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Dr Numerof examines the benefits of Real World Evidence (RWE) and the pitfalls of relying too heavily on Randomised Clinical Trials...

By Rita E. Numerof... on Aug 1, 2012

The pharmaceutical industry is facing a list of unprecedented challenges led by the global economic crisis and concerns about escalating healthcare costs. A series of well-publicized recalls and regulatory settlements have left policymakers and consumers questioning the safety of medical products and their trust in manufacturers.  Related to all of this is the emerging challenge of obtaining product reimbursement.  Payers increasingly demand that all new medicines and technologies provide evidence of value -- clinical and economic -- to secure reimbursement and market access.

With a consolidating payer base increasingly driving healthcare decision-making, there appears to be a growing trend to require more evidence than that offered by randomized clinical trials – the familiar “gold standard”.  Real-world evidence (RWE) is gaining legitimacy as an element of the research agenda, and as an important tool to pick up on potential adverse events and applications that might otherwise go unnoticed because of the nature of random controlled trials (RCTs). 

What is Real-World Evidence?

RWE studies are observational studies based on actual use of a product in “real life” clinical practice – in other words, with “typical” patients. Growing interest in RWE studies can be seen as a reaction to the limitations of RCTs.

RCTs -- seen as the “gold standard” for evidence generation -- have two limitations that are becoming increasingly problematic. One is that they typically restrict the type of patient that is included in treatment and control groups to those with an uncomplicated profile of the condition of interest. In the real world, patients have comorbid conditions that impact their reactions to the treatment of interest. When the treatment is used under more realistic conditions, the impact of more complicated conditions may manifest as adverse events. There may also be positive impacts that, because of the narrow patient profile, haven’t been noticed in RCTs.

Companies often rely too heavily on these narrow studies to establish product safety and performance parameters for broader populations that may not experience the same outcomes.  The result has been an increase in demands for post-market surveillance, Risk Evaluation and Mitigation Strategies (REMS), and product withdrawals and recalls.

One example where the lack of RWE had disastrous consequences is Vioxx.  On September 30, 2004, Merck withdrew Vioxx from the market.  This recall came after it was disclosed that information existed linking Vioxx to between 80,000 and 140,000 cases of cardiac-related events.  But Merck claimed that their RCTs did not show any significant increase in these types of events compared to placebo.  Had they collected or studied RWE (there was quite a bit of evidence in medical records and databases), Merck could have avoided this disaster.   

The second limitation of RCTs is that that they typically only involve the experimental group and a placebo control group. Payers increasingly want to see comparative data against the current “gold standard” treatment, and such data is often more available in the context of RWE studies.

Interest in RWE is growing because it includes data from non-interventional observational studies, retrospective database studies (registries), and review of data from medical records.  While many in the global industry are doing more observational studies, American companies frequently lag behind their counterparts in Australia and the European Union in the use of retrospective database analysis.  Manufacturers have historically overvalued RCTs, but they will have to adjust their focus as a number of stakeholders shift away from them. 

Payer Demand for RWE

Incidents like the Vioxx example, coupled with pressure to reduce healthcare costs, have led payers to demand RWE to demonstrate the product value and establish appropriate reimbursement.  Recognizing that they have significant patient information, payers are beginning to mine their own data to influence care and treatment decisions.  To stay ahead of the curve, it’s critical to understand what data payers will find valuable:

• Payers value data that demonstrates a reduced risk of complications and side effects.  Real world evidence showing better health outcomes and lower costs over time can be critical to establishing a compelling value case and justifying a product’s upfront cost. 
• Payers value data that shows RWE demonstrating safety and effectiveness for a range of higher-risk patients, such as those with comorbidities.  Payers are interested in determining how to engage ‘difficult to treat’ patients (e.g. non-compliant or non-responders) and non-compliant patients with non-healthy lifestyles (e.g. poor eating habits, obesity, etc.) as well as utilize data that can help them predict non-adherence. 
• Payers generally view simplicity and ease of treatment as having a beneficial impact on cost -- for example, less frequent dosing, fewer side effects, or use of a single medication (vs. multiple medications).  Payers consistently have invested significant time and resources into looking at ways to improve adherence.  Chronic diseases, such as diabetes, cardiovascular disease, and asthma have been of particular interest to payers for years because medical costs associated with non-adherence can be significant. 

Gathering RWE to meet payer demands in each of these areas will be pharmaceutical companies’ best bet to secure premium reimbursement and market access.

Manufacturers Must Shift Gears Too

As payer interest in RWE rises, manufacturers need to develop the tools, platforms, and organizational capabilities to enable them to respond.  Engaging a broader set of stakeholders with different data and higher-level, strategic conversations -- vs. discussions about product-specific features -- will require manufacturers to identify and define the capability set, accountabilities, deliverables, key interfaces, and decision-making authority for individuals responsible for effectively engaging decision-makers in payer organizations.

These relationships must be seen as bringing an understanding of the payer’s most pressing issues, business challenges, and existing programs, along with an ability to develop collaborative solutions that are not seen as biased or self-serving.  By leveraging existing best practices within the organization and the industry to develop tools, organizations can consistently and sustainably uncover payer-specific needs and engage in value-additive conversations.

Are You Ready?

Medical products companies can’t afford not to adopt real-world evidence as a key part of product development from both a safety and reimbursement perspective.  RWE can enable manufacturers to develop more effective studies to demonstrate value and identify product issues sooner.  It will be the foundation for value-based pricing that will redefine the basis of competition and market access.  Furthermore, branded products without solid RWE will be passed over for what is considered to be “best-in-class” by payers, particularly as many payers see randomized clinical trial data as insufficient for most of their needs/interest in controlling medical costs.   Going forward, having RWE will increasingly be ‘table stakes’ for market access -- and pharmaceutical manufacturers that lack this evidence will be caught playing catch-up.