Table 4.
Knowledge gaps that impede post-traumatic knee osteoarthritis prevention trials design and delivery.
| Aspect of triala design | Area | Gap |
|---|---|---|
| Population | Eligibility | What participant characteristics/features/markers are best to consider when including participants in trials? |
| Stratification | Should participants be stratified? Should stratification be done at enrollment or after? Should stratification be by participant characteristics (e.g., sex) or factors related to risk of OA, or intervention responsiveness? |
|
| Intervention | Timing | What is the best approach to define the window of opportunity for any given intervention? |
| Delivery | How is the acceptability (participants and providers) of an intervention (including dose and delivery mode) determined? | |
| Underlying mechanism | What are the mechanisms underlying the beneficial effect of interventions (e.g., exercise and lifestyle change, surgery, pharmaceutical) on pain, symptoms and function in persons at increased risk of knee PTOA? | |
| Comparator | Usual care | What is the definition of usual care for people at risk of OA after a traumatic knee injury? How does usual care vary internationally (and what is the best way to cater to this)? |
| Placebo | What is a credible placebo condition (controls for natural history, regression to the mean and contextual effects including attention, without offering a treatment effect) for education and exercise-based interventions? | |
| Other confounders | What is the best way to control for other factors that confound the intervention and outcome relationship (e.g., participant characteristics that change over time, other interventions)? | |
| Outcome | Primary symptomatic outcome | What is the optimum single symptomatic outcome (including composite outcomes) for use in trials that is reliable, valid, sensitive to change, meaningful to patients and clinicians, and acceptable to regulators? |
| Surrogate outcomes | What is the optimal method to define the transition from joint injury to early OA (relevant to eligibility criteria, end-point(s)) to ensure surrogate outcome(s) correlate with the stages of this transition appropriately? |
OA (osteoarthritis), PTOA (post-traumatic osteoarthritis).
a
The term trial throughout this table refers to secondary PTOA prevention trials.