Whittaker Jackie L, Kalsoum Raneem, Bilzon James, Conaghan Philip G, Crossley Kay, Dodge George R, Getgood Alan, Li Xiaojuan, Losina Elena, Mason Deborah J, Pietrosimone Brian, Risberg May Arna, Roemer Frank, Felson David, Culvenor Adam G, Meuffels Duncan, Gerwin Nicole, Simon Lee S, Lohmander L Stefan, Englund Martin, Watt Fiona E
Department of Physical Therapy, University of British Columbia, Vancouver, Canada.
Arthritis Research Canada, Vancouver, Canada.
Osteoarthr Cartil Open. 2024 Feb 23;6(2):100449. doi: 10.1016/j.ocarto.2024.100449. eCollection 2024 Jun.
The global impact of osteoarthritis is growing. Currently no disease modifying osteoarthritis drugs/therapies exist, increasing the need for preventative strategies. Knee injuries have a high prevalence, distinct onset, and strong independent association with post-traumatic osteoarthritis (PTOA). Numerous groups are embarking upon research that will culminate in clinical trials to assess the effect of interventions to prevent knee PTOA despite challenges and lack of consensus about trial design in this population. Our objectives were to improve awareness of knee PTOA prevention trial design and discuss state-of-the art methods to address the unique opportunities and challenges of these studies.
An international interdisciplinary group developed a workshop, hosted at the 2023 Osteoarthritis Research Society International Congress. Here we summarize the workshop content and outputs, with the goal of moving the field of PTOA prevention trial design forward.
Workshop highlights included discussions about target population (considering risk, homogeneity, and possibility of modifying osteoarthritis outcome); target treatment (considering delivery, timing, feasibility and effectiveness); comparators (usual care, placebo), and primary symptomatic outcomes considering surrogates and the importance of knee function and symptoms other than pain to this population.
Opportunities to test multimodal PTOA prevention interventions across preclinical models and clinical trials exist. As improving symptomatic outcomes aligns with patient and regulator priorities, co-primary symptomatic (single or aggregate/multidimensional outcome considering function and symptoms beyond pain) and structural/physiological outcomes may be appropriate for these trials. To ensure PTOA prevention trials are relevant and acceptable to all stakeholders, future research should address critical knowledge gaps and challenges.
骨关节炎的全球影响正在扩大。目前尚无改善病情的骨关节炎药物/疗法，因此对预防策略的需求日益增加。膝关节损伤的患病率很高，发病情况独特，且与创伤后骨关节炎（PTOA）有很强的独立关联。尽管在该人群的试验设计方面存在挑战且缺乏共识，但许多研究团队仍在开展研究，最终将进行临床试验，以评估预防膝关节PTOA的干预措施的效果。我们的目标是提高对膝关节PTOA预防试验设计的认识，并讨论应对这些研究独特机遇和挑战的最新方法。
一个国际跨学科团队举办了一次研讨会，该研讨会在2023年国际骨关节炎研究学会大会上举行。在此，我们总结了研讨会的内容和成果，目标是推动PTOA预防试验设计领域向前发展。
研讨会的亮点包括关于目标人群（考虑骨关节炎结局的风险、同质性和改变可能性）、目标治疗（考虑给药方式、时机、可行性和有效性）、对照（常规治疗、安慰剂）以及主要症状性结局的讨论，其中考虑了替代指标以及膝关节功能和疼痛以外的症状对该人群的重要性。
存在在临床前模型和临床试验中测试多模式PTOA预防干预措施的机会。由于改善症状性结局符合患者和监管机构的优先事项，共同主要症状性结局（考虑功能和疼痛以外症状的单一或综合/多维结局）和结构/生理结局可能适用于这些试验。为确保PTOA预防试验对所有利益相关者都具有相关性和可接受性，未来的研究应解决关键的知识空白和挑战。
