ReviewOsteoarthritis and cartilage2019
Proposed study designs for approval based on a surrogate endpoint and a post-marketing confirmatory study under FDA's accelerated approval regulations for disease modifying osteoarthritis drugs.
Review in Osteoarthritis and cartilage, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed.
- Therapeutic subtypes of knee osteoarthritis: differential treatment effects among predicted endotypes in past clinical trials.Arthritis research & therapy · 2026Article
- Weight loss ameliorates symptoms of osteoarthritis and is correlated with alterations in soluble bone and cartilage markers: an analysis of patient-reported outcomes and biomarkers.BMC rheumatology · 2026Article
- Injectable hydrogel microspheres delivering cartilage-targeted LGR5-engineered exosomes for osteoarthritis therapy.Materials today. Bio · 2026Article
- Article
- The inflammatory endotype in osteoarthritis: Reflections from the 2024 OARSI clinical trials symposium (CTS) with a special emphasis on feasibility for clinical development.Osteoarthritis and cartilage open · 2025Review
- Perspective: Empowering osteoarthritis drug development through assessment of synovitis by CE-MRI: A new approach in clinical trials.Osteoarthritis imaging · 2025Article
- Which Endpoints Should be Applied in Interventional Trials? -: From Single Uni-dimensional Assessment Tailored to a Drug's Mechanism of Action to Multi-Component Measures and Multi-Domain Composites.Osteoarthritis imaging · 2025Article
- Association between type III collagen degradation and local tissue damage of a single joint.Osteoarthritis and cartilage open · 2024Article
- Surrogate endpoints for neonatal outcome: A rapid review.Health science reports · 2024Article
- Molecular biomarker approaches to prevention of post-traumatic osteoarthritis.Nature reviews. Rheumatology · 2024Review
- Biomarkers in osteoarthritis: current status and outlook - the FNIH Biomarkers Consortium PROGRESS OA study.Skeletal radiology · 2023Review
- Reflections from the OARSI 2022 clinical trials symposium: The pain of OA-Deconstruction of pain and patient-reported outcome measures for the benefit of patients and clinical trial design.Osteoarthritis and cartilage · 2023Review
- Placebo effects in osteoarthritis: implications for treatment and drug development.Nature reviews. Rheumatology · 2023Review
- Targeting FoxO transcription factors with HDAC inhibitors for the treatment of osteoarthritis.Annals of the rheumatic diseases · 2023Article
- Latest insights in disease-modifying osteoarthritis drugs development.Therapeutic advances in musculoskeletal disease · 2023Review
- US Food and Drug Administration Accelerated Approval Program for Nononcology Drug Indications Between 1992 and 2018.JAMA network open · 2022Article
- Reflections from the 2021 OARSI clinical trial symposium: Considerations for understanding biomarker assessments in osteoarthritis drug development - Should future studies focus on disease activity, rather than status?Osteoarthritis and cartilage open · 2022Article
- Multivariable Modeling of Biomarker Data From the Phase I Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium.Arthritis care & research · 2022Article
- The current state of the osteoarthritis drug development pipeline: a comprehensive narrative review of the present challenges and future opportunities.Therapeutic advances in musculoskeletal disease · 2022Review
- Repurposed and investigational disease-modifying drugs in osteoarthritis (DMOADs).Therapeutic advances in musculoskeletal disease · 2022Review
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Authors and funding
7 authors.
Funding
Abstract
In 1992, the Food and Drug Administration (FDA) instituted the accelerated approval regulations that allow drugs or biologics for serious conditions that fill an unmet medical need to be approved on the basis of a surrogate endpoint or an intermediate clinical endpoint. The current definition of a serious condition includes chronic disabling conditions, such as osteoarthritis (OA), and thereby provides expanded opportunities for the use of biomarkers for regulatory approval of drugs for OA. The use of surrogates or intermediate clinical endpoints for initial regulatory approval of a drug or biologic requires confirmation in a post-marketing study of a drug effect on a clinically relevant outcome, such as on how a patient feels, functions or survives. Current FDA guidance requires that the post-marketing approval (PMA) study be ongoing during the time of initial drug approval. This white paper arose out of the need to brainstorm trial designs that might be suitable for PMA of drugs initially approved, on the basis of a surrogate or intermediate clinical endpoint, for treatment of OA to alter disease progression, abnormal function or pathological changes in the morphology of the joint. In this white paper we define the concept and regulations regarding accelerated approval and propose two major study design scenarios for PMA trials in OA. The long-term goal is to discuss and refine these designs in consultation with regulatory agencies in order to facilitate development of drugs to fill the large unmet need in OA.
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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.