Exactly what I was saying earlier. This is a phase II study people.
Phase I, safety and dosage amounts; Phase II, effectiveness, dose frequency, mechanism of action, etc; Phase III, all about powering to a primary measure of efficacy.
Phase II trials are literally a learning curve to work out exactly how to design your final phase III trial so you get a statistically valid result on your primary hypothesis on your blinded RCT.
Obviously the mkt liked the headlines, then likely read into the lack of statistically powered cartilage improvement in twice a week injection patients (around 20 of them) at 168 days (whilst the once a week injection saw 20% improvement). Now the company go away and look at that data, which is just one small aspect of heaps of data.
At day 56, Paradigm previously reported that participants receiving twice-weekly iPPS demonstrated a statistically significant improvement at Day 56 in pain, function, stiffness, and overall WOMAC of ≥30% and ≥50% improvement in pain were 73% and 60%, respectively.
Welcome to the difficulty of 'controlled' trials. Here's a hypothetical. Those patients with twice a week injections get such good early pain improvements, they go out and exercise too vigourously (after years of pain and inability) and erode any early cartilage improvements. Other regenerative treatments have rarely shown significant cartilage creation before 20 weeks. Whereas the once a week group who don't see such impressive early pain and function improvements, remain relatively sedentary which allowed for cartilage to establish against a context of less demanding/dynamic usage, hence the 20% cartilage improvement at 168 days in the once a week injection cohort.
I had some success with PRP years ago in two worn long bicep tendons from years of boxing. My Doctor remarked how well I benefitted versus his other patients. "What advice do you give them?" I asked. "To take it easy for a couple of weeks" he replied. I then informed him all about the cautious but progressive loading regime I engaged after his injections for months (before daring to try to box), with an understanding of biomechanical load and tendon adaption synthesis, whilst his other patients probably just went and tried playing tennis again on a dodgy patella tendon a couple of weeks later and then wondered why PRP did little for them! Tendons take months to even begin to heal, cartilage longer, if at all in poor vascular areas.
Trial operators cannot control the day to day habits of their patients. Perhaps what I suggest above is happening. Perhaps the company decides to go with once a week injections for greater cartilage improvements over early WOMAC improvements. Perhaps the company decides to split the Phase III trial into three groups, one with treatment alone, one with strict protocols on cautious progressive exercise regimes.
Expand
(20min delay)