Charles Jillings, CEO of Utilico, energized by strong economic momentum across Latin America. Watch the video here.
Good that there are better and better treatments in case we or our loved ones, or the world need it.
Downside of this is that say SNG got on to the Recovery trial, SOC is improving all the time. The goalposts to show statistically significant benefit over SOC gets more and more difficult.
If SNG need to get through another trial and get to market they really can't afford to **** around and waste more time. They really should be moving this on to the hand of people capable to getting a large P3 trial done quickly.
You could be right Trinityman.
But another option is that SNG were just arrogant/complacent that there would be positive results from the Sprinter trial and put the building blocks for commercialisation in place too early.
I just hope they are taking this apart and not spending (what used to be) our money on supporting all this framework unless they have a plan to use it.
I looked at a chi squared test at the time of the home trial result and it showed that a study of the size of the
combined Active2 and home trial cohorts behaving as the home trial did would have reached significance.
Not sure if it would be valid or useful to look at the combined data, but makes clear that repeated small trials are
just ****ing in the wind.
Have not managed to read all the post here so apologies if this has been said..
Combined/metanalysis of the Active2 and home trial data could be very interesting.
If Active2 data is similar to that of the home trial, it is possible the combined dataset might have power to show a significant reduction in hospitalisations.
That could be a very useful finding from the point of applying for EUA.
Thanks Tommy D
From the Nature article on the Recovery trial:
'I have also been a bit surprised that some of the trials sponsored by pharmaceutical companies appear to be quite underpowered and small, given that there's no shortage of patients. It's hard to see the rationale for doing trials in fewer than 1,000 patients for a pharmaceutical company that's trying to get regulatory approval for a drug. I'm not sure what the barriers are to bigger trials, and I think that's an important point that needs some reflection.'
'I also hope that RECOVERY — as well as the REMAP-CAP trial — have made some pharmaceutical companies rethink clinical trials. Initially, companies would say to us “we're not very interested in your trial. It's too simple, too big, and it won't meet regulatory requirements”. But they come back to us once their very complicated, underpowered trials have given them an equivocal result. I think this will make drug companies think again about whether they want to spend tens of millions on a trial in 1,000 patients, or work with a national platform trial that will cost them a lot less and will give them a more definitive answer.
Yes, great find. I don't know what statistical test it was running.
But I suspect that if the trial had been larger, even 900 patients, or double the size, it would have given a significant result.
So, eg trying 64 placebo and 40 sng.
I think we didn't need to do better, just have a bigger trial to get to a significant result.
No this does not mean rights issue.
The platform trials are government run and able to provide protocols with large number of patients.
This allows suitably powered trials to be completed quickly at no cost to the company.
From the limited statistical analysis I could do on the data presented, I strongly believe that the P3 was just too small and underpowered to provide statistically significant results in the context of change in standard of care.
The placebo group did much better in the P3 study because of the improvement in standard of care, including steroids and remdesivir, I think the further improvement (36-40%) in progression to severe disease and death with SNG over the placebo group would be statistically significant in a trial with a larger number of patients.
So what they are saying is that SNG probably did work, but we need to repeat the P3 in a large free government funded platform trial to prove this. This is not all over by any means.
With reference to my post two below on why the trial failed.
In the presence of steroids, SNG still showed upto 40% reduction in deaths/severe disease. SNG was clearly working well with the steroids.
My point 1 is a much bigger factor in why the trial failed.
I think there is some confusion here.
In the context of this trial, certainly for the sd/death data, we wanted a statistically significant difference between the treatment and placebo groups.
1) If you add steroid to both groups and the placebo group do better because of the steroid, the difference between the groups is smaller. SNG was still effective and the result showed a strong trend but would have needed a bigger number of patients to be suitably powered to show significance. Unfortunately Synairgen did an underpowered trial.
2) It is also possible that the effectiveness of interferon is reduced in the presence of steroid.
