1 ESCOLHA DO BANCO DE DADOS

1.1 Transplante de medula óssea – clássico e mudança no tempo (Inca)

Estes dados provêm de uma coorte de 96 pacientes submetidos a transplante de medula óssea para tratamento de leucemia mieloide crônica, no período de junho de 1986 a junho de 1998, no Centro de Transplante de Medula Óssea do Instituto Nacional do Câncer (Cemo – Inca). O acompanhamento dessa coorte possibilitou o estudo do efeito de fatores prognósticos para a ocorrência de doença do enxerto contra hospedeiro aguda e crônica, da sobrevivência livre de doença e da sobrevivência global. As covariáveis registradas para cada paciente estão descritas na tabela a seguir. Para mais detalhes acerca dessa coorte e do ajuste de modelo de sobrevivência de Cox clássico e Cox estendido, consulte Byington (1999).

Estes dados estão organizados em dois arquivos. O arquivo tmoclas.dat tem o formato clássico, com uma linha para cada paciente.

O arquivo tmopc.csv está preparado para uma análise de sobrevivência com covariáveis tempo-dependentes em que a variável que muda no tempo é a recuperação das plaquetas (reqplaq), doença do enxerto crônica (decr) e aguda (deag).

1.1.1 Variável: Descrição

  • id: identificador do paciente

  • sexo: 1 = masculino, 2 = feminino

  • idade: idade na data do transplante (5 a 53 anos)

  • status: 0 = censura, 1 = óbito

  • deag: doença enxerto aguda: 0 = não, 1 = sim

  • decr: doença enxerto crônica: 0 = não, 1 = sim

  • recplaq: 0 = plaquetas não recuperadas, 1 = recuperadas

  • fasegr: fase da doença na data do transplante agrupada: CP1 = 1a crônica e Other = outras

  • inicio: data do transplante ou da mudança de covariável

  • fim: data de mudança de covariável ou do fim do estudo

1.1.2 Dados

## Loading required package: rio
## 
## Attaching package: 'rio'
## The following object is masked from 'package:plotly':
## 
##     export

2 ESTIMADOR KAPLAN-MEIER

## Call: survfit(formula = Surv(t, censur) ~ 1)
## 
##  time n.risk n.event survival std.err lower 95% CI upper 95% CI
##    31    194       1    0.995 0.00514        0.985        1.000
##    32    190       2    0.984 0.00895        0.967        1.000
##    39    174       1    0.979 0.01054        0.958        1.000
##    40    173       1    0.973 0.01190        0.950        0.997
##    48    164       1    0.967 0.01322        0.942        0.993
##    51    160       1    0.961 0.01446        0.933        0.990
##    54    159       3    0.943 0.01757        0.909        0.978
##    63    149       1    0.937 0.01856        0.901        0.974
##    65    145       1    0.930 0.01952        0.893        0.969
##    69    144       1    0.924 0.02043        0.885        0.965
##    70    143       1    0.917 0.02128        0.876        0.960
##    71    142       1    0.911 0.02209        0.869        0.955
##    74    140       1    0.904 0.02287        0.861        0.950
##    76    138       1    0.898 0.02362        0.853        0.945
##    78    135       1    0.891 0.02437        0.845        0.940
##    79    133       1    0.884 0.02509        0.837        0.935
##    83    130       1    0.878 0.02580        0.828        0.930
##    84    127       1    0.871 0.02651        0.820        0.924
##    98    123       1    0.864 0.02722        0.812        0.919
##   100    121       1    0.856 0.02791        0.803        0.913
##   101    120       1    0.849 0.02858        0.795        0.907
##   104    118       1    0.842 0.02923        0.787        0.901
##   120    110       1    0.834 0.02995        0.778        0.895
##   128    107       1    0.827 0.03067        0.769        0.889
##   139    105       1    0.819 0.03137        0.760        0.883
##   149     97       1    0.810 0.03216        0.750        0.876
##   162     92       1    0.802 0.03300        0.739        0.869
##   185     86       1    0.792 0.03390        0.728        0.862
##   200     82       1    0.783 0.03484        0.717        0.854
##   210     81       1    0.773 0.03572        0.706        0.846
##   211     80       1    0.763 0.03656        0.695        0.838
##   214     77       1    0.753 0.03741        0.683        0.830
##   216     76       1    0.743 0.03820        0.672        0.822
##   244     67       1    0.732 0.03921        0.659        0.813
##   261     64       1    0.721 0.04023        0.646        0.804
##   263     63       1    0.709 0.04119        0.633        0.795
##   281     59       1    0.697 0.04221        0.619        0.785
##   313     58       1    0.685 0.04316        0.606        0.775
##   347     55       1    0.673 0.04414        0.592        0.765
##   370     53       1    0.660 0.04510        0.577        0.755
##   371     52       1    0.648 0.04598        0.563        0.744
##   415     49       1    0.634 0.04690        0.549        0.733
##   425     48       1    0.621 0.04775        0.534        0.722
##   427     47       1    0.608 0.04853        0.520        0.711
##   434     46       1    0.595 0.04924        0.506        0.699
##   453     42       1    0.581 0.05006        0.490        0.687
##   475     40       1    0.566 0.05087        0.475        0.675
##   488     38       1    0.551 0.05167        0.459        0.662
##   522     36       1    0.536 0.05245        0.442        0.649
##   672     30       1    0.518 0.05366        0.423        0.635

