You might be interested in a review article that came out yesterday in a journal called Alzheimer’s & Dementia: Translational Research & Clinical Interventions.  It discusses the unique challenges in the design of clinical neuroprotection trials in PSP.

(“Neuroprotective” treatments, as many of these posts have explained, attempt to slow the rate of worsening after the diagnosis is made.  Measures to prevent disease in healthy people, like a flu shot, is called “preventative” and those to repair damage are “restorative.”  PSP is further from either of those than it is from protective treatment.)

The article points out that a major goal for PSP trials is reducing the number of subjects needed: the “N.”  That’s because the rarity of PSP makes it difficult to find qualified participants, and fewer of those means longer recruitment time and sometimes, longer trial periods. One way around that problem is more sensitive outcome measures, and that’s one goal of the search for better biomarkers. 

Another way around the problem of keeping the size of PSP trials manageable is to form an expectation at the study’s outset, based on existing research, of each subject’s likely progression over the next 12 months, calculate what percentage of that expectation actually occurs, and then compare active drug with placebo groups on their respective averages of that percentage.   

Another approach is to specify disability milestones such as progressing from independent gait to needing occasional assistance, or from a walker to a wheelchair, and then comparing the active drug and placebo groups according to how many milestones they reached over the 12 months.  One type of milestone is called the “minimum clinically important difference.” That’s the main driver of the article and I’ll explain it in a future post.

The authors of the new paper are myself and a statistician, Dr. Ronald Thomas, at University of California, San Diego.  It’s written at a level that most of you will be able to understand and I’d love to hear your honest reactions in the comments area.