The Japan Registry for Adult Subjects of Spinal Muscular Atrophy (jREACT-SMA): Protocol for a Longitudinal Observational Study
Bibliographic record
Abstract
BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive genetic neuromuscular disorder with progressive muscle weakness and atrophy, mainly caused by lower motor neuron degeneration resulting from decreased levels of the survival motor neuron protein. Recently, 3 disease-modifying therapies for SMA (nusinersen, onasemnogene abeparvovec, and risdiplam) were approved in Japan that are expected to improve the prognosis of patients with SMA. Long-term clinical follow-up of adult patients treated with disease-modifying therapies and the natural history of SMA are essential to assess the real-world effectiveness of available treatments. Until recently, nusinersen was the only treatment option for patients with SMA in Japan; however, because Japanese approval of nusinersen was based on global clinical trials in infants and children aged 0-15 years with SMA, the effectiveness of nusinersen in adult patients has not been fully assessed in Japan. In addition, longitudinal clinical data of adult patients have not been systematically collected in Japan. OBJECTIVE: This longitudinal observational study of adult patients with SMA who have been diagnosed with 5q-SMA in Japan aims to gain a better understanding of the natural history of SMA, as well as the long-term effectiveness of disease-modifying therapies. Here, we describe the protocol for the study. METHODS: The Japan Registry for Adult Subjects of Spinal Muscular Atrophy (jREACT-SMA) study is a longitudinal (prospective and retrospective) observational study with a 60-month prospective follow-up being conducted at 19 investigational sites using the newly established jREACT-SMA registry. Patients aged ≥18 years with genetically confirmed 5q-SMA were planned to be enrolled in the registry from December 2020 to May 2022. The planned enrollment was 100 patients. The protocol was approved on September 28, 2020 (approval 2020-0289) by the ethical review committee of Nagoya University. Registration, demographics, genetic diagnosis, motor functions, patient-reported outcomes/quality-of-life outcomes, and other clinical data have been or will be collected. RESULTS: As of May 2022, 113 patients had been enrolled, and the completion of patient registration has been extended from May 2022 to December 2022. Data at registration and during the follow-up period were and will be prospectively collected at least once a year until November 2025 (maximum 60 months). Data analyses will be conducted when all data have been collected. Results are expected to be available in 2026 and the study is expected to be completed by March 2027. CONCLUSIONS: This jREACT-SMA study will provide longitudinal prospective follow-up data in adult patients with SMA in Japan, including data on the natural history of the disease and data on the long-term effectiveness of disease-modifying therapies. TRIAL REGISTRATION: University Hospital Medical Information Network Center Clinical Trials Registry UMIN000042015; https://rctportal.niph.go.jp/en/detail?trial_id=UMIN000042015. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38878.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.024 | 0.016 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.002 | 0.004 |
| Science and technology studies | 0.003 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.016 | 0.004 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".