Load Packages

library(fragilityindex)

Calculate Fragility Indices in Psoriasis

To calculate the fragility indices, we used the fragility.index function from CRAN.
The fragility index function uses the following four numberes that we concatenated in excel and copied into the fragility.index function to calculate each “FI” : intevention event, control event, intervention n, control n where “event” is the number of subjects that met the primary endpoint and n is the total number of subjects enrolled in the arm. Of note, we adjusted the confidence level based on the alpha used in the drug development program. For example, if a trial had two primary endpoints and the alpha was split evenly so that the each trial used a 0.025 alpha, we adjusted the confidence level to 0.975

Enbrel

fragility.index(23,6,169,168,conf.level=0.95)

## $index
## [1] 6

fragility.index(53,6,167,168,conf.level=0.95)

## $index
## [1] 32

fragility.index(66,6,204,204,conf.level=0.95)

## $index
## [1] 42

fragility.index(79,6,168,168,conf.level=0.95)

## $index
## [1] 55

fragility.index(94,6,203,204,conf.level=0.95)

## $index
## [1] 69

Remicaid

fragility.index(220,4,313,208,conf.level=0.95)

## $index
## [1] 125

fragility.index(71,3,99,51,conf.level=0.95)

## $index
## [1] 26

fragility.index(242,2,301,77,conf.level=0.95)

## $index
## [1] 52

fragility.index(237,4,314,208,conf.level=0.95)

## $index
## [1] 137

fragility.index(87,3,99,51,conf.level=0.95)

## $index
## [1] 35

Humira

Of note, for Humira, no SAP was available therefore a default conf.level was chosen of 0.95

fragility.index(578,26,814,398,conf.level=0.95)

## $index
## [1] 235

fragility.index(506,17,814,398,conf.level=0.95)

## $index
## [1] 207

fragility.index(77,9,99,48,conf.level=0.95)

## $index
## [1] 21

fragility.index(70,5,99,48,conf.level=0.95)

## $index
## [1] 21

Stelara

fragility.index(171,8,255,255,conf.level=0.975)

## $index
## [1] 138

fragility.index(273,15,409,410,conf.level=0.975)

## $index
## [1] 228

fragility.index(170,8,256,255,conf.level=0.975)

## $index
## [1] 137

fragility.index(311,15,411,410,conf.level=0.975)

## $index
## [1] 267

Cosentyx

fragility.index(174,11,245,248,conf.level=0.975)

## $index
## [1] 141

fragility.index(125,6,245,248,conf.level=0.975)

## $index
## [1] 96

fragility.index(219,16,327,326,conf.level=0.975)

## $index
## [1] 175

fragility.index(167,9,327,326,conf.level=0.975)

## $index
## [1] 129

fragility.index(200,11,245,248,conf.level=0.975)

## $index
## [1] 171

fragility.index(160,6,245,248,conf.level=0.975)

## $index
## [1] 131

fragility.index(249,16,327,326,conf.level=0.975)

## $index
## [1] 207

fragility.index(202,9,327,326,conf.level=0.975)

## $index
## [1] 164

Taltz

fragility.index(354,14,433,431,conf.level=0.975)

## $index
## [1] 311

fragility.index(386,17,433,431,conf.level=0.975)

## $index
## [1] 345

fragility.index(292,4,351,168,conf.level=0.975)

## $index
## [1] 122

fragility.index(315,4,351,168,conf.level=0.975)

## $index
## [1] 135

fragility.index(310,13,385,193,conf.level=0.975)

## $index
## [1] 126

fragility.index(336,14,385,193,conf.level=0.975)

## $index
## [1] 141

Siliq

fragility.index(168,3,222,220,conf.level=0.95)

## $index
## [1] 145

fragility.index(185,6,222,220,conf.level=0.95)

## $index
## [1] 161

fragility.index(481,12,612,309,conf.level=0.99)

