Patient-reported outcomes — particularly those related to general physical and arm function — effectively reflect disease severity in people with late-onset Pompe disease as assessed with validated clinical measures, a study suggests.
Selected outcomes, part of the Patient-Reported Outcomes Measurement Information System (PROMIS), were found to represent the disease’s impact on patients’ health-related quality of life and to address unmet needs.
These findings suggest that selected PROMIS questionnaires may be used to assess Pompe disease severity and to monitor changes over time both in clinical trials and in the clinic, helping to provide a new level of understanding of the disorder and its progression.
Future studies, however, are needed to validate these questionnaires in larger groups of Pompe patients and over time, the researchers said.
While clinical outcomes can measure physical, physiological, and biochemical data about a patient, they cannot assess all the effects of a disease or treatment. Patient-reported outcomes allow people to report the status of their condition as a whole or as specific symptoms or signs without interpretation by a clinician.
They also provide insight into patients’ perceptions of how their disease or treatment is affecting their quality of life, especially important to those whose chronic diseases include considerable economic strain and overall disease burden.
As such, the combined used of clinical assessments and patient-reported outcomes “may provide a substantial body of evidence to support the conclusion that a treatment … is providing clinical benefit,” the researchers at Amicus Therapeutics and Duke University Medical Center wrote.
However, patient-reported outcomes that can be widely used in therapy development and clinical trials are not yet validated for all diseases.
The team evaluated five patient-reported outcome measures from PROMIS and their association with objective measures of disease severity in late-onset Pompe.
Funded by the National Institutes of Health, PROMIS provides a set of patient-reported measures to assess a disease’s impact on a person’s physical, mental, and social well-being.
The selected PROMIS questionnaires assessed clinically relevant signs and symptoms of Pompe disease: pain interference on a patient’s life, upper extremity function, fatigue, physical function, and shortness of breath.
The researchers analyzed potential associations between these questionnaires and three related clinical outcome measures: the 6-minute walk test (6MWD), the Manual Muscle Test (MMT; overall, upper body, and lower body), and forced vital capacity (FVC).
While the 6MWD measures the distance an individual is able to walk on a hard, flat surface in that time, the MMT assesses muscle strength and function. In turn, FVC measures the total amount of air that can be blown forcefully after a deep breath.
In the study, 30 adults (18 women and 12 men) with late-onset Pompe participating in a Duke natural history study of the disease completed the five PROMIS questionnaires and underwent clinical assessment (6MWD, MMT, and FVC) during a single visit.
Their mean age was 51 (range, 18–79 years), and they were diagnosed at a mean age of 44; all were able to walk unaided.
In parallel, five members of Amicus’ patient advisory board — two patients, two caregivers, and one caregiver and patient advocacy organization leader — rated the overall relevance of the selected PROMIS questionnaires. They also determined whether questions in these measures represented a symptom and/or a sign for which there is an unmet need in Pompe disease.
Notably, the advisory board did not evaluate the interference pain questionnaire, which is a study limitation, the researchers said.
Results showed moderate to strong associations between the 6MWD and MMT (overall, upper, and lower body) scores, and those of the physical and upper extremity function PROMIS questionnaires.
“The correlations indicate that the clinical outcome measures assess important concepts related to patient-reported experiences,” the researchers wrote, adding that they supported the use of PROMIS questionnaires “because they confirmed the motor signs and symptoms of functional disability observed in patients with Pompe disease.”
In addition, the patient advisory board rated the four evaluated PROMIS questionnaires as important in representing disease impact on a patient’s health-related quality of life. They also considered that most of the questions did address an unmet need.
These findings suggest that the selected PROMIS questionnaires “are meaningful and address important concepts to patients with Pompe disease,” the team wrote.
“Further studies are needed with additional PROMIS questionnaires, which should include measures of motor function and health-related quality of life, in a larger number of patients followed up [over time],” the researchers added.
Should they prove their worth, these patient-reported outcomes may be used for diagnostic and prognostic purposes, as well as to determine trial eligibility. They could also “provide further insight into understanding patient related disease specific signs and symptoms,” the team concluded.
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