PRO Tool May Better Address MG Symptoms Most Affecting Patients
By analyzing available research and conducting nearly 100 interviews with patients, an international team of researchers crafted a new tool to measure the severity of myasthenia gravis (MG) based on patient experiences.
Called MG Symptoms PRO, this tool has the potential to aid clinical trials by better capturing a treatment’s benefit and to help doctors in monitoring system severity in clinical practice, the researchers wrote.
The tool and its development are described in the study, “Development of the Myasthenia Gravis (MG) Symptoms PRO: a case study of a patient-centred outcome measure in rare disease,” published in the Orphanet Journal of Rare Diseases.
Standardized measures of disease severity are helpful in monitoring a patient’s condition, and critical in evaluating therapies being tested in clinical trials. Some of the most useful measures assess patient-reported outcomes (PRO), or patients’ direct opinions of symptoms that most affect their lives and a potential or existing treatment’s impact.
“Due to this fluctuating and unpredictable disease course and the subjective nature of symptoms such as fatigue, PRO instruments have the potential to provide greater insight into the experience of people living with MG than traditional clinical endpoints, and regulators are encouraging their use as primary efficacy trial endpoints,” the researchers wrote.
Although some PRO instruments have been developed for MG, such as the Myasthenia Gravis Activities of Daily Living (MG-ADL) and the MG Quality of Life 15 (MG-QoL-15), these tools may not accurately reflect the symptoms with the greatest impact on the lived experiences of people with MG. In particular, the researchers noted that available tools tend to overlook fatigue and were largely designed without patient input.
To create their PRO tool, the researchers used a two-step process. First, they conducted a thorough review of the available scientific literature and then asked 60 MG patients about their most impactful symptoms.
In the second step, the team interviewed 36 other patients who were participating in a Phase 2 trial called MG0002 (NCT03052751). That trial tested UCB’s investigational MG therapy rozanolixizumab, which is now in Phase 3 clinical testing (NCT04650854).
“Unlike currently available PRO instruments, the development of the MG Symptoms PRO incorporated patient input at every stage,” the researchers wrote. “Concept elicitation analyses across both steps of the study resulted in a consolidated model of MG patient experience.”
Specifically, the model included two broad categories: direct effects of MG on the body (i.e., symptoms and signs), and more indirect effects of living with the disease, such as how it affects a person’s social life.
“The model was updated and refined at every step of research whilst the distinction of the proximal and distal [direct and indirect] concepts was informed by consultation with MG clinical experts,” the scientists wrote.
Within these broad categories, researchers organized sub-groups of symptoms and other clinical features, and designed questions that could assess these experiences on a numeric scale, which is needed for statistical analyses in clinical trials of possible therapies. After a bit more refinement, questions were collated into the final instrument.
That instrument, the MG Symptoms PRO, assesses 42 items across five scales: ocular (eye-related) muscle weakness, weakness of face muscles (bulbar weakness), respiratory muscle weakness, physical fatigue, and muscle weakness and fatigue.
“The scales were purposefully designed as standalone to enhance score interpretation, and to allow for modular use (each scale can be used independently, depending on the specific concept of interest to be measured), given the heterogeneity [variability] of MG,” the researchers wrote.
“The extensive qualitative patient input has ensured that the MG Symptoms PRO contains items covering all concepts relevant to the patient experience of MG, and worded in an appropriate way, whilst removing items linked to less relevant concepts,” they added.
While noting that further research is needed to validate the new instrument, the researchers suggested that the MG Symptoms PRO “has great potential for both demonstration of treatment benefits in a clinical trial context and monitoring of symptom severity in a clinical practice setting.”
Their development steps could also be a model in crafting PRO tools for other rare diseases, they wrote.
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