2.1 Gráfico KAPLAN-MEIER

3 ESTIMADOR DE NELSON-AALEN

## Call: survfit(formula = coxph(Surv(t, censur) ~ 1, method = "breslow"))
## 
##  time n.risk n.event survival std.err lower 95% CI upper 95% CI
##    31    194       1    0.995 0.00513        0.985        1.000
##    32    190       2    0.984 0.00891        0.967        1.000
##    39    174       1    0.979 0.01050        0.958        1.000
##    40    173       1    0.973 0.01186        0.950        0.997
##    48    164       1    0.967 0.01318        0.942        0.993
##    51    160       1    0.961 0.01441        0.933        0.990
##    54    159       3    0.943 0.01748        0.910        0.978
##    63    149       1    0.937 0.01846        0.901        0.974
##    65    145       1    0.931 0.01943        0.893        0.969
##    69    144       1    0.924 0.02033        0.885        0.965
##    70    143       1    0.918 0.02119        0.877        0.960
##    71    142       1    0.911 0.02199        0.869        0.955
##    74    140       1    0.905 0.02277        0.861        0.950
##    76    138       1    0.898 0.02353        0.853        0.945
##    78    135       1    0.892 0.02427        0.845        0.940
##    79    133       1    0.885 0.02499        0.837        0.935
##    83    130       1    0.878 0.02570        0.829        0.930
##    84    127       1    0.871 0.02641        0.821        0.925
##    98    123       1    0.864 0.02712        0.813        0.919
##   100    121       1    0.857 0.02781        0.804        0.913
##   101    120       1    0.850 0.02848        0.796        0.908
##   104    118       1    0.843 0.02913        0.788        0.902
##   120    110       1    0.835 0.02984        0.779        0.896
##   128    107       1    0.827 0.03056        0.770        0.889
##   139    105       1    0.820 0.03126        0.760        0.883
##   149     97       1    0.811 0.03205        0.751        0.876
##   162     92       1    0.802 0.03288        0.740        0.869
##   185     86       1    0.793 0.03378        0.730        0.862
##   200     82       1    0.783 0.03472        0.718        0.855
##   210     81       1    0.774 0.03560        0.707        0.847
##   211     80       1    0.764 0.03643        0.696        0.839
##   214     77       1    0.754 0.03727        0.685        0.831
##   216     76       1    0.744 0.03806        0.674        0.823
##   244     67       1    0.733 0.03906        0.661        0.814
##   261     64       1    0.722 0.04008        0.648        0.805
##   263     63       1    0.711 0.04103        0.635        0.796
##   281     59       1    0.699 0.04204        0.621        0.786
##   313     58       1    0.687 0.04299        0.608        0.776
##   347     55       1    0.674 0.04396        0.594        0.766
##   370     53       1    0.662 0.04491        0.579        0.756
##   371     52       1    0.649 0.04579        0.565        0.745
##   415     49       1    0.636 0.04670        0.551        0.735
##   425     48       1    0.623 0.04755        0.536        0.724
##   427     47       1    0.610 0.04832        0.522        0.712
##   434     46       1    0.597 0.04903        0.508        0.701
##   453     42       1    0.583 0.04985        0.493        0.689
##   475     40       1    0.568 0.05065        0.477        0.677
##   488     38       1    0.554 0.05144        0.461        0.664
##   522     36       1    0.538 0.05222        0.445        0.651
##   672     30       1    0.521 0.05341        0.426        0.637

3.1 Gráfico NELSON-AALEN

4 TEMPO MEDIANO

survfit(Surv(t,censur)~1)
## Call: survfit(formula = Surv(t, censur) ~ 1)
## 
##       n  events  median 0.95LCL 0.95UCL 
##     259      53      NA     453      NA

