POINTS TO REMEMBER:
Clinical laboratory data is usually integrated into the clinical database via direct data entry or through importation of electronic data files. Lab data rarely arrives ‘analysis-ready’, usually requiring Reformatting, Data cleaning, Conversions, or Flagging. To streamline the processing effort prior to analysis our approach has been to reformat the laboratory data as much as possible into standard data set structures, which then allow for usage of standard SAS data review and reporting modules.
SDTM
Natural key structure of LB for tabulation:
STUDYID
USUBJID
LBTESTCD (Topic variable): Short name of the measurement, test, or examination described in LBTEST. It can be used as a column name when converting a dataset from a vertical to a horizontal format. The value in LBTESTCD cannot be longer than 8 characters, nor can it start with a number (e.g.”1TEST”). LBTESTCD cannot contain characters other than letters, numbers, or underscores. Examples: ALT, LDH.
LBSPEC: Defines the type of specimen used for a measurement. Examples: SERUM, PLASMA, URINE.
VISITNUM, 1. Clinical encounter number.
2. Numeric version of VISIT, used for sorting.
LBTPTREF(Time Point Reference ): Name of the fixed reference point referred to by LBELTM, LBTPTNUM, and LBTPT. Examples: PREVIOUS DOSE, PREVIOUS MEAL.
LBTPTNUM: Numerical version of LBTPT to aid in sorting.
lbtpt: 1. Text Description of time when specimen should be taken.
2. This may be represented as an elapsed time relative to a fixed reference point, such as time of last dose. See LBTPTNUM and LBTPTREF. Examples: Start, 5 min post.
Structure:
One record per analyte per planned time point number per time point reference per visit per subject
ADAM: ADLBVariables:
General Introduction:
BLOOD COMPONENTS AND COMPOSITION
Human Blood is made up of about 45 percent cellular components (primarily Red Blood Cells (RBC), White Blood Cells (WBC), and platelets) and 55 percent fluid (Plasma).
CENTRAL VS LOCAL LABS
The laboratory data collected for clinical trials is typically handled by two types of labs. Central Labs, such as Covance, CCLS, and Quintiles and local labs which are general on-site in the hospital, or medical unit where the patient visit is taking place. Each type of lab has advantages or problems associated with it. Central labs have the advantage in that each test will be conducted using a standard procedure, which makes for better direct comparison among patients. Data is usually provided electronically. In most cases the central lab will also apply the normal ranges to each patient and lab test, as well as provide the results in the units specified by the sponsor or at least in common unit based on their own defaults. But of course the samples need to be sent to the central lab which means there is a delay in results to the investigator. Local labs are most often used when an immediate result is needed to allow dosing or entry into the trial. The data is usually captured directly on the case report form. Local labs also complicated by the fact that you have to collect normal ranges from each lab, and sometimes they are not available. The unit of collection is dependent on the lab and will often vary from lab to lab. Standardization of the results to a single unit is often required.
UNITS OF MEASUREMENTS
The units of measurement for a given lab test often very from lab to lab, in part based on the country the lab is located in. The labs in the US often use what is referred to as Conventional Units, while international labs use SI (Systeme Internationale). SI units are usually preferred for international trials, while US only trials often make use of the conventional units. In some cases the tests are expressed and analysis in both units.
Prior to analysis, it’s important that all the values in a given lab test are expressed in terms of a single unit and It is also important that that lab test be labeled with a single Parameter Name
Parameter Name
proc format;
value $lbtest
'ACANTHOCYTES'='ACANTHOCYTES'
'ALBU','ALBUMIN'='ALBUMIN'
'ALKPH','ALKALINE PHOSPHATASE'='ALKALINE PHOSPHATASE‘
;
lbtest = put(labvar,$lbtest.);
single unit
select(lbtest);
when('BASOPHILS, ABS') do;
select(labunit);
when('K/UL','10^9/L') do;
factor=1;
lbstresu='10^9/L';
end;
otherwise factor=.;
end;
end;
lbstresn=lborresn*factor;
TYPICAL LAB SUMMARIES
Lab summary tables will vary from study to study depending on what the objectives of that particular clinical trial, Of the more common types are table displaying descriptive statistics such as TABLE 1. They usually describe the lab value and its change or percent change from baseline at various visits or time points. The most common statistics are usually the mean, median, standard deviation, minimum and maximum values. This table would then be repeated for any lab tests collected.
When there is a large variation in the results that makes direct comparison difficult, such as cases where local labs are used, shift tables are often used. The lab values are classified as above the normal range, within the normal range, or below the normal range. And then these values are summarized based on the change of categories between baseline and some subsequent time point (usually the last visit in the study). An example of this type of table is shown in Table 2.
Another common type of table is to categorize the values into clinically significant categories, such as below a predefined critical value. Then the number of patients who fall into the categories are summarized. Table 3 is an example of this type of table.
In the United States, the National Cancer Institute publishes Common Terminology Criteria (formerly referred to as Common Toxicity Criteria) for Adverse Events to set a common standard for assigning severity grades to Adverse Events. Events are graded on a scale of one to five with one meaning “mildly abnormal” and five meaning “death.”
Usually only Oncology studies require them. The sponsor of the study is expected to provide the version to be used.
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf
Not all lab tests have CTC grades. The CTC grade can be already attached to original data. If not, the derivation is required and is depended on lab test normal ranges.
LABORATORY EVENTS
Many central laboratories now provide their data with the National Cancer Institute Common Toxicity Criteria (NCICTC) coding included. When mapped to the LB domain in SDTM, we find this information recorded in the variables LBTOXGR (toxicity grade value using a standard toxicity scale) and LBTOX (Description of toxicity quantified by LBTOXGR).
LBTOX can thus be thought of as an event contained within the laboratory data. These laboratory events are easily mapped to a standard dictionary, such as MedDRA. It’s worth noting that the mapping of laboratory data to the MedDRA terminology may or may not be done in SDTM; if it isn’t done in SDTM, it would then be part of the derivation of the analysis dataset. Once MedDRA hierarchy categories are added to laboratory data, they can be used to produce laboratory event tables, similar to adverse event tables.
Here is an example of a Laboratory Events table layout, summarized by two levels of hierarchy (MedDRA System Organ Class and Preferred Term), and also broken down by grade. It is also similar to an standard Adverse Event table, since it summarizes records using a hierarchical dictionary, and counts unique subjects within each category.
Table 4 is an example of this.
