The Increasing Importance Of Real-World Evidence In Drug Development

By Suzanne Elvidge, Contributing Writer
Follow Me On Twitter @suzannewriter

Market access is all about getting the right drugs to the right patients at the right time and for the right price. But to do so, every pharma or biotech company must face a mounting set of challenges, including, most prominently, high research costs and tighter budgets.

That’s why a formalized and optimized market access strategy is essential these days. One of the most important components of that strategy (i.e., plan) is real-world evidence that reflects how patients use and benefit from drugs in an everyday setting.

GENERATING AND ANALYZING REAL-WORLD EVIDENCE
Real-world data is increasingly demanded by payers, providers, and health technology assessment (HTA) bodies as a reflection of a drug’s cost-effectiveness. This raw data is collected when drugs are used in a real-world setting outside the constraints of standard clinical trials. It can be generated from a variety of sources, including patients’ electronic medical records, wearable sensors, devices and apps designed to support disease management, and patient-reported outcomes (PROs). Another source of real-world data is from discussions between patients on social media. Real-world data on drug efficacy, safety, and everyday use is available from Phase 4 studies, retrospective studies, or analysis of data in registries. Compiling and analyzing all of this data creates a package of usable and relevant real-world evidence that is much more patient-centric than data from randomized controlled trials (RCTs).

BUILDING BETTER CLINICAL TRIALS
RCTs are used to assess the safety and efficacy of new drugs under standardized conditions, enrolling only people who fit within strict criteria of age, severity of disease, gender, and even body mass index (BMI). This narrow set of criteria can mean that drugs appear to perform better or worse than in everyday use, according to Raf de Wilde, who is a global pricing and market access expert at Valid Insight, a global provider of strategic market access consulting and evidence development services. He cites NOACs (novel oral anticoagulants) as an example. In clinical trials, it was difficult to show better efficacy for NOACs compared with Warfarin (a blood thinner) in preventing strokes associated with atrial fibrillation. However, in everyday use, NOACs were more effective as patients are more likely to stick with NOACs than Warfarin treatment. In contrast, some drugs can perform more poorly in the real world, as the patients may not fit the RCT criteria – they may be older or younger, be at a more advanced stage of disease, or have comorbid conditions for which they are taking other medications.

As the costs of developing innovative drugs climb and drug budgets are under the joint pressures of changing patient demographics and funding cuts, payers are becoming more cautious about believing the data from clinical trials, particularly for new and high-cost drugs. Instead, payers are increasingly looking for real-world evidence of a drug’s cost-effectiveness, either by reducing the costs of disease management or improving patient outcomes. Usually, real-world evidence isn’t available until after a drug is launched, but there are ways to get real-world-type data in clinical trials, for example, by using observational pragmatic studies. These studies enroll patients who are more like the general population (i.e., closer to routine clinical practice) and compare the new drug with existing treatments rather than a placebo.

Real-world evidence plays a role early in drug development, where understanding the current and future market landscape is important for therapeutic area and lead candidate selection. It can affect the design of clinical trials, for example, by highlighting the endpoints that will be of most relevance to patients and physicians (e.g., focusing on abilities useful to daily living rather than timed walking tests in neurodegenerative disease). By understanding the size and location of patient populations, real-world evidence also can help when recruiting for clinical trials. This is especially important for studies of drugs for rare diseases or disease subtypes, where companies struggle to recruit from a small patient population.

"It’s important not to underestimate how far real-world evidence can take us in the overall mission to improve health outcomes and to achieve commercial success."

Steve Bradshaw
Managing Director, Valid Insight

 

CREATING A POWERFUL VALUE STORY FOR PAYERS AND REGULATORS
To gain the best possible market access outcomes, pharma companies can use real-world evidence to build effective and compelling value stories. As well as clinical data, these stories should include population size, disease burden and unmet need, drugs in the pipeline, and the effectiveness and cost of competitors. In addition, to optimize market access, companies need to think about the needs of payers and regulators.

