3 Questions for Validating Your Rare Disease Outcomes and Endpoints

rare disease research, rare disease clinical trials

Understanding the patient’s experience with their illness should be used to inform everything from study design, to product formulation, to the endpoints chosen to measure success in each study. Programs driven by patient insights are agile enough to pivot, helping move the study closer to receiving approval and reaching full market potential in the patient population.

The push for trials tailored more toward patient needs has produced clinical trials that fit better into a patient’s life, but we still have a long way to go. Beyond trial participants, clinical researchers focused on patient-centric trials should consider the factors which will inform a patient’s cost-benefit analysis if the drug makes it to market. Patients with rare diseases often face a long diagnostic odyssey and may ultimately find they have few or no treatment options after receiving their diagnosis. Even if treatment options are available, it does not mean patients will utilize any treatment approved for their disease. Treatments for rare diseases are frequently extremely expensive, can produce side effects, and may have safety risks.

It is essential for market success that clinical trial outcomes and endpoints account for the patient’s needs. Endpoints must be efficacious with clinically meaningful endpoints that are patient-forward and patient-informed. In identification of outcomes and endpoints for your rare disease study, ask:

  1. Are my endpoints meaningful to patients and the illness they face?

For regulatory approval with most agencies, a program must show a product to be safe and effective, but it also must be clinically meaningful to a patient. Engage patients, caregivers, and Key Opinion Leaders (KOL) feedback directly to help determine the most appropriate endpoints for a treatment serving the rare disease population. Understand the illness from the patient’s perspective— how the disease truly impacts their quality of life, hopes, dreams, commitments. Direct and open dialogue exploring the experience of living with the disease can help you identify the key stressors, impacts, and symptoms most difficult for the patient. This information can help ensure your product’s endpoints measure improvements in symptoms that matter to a patient population.

Once you’ve explored endpoint possibilities and made your selection, review those endpoints directly with patients and caregivers to be sure you are interpreting their experience correctly and possibly providing a treatment they would choose.

Utilizing novel endpoints in rare disease studies increases the need to validate with patients and clinicians to be sure you have chosen worthwhile endpoints to prove the value of your product.

     2. Can the rare disease endpoint be reasonably and reliably measured in this population?

The endpoints you choose to prove your product’s value to the patient must be clearly defined, reliable, and appropriate to your study’s phase. Utilizing fit-for-purpose endpoints requires proof of the validity, ability to affect change, and interpretation of the endpoint. Documentation of your endpoint validation will be needed for regulatory approval.

Validation of endpoints should take place with review from patients, caregivers, and KOLs as well. Every disease has its own unique patient population and journey, and it’s important to consider all as you weigh the feasibility of and select endpoints.

Consider, for example, an outcome assessment for an endpoint which must be measured through a blood draw—if your patient is a child, you must consider if the required blood volume is reasonable to take from a child. You must consider timing—if fasting is required, can this sample feasibly be drawn in the early morning, before parent’s work and the child’s school? Is the frequency of draws demanding of the patient/family? If so, can you utilize home healthcare to gather the sample? Can you coordinate the blood draw to happen during their normal standard of care appointment?

Every endpoint identified needs to be placed into the real-life-context of measuring the outcome assessment with a patient, to evaluate the reality of measurement. Measurements should only be taken when necessary to prove efficacy of the product. KOLs are valuable partners in exploring what outcomes can be utilized and in refining the outcome.

     3. Will my endpoints produce sufficient/appropriate data to secure regulatory approval in my target indication?

When determining and validating endpoints, it is important to work with the regulatory agencies you wish to seek approval. Reviewing intended endpoints with agencies in advance of use ensures you are using endpoints they believe capable of producing the efficacy data needed to provide an approval on your product. Buy-in on endpoints in advance – as early in the process as possible – provides a safeguard during later regulatory process and data reviews. This buy-in is especially important when you have chosen to use a fit-for-purpose endpoint which the regulatory body may not have seen before. Since guidelines do not always exist for endpoints, using them requires close documentation of support from all relevant stakeholders.

Close partnership with patients and stakeholders in their treatment experience will provide you the insights needed to identify and choose key endpoints for your rare disease clinical trial. Beyond endpoints, patients and their care circles can provide valuable input to direct your rare disease program.

Want to learn more? Our e-book, Your Strategy for Patient Forward Research: 5 Key Steps to Designing and Operationalizing Meaningful Rare Disease Trials will help you evaluate the rest of your rare disease strategy to maximize your program’s chances of success. Worldwide’s rare disease team brings together scientific and therapeutic depth with operational expertise to help you navigate obstacles and turn hurdles into hope. Our established relationships with advocacy groups, patients, and KOLs can help you make your program patient-forward.

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