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Standardized Histomorphometric Evaluation of Osteoarthritis in a Surgical Mouse Model
Published on: May 6, 2020
Safety issues in the development of treatments for osteoarthritis: recommendations of the Safety Considerations
1Division of Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto, CA, USA. vstrand@stanford.edu
Objective:
The symptomatic treatment of osteoarthritis (OA) remains to be improved, as many patients do not respond well to current palliative therapies and/or suffer unacceptable adverse events. Given the unmet need for innovative, effective and well-tolerated therapies, it is important to develop the means to estimate the ongoing safety profile of novel therapeutic agents over short- and longer term use.
Design:
Methods are presented to estimate the number of serious adverse events (SAEs) of interest considered as "acceptable" per 1000 patient-years exposure and to estimate the numbers of patient-years needed in a randomized controlled trial (RCT) to meet objectives. As exposure is increased, more evidence is accrued that the overall risk is within study limits. It is equally important that requirements for delineating the safety of promising new therapies not create barriers that would preclude their development. Therefore, ongoing surveillance of occurrence of SAEs of interest during clinical development is proposed, for example after every incremental 500 patient-years exposure are accrued.
Results:
This paper and others in this special issue focus on identification of safety signals for symptomatic treatments of OA. Much less information is available for agents aimed at slowing/preventing structural progression but it is expected that a higher risk profile might be considered acceptable in the context of more promising benefit.
Conclusion:
This paper provides a proposal and supporting data for a comprehensive approach for assessing ongoing safety during clinical development of both palliative and disease-modifying therapies for OA.
Insights
Developing new osteoarthritis (OA) treatments requires robust safety assessments. This study proposes methods to evaluate serious adverse events (SAEs) during clinical trials for OA therapies, ensuring patient safety and drug development.
Area of Science:
- Pharmacovigilance and clinical trial methodology.
- Osteoarthritis (OA) therapeutics development.
Background:
- Current osteoarthritis (OA) treatments have limitations in efficacy and tolerability.
- There is a critical need for novel OA therapies with improved safety profiles.
- Assessing the safety of new OA drugs requires robust methodologies.
Framework:
- Proposes a framework for estimating acceptable serious adverse event (SAE) rates per 1000 patient-years.
- Outlines methods for determining required patient-years in randomized controlled trials (RCTs) for safety assessment.
- Advocates for continuous safety surveillance during clinical development, with regular data reviews.
Implementation:
- Suggests ongoing monitoring of SAEs of interest throughout the clinical development process.
- Recommends periodic safety reviews, e.g., after every 500 patient-years of exposure.
- Provides a comprehensive approach for assessing safety signals of OA treatments.
Implications:
- Facilitates the development of safer and more effective OA therapies.
- Aims to balance the need for rigorous safety evaluation with the timely progression of drug development.
- Supports the assessment of both symptomatic and disease-modifying OA treatments.