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The heart of the matter - Part Three

Is pharma doing enough to maximise real world evidence?

The heart of the matterIn the modern game of pharma Buzzword Bingo, ‘real world evidence’ (RWE) is likely to feature prominently on any winning card. The term is currently de rigueur across pharma, and understandably so; getting it right may determine how brands perform in an evolving healthcare environment. Jargon or otherwise, RWE certainly merits discussion. But it’s time for the talking to stop. If pharma is to succeed in meeting the evidence needs of its most influential customers, the gap between rhetoric and reality must narrow significantly. Companies have talked the talk - now they must turn up the volume and transform RWE from a buzzword to a byword for value-added research. Collectively, the industry needs to make RWE happen. The question is: how?

Actually, the first question is: why? We don’t need to look far for the answer; payers all over the world are demanding additional data to support the reimbursement of innovation. Healthcare systems need to derive increased value from medicines in targeted populations to maximise healthcare resources whilst, simultaneously, providing optimal patient outcomes. This is forcing pharmaceutical companies to consider generating evidence of effectiveness in the real world that reflects the diverse needs of all key stakeholders. The old model, built on the traditional bedrock of RCTs, is not dead. But it’s no longer enough.

Getting real
Current activity at major payer institutes provides fitting real world evidence that RWE is becoming a strategic priority. In Europe, bodies like NICE and IQWiG are dictating play and exploring new models of assessing the effectiveness of new medicines. And with every innovation that fails to achieve HTA recommendation, they’re exposing gaps in research methodologies that are symptomatic of an RCT-centred approach.

NICE is participating in a pan-European initiative to construct a uniform framework for the use of RWE. IMI GetReal, a consortium that includes EMA, HTA bodies, academia, patient organisations and pharma, aims to improve the efficiency of medicine development processes by developing a framework to assess the relative effectiveness of medicines. The project brings these stakeholders together to share perspectives on how effectiveness can best be assessed during regulatory and HTA decision-making. It will pave the way for advancing the development of new approaches for incorporating RWE into drug development.

“RCTs are still the gold standard due to their high internal validity,” says Dr Pall Jonsson, senior scientific advisor, IMI GetReal, NICE. “However, they don’t allow for assessment of a drug’s effectiveness in real-world populations; they provide measures of safety and efficacy. By contrast, HTA agencies base their decisions predominantly on the health benefits of a drug relative to existing treatment options – ‘relative effectiveness’. At present, there’s a gap between the data required by regulators and those required by payers. Good quality RWE, when appropriately used, is often able to bridge that gap and provide evidence of relative effectiveness in real practice.

”GetReal is a logical initiative given healthcare buyers’ demands for the demonstration of clinical benefit in local practice. “Previous assessments have highlighted uncertainty around the effectiveness of drugs outside the clinical trial setting – and RWE is one way of reducing this uncertainty in HTA decision-making, especially if incorporated alongside traditional RCTs,” says Pall. “GetReal is a collaborative attempt to develop methodology and establish standard approaches to when and how RWE should be used. This is very much on the agenda. There is no point in stakeholders closing their eyes and pretending nothing is changing. We’re moving in the direction of greater use of RWE, but we need to test what’s appropriate and how best we can do it.”

RWE is also beginning to carry greater weight in Germany. In 2011, the Federal Joint Commission (FJC) delegated health technology assessment responsibilities to IQWiG. Final reimbursement decisions, however, remain with the FJC, which acts as a Health Technology appraisal body based on, but not bound by, IQWiG recommendations. IQWiG’s evaluations are currently assessing a drug’s ‘added benefit’; but the 2011 law allows a subsequent health economic analysis when commissioned by the FJC. Whilst the former is largely based on RCT data, cost-effectiveness analysis is increasingly open to RWE. 

A catalyst of RWE use in Germany is a legislative change that’s enabling research-based access to healthcare information – specifically, patient data from statutory health insurance funds. “This patient-level data is valuable Real World Evidence,” says Prof Dr Stefan Lhachimi, formerly deputy head of health economics, IQWiG, and now Professor for Evidence-Based Public Health, University Bremen. “Access to health insurance databases allows researchers virtually to track the movement of every insuree, including diagnosis, hospital activity and medicines prescribed. This is important RWE and IQWiG is now willing to use it for elements of the health economic analysis.”

Another dataset, used by hospitals to calculate Diagnosis Related Groups, enables researchers to identify trends in treatment costs. Such observational data will increasingly be used to support HTAs. But RWE use is not restricted to health economic analysis. “RWE can help calculate the disease burden, eg prevalence or incidence. Here it’s not just acceptable, it’s often the only meaningful source,” says Stefan. “Moreover, the FJC is arguably even more open to using RWE - particularly in research questions around quality of treatment and patient satisfaction.”