## $index
## [1] 207

fragility.index(272,65,612,300,conf.level=0.96)

## $index
## [1] 47

fragility.index(528,25,612,309,conf.level=0.99)

## $index
## [1] 221

fragility.index(229,58,624,313,conf.level=0.96)

## $index
## [1] 36

fragility.index(497,13,624,315,conf.level=0.99)

## $index
## [1] 214

fragility.index(531,19,624,315,conf.level=0.99)

## $index
## [1] 228

Tremfya

fragility.index(280,12,329,174,conf.level=0.95)

## $index
## [1] 124

fragility.index(241,5,329,174,conf.level=0.95)

## $index
## [1] 108

fragility.index(417,21,496,248,conf.level=0.95)

## $index
## [1] 173

fragility.index(347,6,496,248,conf.level=0.95)

## $index
## [1] 150

Ilumya

fragility.index(197,9,309,154,conf.level=0.95)

## $index
## [1] 75

fragility.index(179,11,309,154,conf.level=0.95)

## $index
## [1] 64

fragility.index(188,9,307,156,conf.level=0.95)

## $index
## [1] 72

fragility.index(168,7,307,156,conf.level=0.95)

## $index
## [1] 64

Cimzia

Of note, for Cimzia, no SAP was available therefore a default conf.level was chosen of 0.95

fragility.index(43,2,95,51,conf.level=0.95)

## $index
## [1] 13

fragility.index(62,4,95,51,conf.level=0.95)

## $index
## [1] 21

fragility.index(56,1,91,49,conf.level=0.95)

## $index
## [1] 21

fragility.index(74,6,91,49,conf.level=0.95)

## $index
## [1] 27

fragility.index(114,2,165,57,conf.level=0.95)

## $index
## [1] 29

fragility.index(48,2,88,51,conf.level=0.95)

## $index
## [1] 17

fragility.index(66,4,88,51,conf.level=0.95)

## $index
## [1] 26

fragility.index(57,1,87,49,conf.level=0.95)

## $index
## [1] 23

fragility.index(71,6,87,49,conf.level=0.95)

## $index
## [1] 27

fragility.index(125,2,167,57,conf.level=0.95)

## $index
## [1] 33

Skyrizi

fragility.index(229,5,304,102,conf.level=0.95)

## $index
## [1] 62

fragility.index(267,8,304,102,conf.level=0.95)

## $index
## [1] 74

fragility.index(220,2,294,98,conf.level=0.95)

## $index
## [1] 61

fragility.index(246,5,294,98,conf.level=0.95)

## $index
## [1] 68

Otezla

fragility.index(186,15,562,282,conf.level=0.95)

## $index
## [1] 60

fragility.index(79,8,274,137,conf.level=0.95)

## $index
## [1] 19

Raptiva

fragility.index(99,7,369,187,conf.level=0.95)

## $index
## [1] 29

fragility.index(63,3,162,170,conf.level=0.951)

## $index
## [1] 46

fragility.index(51,6,232,122,conf.level=0.95)

## $index
## [1] 11

Amevive

fragility.index(51,7,367,186,conf.level=0.95)

## $index
## [1] 8

fragility.index(35,8,166,168,conf.level=0.95)

## $index
## [1] 14

Calculate Fragility Quotient in Psoriasis

To calculate the fragility quotients (FQ), the FI determined from the fragility.index function is divided by the total number of subjects enrolled in trial arms per endpoint.
To determine FQ, The FI is divided by the summation of the control n and intervention n.

