Ann: Results of Phase 2 Clinical Trial, page-149

The results from the Harding study were published:  Effectiveness of an acellular synthetic matrix inthe treatment of hard-to-heal leg ulcers.Int Wound J.2014 Apr;11(2):129-37. doi: 10.1111/iwj.12115. Epub 2013 Jul 9.  

Unfortunately the paper is not open access so (mostof) you will have to take my word for things a bit.  But the key finding was:  “The incidence of complete healing was 16 of 45patients, that is 35·6% (Figure 3), and the median wound area percentagereduction was 70·8% (Table 3).”

Harding thought the results were positive and heconcluded: “It may therefore be hypothesised that earlyreferral and addition of the ECM protein as an adjunct to standard care maybring about a significant improvement in patient outcomes.” 

So the study results are exploratory – theygenerate a hypothesis that the treatment MAY be beneficial. 

FTT come along and conduct a RCT to test theHarding hypothesis. The results are around the Harding mark - around 37% getcomplete healing and the average wound are reduction was around 60%. Trouble is this about the same as the SC + placebo comparator.  FTT think the SC provided in the trial was betterthan routine care.

So how does this happen?  Well it sneaks up on you. SC in its natural state isa dogs breakfast – it varies across sites and even within sites (luck of thedraw the quality of the treatment you receive). So by going up against it withyour new product you are always open to the criticism you choose sites withcrappy SC. 

But it had one compelling advantage. It was free –after you randomised the site picked up the costs for SC and you picked up thecosts for the new treatment.  Right up until about a decade (?) ago when the USgovernment twigged to the earner here. If the trial randomises patients totreatments in effect the trial is deciding the treatments patients receive andit should pay for them – all of them including SC. 

On the upside by paying for SC you were now able tostandardise it. But standardise it to what?  The first answer people sayis best practice guidelines based treatment. But this will always be far betterthan routine care; so you are up against a powerful foe. 

So a cleverer approach is to standardise acrosssites to SC delivered at the best site. But there is a problem. What happens isby paying for SC this injects a big wack of cash into sites and re-moralisesstaff. Who as good health professionals use the money to provide bettertreatment in routine care; and better than you lowered SC bar treatment. And then all this interacts with yourcost-effectiveness modelling of outcomes in ways no-one can understand excepthealth economists and the problem is no-one can understand them. So its all very tricky. 

But I would hazard a guess the people designingthis trial were pretty internal validity type guys. So control for everything.As opposed to external validity where you test against a real world loosercomparator of SC which more closely resembles routine care. So for the salt inthe wound … by paying for gold standard SC you pay for the pleasure of failing. 

But I think the question you guys have is was theefficacy signal from Harding strong enough to warrant spending $20m on a trial.Or was it all a con from the start. 

Well you have good grounds for being a little waryof the Harding results – he was on the TIS scientific board – and most of theauthors had links back to TIS.   Hopefully FFT did get some independent expertopinions about the degree of efficacy based on the cohort he was working with.I also understand from an early investor presentation that FTT ran somepropensity score matching back to a comparator from a large published UK dataon chronic VLU.  Exactly how rigorous this all was you will neverknow without being able to study it closely.  

All this aside I did like this trial … one ofthe best at this MC level I think I have seen. So the results are a realbugger.  I don’t think that even with my general negativityI would really have argued with the Sinartra probability of success he gave of65%. Unfortunately from what I can see here I don’t think everyone placed theirbets according to a 65% POS. Hence the pain.

And for full disclosure I should say I count CB asa “virtual” friend – although we haven’t corresponded for a year or more. And Inever really looked at this trial much before now (and even now it’s reallyjust a skim through) … so it is entirely possible I have got the wrong end ofthe stick somewhere.