Hello Brian, 1) Is the meeting in New Jersey? If not, you got a deal ;-)
2) Did the HA specifically request optimization of a weighted score/utility index? Sounds to me as if they are merely asking you to assess probability distributions (alpha level, power to reject null hypothesis or the like) for the other relevant endpoints while you are allowed to optimize for the primary only. It is of course possible to optimize for a weighted composite score of multiple endpoints, for sure you can simulate different designs and compute such a score for each. But I would think you can get it down to the simpler task of the secondaries meeting some specified restrictions while you optimize for the primary. Whether you simulate with NONMEM, Pharsigt Trial Simulator or whatever it should certainly be possible to output values of multiple variables in your model. Well, this is assuming that the HA agree with your choice of primary. Could it be the case they are actually suggesting you change that? Good luck, Andreas ________________________________________ From: owner-nmus...@globomaxnm.com [owner-nmus...@globomaxnm.com] On Behalf Of Leonid Gibiansky [lgibian...@quantpharm.com] Sent: Sunday, August 29, 2010 7:12 AM To: Corrigan, Brian (Clin Pharm) Cc: nmusers Subject: Re: [NMusers] Trial optimization across multiple endpoints Brian, 1) Why not? 2) I am not sure what is the difficulty here. It is quite usual to optimize efficacy with the restriction on safety (for example, to select doses to provide maximum effect with the restriction on maximum allowable measure of adverse events). It is also quite usual to select sampling scheme to achieve the desired estimation precision for several parameters (similar to many-endpoints problem). If we are talking about p-value of the effect, it could be a study design that allows to get a desired p-value for several (primary and secondary) end points. What is exactly the problem in your particular case? Thanks Leonid -------------------------------------- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web: www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel: (301) 767 5566 On 8/28/2010 8:55 PM, Corrigan, Brian (Clin Pharm) wrote: > Folks: > I knew that 15 plus years of NMUSER messages in my inbox would pay-off > someday................. > I am asking for you help with a question from a non-US health authority > for an upcoming meeting.....not really a NONMEM question, but more of a > general modelng question. > We have proposed some trial design and optimization work (comparing > various trial durations, designs, etc) based on a primary endpoint > (ADAS-cog) used universally in the longitudinal disease progression > trials for this indication (mild to moderate AD). The health authority > opinion is that the trial optimization results could be misleading, as > they are based only on one endpoint, and other endpoints (including a > co-primary) would need to be taken into account in the overall assesment. > My questions are > 1) Does anybody else want to go to the meeting in my place? > 2) Assuming I get no positive responses to question 1 above, is anyone > aware of any model base trial simulations and optimization activities > that have utilized more than one endpoint simultaneously? Any that look > at two endpoints and weight them in some sort of utility index, or any > that just even look at two endpoints and compare the trial simulation > results at the end? > Much thanks, > > Brian Corrigan, PhD > Pfizer Global Research and Development > 50 Pequot Avenue > > New London, CT > 06320 > 860-732-9189 >