5 TEMPO MÉDIO

## Call: survfit(formula = Surv(t, censur) ~ 1, conf.type = "plain")
## 
##  time n.risk n.event survival std.err lower 95% CI upper 95% CI
##    31    194       1    0.995 0.00514        0.985        1.000
##    32    190       2    0.984 0.00895        0.967        1.000
##    39    174       1    0.979 0.01054        0.958        0.999
##    40    173       1    0.973 0.01190        0.950        0.996
##    48    164       1    0.967 0.01322        0.941        0.993
##    51    160       1    0.961 0.01446        0.933        0.989
##    54    159       3    0.943 0.01757        0.909        0.977
##    63    149       1    0.937 0.01856        0.900        0.973
##    65    145       1    0.930 0.01952        0.892        0.968
##    69    144       1    0.924 0.02043        0.884        0.964
##    70    143       1    0.917 0.02128        0.876        0.959
##    71    142       1    0.911 0.02209        0.867        0.954
##    74    140       1    0.904 0.02287        0.859        0.949
##    76    138       1    0.898 0.02362        0.851        0.944
##    78    135       1    0.891 0.02437        0.843        0.939
##    79    133       1    0.884 0.02509        0.835        0.934
##    83    130       1    0.878 0.02580        0.827        0.928
##    84    127       1    0.871 0.02651        0.819        0.923
##    98    123       1    0.864 0.02722        0.810        0.917
##   100    121       1    0.856 0.02791        0.802        0.911
##   101    120       1    0.849 0.02858        0.793        0.905
##   104    118       1    0.842 0.02923        0.785        0.899
##   120    110       1    0.834 0.02995        0.776        0.893
##   128    107       1    0.827 0.03067        0.767        0.887
##   139    105       1    0.819 0.03137        0.757        0.880
##   149     97       1    0.810 0.03216        0.747        0.873
##   162     92       1    0.802 0.03300        0.737        0.866
##   185     86       1    0.792 0.03390        0.726        0.859
##   200     82       1    0.783 0.03484        0.714        0.851
##   210     81       1    0.773 0.03572        0.703        0.843
##   211     80       1    0.763 0.03656        0.692        0.835
##   214     77       1    0.753 0.03741        0.680        0.827
##   216     76       1    0.743 0.03820        0.669        0.818
##   244     67       1    0.732 0.03921        0.655        0.809
##   261     64       1    0.721 0.04023        0.642        0.800
##   263     63       1    0.709 0.04119        0.629        0.790
##   281     59       1    0.697 0.04221        0.615        0.780
##   313     58       1    0.685 0.04316        0.601        0.770
##   347     55       1    0.673 0.04414        0.586        0.759
##   370     53       1    0.660 0.04510        0.572        0.749
##   371     52       1    0.648 0.04598        0.557        0.738
##   415     49       1    0.634 0.04690        0.542        0.726
##   425     48       1    0.621 0.04775        0.528        0.715
##   427     47       1    0.608 0.04853        0.513        0.703
##   434     46       1    0.595 0.04924        0.498        0.691
##   453     42       1    0.581 0.05006        0.482        0.679
##   475     40       1    0.566 0.05087        0.466        0.666
##   488     38       1    0.551 0.05167        0.450        0.652
##   522     36       1    0.536 0.05245        0.433        0.639
##   672     30       1    0.518 0.05366        0.413        0.623

5.1 Gráfico TEMPO MÉDIO

5.1.1 Resultado Tempo médio

## [1] 476.7986

6 CURVA TTT

## 
## -- Column specification --------------------------------------------------------
## cols(
##   id = col_double(),
##   sexo = col_double(),
##   idade = col_double(),
##   status = col_double(),
##   inicio = col_double(),
##   fim = col_double(),
##   deag = col_double(),
##   decr = col_double(),
##   recplaq = col_double(),
##   fasegr = col_character()
## )
##     time censur Cum.Total.Time       TTT        i/n
## 68    31      1           7412 0.1501104 0.01886792
## 71    32      1           7602 0.1539583 0.03773585
## 73    32      1           7602 0.1539583 0.05660377
## 86    39      1           8865 0.1795370 0.07547170
## 87    40      1           9038 0.1830407 0.09433962
## 97    48      1          10373 0.2100776 0.11320755
## 100   51      1          10856 0.2198594 0.13207547
## 102   54      1          11333 0.2295198 0.15094340
## 103   54      1          11333 0.2295198 0.16981132
## 104   54      1          11333 0.2295198 0.18867925
## 111   63      1          12700 0.2572048 0.20754717
## 115   65      1          12992 0.2631185 0.22641509
## 116   69      1          13568 0.2747838 0.24528302
## 117   70      1          13711 0.2776799 0.26415094
## 118   71      1          13853 0.2805557 0.28301887
## 121   74      1          14275 0.2891022 0.30188679
## 122   76      1          14551 0.2946919 0.32075472
## 125   78      1          14823 0.3002005 0.33962264
## 127   79      1          14956 0.3028941 0.35849057
## 132   83      1          15477 0.3134455 0.37735849
## 133   84      1          15604 0.3160176 0.39622642
## 137   98      1          17338 0.3511351 0.41509434
## 139  100      1          17581 0.3560565 0.43396226
## 140  101      1          17701 0.3584867 0.45283019
## 143  104      1          18057 0.3656966 0.47169811
## 150  120      1          19845 0.4019078 0.49056604
## 153  128      1          20711 0.4194463 0.50943396
## 155  139      1          21872 0.4429593 0.52830189
## 163  149      1          22884 0.4634546 0.54716981
## 168  162      1          24095 0.4879802 0.56603774
## 174  185      1          26136 0.5293153 0.58490566
## 178  200      1          27388 0.5546712 0.60377358
## 179  210      1          28198 0.5710756 0.62264151
## 181  211      1          28278 0.5726958 0.64150943
## 183  214      1          28511 0.5774146 0.66037736
## 184  216      1          28663 0.5804929 0.67924528
## 194  244      1          30687 0.6214837 0.69811321
## 196  261      1          31779 0.6435992 0.71698113
## 197  263      1          31905 0.6461510 0.73584906
## 201  281      1          32991 0.6681451 0.75471698
## 202  313      1          34847 0.7057334 0.77358491
## 205  347      1          36754 0.7443547 0.79245283
## 207  370      1          37988 0.7693461 0.81132075
## 208  371      1          38040 0.7703992 0.83018868
## 211  415      1          40242 0.8149948 0.84905660
## 212  425      1          40722 0.8247160 0.86792453
## 213  427      1          40816 0.8266197 0.88679245
## 214  434      1          41138 0.8331409 0.90566038
## 218  453      1          41977 0.8501327 0.92452830
## 220  475      1          42872 0.8682585 0.94339623
## 222  488      1          43378 0.8785062 0.96226415
## 224  522      1          44603 0.9033153 0.98113208
## 230  672      1          49377 1.0000000 1.00000000
## Barlow-Proschan's test
## W=24.5105 k=53
## Z=-0.7155 p.value=0.2371

