Concept End Points Informing Design Considerations for Confirmatory Clinical Trials in Osteoarthritis
| Autor: | Gregory Levin, Nikolay P Nikolov, Robert Abugov, Rebecca Rothwell, Yura Kim |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
musculoskeletal diseases
030203 arthritis & rheumatology medicine.medical_specialty business.industry Incidence Total knee replacement Outcome measures MEDLINE Pain Osteoarthritis Osteoarthritis Knee medicine.disease Clinical trial 03 medical and health sciences 0302 clinical medicine Rheumatology Sample size determination Physical therapy medicine Clinical endpoint Humans Observational study Arthroplasty Replacement Knee business Pain Measurement |
| Zdroj: | Arthritis Care & Research. 74:1154-1162 |
| ISSN: | 2151-4658 2151-464X |
| Popis: | Objective There is an unmet need for therapies that target the underlying pathophysiology of osteoarthritis (OA). However, defining appropriate measures for clinical trials of such therapies is challenging. Our objective is to propose concept clinical endpoints that directly capture clinical benefit in this setting and evaluate the feasibility of their use. Methods This analysis used the multi-center, longitudinal, observational Osteoarthritis Initiative (OAI) database. OAI participants primarily had knee OA, with follow-up of up to nine years and assessments of joints, surgical interventions, performance outcomes, and patient-reported outcomes (PROs). We examined this dataset to identify existing outcome measures of direct clinical benefit. We evaluated the feasibility of conducting trials using these candidate endpoints by estimating incidence rates and resulting required sample sizes and study durations in time-to-event analyses. Results We identified candidate endpoints based on total knee replacement (TKR) and composite endpoints defined by TKR and conservative thresholds of PROs of pain and function. Using time to TKR as an endpoint, a study with an average follow-up time of three years requires approximately 3,000 to 18,000 subjects depending on effect size. Alternatively, a composite endpoint such as 'time to TKR or severe pain or severely impaired functioning', the required sample sizes ranged from approximately 2,000 to 11,000 for a three-year study. Conclusion The proposed concept endpoints can reliably and feasibly evaluate effectiveness of therapies for this unmet need. In particular, the composite endpoint approach can substantially reduce sample sizes (up to approximately 40%) compared to the use of TKR alone. |
| Databáze: | OpenAIRE |
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