However, I think that 1 rather than 2 is the biggest reason for failure to get significance for severe disease/death. It is important not to confuse the two issues and blame steroids. This is not the reason the trial failed. It failed because it was not designed well enough and was underpowered.
Thanks Wigster.
Reminds me of a genuine conference paper I once saw.
The study was examining motion sickness.
The grant had covered purchase of a Porsche to carry out the trial.
Guy presenting the paper looked very pleased with himself.
Ah alpha dog, great post while I was typing.
I used the per protocol data. Not sure why we got different answers.
Was your the intention to treat group?
But nonetheless, does show that a properly powered trial with death/severe disease as primary endpoints really does need to be done by someone.
No this can't be done.
From what was reported data were 16 day and 35 day for P2 and P3 respectively,
Standard of care changed.
You need to specify a protocol for a drug trial then do that, you can't just drag figures out of post hoc analyses.
However, I did look at it anyway with a chi-squared test and p2/p3 combined data for severe disease/death would have given a significant effect at p=0.0355. This certainly does warrant another study, it is a headline grabbing effect and makes clear that SNG would save a lot of lives. However, it would not be a small trial. It would probably need at least 1000 patients and probably more to be suitably powered. Not something SNG have any chance of doing themselves at the moment. It could be via a large platform trial, but only if the protocol was right for SNG, not if it was just 'being on a trial' and meandering through another few years with another disappointing outcome. The other alternative is to sell on to a major who would be able to do a well planned, suitably powered repeat P3 probably fairly quickly.
Not much point in looking at it, but checked combined P2 and P3 severe disease and death data.
What I can see is different, 16 day and 35 day respectively.
Cant do their analysis, but enough for a chi-squared test.
For P2 + P3; per protocol data
placebo 261+43 = 304
SNG 256 + 43 = 299
severe disease or death, placebo 32+11 = 43
severe disease or death, SNG 20 + 6 = 26
Don't guarantee my calculations, but looks like this would have been significant at p= 0.0356.
We were so close, effect is there we just didn't show it in this trial.
Given the AZ and molnupiravir data fiascos that got through to EUA, pity we can't discuss these things with FDA.
Great post Jim, thank you.
Agree on all you say. I tried a chi-square on the severe disease and death figures.
If this had been a primary end point and they had stuck to the original 900 patients this would have given a significant result at p=0.0263.
We were very close, just didn't choose our strongest primary end points and the trial was slightly too small.
What this means is that SNG does work, just this trial didn't show what we needed. So going into a larger platform trial of hospitalised patients with the correct end points looks like a very good plan. Also this gives clear direction to a major on the P3 trial they would need to run to get a blockbuster drug. This may make us a clear takeover target in the not too distant future.
Thanks for the positive. This really is not over, plenty more to come from SNG.
Sakura,
Most posters here have avidly followed the Covid research findings over the past 18 months and these help inform their investment decisions.
Possibly you have researched interferon as a treatment in the past, but what you are missing is the overwhelming evidence that Covid is exceptionally good at bypassing our interferon immune response. Furthermore there is overwhelming evidence that people most susceptible to severe covid are those with genetic or antibody issues with their own interferon response.
If you are really informed in any way about interferon as a treatment I am sure you will be capable of researching the particular potential it has for Covid.
I am sure we are all grateful for your concern for our investments, but you may wish to better inform yourself before posting further on this board.
This 'moderately ill' person in the molnupiravar trial sounds quite unwell.
Normal adult respiratory rate is 12 to 20 per minute.
Raised to over 24 sounds like they are breathless.
Normal blood O2 level is over 95%, so SpO2 of 90-93% is in the hypoxic range.
This person would likely be breathless.
Would be so good if the was a treatment for people who are breathless with Covid infections.
Oh ...
With respect Doc, I happen to be a real doc.
If you read what I said, the reduction to 60% efficacy for AZ 2 doses is exactly what is reported from real world testing and is reduced because delta partially evades this vaccine.
Certainly not going to pick a fight with you when you are the guardian of the board and I have a busy day ahead.