Payers may distrust data from pharma companies, and as a result, are beginning to collate their own real-world evidence, seeing it as more relevant than clinical trials data or data produced by pharma companies, says de Wilde. One example includes the use of MUR (medicines use review) data to understand how patients are using drugs, such as how often they are refilling prescriptions. KCE, the Belgian health technology assessment body, is capturing and using real-world data, such as how persistent patients are in taking their Alzheimer’s disease drugs. Healthcare plans in the U.S. are also using real-world evidence when looking at the impact of different drugs on costs. As de Wilde adds, if the industry doesn’t produce real-world evidence, its key stakeholders will. Finally, drug-value stories based on real-world evidence can help physicians decide which drug to prescribe since the physician can see the outcomes from patients with similar profiles. These stories can also help physicians educate patients about the side effects that they might expect, what they can do to manage the side effects and improve their quality of life, and when to alert healthcare professionals about serious side effects.

GAINING EARLIER APPROVAL THROUGH REAL-WORLD EVIDENCE
There are a number of initiatives designed to accelerate drug approval, and therefore, earlier access to drugs, that rely on follow-up real-world data collection. “The real-world data generated through accelerated pathways may provide answers to payers’ questions about how the drugs are used in real day-to-day clinical practice,” says Steve Bradshaw, managing director of Valid Insight.

The European Union has a number of accelerated approval processes in place, including conditional marketing authorization and an adaptive pathways process. Conditional marketing authorization allows early approval based on interim data for drugs that target seriously debilitating or life-threatening disorders, rare diseases with orphan designation, or emergency health situations. Companies have to commit to collecting real-world data or continuing clinical trials to support full approval. The adaptive pathways process allows patients and physicians to access drugs pre-approval based on data from a small group of patients or by using a surrogate endpoint. Again, the company has to continue to collect real-world data to support full approval.

The U.K. has an Early Access to Medicines Scheme (EAMS), which also allows seriously ill patients with major unmet needs and no other options to access drugs pre-approval (potentially as early as the end of Phase 2 trials). Japan is putting together its sakigake (pioneer) strategy to allow conditional approval for regenerative medicines, with full approval allowed based on real-world evidence. The U.S.’s accelerated approval process allows drugs to gain early approval based on surrogate markers or intermediate clinical endpoints, followed with Phase 4 confirmatory trials for full approval.

Of course, there are still challenges associated with drugs that are approved using these accelerated pathways. In some countries the drugs are paid for by the pharma companies, but in others, the funding comes from the health providers. In the latter case, some payers, according to de Wilde, may still feel there isn’t sufficient data and will want to wait until the full evidence is available on the efficacy and cost-effectiveness.

EXTENDING THE LIFE CYCLE AND GETTING NEW INDICATIONS
Many companies just focus on market access and real-world evidence when planning to launch a new drug. But Bradshaw says, “A market access strategy isn’t just about planning for launch; it’s about how we can gain and sustain market access through to patent expiry and beyond. It’s important not to underestimate how far real-world evidence can take us in the overall mission to improve health outcomes and to achieve commercial success. We see real-world evidence being particularly useful to substantiate incremental value, especially where the benefits might be impossible to determine through a standard clinical development program.”

Real-world evidence also can help maintain brand loyalty by affirming the safety, efficacy, and cost-effectiveness of a drug in everyday use. It can build trust between healthcare professionals and pharma companies and prolong the life cycle of a drug, even once generics reach the market. Real-world evidence based on data collected from patients — for example, using wearables or technology-enabled delivery devices — can be used to confirm the proper use of a drug to physicians and report its correct use to payers.

As an example, De Wilde cites the development of easypod by Merck Serono and PDD, an electronic injector for Merck’s recombinant human growth hormone, Saizen. As well as making administration easier for patients, the easypod records how much drug is administered and how often, which could be valuable information to physicians and help detect any misuse of the device to increase muscle size. De Wilde adds that companies could use this kind of technology to support market access by saying, “We believe our system will ensure that patients will manage their treatment better and for longer, or we will give you your money back.”

LOOKING TO THE FUTURE
There are still a number of challenges that need to be resolved. The collection and analysis of real-world data can currently be costlier than data generation through RCTs. However, advances in technology and support through collaboration may help to resolve this in the future. Data privacy also remains a stumbling block, as medical data is very personal. On a larger scale, current regulations limit data sharing between Europe and the US.

By working on the challenges and making the most of the opportunities, real-world evidence has potential to be a powerful part of a market access strategy, from clinical trials to approval and beyond.