Skip to 0 minutes and 14 seconds All right so hopefully now you can formulate the null hypothesis and know the difference between superiority and non-inferiority Remember superiority is there is no difference and non-inferiority is there is a difference. You assess the anti margin for appropriateness. You compare this to the effect size. You can either find NI margins and guidelines or look at other trials and try to make sure that what they chose was appropriate because remember if they use a smaller margin it’s easier to find non-inferiority which again is a type 1 error that we don’t want to have occurred.
Skip to 0 minutes and 49 seconds You want to make sure that they give you both ITT and PP results which they don’t always and again we knowing that doing only providing ITT could give you a false positive for a non-inferiority. You’re going to translate the confidence intervals graphically and this probably is one of the most difficult things to do because you’re going to have to set up your tables correctly so I’d highly recommend that you keep the information and you review it each time that you put it in there. I like that zone of non-inferiority in there to make it clear.
Skip to 1 minute and 21 seconds So you’re not getting talked in non-inferiority if it possibly isn’t making sure you can graph it with the confidence intervals the Delta margin and the zone or not if your audience set up a graph is the key piece to be able to do that and then you’re going to summarize the clinical relevance of the results into context with the entire study. All right summarizing the clinical relevance. There are usually a few pieces of information I think are incredibly important to take either the results of a superiority or non-inferiority trial into consideration when you’re making clinical judgment.
Skip to 2 minutes and 0 seconds Obviously, safety is hugely important, you need to make sure you look at them you need to see if you can do NNT or NNH because irrespective if it’s a non-inferiority trial the adverse reaction should be listed in a superior state. So you’re gonna want to look to see if the safety truly does coincide with the non-inferior that it’s the safety profile is better in a non-inferiority study.
Skip to 2 minutes and 25 seconds You also want to make sure that you do a full take of the article just like you do a superiority there’s those consort checklist go through I’ll keep that checklist handy until you feel comfortable looking at the different criteria until you feel comfortable and then you can just do it on your own but it’s important to make sure that all those pieces are met because it’s much easier to find non-inferiority in an NI trial It’s much more difficult to find superiority but you could just set up the trial as I showed you in one example to find out inferiority very easily and it may not be there.
Skip to 2 minutes and 58 seconds Use the facts acronym that my colleagues and I came up with to help you to be able to find the key pieces of information and then irrespective of what it showed you really need to look at it from a clinically relevant standpoint did the patients actually improve is it something that truly is good enough that you would give to your patients in replace of the standard that it was compared to and then you want to look at cost clinical practice guidelines and convenience.
Skip to 3 minutes and 26 seconds Now I know people most people have insurance or health plans or something but still cost is still an issue to people and so you need to make sure as the cost and the benefits including the indirect and direct that’s a big issue with warfarin and the new anticoagulants because you still have all the therapeutic drug monitoring with warfarin but the drug is a lot cheaper. So you want to make sure you look at all those considerations because if it cost too much and a patient won’t take it the rest of it doesn’t really matter and then what does the current guideline say about this medication.
Skip to 3 minutes and 59 seconds Again looking at Delta margins and other things, and how do they fit in there do they change do they not change? how do they relate to what’s already in the guidelines? And then greater patient convenience that’s always something to look at if it’s an IV instead of an oral that a patient can take like we look for them wanting to switch will not be as great So these taken in context with all of the information that we’ve looked at with the facts and the NI and everything will help you to make more specific recommendations for patients and individual patients. based on the information in a clinical trial.
Skip to 4 minutes and 34 seconds So just to conclude need to question everything especially non-inferiority trials that have been shown in several studies to be less reliable than superiority trials. You need to investigate and analyze as much as possible that’s why journal clubs are great because it’s hard to find things on your own but you might be able to find things together when you’re reviewing them. And then share your findings with others when you do it just like the example that I gave that you were asked by your supervisor to review HR, OR and RR with your staff to be able to make sure that we’re making optimal patient care decisions by analyzing these trials correctly.
Summary: Considerations in Clinical Relevance
Prof. Mary Ferrill demonstrates important principles and concludes this week.
Again, we are reminded to use the FACTS to evaluate the studies. What we are supposed to do is to formulate the null hypothesis, assess the NI margin, compare the ITT and PP results, translate the CI results graphically, and finally summarize the clinical relevance of the results.
Also, we need to consider three aspects of clinical relevance: Safety, Efficacy, and Cost/CPG/Convenience.
In conclusion, when we face a clinical trial, we have to question everything, especially on non-inferiority trials. Then, we need to investigate and analyze as much as possible, and finally share our findings with others.
This is the end of this week, if you have any questions or thoughts, please share them below.