ReviewOrphanet journal of rare diseases2021
The multi-domain responder index: a novel analysis tool to capture a broader assessment of clinical benefit in heterogeneous complex rare diseases.
Review in Orphanet journal of rare diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 8 registered trials, which are not on this map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Study of Recombinant Human N-acetylgalactosamine 4-sulfatase (rhASB) in Patients With MPS VI
A Phase II/III, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Weekly and Every Other Week Dosing Regimens of Iduronate-2-Sulfatase Enzyme Replacement Therapy in Patients With MPS II
A Multicenter, Multinational Open-Label Extension Study of Recombinant Human N-acetylgalactosamine 4-sulfatase (rhASB) in Patients With Mucopolysaccharidosis VI
A Multicenter, Multinational, Open-Label Extension Study of the Safety and Efficacy of Aldurazyme® (Laronidase) in Patients With Mucopolysaccharidosis I
A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Multinational, Clinical Study of Recombinant Human Alpha L-Iduronidase In Patients With Mucopolysaccharidosis I
A Randomized, Placebo-Controlled, Blind-Start, Single-Crossover Phase 3 Study to Assess the Efficacy and Safety of UX003 rhGUS Enzyme Replacement Therapy in Patients With MPS 7
A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Sialic Acid Extended-Release Tablets in Patients With GNE Myopathy (GNEM) or Hereditary Inclusion Body Myopathy (HIBM)
A Long-Term Open-Label Treatment and Extension Study of UX003 rhGUS Enzyme Replacement Therapy in Subjects With MPS 7
Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Anakinra in Sanfilippo syndrome: a phase 1/2 trial.Nature medicine · 2024Trial
- Outcome strategies for clinical trials in Neuropaediatric rare diseases.Neuroscience applied · 2026Review
- Navigating Drug Discovery for Myhre Syndrome: The Complexity of a Multisystemic Rare Disease.American journal of medical genetics. Part C, Seminars in medical genetics · 2025Review
- Beyond Seizures as an Outcome Measure: A Global Severity Scoring System for CDKL5 Deficiency Disorder.Brain and behavior · 2025Observational
- Longitudinal characterization of clinical, developmental, and behavioral phenotypes in 101 children and adults with FOXG1 syndrome.Journal of neurodevelopmental disorders · 2025Article
- Clinical Trial End Points for Childhood CKD.Journal of the American Society of Nephrology : JASN · 2025Article
- Caregiver Global Impression Observations from EMBARK: A Phase 3 Study Evaluating Delandistrogene Moxeparvovec in Ambulatory Patients with Duchenne Muscular Dystrophy.Neurology and therapy · 2025Article
- A framework for N-of-1 trials of individualized gene-targeted therapies for genetic diseases.Nature communications · 2024Review
- Pathway for Development and Validation of Multi-domain Endpoints for Amyloid Light Chain (AL) Amyloidosis.Therapeutic innovation & regulatory science · 2024Review
- Istore: a project on innovative statistical methodologies to improve rare diseases clinical trials in limited populations.Orphanet journal of rare diseases · 2024Article
- Generalized pairwise comparisons of prioritized outcomes are a powerful and patient-centric analysis of multi-domain scores.Orphanet journal of rare diseases · 2023Article
- Targeting shared molecular etiologies to accelerate drug development for rare diseases.EMBO molecular medicine · 2023Review
- Impact of the COVID-19 pandemic on health care and daily life of patients with rare diseases from the perspective of patient organizations - a qualitative interview study.Orphanet journal of rare diseases · 2023Article
- Scaling genetic resources: New paradigms for diagnosis and treatment of rare genetic disease.American journal of medical genetics. Part C, Seminars in medical genetics · 2023Article
- Designing clinical trials for rare diseases: unique challenges and opportunities.Nature reviews. Methods primers · 2022Article
- MPSI Manifestations and Treatment Outcome: Skeletal Focus.International journal of molecular sciences · 2022Review
- Review of neuropsychological outcomes in isolated methylmalonic acidemia: recommendations for assessing impact of treatments.Metabolic brain disease · 2022Review
- Neurocognitive assessment platform for clinical trials in PKU: White paper developed by the NPKUA neurocognitive workgroup.Molecular genetics and metabolismArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In traditional clinical trial design, efficacy is typically assessed using a single primary endpoint in a randomized controlled trial to detect an expected treatment effect of a therapy in a narrowly selected patient population. This accepted paradigm is based on clinical evaluations that may not actually capture the breadth of the impact of a disease, which is especially true in the setting of complex, multisystem, rare diseases with small, extremely heterogeneous patient populations. The multi-domain responder index (MDRI) is a novel approach that accommodates complex and heterogeneous disease manifestations and evaluates a broad array of clinical disease without impairing the power or rigor of a study to fully understand a treatment. The MDRI sums the scores corresponding to clinically significant thresholds of change for each component domain in each individual patient, capturing the mean clinically meaningful change across multiple domains within individuals. This novel approach combines and then sums the results of independent domain endpoint responder analyses into one responder score to provide a broad basis for the assessment of efficacy. The impact of a treatment across multiple, physiologically independent domains, can be assessed clinically, reducing the adverse impact of heterogeneity on trial outcomes and allowing eligibility criteria to enroll a wider range of patients, ultimately resulting in efficacy and safety assessments of a therapy across a broad group of heterogeneous patients in rare disease programs.Trial registration The following studies are referenced within this manuscript (CLINICALTRIALS.GOV registration numbers): NCT00912925; NCT00146770; NCT00067470; NCT00104234; NCT00069641; NCT02230566; NCT02377921; NCT02432144.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.