Enbrel

fragility.index(23,6,169,168,conf.level=0.95)

## $index
## [1] 6

6/(169+168)

## [1] 0.01780415

fragility.index(53,6,167,168,conf.level=0.95)

## $index
## [1] 32

32/(167+168)

## [1] 0.09552239

fragility.index(66,6,204,204,conf.level=0.95)

## $index
## [1] 42

42/(204+204)

## [1] 0.1029412

fragility.index(79,6,168,168,conf.level=0.95)

## $index
## [1] 55

55/(168+168)

## [1] 0.1636905

fragility.index(94,6,203,204,conf.level=0.95)

## $index
## [1] 69

69/(203+204)

## [1] 0.1695332

Remicaid

fragility.index(220,4,313,208,conf.level=0.95)

## $index
## [1] 125

125/(313+208)

## [1] 0.2399232

fragility.index(71,3,99,51,conf.level=0.95)

## $index
## [1] 26

26/(99+51)

## [1] 0.1733333

fragility.index(242,2,301,77,conf.level=0.95)

## $index
## [1] 52

52/(301+77)

## [1] 0.1375661

fragility.index(237,4,314,208,conf.level=0.95)

## $index
## [1] 137

137/(314+208)

## [1] 0.2624521

fragility.index(87,3,99,51,conf.level=0.95)

## $index
## [1] 35

35/(99+51)

## [1] 0.2333333

Humira

Of note, for Humira, no SAP was available therefore a default conf.level was chosen of 0.95

fragility.index(578,26,814,398,conf.level=0.95)

## $index
## [1] 235

235/(814+398)

## [1] 0.1938944

fragility.index(506,17,814,398,conf.level=0.95)

## $index
## [1] 207

207/(814+398)

## [1] 0.1707921

fragility.index(77,9,99,48,conf.level=0.95)

## $index
## [1] 21

21/(99+48)

## [1] 0.1428571

fragility.index(70,5,99,48,conf.level=0.95)

## $index
## [1] 21

21/(99+48)

## [1] 0.1428571

Stelara

fragility.index(171,8,255,255,conf.level=0.975)

## $index
## [1] 138

138/(255+255)

## [1] 0.2705882

fragility.index(273,15,409,410,conf.level=0.975)

## $index
## [1] 228

228/(409+410)

## [1] 0.2783883

fragility.index(170,8,256,255,conf.level=0.975)

## $index
## [1] 137

137/(256+255)

## [1] 0.2681018

fragility.index(311,15,411,410,conf.level=0.975)

## $index
## [1] 267

267/(411+410)

## [1] 0.3252132

Cosentyx

fragility.index(174,11,245,248,conf.level=0.975)

## $index
## [1] 141

141/(245+248)

## [1] 0.2860041

fragility.index(125,6,245,248,conf.level=0.975)

## $index
## [1] 96

96/(245+248)

## [1] 0.1947262

fragility.index(219,16,327,326,conf.level=0.975)

## $index
## [1] 175

175/(327+326)

## [1] 0.2679939

fragility.index(167,9,327,326,conf.level=0.975)

## $index
## [1] 129

129/(327+326)

## [1] 0.1975498

fragility.index(200,11,245,248,conf.level=0.975)

## $index
## [1] 171

171/(245+248)

## [1] 0.346856

fragility.index(160,6,245,248,conf.level=0.975)

## $index
## [1] 131

131/(245+248)

## [1] 0.2657201

fragility.index(249,16,327,326,conf.level=0.975)

## $index
## [1] 207

207/(327+326)

## [1] 0.3169985

fragility.index(202,9,327,326,conf.level=0.975)

## $index
## [1] 164

164/(327+326)

## [1] 0.2511485

Taltz

fragility.index(354,14,433,431,conf.level=0.975)

## $index
## [1] 311

311/(433+431)

## [1] 0.3599537

fragility.index(386,17,433,431,conf.level=0.975)

## $index
## [1] 345

345/(433+431)

## [1] 0.3993056

fragility.index(292,4,351,168,conf.level=0.975)

## $index
## [1] 122

122/(351+168)

## [1] 0.2350674

fragility.index(315,4,351,168,conf.level=0.975)

## $index
## [1] 135

135/(351+168)

## [1] 0.2601156

fragility.index(310,13,385,193,conf.level=0.975)

## $index
## [1] 126

126/(385+193)