7 OBTENDO AJUSTES DOS MODELOS EXPONENCIAL

## $par
## [1] 964.381
## 
## $value
## [1] 417.2415
## 
## $counts
## function gradient 
##       11       10 
## 
## $convergence
## [1] 0
## 
## $message
## NULL
## 
## $hessian
##              [,1]
## [1,] 5.712764e-05
##             l      AIC    CAIC      BIC
## [1,] 834.4829 836.4829 836.577 840.0398
##      parametros       EP   tvalue       valorp       LI       LS
## [1,]    964.381 132.3052 7.289064 1.889554e-12 703.8502 1224.912

8 OBTENDO AJUSTES DOS MODELOS WEIBULL

## $par
## [1] 929.0164139   0.7295653
## 
## $value
## [1] 371.7855
## 
## $counts
## function gradient 
##      160      100 
## 
## $convergence
## [1] 1
## 
## $message
## NULL
## 
## $hessian
##               [,1]         [,2]
## [1,] -1.831779e-05   0.05475863
## [2,]  5.475863e-02 137.15171549
##             l      AIC     CAIC      BIC
## [1,] 743.5709 747.5709 747.7284 754.6846
##       parametros         EP   tvalue       valorp        LI        LS
## [1,] 929.0164139        NaN      NaN          NaN       NaN       NaN
## [2,]   0.7295653 0.05765385 12.65424 3.375429e-29 0.6160354 0.8430953

9 SOBREVIVÊNCIA ESTIMADA VERSUS KAPLEN-MEIER

## 
## -- Column specification --------------------------------------------------------
## cols(
##   id = col_double(),
##   sexo = col_double(),
##   idade = col_double(),
##   status = col_double(),
##   inicio = col_double(),
##   fim = col_double(),
##   deag = col_double(),
##   decr = col_double(),
##   recplaq = col_double(),
##   fasegr = col_character()
## )
## The following objects are masked from tmopc (pos = 3):
## 
##     deag, decr, fasegr, fim, id, idade, inicio, recplaq, sexo, status

9.1 Gráfico SOBREVIVÊNCIA VERSUS KAPLEN-MEIER

#AJUSTE DE REGRESSÃO (PARAMÉTRICO)

options(warn=-1)
require(survival)
library(readr)

tmopc <- read_delim("tmopc.csv", ";", escape_double = FALSE, 
                    trim_ws = TRUE)
## 
## -- Column specification --------------------------------------------------------
## cols(
##   id = col_double(),
##   sexo = col_double(),
##   idade = col_double(),
##   status = col_double(),
##   inicio = col_double(),
##   fim = col_double(),
##   deag = col_double(),
##   decr = col_double(),
##   recplaq = col_double(),
##   fasegr = col_character()
## )
attach(tmopc)
## The following objects are masked from tmopc (pos = 3):
## 
##     deag, decr, fasegr, fim, id, idade, inicio, recplaq, sexo, status
## The following objects are masked from tmopc (pos = 4):
## 
##     deag, decr, fasegr, fim, id, idade, inicio, recplaq, sexo, status
t=tmopc$fim
censur=tmopc$status
RE=tmopc$recplaq
CR=tmopc$decr
AG=tmopc$deag

y=log(t)

