Good morning to you all. Have been reading with interest your valuable opinions.
I would like to add mine. First let's talk about EUA. I agree that we should have been given a EUA long time ago. FDA can request the data from DSMC, have a look and decide that is worth saving lives, mostly with a demonstrably safe drug. However this will not happen. We are a small company, we don't have friends in high places and our administrations are not the best to say the least. For those that know the story of CYDY and other small companies this should be evident. If it is not, forget the point above and rationalize your own opinions, which is fine.
But this is not he point. imo we don't have EUA due to a flawed system managed by a incompetent organization.
Now, we need to go through it as we are doing business in the USA.
In regards to approval, I disagree with most of you. Unbinding the data will not be beneficial. There is always the hanging sword of misuse and the trial being rendered invalid. I would be nervous of some of the data being miss-used (one way or another) and prefer we enroll 63 patients rapidly and reach the 75% goal.
Remeber: the board is working FOR us and we should follow their advise. Why??? They have seen the data and the analysis (one of them made it).
Why? Let's assume we had a ratio in number of deaths (LL/SOC) of 17.% vs 33.8% or 23/22 deaths (47.7% reduction of deaths), this will produce a p-value of 0.01681. Shall we stop the trial ??? These are pretty compelling numbers !!!!
Well, no. Simply because the POWER of this is just 70.1%. If one brings this data to Health Canada or MHRA and tell them: please approve us, look at these results !!! They will say: sorry, this is not statistically significant .... We need to remember that we have to have both a good p-value AND a good power.
The latter is often not mentioned in trials. Why? Because most are over-powered. GILD makes a trial with 2000 patients, are we going to tallk about the power? No. But we designed our trial with 390 for good reasons (money, resources, time-frame) so we need to live with his.
What is very encouraging is that the statistician of the DSMC considered that with 75% of patients we can probably meet statistical significance (p + power). This would indicate that we are now somewhere in the range 0.0065 - 0.016 meaning we could possible have a well-powered result with 293 patients.
All numbers above just imo, of course.
Let's keep our cool. If LL works we will have our day in court, even if this is not impartial.
I would like to add mine. First let's talk about EUA. I agree that we should have been given a EUA long time ago. FDA can request the data from DSMC, have a look and decide that is worth saving lives, mostly with a demonstrably safe drug. However this will not happen. We are a small company, we don't have friends in high places and our administrations are not the best to say the least. For those that know the story of CYDY and other small companies this should be evident. If it is not, forget the point above and rationalize your own opinions, which is fine.
But this is not he point. imo we don't have EUA due to a flawed system managed by a incompetent organization.
Now, we need to go through it as we are doing business in the USA.
In regards to approval, I disagree with most of you. Unbinding the data will not be beneficial. There is always the hanging sword of misuse and the trial being rendered invalid. I would be nervous of some of the data being miss-used (one way or another) and prefer we enroll 63 patients rapidly and reach the 75% goal.
Remeber: the board is working FOR us and we should follow their advise. Why??? They have seen the data and the analysis (one of them made it).
Quote:Results
The arguments in favor of early release of interim data include the need to provide reliable data in a timely manner to patients and physicians, the potential to increase the enthusiasm of trial investigators, and to restore equipoise. However interim data, even where these include complete results on a short-term outcome measure, provide an unreliable and biased assessment of the overall benefit-to-risk profile of the trial treatments. Pre-judgment based on over-interpretation of such interim data can affect recruitment, treatment delivery, and follow-up, risking the ability of the trial to achieve its goals.
Why? Let's assume we had a ratio in number of deaths (LL/SOC) of 17.% vs 33.8% or 23/22 deaths (47.7% reduction of deaths), this will produce a p-value of 0.01681. Shall we stop the trial ??? These are pretty compelling numbers !!!!
Well, no. Simply because the POWER of this is just 70.1%. If one brings this data to Health Canada or MHRA and tell them: please approve us, look at these results !!! They will say: sorry, this is not statistically significant .... We need to remember that we have to have both a good p-value AND a good power.
The latter is often not mentioned in trials. Why? Because most are over-powered. GILD makes a trial with 2000 patients, are we going to tallk about the power? No. But we designed our trial with 390 for good reasons (money, resources, time-frame) so we need to live with his.
What is very encouraging is that the statistician of the DSMC considered that with 75% of patients we can probably meet statistical significance (p + power). This would indicate that we are now somewhere in the range 0.0065 - 0.016 meaning we could possible have a well-powered result with 293 patients.
All numbers above just imo, of course.
Let's keep our cool. If LL works we will have our day in court, even if this is not impartial.
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