Chapter 4 Introduction to CRASH-2

Since a key principle of IDA is not to touch the research questions, before IDA commences the research aim and statistical analysis plan need to be in place. IDA may lead to an update or refinement of the analysis plan. To demonstrate the workflow and content of IDA, we created a hypothetical research aim and corresponding statistical analysis plan, which is described in more detail in the section Crash2_SAP.Rmd.

Hypothetical research aim for IDA is to develop a multivariable model for early death (death within 28 days from injury) using nine independent variables of mixed type (continuous, categorical, semicontinuous) with the primary aim of prediction and a secondary aim of describing the association of each variable with the outcome.

A prediction model was developed and validated based on this data set in “Predicting early death in patients with traumatic bleeding” Perel et al, BMJ 2012, [supplement available at]. The assumed research aim is in line with the prediction model

4.1 CRASH-2 Description

Clinical Randomisation of an Antifibrinolyticin Significant Haemorrhage(CRASH-2) was a large randomised placebo controlled trial among trauma patients with, or at risk of, significant haemorrhage, of the effects of antifibrinolytic treatment on death and transfusion requirement. The study is described at the original trial website. A public version of the data set is found at a repository of public data sets hosted by the Vanderbilt University’s Department of Biostatistics (Prof. Frank Harrell Jr.).

The data set includes 20,207 patients and 44 variables.

Note: In contrast to the analysis described in Perel et al, variables describing the economic region and the treatment allocation are missing in the public version of the data set, and while the data set contains 20,207 patients, the research paper mentions 20,127 patients having been included in the study.

4.2 Crash2 dataset contents

4.2.1 Source dataset

We refer to the source data set as the dataset available online here

Display the source dataset contents. This dataset is in the data-raw folder of the project directory.

Data frame:crash2

20207 observations and 44 variables, maximum # NAs:17121

Name	Labels	Units	Levels	Class	Storage	NAs
entryid	Unique Numbers for Entry Forms			integer	integer	0
source	Method of Transmission of Entry Form to CC		5		integer	0
trandomised	Date of Randomization			Date	double	0
outcomeid	Unique Number From Outcome Database			integer	integer	80
sex			2		integer	1
age					integer	4
injurytime	Hours Since Injury			numeric	double	11
injurytype			3		integer	0
sbp	Systolic Blood Pressure	mmHg		integer	integer	320
rr	Respiratory Rate	/min		integer	integer	191
cc	Central Capillary Refille Time	s		integer	integer	611
hr	Heart Rate	/min		integer	integer	137
gcseye	Glasgow Coma Score Eye Opening			integer	integer	732
gcsmotor	Glasgow Coma Score Motor Response			integer	integer	732
gcsverbal	Glasgow Coma Score Verbal Response			integer	integer	735
gcs	Glasgow Coma Score Total			integer	integer	23
ddeath	Date of Death			Date	double	17121
cause	Main Cause of Death		7		integer	17118
scauseother	Description of Other Cause of Death		227		integer	0
status	Status of Patient at Outcome if Alive		3		integer	3169
ddischarge	Date of discharge, transfer to other hospital or day 28 from randomization			Date	double	3185
condition	Condition of Patient at Outcome if Alive		5		integer	3251
ndaysicu	Number of Days Spent in ICU			numeric	double	182
bheadinj	Significant Head Injury			integer	integer	80
bneuro	Neurosurgery Done			integer	integer	80
bchest	Chest Surgery Done			integer	integer	80
babdomen	Abdominal Surgery Done			integer	integer	80
bpelvis	Pelvis Surgery Done			integer	integer	80
bpe	Pulmonary Embolism			integer	integer	80
bdvt	Deep Vein Thrombosis			integer	integer	80
bstroke	Stroke			integer	integer	80
bbleed	Surgery for Bleeding			integer	integer	80
bmi	Myocardial Infarction			integer	integer	80
bgi	Gastrointestinal Bleeding			integer	integer	80
bloading	Complete Loading Dose of Trial Drug Given			integer	integer	80
bmaint	Complete Maintenance Dose of Trial Drug Given			integer	integer	80
btransf	Blood Products Transfusion			integer	integer	80
ncell	Number of Units of Red Call Products Transfused			numeric	double	9963
nplasma	Number of Units of Fresh Frozen Plasma Transfused			integer	integer	9964
nplatelets	Number of Units of Platelets Transfused			integer	integer	9964
ncryo	Number of Units of Cryoprecipitate Transfused			integer	integer	9964
bvii	Recombinant Factor VIIa Given			integer	integer	374
boxid	Treatment Box Number			integer	integer	0
packnum	Treatment Pack Number			integer	integer	0

Variable	Levels
source	telephone
	telephone entered manually
	electronic CRF by email
	paper CRF enteredd in electronic CRF
	electronic CRF
sex	male
	female
injurytype	blunt
	penetrating
	blunt and penetrating
cause	bleeding
	head injury
	myocardial infarction
	stroke
	pulmonary embolism
	multi organ failure
	other
scauseother
	Acute Hypoxia
	ACUTE LUNG INJURY
	Acute Pulmonary Oedema
	Acute Renal Failure
	ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)
	acute respiratory failure
	acute respiratory failure+sepsis
	air amboli (embolism)
	Air embolism caused by penetrating lung trauma
	...
status	discharged
	still in hospital
	transferred to other hospital
condition	no symptoms
	minor symptoms
	some restriction in lifestyle but independent
	dependent, but not requiring constant attention
	fully dependent, requiring attention day and night

4.2.2 Updated analysis dataset

Additional meta-data is added to the original source data set. We write this new modified data set back to the data folder after adding additional meta-data for the following variables:

age - add label “Age” and unit “years”.
injury time - add unit “hours”.
total Glasgow coma score - add unit “points”.

At the stage we select the variables of interest to take in to the IDA phase by dropping variables we do not check in IDA.

As a cross check we display the contents again to ensure the additional data is added, and then write back the changes to the data folder in the file “data/a_crash2.rds”.

Input object size: 1221480 bytes; 12 variables 20207 observations New object size: 1223272 bytes; 12 variables 20207 observations Input object size: 1546808 bytes; 14 variables 20207 observations New object size: 1385720 bytes; 14 variables 20207 observations

Data frame:a_crash2

20207 observations and 14 variables, maximum # NAs:17121

Name	Labels	Units	Levels	Class	Storage	NAs
entryid	Unique Numbers for Entry Forms			integer	integer	0
trandomised	Date of Randomization			Date	double	0
ddeath	Date of Death			Date	double	17121
age	Age	years		integer	integer	4
sex	Sex		2		integer	1
sbp	Systolic Blood Pressure	mmHg		integer	integer	320
hr	Heart Rate	/min		integer	integer	137
rr	Respiratory Rate	/min		integer	integer	191
gcs	Glasgow Coma Score Total	points		integer	integer	23
cc	Central Capillary Refille Time	s		integer	integer	611
injurytime	Hours Since Injury	hours		numeric	double	11
injurytype	Injury type		3		integer	0
time2death					integer	17121
earlydeath	Death within 28 days from injury			integer	integer	0

Variable	Levels
sex	male
	female
injurytype	blunt
	penetrating
	blunt and penetrating

4.3 Section session info

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