On 29 June 2016, key stakeholders and decision-makers in the field of real-world evidence met to take part in the DIA 2016 seminar “Europe and the US: Making Outcomes-Based Health Care Possible”. As Europe and the US continue to examine ways to develop therapies on the basis of their “real world” performances, the session aimed to discuss benefits and challenges of outcomes-based health care, as well as the remaining barriers to implementation.Speakers taking part were: 

• Hans-Georg Eichler, Senior Medical Officer, European Medicines Agency, European Union
  
• Gigi Hirsch, Executive Director, Massachusetts Institute of Technology (MIT) Center For Biomedical Innovation
  
• Richard Bergström, Director General, European Federation of Pharmaceutical Industries and Associations (EFPIA)
  
• Steve Rosenberg, Senior Vice President and General Manager, Oracle Health Sciences
  
• Duane Schulthess, Managing Director, Vital Transformation, (moderator)

The session concluded with a Q&A, opening the floor to questions from the audience and also including prepared survey questions for both audience members and panelists to consider. Opening the panel, moderator Duane Schulthess outlined some of the day’s learning objectives, which included:

• Describing the concept of outcomes-based health care;
• Defining real world evidence, Adaptive Pathways, and Precision Medicine; Identifying how we can use health data to improve the efficiency of clinical trials and research (better targeting, smaller trials, flexible models); and
• Recognising the links between failures rates, trial sizes, and investments into new therapies.

With these objectives at hand, the panelists began their presentations. Speaking first was Hans-Georg Eichler, Senior Medical Officer, European Medicines Agency, European Union. He noted that for outcomes-based healthcare to succeed, “we need to know the outcomes of a treatment, both at a population level and an individual level.” What, he asked, do we need to achieve this? Firstly, Eichler noted that it was not—in his mind—a question of replacing Randomised Control Trials (RCTs). He referred to the need for “RCT-plus”. Rather than replacing RCT’s, we need to expand our toolbox, and RCT data needs to be complemented with more information, notably more real world information.

Towards this end, we need access to large volumes of real world data. We also need rapid-cycle analysis, “the ability to process this data, almost in real time, in order to update decisions and minimize realized harm”. This information can be used by regulatory decision-makers to adapt regulatory labels, as well as by payers to adapt reimbursement decisions.

In Europe, Eichler noted, many initiatives are working together towards achieving these points, bringing us closer to realizing the goal of an “RCT-plus” toolbox. Examples cited by Eichler included Innovative Medicines Initiative projects such as ADAPT SMART, and the European Medicines Agency’s adaptive pathways pilot. The hurdles standing in the way of successfully implementing outcomes-based medicine are, he conceded, both technical and political. Collaborative initiatives like ADAPT SMART work to address both types of challenges.

Following Eichler’s remarks, Gigi Hirsch, Executive Director, Massachusetts Institute of Technology (MIT) Center For Biomedical Innovation, took the stage. Hirsch oversees MIT’s NEW Drug Development ParadIGmS (NEWDIGS) programme, a collaborative “think and do” tank focused on enhancing the capacity of the global biomedical innovation system to reliably and sustainably deliver new, better, affordable therapeutics to the right patients faster. MIT NEWDIGS takes a systems approach to designing, evaluating and catalyzing important advancements that are so complex and cross-cutting that they cannot be addressed by a single organization or market sector.

Like Eichler, Hirsch stressed the inherent uncertainty that is part of biomedical innovation, citing the line “Knowledge is an unending adventures at the edge of uncertainty” and noting that this “pretty well describes what we do in biomedical innovation.” The problem is ultimately that every stakeholder has to make important decisions under very uncertain conditions. NEWDIGS looks largely at adaptive decision-making, which consists first of a key decision about patient access—specifically the timing and conditions under which patients receive access to products. While this is the central focus for most when looking at adaptive pathways, this decision must be tightly linked with a plan for the generation of evidence to address remaining uncertainties, and for use of this information to reassess and refine the access decisions.

