An Important Dialogue About Orphan Drugs

The Institute for Clinical and Economic Review (ICER) today outlined how it plans to consider the value of orphan drugs, treatments that are used for conditions affecting very small populations of people who often have no existing treatment options.

This is a good conversation to get started, but it is not an easy one.

Rare conditions—or even ultra-orphan conditions—usually affect the youngest, most vulnerable populations and are often fatal. Although one-third of all new drugs approved by the Food and Drug Administration (FDA) have been for rare diseases, according to the National Organization for Rare Disorders, more than 90% of patients with rare diseases are still being treated with medicines that the FDA has not approved for their condition. 

The costs of treating a rare condition are not limited to pharmaceutical costs alone. That isn’t to ignore their price, but also to recognize that the care of these patients is often complex. It requires support from a wide range of caring people—physicians, nurses, caregivers and many others—to manage a patient’s condition and provide the kind of unique care they need.

While it’s encouraging to see that ICER began the conversation about the value of these treatments with a wide group of stakeholders, including patients, it’s a discussion that needs more time.

We are just at the start of this important dialogue, and given the ethics of how best to treat orphan diseases, we don’t want to rush through the conversation about how we address these challenges in the United States. There may be a temptation to look to the ICER framework as the first option or only approach to considering how to value orphan drugs, but we don’t want to further limit options, especially when so few already exist for patients with rare conditions.

Taking a closer look, ICER’s proposal for assessing treatments for rare diseases presents both concerns and potential bright spots. Among these:

  • It is encouraging that ICER is seeking to provide context about the unique challenges of generating evidence for orphan treatments.
  • It is concerning, however, that ICER is continuing to rely on a quality-adjusted-life year (QALY), which has considerable limitations and flaws, such as ethical considerations, methodologic issues and disease-specific considerations. These flaws are magnified for orphan conditions.
    • Because the orphan disease populations are so small, it can be difficult to generate clinical evidence. The QALY inputs are based on this evidence and other limited factors, which can create great uncertainty about the estimates used to calculate value. Additionally, many of the important patient and societal benefits cannot be captured by the QALY.
    • Similarly, using a QALY to calculate a value-based price benchmark (VBPB) for orphan treatments creates a misleading number that does not capture important patient and societal benefits,  and hence fails to account for much of the treatment’s value.
  • While it is commendable that ICER is seeking to give credit for the potentially disproportionate research and development costs that can be incurred by orphan treatments, these costs are incurred over a portfolio of potential products and are very difficult to measure for a single product. ICER should focus instead on the value of the treatment, seeking ways to give credit for the patient and societal benefits that cannot be captured by the QALY.
  • To its credit, ICER plans to include an in-depth qualitative section in its reports on patient and societal benefits, and will broaden beyond its usual frame to include factors such as the impact on family, school, and community, which are especially important considerations for orphan diseases. However, it is important for ICER and experts in methodology to identify ways to quantitatively incorporate these important factors into value assessments so they are not overlooked.

ICER plans to accept comments on its proposal for the next 60 days, but even that is a short time in which to find a solution to such a complex issue. It’s important to continue the dialogue, consider a wide range of options, and include all stakeholders in the conversation.