Design of a Non-Interventional Study to Validate a Set of Patient- and Caregiver-Oriented Measurements to Assess Health Outcomes in Spinal Muscular Atrophy (SMA-TOOL Study)

Abstract

Introduction There is a need to optimize the current clinical outcome measures in spinal muscular atrophy (SMA) incorporating patients’ and caregivers’ perspectives. The aim of this study is to evaluate the psychometric properties (validity, reliability and sensitivity to change) of a set of existing questionnaires and newly created items grouped in a “toolbox” to assess the impact of SMA on the physical, psychological and activities of daily living domains of the patient’s life. Methods This non-interventional, prospective study will be conducted at 12 neuromuscular clinics specialized in the management of patients with SMA in Spain. An expert panel of pediatric and adult neurologists, rehabilitation physicians, and a patient representative participated in the study design and selected key disease dimensions to explore and their respective measurements: mobility-independence, fatigue and endurance, pain, fatigability, breathing and voice, sleep and rest, and vulnerability. Patients aged 2 years or older with a confirmed diagnosis of 5q-autosomal recessive SMA (genetic confirmation of homozygous deletion or heterozygosity predictive of loss of function of the SMN1 gene) will be recruited. Planned Outcomes The development of robust outcome measures in collaboration with the patient community is essential to determine what is meaningful to patients and their caregivers. This study will provide us with a comprehensive set of tools to better capture the course of the disease and the response to treatments.

Therapeutic Decision-Making Under Uncertainty in the Management of Spinal Muscular Atrophy: Results From DECISIONS-SMA Study

“…The therapeutic landscape of SMA has become more complex with the approval of new therapies unveiling physicians’ inherent uncertainties when starting a new agent [ 5 , 10 , 24 ]. Most studies have been evaluating therapeutic decision-making in SMA from the perspective of patients and their caregivers and family members [ 13 – 16 , 28 – 31 ]. Briefly, these studies highlighted the importance of maintaining functional status and the need to develop sensitive scales able to detect small changes in a patient-centered spectrum of dimensions beyond motor function.…”

“…Participants were exposed to 11 simulated case scenarios or case vignettes (Supplementary Material; answers in bold were considered suboptimal treatment decisions). Case scenarios were designed by a research team led by GS and IM and based on the most common situations experienced by pediatric neurologists in clinical practice and after reviewing SMA clinical trials and patients’ and caregivers’ preferences from the literature [ 5 , 10 , 13 – 16 ].…”

Validation of a Set of Instruments to Assess Patient- and Caregiver-Oriented Measurements in Spinal Muscular Atrophy: Results of the SMA-TOOL Study

“…The set of outcome measurements included the SMA Independence Scale (SMAIS), the Neuro-QoL Fatigue Computer Adaptive Test (CAT), the Neuro-QoL Pain Short Form–Pediatric Pain, the PROMIS adult Pain Interference CAT, and new items developed using qualitative methods by Fundación Atrofia Muscular España (FundAME) to assess perceived fatigability, breathing and voice, sleep and rest, and vulnerability [ 21 – 27 ]. This set was selected by a multidisciplinary research team of pediatric and adult neurologists, rehabilitation physicians, and a patient representative [ 27 ]. Patients and parents completed the study questionnaires in person during their regular follow-up visits at the neuromuscular units.…”

“…Higher scores in both scales indicate worse self-reported pain. The perceived fatigability, breathing and voice, sleep and rest, and vulnerability assessments consist of 10–11, 8, 3, and 9 self-reported items, respectively [ 27 ]. Neuro-QoL tests and FundAME’s items were fulfilled by caregivers in the case of patients under 8 years of age.…”

Treatment of spinal muscular atrophy in European countries: A call to action

“…This limits their usefulness and emphasizes the need to implement additional outcome measures in these patients [12,13]. Several bedside multidimensional tests and patient-reported outcome measures have already been proposed and validated for SMA patients [13,14] and may help in the decision-making process at an individual level [7], but these are usually neglected by regulators. Furthermore, long-term stabilization in a neurodegenerative disease such as SMA may be considered clinically significant [12].…”