, “we have to bring in other pharma companies and people who are trying to demonstrate similar types of value.”
As for the project’s “customized data platform,” one of the things Resnick believes is needed is getting people comfortable with using real-world information. “If you think about what it takes to do clinical studies,” he says, “you need statisticians, epidemiologists, and others with highly specialized skills. Our research is about providing the tools and the abilities and the user interfaces to allow more people to work with the information a lot more credibly.” There can’t be a scenario, he says, in which the ability to make claims in a real-world evidence setting is dependent on the number of biostatisticians or the number of SAS programmers that exist in the universe. Instead there should be innovative thinking about how to take different data sets from different markets and bring them together for practical solutions. “If a hospital has an EPR [electron paramagnetic resonance spectrometer] and the lab around the corner is collecting lab data and the NHS is holding onto mortality information, how do we pull all these different pieces together and connect them in a way that is meaningful for the end user?”
But leaving behind the randomized controlled trial (RCT)—the “gold standard” in clinical evidence—could be an invitation to criticism. Observation studies and other meta-analyses have been accused of lacking the robustness, integrity, and the individual patient focus of the RCT. Resnick does not challenge that the RCT will be a key part of the overall value proposition for the foreseeable future, but highlights that “they are incredibly expensive to run. They are not reflective of reality—they’re ‘controlled’ by definition—so you have patient protocols that are carefully managed, physicians that are carefully chosen; you’re doing a whole lot of things that don’t actually reflect the treatment pathway.” Far from replacing the RCT, however, real-world evidence will serve to complement it. “RCTs give you a lot of key information about products, but they don’t tell you everything. If you’re in Germany, you want to understand how the patients respond within the German healthcare system. Real-world data is going to be able to give you the pieces that RCTs can’t: how the individual patient segments are responding; how individual systems and patients fare when you overlay the information on the treatment pathways within an individual market.” A lot of the concern about real-world evidence is just a lack of understanding of how to work with it, says Resnick. “There’s a set of standards and codes of practice that make it much more accessible now. The sooner that this dialogue can begin, the sooner people can recognize the complementary value of real-world evidence. The science has come a long way in the past few years.”
Application to Diagnostics
Indeed, in keeping with this progress, the emphasis of the industry in developing diagnostic tools that target patients most likely to benefit from a particular therapy is also a “really important driver ” for the real-world evidence partnership. Understanding where the patient segments exist, filling out as many of the outcome variables as you can, and understanding how these all connect is “clearly one of the trends right now,” says Resnick. But could there be an arrangement, in an outcomes-based contract, where the payer would help to share the cost of these tools? Resnick believes so. “One of the biggest impediments to this happening is that building an infrastructure to ensure the integrity of outcomes in a pay-for-performance arrangement is expensive.” But he envisions lots of “win-win scenarios” when the incentives for stakeholders to look at each other as individual forces within the system, each with their own agenda, are removed. He reiterates that stakeholders need to start thinking about where they are all connected. “We’re connected in the sense that we are all concerned with getting the right people the right care at the right time, with the right level of efficiency. If that common pursuit is made clear, there’s room to compromise.”
Resnick agrees that the future is veering toward the concept of coverage with evidence development, upon which authorization to market come only after hard evidence of clinical and cost effectiveness proves a company’s arguments have merit. The extent to which certain markets mature will affect the rate at which they move in this direction, he explains, but there’s no question the trend has already started. The question is, Will this be manifested in broader use of risk sharing agreements and health management contracts that commit companies such as AZ to provide services “beyond the pill” to secure a public health outcome in treatment of chronic disease? “Our sense is that real-world evidence is part of that story—how you actually communicate the outcome and communicate to the right patient and the right time,” he says. “But what is pharma’s actual role in creating this dynamic? That is crux of the whole discussion. ”
For the moment, there is mounting evidence that RWD strategies can “shift or protect whole market opportunities in and out of pharma’s favor,” according to McKinsey & Co. One example it points to is Novartis’ ophthalmology product Lucentis, for which the U.K.’s National Institute for Health and Clinical Excellence (NICE) agreed to expand coverage after Novartis analyzed clinical data to identify the inflection point in the efficacy of the treatment regimen and agreed to cap the NHS’s cost exposure to no more than 14 treatments. Another is P&G and Sanofi-Aventis’s contract with payer partner Health Alliance in the U.S. regarding the osteoporosis treatment Actonel. The contract, which covered the cost of non-spinal bone fractures incurred by Health Alliance members on Actonel, successfully delayed the transition from Actonel to generics, as well as earning Actonel a preferred formulary position to a competitor product, Boniva.
Fortunately for pharma, the McKinsey report concludes, “the rules of the competition in RWD are still being written.” That simple reason is AZ’s justification for stepping up and becoming part of the debate.