## [1] 0.2179931

fragility.index(336,14,385,193,conf.level=0.975)

## $index
## [1] 141

141/(385+193)

## [1] 0.2439446

Siliq

fragility.index(168,3,222,220,conf.level=0.95)

## $index
## [1] 145

145/(222+220)

## [1] 0.3280543

fragility.index(185,6,222,220,conf.level=0.95)

## $index
## [1] 161

161/(222+220)

## [1] 0.3642534

fragility.index(481,12,612,309,conf.level=0.99)

## $index
## [1] 207

207/(612+309)

## [1] 0.2247557

fragility.index(272,65,612,300,conf.level=0.96)

## $index
## [1] 47

47/(612+300)

## [1] 0.05153509

fragility.index(528,25,612,309,conf.level=0.99)

## $index
## [1] 221

221/(612+309)

## [1] 0.2399566

fragility.index(229,58,624,313,conf.level=0.96)

## $index
## [1] 36

36/(624+313)

## [1] 0.03842049

fragility.index(497,13,624,315,conf.level=0.99)

## $index
## [1] 214

214/(624+315)

## [1] 0.227902

fragility.index(531,19,624,315,conf.level=0.99)

## $index
## [1] 228

228/(624+315)

## [1] 0.2428115

Tremfya

fragility.index(280,12,329,174,conf.level=0.95)

## $index
## [1] 124

124/(329+174)

## [1] 0.2465209

fragility.index(241,5,329,174,conf.level=0.95)

## $index
## [1] 108

108/(329+174)

## [1] 0.2147117

fragility.index(417,21,496,248,conf.level=0.95)

## $index
## [1] 173

173/(496+248)

## [1] 0.2325269

fragility.index(347,6,496,248,conf.level=0.95)

## $index
## [1] 150

150/(496+248)

## [1] 0.2016129

Ilumya

fragility.index(197,9,309,154,conf.level=0.95)

## $index
## [1] 75

75/(309+154)

## [1] 0.161987

fragility.index(179,11,309,154,conf.level=0.95)

## $index
## [1] 64

64/(309+154)

## [1] 0.1382289

fragility.index(188,9,307,156,conf.level=0.95)

## $index
## [1] 72

72/(307+156)

## [1] 0.1555076

fragility.index(168,7,307,156,conf.level=0.95)

## $index
## [1] 64

64/(307+156)

## [1] 0.1382289

Cimzia

Of note, for Cimzia, no SAP was available therefore a default conf.level was chosen of 0.95

fragility.index(43,2,95,51,conf.level=0.95)

## $index
## [1] 13

13/(95+51)

## [1] 0.0890411

fragility.index(62,4,95,51,conf.level=0.95)

## $index
## [1] 21

21/(95+51)

## [1] 0.1438356

fragility.index(56,1,91,49,conf.level=0.95)

## $index
## [1] 21

21/(91+49)

## [1] 0.15

fragility.index(74,6,91,49,conf.level=0.95)

## $index
## [1] 27

27/(91+49)

## [1] 0.1928571

fragility.index(114,2,165,57,conf.level=0.95)

## $index
## [1] 29

29/(165+57)

## [1] 0.1306306

fragility.index(48,2,88,51,conf.level=0.95)

## $index
## [1] 17

17/(88+51)

## [1] 0.1223022

fragility.index(66,4,88,51,conf.level=0.95)

## $index
## [1] 26

26/(88+51)

## [1] 0.1870504

fragility.index(57,1,87,49,conf.level=0.95)

## $index
## [1] 23

23/(87+49)

## [1] 0.1691176

fragility.index(71,6,87,49,conf.level=0.95)

## $index
## [1] 27

27/(87+49)

## [1] 0.1985294

fragility.index(125,2,167,57,conf.level=0.95)

## $index
## [1] 33

33/(167+57)

## [1] 0.1473214

Skyrizi

fragility.index(229,5,304,102,conf.level=0.95)

