The first of a two-part series
Today, payers demand more and better evidence of precise costs and benefits new drugs provide. While obtaining market authorization is a sponsor’s top priority, obtaining reimbursement and market access is equally challenging in today’s landscape. However, it can be difficult to design a drug-development program that meets the requirements of regulators and payers.
In many disease settings, there is no consensus on which clinical outcomes prove a drug’s effectiveness, or which real-world outcomes matter most. As a result, some developers over-engineer clinical trials with ‘just-in-case endpoints’, or collect and analyze excessive real-world evidence (RWE) – which can be expensive and time-consuming.
That said, failing to meet regulators’ and payers’ differing requirements can result in costly re-dos that may leave products in the dreaded limbo between approval and reimbursement. For example, in 2015, hypercholesterolemia drug Repatha was approved by the European Medicines Agency (EMA) after it successfully lowered LDL cholesterol (LDL-C) in randomized controlled trials (RCTs). But EU payers were not accepting of this surrogate endpoint. To win reimbursement, the developer had to conduct further studies to collect more clinically meaningful cardiovascular outcomes, such as heart attacks and hospitalizations.
Further complicating today’s drug development programs are the growing number and influence of stakeholders, whose support is critical to achieving market access. Clinicians, patient advocacy groups (PAGs), health technology assessment (HTA) agencies and experts who compose drug formularies and write evidence-based guidelines all affect the uptake of new products.
Fortunately, there is a potential solution to this challenge:
Mitigating risk
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
The RWE landscape is challenging, requiring developers to balance use of primary and secondary data. Companies must choose the appropriate sources and models to build a dataset that can lower their risk of failure and gain competitive advantage, by filling gaps in their value story. Typical gaps can be identified by asking:
- What are the key value drivers of this product, and are they reflected in the pivotal trials?
- Does the RCT study population reflect the relevant patient population?
- Are patient-relevant endpoints measured and reported? Are they economically quantifiable?
- Are key endpoints used in RCTs surrogates? If so, will they be accepted by payers?
- Will the ease and location of administering the product have an economic impact on adherence?
- Does the comparator used in RCTs represent the current, or best, standard of care?
The answers will help determine the scope and content of your RWE plan, and differentiate your product, even under intense scrutiny. Analytic frameworks to evaluate new cancer drugs have proliferated at institutions such as: The American Society of Clinical Oncology’s Value Framework; the European Society for Medical Oncology’s Magnitude of Clinical Benefit Scale; the Institute for Clinical and Economic Review’s Value Assessment Framework, and Memorial Sloan Kettering Cancer Center’s Drug Abacus. Though none of these frameworks are flawless, companies with cancer drugs can use them to tailor their RWE metrics to demonstrate how their drug impacts costs and disease burden.
Sustained strategy vs. tactical battle
Traditional drug development assumes a health-economic and outcomes analysis at product launch to initiate and drive reimbursement, based largely on existing clinical- trial and observational data. But effective RWE collection and analysis is an ongoing process, requiring prospective data generation and analysis.
Companies must begin to build the value argument for a product as early as Phase II, not just at the end or when challenged by payers and HTA bodies. The value added by the new product must be measured against the highest standard(s) of care, not outdated regimens or placebos.
To reduce costs, RWE strategies should align with commercialization plans; meaning development teams must engage early with commercial teams. Alignment and planning are less expensive than post-launch fire-fighting – scrambling to conduct retrospective studies because market entry is delayed or denied.
Generating quality RWE can be considered a long-term insurance policy. Even if a product wins approval and reimbursement, victory could prove fleeting in a crowded market. Companies need to think about such post-launch realities as:
- What happens in two to three years when competitors enter the market armed with deep RWE laying out an alternative economic case for payers?
- What if competitors generate RWE quantifying benefits, like quality of life, winning over PAGs and key opinion leaders?
Well-designed RWE studies have gained acceptance by regulators and payers, who once viewed them with skepticism. However, markets differ in their appetite for RWE, so companies need country- and region-specific knowledge about how it will be received. For example, German regulators and payers presently seem content with RCTs, while those in the U.S. and the UK are more open to scientifically sound RWE.
Conducting RWE studies can confer commercial advantages throughout a product’s lifecycle, including the ability to identify and engage with physicians and patients, fine-tune distribution channels and establish leadership in a therapeutic area.
In the second part of the series, we will explore how RWE can help re-engineer a drug’s value story, by redesigning the patient care pathway and how patients are driving clinical outcomes.
Photo: Getty Images