##função para obter os criterios
criterios=function(value,d,n){
 #value -valor do optim
 #d - numero de parametros
 #n - numero da dados
 l=2*value
 AIC=l+2*d
 BIC=l+d*log(n)
 CAIC=AIC+(2*(d+2)*(d+3))/(n-d-3)
 resul=cbind(l,AIC,CAIC,BIC)
 return(resul)
}

IC=function(parametros,hessiana,n){
  Var=solve(hessiana)
  EP=diag(sqrt(Var))
  tvalue=parametros/EP
  LI=parametros-qt(0.975,n)*EP
  LS=parametros+qt(0.975,n)*EP
  valorp=pt(tvalue,n,lower.tail = FALSE)/2
  resul=cbind(parametros,EP,tvalue,valorp,LI,LS)
  return(resul)
}

##exponencial
verosi<-function(param){ 
    b0<-param[1]
    b1<-param[2]
    b2<-param[3]
    b3<-param[4]
    
    mu=b0+b1*CR++b2*AG+b3*RE
    z=(y-mu)
    f=exp(z)*exp(-exp(z))
    sb=exp(-exp(z))
    lv<-censur*(log(f))+(1-censur)*log(sb);
    sum(-lv)
  }
  
  valorin<-c(1,1,1,1)
  estima1<-optim(valorin,verosi,method="BFGS",hessian=T);
  estima1
## $par
## [1]  6.124641  0.283440 -1.223466  1.437739
## 
## $value
## [1] 138.7313
## 
## $counts
## function gradient 
##      100       34 
## 
## $convergence
## [1] 0
## 
## $message
## NULL
## 
## $hessian
##          [,1]      [,2]      [,3]     [,4]
## [1,] 53.00000 17.000038 27.000028 34.99997
## [2,] 17.00004 17.000038  7.236813 16.80226
## [3,] 27.00003  7.236813 27.000028 16.23747
## [4,] 34.99997 16.802256 16.237470 34.99997
  n=nrow(tmopc)
  criterios(estima1$value,5,n)
##             l      AIC     CAIC      BIC
## [1,] 277.4625 287.4625 287.9087 305.2467
  parametros=estima1$par
  hessiana=estima1$hessian
  IC(parametros,hessiana,n)
##      parametros        EP     tvalue       valorp         LI         LS
## [1,]   6.124641 0.2884220 21.2349965 3.024913e-59  5.5566901  6.6925916
## [2,]   0.283440 0.3352652  0.8454201 9.966417e-02 -0.3767528  0.9436327
## [3,]  -1.223466 0.2775569 -4.4079828 4.999962e-01 -1.7700214 -0.6769105
## [4,]   1.437739 0.3309213  4.3446555 5.011429e-06  0.7861002  2.0893778
t=tmopc$fim
censur=tmopc$status
RE=tmopc$recplaq
CR=tmopc$decr
AG=tmopc$deag
##função para obter os criterios
criterios=function(value,d,n){
 #value -valor do optim
 #d - numero de parametros
 #n - numero da dados
 l=2*value
 AIC=l+2*d
 BIC=l+d*log(n)
 CAIC=AIC+(2*(d+2)*(d+3))/(n-d-3)
 resul=cbind(l,AIC,CAIC,BIC)
 return(resul)
}

IC=function(parametros,hessiana,n){
  Var=solve(hessiana)
  EP=diag(sqrt(Var))
  tvalue=parametros/EP
  LI=parametros-qt(0.975,n)*EP
  LS=parametros+qt(0.975,n)*EP
  valorp=pt(tvalue,n,lower.tail = FALSE)/2
  resul=cbind(parametros,EP,tvalue,valorp,LI,LS)
  return(resul)
}


##Weibull
verosi<-function(param){ 
    sigma<-param[1]
    b0<-param[2]
    b1<-param[3]
    b2<-param[4]
    b3<-param[5]
    