Hirsch cited the idea of a “three-layer cake” consisting of three questions: First, who are the decision makers; second, what decision are they making; and finally, what is the question they are asking. In that context, we can determine what type of evidence would be adequate to answer their questions. “We need a framework for this that all stakeholders can use,” asserted Hirsch, noting that the evidence and methodology, as well as the data, have to be fit for purpose for any given particular context. This is part of the work currently being done by MIT NEWDIGS.

Richard Bergström, Director General, European Federation of Pharmaceutical Industries and Associations (EFPIA), continued the conversation, discussing tools on the European side that are likewise attempting to create appropriate frameworks for adaptive development. In particular, he focused on the IMI2 Big Data for Better Outcomes (BD4BO) programme. This programme aims to catalyse and support the evolution towards value based and more outcomes-focused sustainable health care, by exploiting the opportunities offered by the wealth of emerging data. The ultimate goal is to maximise the potential of large amounts of data from variable, quickly developing digital and non-digital sources that will be referred to as “big data” in the context of this initiative.

BD4BO provides a platform and resources for defining and developing enablers of the outcomes transparency evolution together with patients, payers, physicians, regulators, researchers, and healthcare decision makers, among others. The key enablers are: definition of outcome metrics; protocols, processes and tools to access high quality data; methodologies and analytics to drive improvements, and digital and other solutions that increase patient engagement.

Bergström noted that there was huge excitement in the industry about the potential promise of real world data. While industry may be joining with diverse stakeholders (such as regulators, payers, and patients) in order to tap into the potential of real world evidence, there is still the need for a shift within national healthcare systems. Market access, he says, remains an issue that needs to be tackled, collaboratively. This is where initiatives like IMI2 can play a valuable role.

Kicking off his presentation, Steve Rosenberg, Senior Vice President and General Manager, Oracle Health Sciences, addressed the intricacies of the many players involved in medicines development, noting: “We talk to everybody in this eco-system.”

Rosenberg spoke at length on the increasing emphasis on value-based medicine. The pharmaceutical industry is being asked to provide value-based proof that its medicines should be paid for in various countries, with value-based reimbursements essentially being a “code” for countries having “less money to spend on healthcare”. “I personally think that medicines are the cheapest way to take care of patients,” Rosenberg noted, emphasising that keeping patients healthy with medicines in the long-term costs far less than treating sick patients.

The key to value-based care, Rosenberg said, is data. The problem is that, while technologies and systems exist for obtaining data, that data is not necessarily usable. “Electronic health records and other systems were put in so fast that they aren’t fit for purpose. We now need to work to mine data and transform it into a usable format,” he said. The last thing that we want is to have the wrong data in front of the right person for analysis—or the wrong person using good data. “All data is good for something, it’s just a question of where it needs to go,” Rosenberg concluded.

Following the speakers’ presentations, the floor was opened to spontaneous questions from the audience. It is increasingly apparent that several challenges need to be addressed in order to implement outcomes-based assessments:

• How do we avoid extraneous “noise” surrounding the use of existing data?
• How we can ensure that the data we collect is meaningful?
• Instead of starting from scratch, how can we tap into and interlink existing regional databases?
• How can the patient, as the ultimate “consumer”, play a greater role in the evaluation of medicines, in particular as we are now working to create new standards?
• Last year 47% of the drugs introduced were orphans and are 2.5 times more likely to be approved. How do we use RWE and outcomes measures to deal with this increasing orphanisation?

Bringing the discussion to a close, moderator Schulthess noted that these are topics that could be discussed for far longer than the given 1.5 hours at hand. Ultimately, it became clear from the day’s discussion that we are a tipping point in how we develop medicines—and to successfully reimagine this process, we need to rethink how we view biomedical innovation as a whole. This also means re-examining current processes, like RCT’s. Speaking on how we view the medicines lifecycle, Hans-Georg Eichler emphasised the importance of continuous examination. “How do we continue the learning curve?” he asked: “Pre and post licensing should not be two different lives, it’s one continuous life.”