Authors: Annie Kennedy and Joff Masukawa.

Rare diseases impact 1 in 10 Americans, and over 400 million people worldwide. The current development and FDA approval process can cost hundreds of millions of dollars – and take an average of 15 years – to develop one therapy. For the 30% of children diagnosed with a rare disease, who won’t live to see their 5th birthday, this wait is unthinkable. Meanwhile, prolonged – and unnecessary – diagnostic delays and inadequate treatment protocols yield increased healthcare costs and irreversible disease progression for individuals living with rare diseases. Even when they are approved, many transformational therapies never each patients because of the current methods we use to assess their value. Changing our value assessment process is fundamental to ensuring it isn’t just one more barrier to care in the lives of patients with rare disease. But doing this work is not easy—it is a multi-step process that involves collaboration and dedication over the long haul.

One immediate challenge we need to overcome in current value assessment frameworks is the confounding variable of patient sample size. With rare diseases we are faced with very small patient populations, and even smaller subsets within each population who are typically eligible for clinical trial participation. While much work has been done to modernize development and regulatory pathways to adjust for the small patient communities within comprising scientific rigor, initiatives to apply similar adaptations within the access environment are still nascent. The existing value assessment frameworks are not structured to align with the adaptive trial models being utilized in small populations and rare disease. Products approved based on surrogate biomarkers, via accelerated approval, with small numbers of trial participants, and limited longitudinal data do not fit with current models for assessing a product’s value. But as more and more life-altering rare disease products move through the pipeline, we are hopeful that the health economics and outcomes research (HEOR) community will be eager to engage with patient community members with direct experience with the products being assessed and the diseases being addressed. Together, we can develop new ways of capturing data that can ultimately help us assess how impactful a product may be to which subsets of patients with a specific rare disease.

There are several ways we can begin to develop data, models, and frameworks to reflect the products experience of small patient communities, and outcomes that are sensitive enough to capture patient preferences within subpopulations. For example, new technology like smart phone apps can gather patient reported outcomes data. Another way to capture patient journey information is to examine insurance claims data. The medical history of those affected by a particular rare condition can be analyzed through the identification and analysis of all episodes of care. This helps to paint a picture of direct care that is received by individuals with the same condition over an extended period of time. But this exercise alone does not reveal the full story of an individual’s lived experience with their diagnosis. Only by listening directly to patients can we fully help inform decision-making.

But beyond gathering more data, truly including the patient experience in the value assessment process is paramount. For example, current value assessment models don’t examine the impact of a therapy on slowing disease progression. Yet this is extremely valuable to people who have rare diseases. Rare disease patient communities have begun to engage in trying to create some of the much needed innovation within the value assessment space. For example, by engaging with ICER, as well as collaborations with partners such as IVI, the National Health Council (NHC), PAVE, and PIPC, the EveryLife Foundation is working towards long-term paradigm shifts in the manner in which patient experience is considered as a part of the value assessment process.

Annie’s own experience in this space was informed by her work with Parent Project Muscular Dystrophy back in 2015 when she worked to connect ICER with rare disease community experts as they began assessing therapies for Duchenne muscular dystrophy. Over time, ICER examined the applicability of its framework to the assessment of rare disease products and ultimately modified its framework for the assessment of ultra-rare diseases. This framework has since been utilized as the first products for Duchenne and spinal muscular atrophy were assessed.

But there is much more work to do, starting with updating ICER’s Assessment Timing for Products Approved Via the Accelerated Pathway to ensure the availability of clinical data to inform the assessment itself. By definition, products approved using the Accelerated Approval Pathway will be approved based on the use of surrogate endpoints. The valuation of these products is compromised as the ICER Evidence Rating Matrix is dependent upon the availability of clinical data including data on long term outcomes and the level of certainty in the evidence. A criteria that is misaligned with available data at the time of approval of products via the Accelerated Approval pathway until additional clinical data has been collected post-approval. In the case of these products, this lack of data at the time of approval is not a reflection of the robustness of the therapy, but rather the regulatory review pathway agreed upon by the sponsor and the FDA.

As new therapies emerge into the marketplace, patients, providers, and payers are faced with challenges as to how to discern which therapies are most appropriate for which patients in which combinations and at which time. 1 in 10 Americans with rare disease are counting on us to do better. We must commit to a collaborative effort on the development of evidence and resources to facilitate this decision-making.

Annie Kennedy is Chief of Policy and Advocacy for the EveryLife Foundation. Joff Masukawa is President of Diligentia LLC.