PREP2 in Clinical Research

 

The challenge

Studying recovery and rehabilitation during the initial days and weeks after stroke is challenging. It can be difficult to detect the effects of a rehabilitation intervention against the background of improvement that patients experience during this time. This is one of the reasons why most motor rehabilitation research is carried out with patients 6 months or more post-stroke. But this is a problem, because most rehabilitation is delivered much sooner after stroke. We need to test interventions at the time of their intended use in clinical practice, which means we need to conduct rehabilitation trials during the initial days and weeks after stroke. You can read more about this here.

How PREP2 can help

PREP2 can be used to select and stratify patients in trials of motor rehabilitation interventions at the sub-acute stage of stroke. Treatment and control groups can be well-matched on baseline clinical characteristics, but differ in their outcomes because they have different underlying prognosis profiles. PREP2 can help you to match the prognosis profiles of your groups, so that you can more confidently attribute any differences in outcomes to your intervention.

Selection: PREP2 can help to select patients most likely to respond to the intervention’s hypothesised mechanism of action. Selecting patients on the basis of clinical scores alone runs the risk of including patients who cannot respond to your intervention, or excluding patients who can.

Stratification: PREP2 can help to ensure that your treatment and control groups have matched prognosis profiles, with similar proportions of patients in each predicted outcome category. Matching your treatment and control groups on the basis of clinical scores alone runs the risk of the two groups having different prognosis profiles, meaning their outcomes will differ regardless of any intervention.

For example, if your intervention is thought to promote recovery of upper limb function by increasing the excitability of the motor cortex in the stroke-affected hemisphere, then you might want to select patients with a functionally intact motor cortex and corticospinal tract. These patients might be more likely to benefit from your intervention than those who have sustained more severe damage to these structures. You could use PREP2 to select patients who are most likely to have a Good or Excellent upper limb outcome. This would let you include MEP+ patients with more severe initial impairment, because you know they still have a functional motor cortex and corticospinal tract. If you simply use a clinical score to exclude patients with more severe initial impairment, you run the risk of excluding patients who are MEP+ and might respond to your treatment, or including patients who are MEP- and can’t respond to your treatment. Ensuring that the treatment and control groups have similar proportions of patients with a Good and Excellent prognosis means that the two groups will be matched for overall outcomes. This should reduce between-group differences and increase the trial’s sensitivity to the effects of your intervention.