When a new therapy for mitochondrial disease is being developed, one of the most important questions is also one of the most difficult: what should researchers measure to tell whether the treatment is working?
There are lots of different ways of measuring change in a clinical trial. Researchers might look at blood tests, muscle strength, walking ability or scores on a clinical assessment, and all of these can provide valuable information about whether a treatment is having an effect.
However, these measures don’t always tell the whole story. For someone living with mitochondrial disease, the changes that matter most might be having enough energy to get through a working day, being able to walk to the shops, spending time with friends without needing days to recover afterwards or simply being able to do more of the things that are important to them.
That’s why listening to patients when deciding what should be measured in a clinical trial can be so valuable. A recently published study involving the pharmaceutical company Khondrion, Radboud University Medical Center in the Netherlands, Harvard Medical School and clinical outcomes research specialists Clinical Outcomes Solutions provides a powerful example of what this can look like in practice.
The researchers carried out in-depth interviews with adults living with mitochondrial disease caused by the m.3243A>G variant, asking them about their experiences of fatigue and how it affected their everyday lives. The feedback showed that fatigue meant much more than simply ‘feeling tired’. Participants described both physical and mental fatigue, alongside a wide range of other symptoms, and talked about the impact their condition had on physical activity, work, social life and their ability to carry out everyday tasks.
Importantly, these conversations were used to help the researchers understand whether the tools being used to measure fatigue were actually capturing the things that mattered to patients. They found that an existing questionnaire captured the main aspects of physical fatigue well, but failed to adequately capture mental fatigue. This led to the development of an additional measure specifically designed to capture mental fatigue, which was then tested with patients to ensure the questions were understandable and relevant to their experience.
This work is particularly relevant to the development of sonlicromanol, an investigational treatment being developed by Khondrion for people with m.3243A>G mitochondrial disease. Sonlicromanol is now being evaluated in KHENERFIN, a Phase 3 clinical trial, where physical fatigue and lower-limb function are being measured as key outcomes, with mental fatigue captured as an additional dimension.
The publication therefore goes beyond describing the symptoms of mitochondrial disease, showing how the experiences of people living with the condition can influence what researchers measure and, ultimately, how they judge whether a potential treatment has made a meaningful difference.
Listening to lived experience
This study reflects a wider and very welcome shift towards recognising the contribution people living with a condition can make to the development of new treatments.
Researchers and clinicians bring essential scientific and medical expertise, but there are some things that can only really be understood by asking the people who experience them. Fatigue is a particularly good example. A clinical assessment might tell researchers something about a person’s physical ability, but it can’t necessarily tell them what it feels like to live with fatigue every day, which aspects are most difficult or what kind of improvement would make the biggest difference to their life.
When deciding what to measure in a clinical trial, both perspectives matter. Researchers need measures that can reliably detect whether a potential treatment is having an effect, but those measures also need to capture changes that are meaningful to the people the treatment is ultimately being developed for.
The role of patient organisations
Patient organisations like The Lily Foundation have an important role to play in making this kind of research possible.
We can’t provide a single voice on behalf of the entire mitochondrial disease community, nor should we try to. Mitochondrial disease is far too varied, and the things that matter most to one person may be very different from those that matter to someone else.
What we can do is help create opportunities for researchers to hear directly from people with different diagnoses, symptoms and experiences. Patient organisations often have long-standing relationships with the communities they represent, and that trust can be particularly important when research asks people to share very personal details about the impact of their condition on their life.
Jasper Levink, CEO of Khondrion, said: “Research like this is only possible with patients willing to share their experience in such personal detail, and with the trust and connections that patient organisations build within the community.”
At The Lily Foundation, we sit in the perfect position between the research community and the people that research is ultimately intended to benefit. We work closely with researchers and clinicians, but we hear directly from families about the everyday reality of living with mitochondrial disease, including many of the challenges that can be difficult to capture during a clinic appointment or through a standard assessment.
As more potential treatments for mitochondrial disease move through development, listening to those experiences will become increasingly important. A treatment may improve a laboratory value or produce a change on a clinical scale, but researchers also need to understand whether that change represents a meaningful improvement for the person taking it.
This newly published study is a powerful example of what can happen when patients are given the opportunity to describe what matters to them in their own words, and those experiences can then be used to help shape how the impact of a potential treatment is measured.