    if(any(sigma < 1e-20)) return(.Machine$double.xmax^.5)
    mu=b0+b1*CR+b2*AG+b3*RE
    z=(y-mu)/sigma
    f=(1/sigma)*exp(z)*exp(-exp(z))
    sb=exp(-exp(z))
    lv<-censur*(log(f))+(1-censur)*log(sb);
    sum(-lv)
}
  valorin<-c(1,6.124641,  0.283440, -1.223466,  1.437739)
  valorin
## [1]  1.000000  6.124641  0.283440 -1.223466  1.437739
  estima2<-optim(valorin,verosi,method="BFGS",hessian=T);
  estima2
## $par
## [1]  0.6719950  5.4754078  0.3458521 -0.8683463  1.6008134
## 
## $value
## [1] 132.6471
## 
## $counts
## function gradient 
##       40       11 
## 
## $convergence
## [1] 0
## 
## $message
## NULL
## 
## $hessian
##            [,1]       [,2]      [,3]      [,4]      [,5]
## [1,]  339.20492 -105.66050 -30.26532 -26.61026 -59.41548
## [2,] -105.66050  117.37004  37.64756  59.79576  77.51054
## [3,]  -30.26532   37.64756  37.64756  14.67174  37.17204
## [4,]  -26.61026   59.79576  14.67174  59.79576  33.53393
## [5,]  -59.41548   77.51054  37.17204  33.53393  77.51054
  n=nrow(tmopc)
  criterios(estima2$value,5,n)
##             l      AIC     CAIC      BIC
## [1,] 265.2941 275.2941 275.7404 293.0783
  parametros=estima2$par
  hessiana=estima2$hessian
  IC(parametros,hessiana,n)
##      parametros         EP    tvalue       valorp          LI         LS
## [1,]  0.6719950 0.06921188  9.709244 8.275721e-20  0.53570538  0.8082847
## [2,]  5.4754078 0.23931967 22.879055 9.974494e-65  5.00414777  5.9466679
## [3,]  0.3458521 0.22526146  1.535336 3.148048e-02 -0.09772504  0.7894292
## [4,] -0.8683463 0.20320253 -4.273304 4.999932e-01 -1.26848570 -0.4682069
## [5,]  1.6008134 0.22824826  7.013475 5.051930e-12  1.15135476  2.0502720

10 LOG NORMAL

options(warn=-1)
##log-normal
verosi<-function(param){ 
    sigma<-param[1]
    b0<-param[2]
    b1<-param[3]
    b2<-param[4]
    b3<-param[5]
    
    if(any(sigma < 1e-20)) return(.Machine$double.xmax^.5)
    mu=b0+b1*CR+b2*AG+b3*RE
    z=(y-mu)/sigma
    f=((1)/(sqrt(2*pi)*sigma))*(exp(-0.5*((z)^(2))))
    sb=1-pnorm(z)
    lv<-censur*(log(f))+(1-censur)*log(sb);
    sum(-lv)
  }

  n=nrow(tmopc)
  valorin<-c(0.6719950,  5.4754078,  0.3458521, -0.8683463,  1.6008134)
  estima3<-optim(valorin,verosi,method="BFGS",hessian=T);
  estima3
## $par
## [1]  0.9891433  5.3193416  0.4812332 -0.8285952  1.3303994
## 
## $value
## [1] 127.6028
## 
## $counts
## function gradient 
##       36       11 
## 
## $convergence
## [1] 0
## 
## $message
## NULL
## 
## $hessian
##           [,1]      [,2]      [,3]      [,4]      [,5]
## [1,] 196.95978 -95.99080 -24.77648 -25.47159 -59.92532
## [2,] -95.99080 112.00697  34.67778  45.40716  75.21735
## [3,] -24.77648  34.67778  34.67778  10.79456  33.65570
## [4,] -25.47159  45.40716  10.79456  45.40716  27.78629
## [5,] -59.92532  75.21735  33.65570  27.78629  75.21735
  criterios(estima3$value,5,n)
##             l      AIC     CAIC      BIC
## [1,] 255.2055 265.2055 265.6517 282.9897
  parametros=estima3$par
  hessiana=estima3$hessian
  IC(parametros,hessiana,n)
##      parametros         EP    tvalue       valorp          LI         LS
## [1,]  0.9891433 0.09726706 10.169356 2.924466e-21  0.79760840  1.1806783
## [2,]  5.3193416 0.22505117 23.636143 3.299173e-67  4.87617861  5.7625046
## [3,]  0.4812332 0.22786696  2.111904 8.913090e-03  0.03252547  0.9299410
## [4,] -0.8285952 0.20130920 -4.116032 4.999870e-01 -1.22500634 -0.4321841
## [5,]  1.3303994 0.22325440  5.959118 2.062731e-09  0.89077456  1.7700243

11 LOG LOGÍSTICA

options(warn=-1)
##log-logística
verosi<-function(param){ 
    sigma<-param[1]
    b0<-param[2]
    b1<-param[3]
    b2<-param[4]
    b3<-param[5]
    
    if(any(sigma < 1e-20)) return(.Machine$double.xmax^.5)
    mu=b0+b1*CR+b2*AG+b3*RE
    z=(y-mu)/sigma
    f=(1/sigma)*exp(z)*(exp(1+exp(z)))^(-2)
    sb=(1)/(1+exp(z))
    lv<-censur*(log(f))+(1-censur)*log(sb);
    sum(-lv)
  }

