GM Junior India, 20171117 04:55 (edited by GM on 20171117 05:07) Posting: # 17986 Views: 1,416 

Hello All, As I am new to the endpoint studies, how can we calculate 90% CI for continuous variable in clinical endpoint studies? As per my understanding, there are two ways. One is ±20 rule for the difference of means and 80120% rule for ratio of means of untransformed data. Based on this reference 90% CI Calculation But as per OGD, the 90%CI should lies in 80125% for untransformed data. Please see the point no.21 in the OGD (see Clindamycin Phosphate). This is me a lot. Please clarify. Edit: URL corrected. Please don’t link to a GoogleIndia search term. [Helmut] 
ElMaestro Hero Denmark, 20171118 21:17 @ GM Posting: # 17987 Views: 1,157 

Hi GM, the tradition is to use 80.00%125.00% for a ratio of continuous variables. This makes extremely good sense under a certain set of assumptions. You refer to section 21 of the guidance, but this does not relate to continuous variables. It applies to dichotomous variables instead. Rule of thumb: For a difference, the acceptance range is symmetric. For a ratio the lower acceptance limit equals the reciprocal upper limit, naturally. Most BE issues you will come across have elements of both if logs are involved. — I could be wrong, but… Best regards, ElMaestro  Bootstrapping for dissolution data is a relatively new hobby of mine. 
GM Junior India, 20171119 12:13 @ ElMaestro Posting: # 17992 Views: 1,130 

Hello ElMaestro, Thankyou for the reply. » » the tradition is to use 80.00%125.00% for a ratio of continuous variables. This makes extremely good sense under a certain set of assumptions. » Is it possible for untransformed data also? If possible what are the limits i.e., 80125 or 80120. » You refer to section 21 of the guidance, but this does not relate to continuous variables. It applies to dichotomous variables instead. » Actually I need clarification on section 20 of the same guideline mentioned above. My apologies for mentioning wrong section earlier. » Rule of thumb: For a difference, the acceptance range is symmetric. For a ratio the lower acceptance limit equals the reciprocal upper limit, naturally. Most BE issues you will come across have elements of both if logs are involved. How can we will calculate 90% CI for ratio of means of untransformed continuous variable using PROC GLM in SAS. Please help me in this regards. Thankyou GM. 
ElMaestro Hero Denmark, 20171120 20:41 @ GM Posting: # 17993 Views: 1,070 

Hi GM, » How can we will calculate 90% CI for ratio of means of untransformed continuous variable using PROC GLM in SAS. Why is it that you want the endpoint to be untransformed? Statistically normal distributions are wonderful because any two normal distributions added (= subtracted) will yield a new normal distrution. But try and divide them and you are facing a mathematical challenge that is in no way straightforward to deal with. If you want to do a parametric CI on a ratio then the only way forward that I know of is a transformation one way or another so that the endpoint can reasonably be assumed normal. So I am sorry that I cannot answer your question in the way you have asked it. Having said this I am of the impression that you don't really need a 90% CI for a ratio of untransformed means. — I could be wrong, but… Best regards, ElMaestro  Bootstrapping for dissolution data is a relatively new hobby of mine. 
GM Junior India, 20171121 06:02 @ ElMaestro Posting: # 17995 Views: 1,059 

Hello ElMaestro, Sorry I am understanding the guidance (see Clindamycin OGD)wrongly, as I already told "am new to endpoint studies". As per the OGD section #6, the primary end point is, Percent change from baseline to week 12 in the inflammatory (papules and pustules) lesion count. As per the OGD section #20, Equivalence Analysis The compound hypothesis to be tested is: H0: µT / µR ≤ θ1 or µT / µR ≥ θ2 versus HA : θ1 < µT / µR < θ2 Where µT = mean of test treatment, and µR = mean of reference treatment Typically, we reject H0 with a type I error α = 0.05 (two 1sided tests), if the 90% confidence interval for the ratio of means between test and reference products (µT / µR) is contained within the interval [θ1, θ2], where θ1 = 0.80 and θ2 = 1.25. Here as per my understanding, the primary endpoint is untransformed data. That's why I had this confusion. and why 90% CI interval given as 00.801.25? if the primary endpoint is lntransformed data then there is no problem to calculate ratio of means or difference of means as you said earlier. Sorry if I am confusing everybody. Kindly give me some idea on this. Thanks in advance, GM 
DavidManteigas Regular Portugal, 20171121 10:01 @ GM Posting: # 17996 Views: 1,026 

Hi GM, As El Maestro explained, when your test hypothesis is a ratio (multiplicative model) then you must work with ln transformed data. The guidance is clear on that as it also defines the acceptance range as 0.8 to 1.25 (multiplicative model). If in some guideline they state the hypothesis as treatment differences (H0: u1u2=0) and a symmetric equivalence range (0.8 to 1.2) then they would be suggesting an analysis on untransformed data. This is true regardless of the type of your endpoint as long as it is a continuous endpoint. As simple as that Regards, David 