From: Hyun-Woo Lee on 5 Aug 2010 02:04 Hello, I am working on fitting nonlinear mixed model to my data using proc nlmixed. My model has five fixed effects & four random effects. In order to deal with the following problem: WARNING: The final Hessian matrix is full rank but has at least one negative eigenvalue. Second-order optimality condition violated. I have used the Cholesky parametization as suggested by numerous sources (book, etc) The code is the following: ------------------------------------------------------------------------------------------------------------------------------------------ proc nlmixed data=patient method=firo; parms Min=95 Max=105 EC50=1000 Slope1=-0.5 Slope2=-0.5 s2e=0.5 t11=0 t22=0 t33=0 t44=0 t12=0 t13=0 t14=0 t23=0 t24=0 t34=0; part1 = (Max) - (Min+u2); part2 = 1+ (1/(1+((time/(EC50+u3))**(2*(Slope1+u4)*(Slope2+u5)/ (ABS((Slope1+u4)+(Slope2+u5)))))))*((time/(EC50+u3))**(-(Slope1+u4))); part3 = (1- (1/(1+((time/(EC50+u3))**(2*(Slope1+u4)*(Slope2+u5)/ (ABS((Slope1+u4)+(Slope2+u5))))))))*((time/(EC50+u3))**(- (Slope2+u5))); cov1= t11*t11; cov2= t11*t12; cov3= t11*t13; cov4= t11*t14; cov5= t12*t12 + t22*t22;; cov6= t12*t13 + t22*t23; cov7= t12*t14 + t22*t24; cov8= t13*t13 + t23*t23 + t33*t33; cov9= t13*t14 + t23*t24 + t33*t34; cov10= t14*t14 + t24*t24 + t34*t34 + t44*t44;; model vol ~ normal((Min+u2)+(part1/(part2+part3)), s2e); random u2 u3 u4 u5 ~ normal([0,0,0,0], [cov1,cov2,cov3,cov4,cov5,cov6,cov7,cov8,cov9,cov10]) subject=patient; run; --------------------------------------------------------------------------------------------------------------------- Assuming I have done things correctly, I no longer get the negative eigenvalue in Hessian Matrix message. & I do get stats (estimates, p-values, etc) for the t11, t12, t13, ...t44 & so on. My question is, how to apply the stats to the var-covar matrix elements. for the estimates, should I use the formula that I have defined above? i.e. the estimate for covariance element 3 would be the multiplication of the estimates for the t11 & t13: cov3 = t11*t13 ? Would it be the same for the p-values? should the p-value for the covariance element 3 be the multiplication of the p-values of t11 & t13, for example? But the problem is that if I use this method, I get some p-values that are over 1. That's what makes me confusing. Any help would be appreciated. Thank you very much
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