  n=nrow(tmopc)
  valorin<-c(0.9891433,  5.3193416,  0.4812332, -0.8285952,  1.3303994)
  estima4<-optim(valorin,verosi,method="BFGS",hessian=T);
  estima4
## $par
## [1]  0.5791330  5.3969886  0.5234551 -0.6807722  1.2732405
## 
## $value
## [1] 241.5104
## 
## $counts
## function gradient 
##       31       12 
## 
## $convergence
## [1] 0
## 
## $message
## NULL
## 
## $hessian
##            [,1]       [,2]      [,3]      [,4]      [,5]
## [1,]  455.65810 -145.59387 -37.65247 -56.05451 -84.81516
## [2,] -145.59387  129.04409  40.10253  69.86588  78.81756
## [3,]  -37.65247   40.10253  40.10253  18.23727  39.25945
## [4,]  -56.05451   69.86588  18.23727  69.86588  33.13828
## [5,]  -84.81516   78.81756  39.25945  33.13828  78.81756
  criterios(estima4$value,5,n)
##             l      AIC    CAIC      BIC
## [1,] 483.0207 493.0207 493.467 510.8049
  parametros=estima4$par
  hessiana=estima4$hessian
  IC(parametros,hessiana,n)
##      parametros         EP    tvalue       valorp          LI         LS
## [1,]  0.5791330 0.06087213  9.513928 3.350202e-19  0.45926570  0.6990003
## [2,]  5.3969886 0.22466927 24.021926 1.843410e-68  4.95457759  5.8393996
## [3,]  0.5234551 0.22135468  2.364780 4.694654e-03  0.08757105  0.9593391
## [4,] -0.6807722 0.19221107 -3.541795 4.998822e-01 -1.05926762 -0.3022768
## [5,]  1.2732405 0.21926871  5.806759 4.647011e-09  0.84146412  1.7050169
require(survival)
ajust=survreg(Surv(t,censur)~CR+AG+RE,dist='exponential')
ajust
## Call:
## survreg(formula = Surv(t, censur) ~ CR + AG + RE, dist = "exponential")
## 
## Coefficients:
## (Intercept)          CR          AG          RE 
##   6.1246408   0.2834457  -1.2234639   1.4377342 
## 
## Scale fixed at 1 
## 
## Loglik(model)= -399.7   Loglik(intercept only)= -423.4
##  Chisq= 47.36 on 3 degrees of freedom, p= 2.91e-10 
## n= 259
summary(ajust)
## 
## Call:
## survreg(formula = Surv(t, censur) ~ CR + AG + RE, dist = "exponential")
##              Value Std. Error     z       p
## (Intercept)  6.125      0.288 21.23 < 2e-16
## CR           0.283      0.335  0.85     0.4
## AG          -1.223      0.278 -4.41 1.0e-05
## RE           1.438      0.331  4.34 1.4e-05
## 
## Scale fixed at 1 
## 
## Exponential distribution
## Loglik(model)= -399.7   Loglik(intercept only)= -423.4
##  Chisq= 47.36 on 3 degrees of freedom, p= 2.9e-10 
## Number of Newton-Raphson Iterations: 6 
## n= 259
ajust1=survreg(Surv(t,censur)~CR+AG+RE,dist='weibull')
ajust1
## Call:
## survreg(formula = Surv(t, censur) ~ CR + AG + RE, dist = "weibull")
## 
## Coefficients:
## (Intercept)          CR          AG          RE 
##   5.4752915   0.3458481  -0.8682290   1.6009021 
## 
## Scale= 0.6719733 
## 
## Loglik(model)= -393.6   Loglik(intercept only)= -423
##  Chisq= 58.84 on 3 degrees of freedom, p= 1.04e-12 
## n= 259
summary(ajust1)
## 
## Call:
## survreg(formula = Surv(t, censur) ~ CR + AG + RE, dist = "weibull")
##              Value Std. Error     z       p
## (Intercept)  5.475      0.239 22.88 < 2e-16
## CR           0.346      0.225  1.54 0.12470
## AG          -0.868      0.203 -4.27 1.9e-05
## RE           1.601      0.228  7.01 2.3e-12
## Log(scale)  -0.398      0.103 -3.86 0.00011
## 
## Scale= 0.672 
## 
## Weibull distribution
## Loglik(model)= -393.6   Loglik(intercept only)= -423
##  Chisq= 58.84 on 3 degrees of freedom, p= 1e-12 
## Number of Newton-Raphson Iterations: 6 
## n= 259
ajust2=survreg(Surv(t,censur)~CR+AG+RE,dist='lognorm')
ajust2
## Call:
## survreg(formula = Surv(t, censur) ~ CR + AG + RE, dist = "lognorm")
## 
## Coefficients:
## (Intercept)          CR          AG          RE 
##   5.3193412   0.4812343  -0.8285947   1.3303993 
## 
## Scale= 0.9891421 
## 
## Loglik(model)= -388.6   Loglik(intercept only)= -415.9
##  Chisq= 54.58 on 3 degrees of freedom, p= 8.44e-12 
## n= 259
summary(ajust2)
## 
## Call:
## survreg(formula = Surv(t, censur) ~ CR + AG + RE, dist = "lognorm")
##               Value Std. Error     z       p
## (Intercept)  5.3193     0.2251 23.64 < 2e-16
## CR           0.4812     0.2279  2.11   0.035
## AG          -0.8286     0.2013 -4.12 3.9e-05
## RE           1.3304     0.2233  5.96 2.5e-09
## Log(scale)  -0.0109     0.0983 -0.11   0.912
## 
## Scale= 0.989 
## 
## Log Normal distribution
## Loglik(model)= -388.6   Loglik(intercept only)= -415.9
##  Chisq= 54.58 on 3 degrees of freedom, p= 8.4e-12 
## Number of Newton-Raphson Iterations: 6 
## n= 259
ajust3=survreg(Surv(t,censur)~CR+AG+RE,dist='loglogistic')
ajust3
## Call:
## survreg(formula = Surv(t, censur) ~ CR + AG + RE, dist = "loglogistic")
## 
## Coefficients:
## (Intercept)          CR          AG          RE 
##   5.2755960   0.4864628  -0.8453347   1.3643114 
## 
## Scale= 0.5571912 
## 
## Loglik(model)= -391.1   Loglik(intercept only)= -419.6
##  Chisq= 57.1 on 3 degrees of freedom, p= 2.44e-12 
## n= 259
summary(ajust3)
## 
## Call:
## survreg(formula = Surv(t, censur) ~ CR + AG + RE, dist = "loglogistic")
##              Value Std. Error     z       p
## (Intercept)  5.276      0.228 23.13 < 2e-16
## CR           0.486      0.234  2.08   0.038
## AG          -0.845      0.204 -4.13 3.6e-05
## RE           1.364      0.231  5.90 3.6e-09
## Log(scale)  -0.585      0.106 -5.52 3.3e-08
## 
## Scale= 0.557 
## 
## Log logistic distribution
## Loglik(model)= -391.1   Loglik(intercept only)= -419.6
##  Chisq= 57.1 on 3 degrees of freedom, p= 2.4e-12 
## Number of Newton-Raphson Iterations: 5 
## n= 259
exp(0.4812343)     
## [1] 1.61807
exp(-0.8285947)
## [1] 0.4366625
exp( 1.33039938)
## [1] 3.782554

