tag:blogger.com,1999:blog-1474751880645498536.post5695580607642911851..comments2019-05-07T13:25:01.471-04:00Comments on Medical Evidence Blog: Everyone likes their own brand - Delta Inflation: A bias in the design of RCTs in Critical CareScott K. Aberegg, M.D., M.P.H.http://www.blogger.com/profile/17564774546019869201noreply@blogger.comBlogger3125tag:blogger.com,1999:blog-1474751880645498536.post-78598542675960387482010-05-17T11:07:42.806-04:002010-05-17T11:07:42.806-04:00A couple of other things have occurred to me about...A couple of other things have occurred to me about this graph since we published this paper. Of course, the data points to the right of the graph, with the largest predicted and observed deltas, have wider confidence intervals - which is expected since they used smaller sample sizes. But consider the phenomenon of regression to the mean. These datapoints also lie way to the extreme right of the mean observed delta of all trials - and if regression to the mean applies to this case, if these studies were repeated, the observed delta would probably be much smaller.<br /><br />Also, I realized that we should have tabulated which among the "positive, stat sig" studies (there were few of them) were held up versus not confirmed on repeat study. That would winnow down the "positive" trials in our study to an even more discouraging number. (The original Leuven study would fall out, some would say Xigris would fall out, Annane steroid study would fall out [wait, was the unadjusted analysis even positive?], etc...)Scott K. Aberegg, M.D., M.P.H.https://www.blogger.com/profile/17564774546019869201noreply@blogger.comtag:blogger.com,1999:blog-1474751880645498536.post-72080094933807596322010-05-04T01:27:23.081-04:002010-05-04T01:27:23.081-04:00Tom -
Delta IS a prediction. It is a prediction...Tom - <br /><br />Delta IS a prediction. It is a prediction of the size of the effect. You think it is not? Why not use a delta of 1%? Or 50%? Because the SS required for 1% is insurmountable for most trials, and because 50% is unrealistic for most all therapies with resulting nonsensically wide confidence intervals. So, it is an inevitable conclusion that not just ANY delta is acceptable. Which begs the question - what is a REASONABLE delta? And a reasonable one is one which is anchored to the biological plausible effect of the therapy studied, or to the MCID.Scott K. Aberegg, M.D., M.P.H.https://www.blogger.com/profile/17564774546019869201noreply@blogger.comtag:blogger.com,1999:blog-1474751880645498536.post-6854670136672230632010-05-03T23:13:14.181-04:002010-05-03T23:13:14.181-04:00Scott, there is no reason that the delta used in s...Scott, there is no reason that the delta used in sample size calculations has to be a prediction. In the case of a drug trial, for example, it might be the delta which would be needed to be superior to a competitor, or to justify moving forward with development. In a sense, deltas are always arbitrary. If I choose a sample size to give me 80% power of detecting a delta of 10 units, for example, then at the same time I also have a power of 70% for detecting a delta of 9, and 90% for a delta of 12, etc. When we consider the continuum of possible deltas and pick a point to use in sample size calculations, there are no restrictions on how we pick it, as long as the trial passes ethical muster.Tom Spradlinhttps://www.blogger.com/profile/00030965700500802811noreply@blogger.com