## $index
## [1] 62

62/(304+102)

## [1] 0.1527094

fragility.index(267,8,304,102,conf.level=0.95)

## $index
## [1] 74

74/(304+102)

## [1] 0.182266

fragility.index(220,2,294,98,conf.level=0.95)

## $index
## [1] 61

61/(294+98)

## [1] 0.1556122

fragility.index(246,5,294,98,conf.level=0.95)

## $index
## [1] 68

68/(294+98)

## [1] 0.1734694

Otezla

fragility.index(186,15,562,282,conf.level=0.95)

## $index
## [1] 60

60/(562+282)

## [1] 0.07109005

fragility.index(79,8,274,137,conf.level=0.95)

## $index
## [1] 19

19/(274+137)

## [1] 0.04622871

Raptiva

fragility.index(99,7,369,187,conf.level=0.95)

## $index
## [1] 29

29/(369+187)

## [1] 0.05215827

fragility.index(63,3,162,170,conf.level=0.951)

## $index
## [1] 46

46/(162+170)

## [1] 0.1385542

fragility.index(51,6,232,122,conf.level=0.95)

## $index
## [1] 11

11/(232+122)

## [1] 0.03107345

Amevive

fragility.index(51,7,367,186,conf.level=0.95)

## $index
## [1] 8

8/(367+186)

## [1] 0.01446655

fragility.index(35,8,166,168,conf.level=0.95)

## $index
## [1] 14

14/(166+168)

## [1] 0.04191617

Session Info

sessionInfo()

## R version 3.6.3 (2020-02-29)
## Platform: x86_64-w64-mingw32/x64 (64-bit)
## Running under: Windows 10 x64 (build 17134)
## 
## Matrix products: default
## 
## locale:
## [1] LC_COLLATE=English_United States.1252 
## [2] LC_CTYPE=English_United States.1252   
## [3] LC_MONETARY=English_United States.1252
## [4] LC_NUMERIC=C                          
## [5] LC_TIME=English_United States.1252    
## 
## attached base packages:
## [1] stats     graphics  grDevices utils     datasets  methods   base     
## 
## other attached packages:
## [1] fragilityindex_0.1.0 ggplot2_3.3.2        dplyr_1.0.1         
## 
## loaded via a namespace (and not attached):
##  [1] knitr_1.29       magrittr_1.5     splines_3.6.3    munsell_0.5.0   
##  [5] tidyselect_1.1.0 lattice_0.20-38  colorspace_1.4-1 R6_2.4.1        
##  [9] rlang_0.4.7      stringr_1.4.0    tools_3.6.3      grid_3.6.3      
## [13] gtable_0.3.0     xfun_0.16        withr_2.2.0      htmltools_0.5.0 
## [17] ellipsis_0.3.1   survival_3.2-3   yaml_2.2.1       digest_0.6.25   
## [21] tibble_3.0.3     lifecycle_0.2.0  crayon_1.3.4     Matrix_1.2-18   
## [25] purrr_0.3.4      vctrs_0.3.2      glue_1.4.1       evaluate_0.14   
## [29] rmarkdown_2.3    stringi_1.4.6    compiler_3.6.3   pillar_1.4.6    
## [33] generics_0.0.2   scales_1.1.1     pkgconfig_2.0.3

Fragility Index

Sophia Shalhout & David Miller

1/11/2020

Load Packages

Calculate Fragility Indices in Psoriasis

Enbrel

Remicaid

Humira

Stelara

Cosentyx

Taltz

Siliq

Tremfya

Ilumya

Cimzia

Skyrizi

Otezla

Raptiva

Amevive

Calculate Fragility Quotient in Psoriasis

Enbrel

Remicaid

Humira

Stelara

Cosentyx

Taltz

Siliq

Tremfya

Ilumya

Cimzia

Skyrizi

Otezla

Raptiva

Amevive

Session Info