12 AJUSTE DE REGRESSÃO (COX)

## 
## -- Column specification --------------------------------------------------------
## cols(
##   id = col_double(),
##   sexo = col_double(),
##   idade = col_double(),
##   status = col_double(),
##   inicio = col_double(),
##   fim = col_double(),
##   deag = col_double(),
##   decr = col_double(),
##   recplaq = col_double(),
##   fasegr = col_character()
## )
## The following objects are masked from tmopc (pos = 3):
## 
##     deag, decr, fasegr, fim, id, idade, inicio, recplaq, sexo, status
## The following objects are masked from tmopc (pos = 4):
## 
##     deag, decr, fasegr, fim, id, idade, inicio, recplaq, sexo, status
## The following objects are masked from tmopc (pos = 5):
## 
##     deag, decr, fasegr, fim, id, idade, inicio, recplaq, sexo, status
## Call:
## coxph(formula = Surv(t, censur) ~ CR + AG + RE, data = tmopc, 
##     x = T, method = "breslow")
## 
##   n= 259, number of events= 53 
## 
##        coef exp(coef) se(coef)      z Pr(>|z|)    
## CR -0.43153   0.64951  0.33928 -1.272 0.203411    
## AG  0.97292   2.64566  0.28563  3.406 0.000659 ***
## RE -2.59944   0.07432  0.46353 -5.608 2.05e-08 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
##    exp(coef) exp(-coef) lower .95 upper .95
## CR   0.64951      1.540   0.33403    1.2629
## AG   2.64566      0.378   1.51150    4.6308
## RE   0.07432     13.456   0.02996    0.1843
## 
## Concordance= 0.787  (se = 0.027 )
## Likelihood ratio test= 56.88  on 3 df,   p=3e-12
## Wald test            = 52.06  on 3 df,   p=3e-11
## Score (logrank) test = 80.92  on 3 df,   p=<2e-16
## [1] -240.3676 -211.9269

13 TRV

#HO= EXPONENCIAL MODELO MAIS ADEQUADO
#H1= EXPONENCIAL NÃO É O MAIS ADEQUADO

#TRV
trv=834.4829-743.5709
trv
## [1] 90.912
quiquadrado=1-pchisq(90.912,1)
quiquadrado
## [1] 0
#Portanto o como foi aceito H0 o modelo exponencial é mais adequado para os dados

14 CONCLUSÃO

  • HO= EXPONENCIAL MODELO MAIS ADEQUADO

  • H1= EXPONENCIAL NÃO É O MAIS ADEQUADO

  • Portanto o como foi aceito H0 o modelo exponencial é mais adequado para os dados

15 CRÉDITOS

Criado por :

  • Ester Rosa

  • Gabriel Thompson

  • Mateus Elias

  • Paulo Henrique