Regulatory developments are also a driver for RWE. For instance, the EMA’s adaptive licensing pilot is exploring whether it’s possible to draw inferences from observational studies and whether these data can support decision-making. “Adaptive licensing approaches may, for example, require smaller RCTs but a greater use of surveillance data, such as patients in observational studies or registries,” says Pall. “There are also parallels with the Comparative Effectiveness agenda in the US, where there’s similar potential for RWE. But current acceptability and approaches to RWE vary globally. That’s why it’s important for pharmaceutical companies to engage with HTA bodies and make use of scientific advice. That can prevent many of the difficulties manufacturers may encounter further down the line.”

Implementation: a step guide
With major organisations encouraging the adoption of RWE, proof of the RWE concept is no longer an issue. Implementation has become the key challenge. “Companies need to renew efforts to develop supplementary data from non-interventional observational research and give customers the information they require. The problem is: many don’t know how,” says Andy Turner, head of Complete True Life. “The industry should take the lead from organisations such as NICE and IQWiG and explore how it can optimise sources like patient registries, insurance databases, cohorts and national demographic data to generate supportive RWE. Likewise, observational data, whether from bespoke studies, commercial datasets or syndicated studies, is becoming a crucial part of the dossier of evidence demanded by payers. Marketers understand the value of RWE - but all too often they struggle to generate and apply it effectively.”

The glue
The need to collaborate, both internally and externally, underpins these steps. “Companies need to work cross-functionally,” says Andy. “Medical, marketing, HEOR and market access teams all have a role to play, and their own understanding of how evidence fits into the value generation process. These teams have to break out of their silos and work together. Organisations can do more to align the bridge between clinical and commercial.”

Companies must also identify the right partners to help support them through the process. “A good partner will identify evidence gaps and design solutions that are statistically and academically robust to satisfy all stakeholders,” says Mariam. “The best will be multidisciplinary - combining statisticians, health economists and epidemiologists with marketing and commercial expertise to ensure that the optimal evidence is not only generated, it’s well communicated.”

What next?
RWE is much more than a buzzword - it’s a vital component in the successful commercialization of a drug. “The industry must seize the opportunity,” says Andy. “RWE draws on standard epidemiological tools that companies have long been familiar with – so there’s no reason to be cautious. Better still, the regulators and payers are demanding it. So don’t hold back - it’s time to get real.”

1: Understand where you're playing

The first step is to develop an early understanding of the market environment, and establish what value looks like to all relevant stakeholders. “Pharmaceutical companies need to start developing their value messages very early in the research process – and identify how observational studies, aligned with RCTs, can help support that value story,” says Dr. Mariam Bibi, Director of Real World Evidence, Complete True Life. “Which stakeholders do you need to infl uence and what type of information is going to satisfy their needs? With diverse stakeholder groups that encompass payers, patients and prescribers, those needs will vary enormously. The key is to plan ahead. RWE is a strategic tool, but too often it is used reactively. If real world data is to reach its true potential, it needs to be considered earlier.”

2: Identify evidence gaps

Early insights and landscaping work should also be used to identify evidence gaps that can be validated by RWE. “You have to look at the characteristics of your product and patient population and establish where there are gaps in knowledge,” says Pall. “Look closely at where the body of evidence has fallen in your disease area, and focus on any historical gaps that could benefi t from being plugged with RWE in addition to RCT data. These will be key in designing observational studies.”

3: Define your research questions

Armed with the right environmental foundation, it's then easier to defi ne the research questions that will drive development of the studies and analytics required to meet your evidence needs. “The research question is critical – and it must align with your value proposition. There's a variety of data sources that can meet individual research questions – but it's only by clarifying those questions that you'll be able to identify the most appropriate approach,” says Mariam.

4: Design and implement the studies

“From here, it becomes a matter of designing and implementing the studies,” says Andy. “These will ultimately provide the output to feed into the final evidence plan. Although there are many nuances to observational studies, there are generally three core types; longitudinal, cross-sectional and retrospective. Whatever the study, RWE should be a focus as early as possible in the life cycle – and go all the way through to launch. It's a common misconception that observational research can only be conducted post-launch. That's incorrect. RWE is not just about the product – it's about understanding the disease burden and unmet need in your target area, to help you establish pharmacoeconomic and outcomes requirements. That work has to happen pre-launch. It's valuable supportive data for HTAs.”


  • HTA bodies are recognising the value of RWE in providing evidence of relative effectiveness in real practice
  • Marketers recognise the value of HTA but struggle to generate and apply it effectively
  • Good RWE strategies begin early in the drug lifecycle and continue well beyond launch
  • Cross-functional collaboration, a good multidisciplinary partner and strong value communications will drive optimal RWE 


  The Heart of the Matter - Part 3
PDF File: 1.1 MB

14th October 2014


  The Heart of the Matter - Part 3
PDF File: 1.1 MB



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