A commercial organization contracted by a research and development organization to perform one or more research-related functions.
A committee, independent of the sponsor, composed of clinical research experts that reviews trial data while a clinical trial is in progress to ensure that participants are not exposed to undue risk.
A series of guidelines adopted by the 18th World Medical Assembly in Helsinki, Finland in 1964. The Declaration addresses ethical issues for physicians conducting biomedical research involving humans. Recommendations include the procedures required to ensure subject safety in clinical trials, including informed consent and Ethics Committee reviews.
A drug that has been authorized for use in a clinical trial but has not been granted marketing approval as a treatment for a particular use.
Analysis of clinical trial results that includes all data from participants in the groups to which they were randomized even if they never received the treatment.
Clinical trial protocol is a document that describes the background, rationale, objective(s), design, methodology, statistical considerations, schedule of assessments and organization of a trial.
Overall Survival (OS) duration is measured from the date of randomization to the date of death from any cause.
According to ICH E6: Adverse event is defined as 'Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment'
An adverse event that meets any of the below criteria can be called a serious adverse event:
- results in death
- is life-threatening
- requires inpatient hospitalization or prolongation of existing hospitalization
- results in persistent or significant disability/incapacity
- is a congenital anomaly/birth defect
No, an adverse event can be called a serious adverse event only when it meets a predefined condition (see serious adverse event definition).
The last known assessment prior to treatment start.
Subset the records with assessement date prior to treatment start date (or reference start date) and non-missing result
As there can be multiple assessement before the treatment start date, we need to pick the latest assessment by sorting the observations such that the latest record comes at the end, and pick the latest assessment.
Use the key variables(subject, test, timepoint related variables) on this latest record to populate baseline flag on that record in original input dataset.
After deriving baseline flag variable, we need to subset the baseline records and rename the result variable(s) as baseline variable(s) and merge back onto the original input dataset at subject and test level.
An event can be called treatment-emergent if
1) If it is preexisiting before treatment start but worsens in severity after treatment start
2) Absent before treatment start but occurred after treatment start.
Subset the records with event start date prior to treatment start date to identify the preexisting events.
As there can be multiple occurrences of same event prior to event start, we need to identify the maximum severity of each event (aedecod values) of a subject and subset those records.
Rename the severity variable(AESEV) as baseline severity(BASESEV) and populate it across all records of that event of that subject by merging to the original input dataset at subject and decod level.
An event will now be called treatment emergent if
1) BASESEV is missing and event start date on or after treatment start date
2) BASESEV is not-missing and BASESEV > AESEV and event start date on or after treatment start date.
Number needed to harm (NNH) is defined as the number of individuals who must be treated so that one individual presents an adverse reaction attributable to the treatment
For regulatory agencies:
1) Once trained in the principles of standardized datasets and the use of standard tools, reviewers will be able to work more effectively with less preparation time (in understanding the naming conventions and dataset structure) 2) Will be able to create a usable centralized data pool as the data submitted by different pharmaceutical compaines will be of same structure
For bipharmaceutical companies:
1) Availability of a standard structure minimizes the need to submit same data in multiple formats to different regulatory authorities 2) Acquistisions, in-licensing and out-licensing becomes easy as the data pool of the other companies are also in same structure
For programmers:
Once trained in the usage of standardized datasets, programmers will be instantly familiar with the data structures and will be ready to switch between customers with no preparation time and be able to build utilities to improve efficiency
Clinical Trial Protocol
Blank Case Report Form
Data management annotated Case Report Form
SDTM annotated Case Report Form
Statistical Analysis Plan
CDISC SDTM Implementation Guide
SDTM programming specifications
Tables, Figures, Listings shells document
CDISC ADaM implementation guide
ADaM programming specifications
cSDRG: Clinical Study Data Reviewers guide
ADRG: Analysis Data Reviewers Guide
SDTM define.xml
ADaM define.xml
Both SDTM findings class and ADaM BDS class are used to present the results of a test. In SDTM, we present the result using --STRESC or --STRESN variables, while in ADaM we present the results using AVAL and AVALC variable. As per ADaM standard, the value used in PARAMCD for a test should uniquely qualify the result stored in AVAL or AVALC (that is, no additional qualifiers are needed to explain the test). Whereas in SDTM, we can have additional qualifier variables to the --TESTCD variables to understand the test performed.
Example 1:
If systolic blood pressure is collected in sitting and standing positions for a subject, we use the value of "SYSBP" in VSTESTCD and use VSPOS qualifier to indicate "SITTING" or "STANDING" position of the subject. Here, VSPOS is qualifying the VSTESTCD variable for the result stored in VSSTRESN or VSSTRESC. As we cannot have any additional qualifiers for PARAMCD variable value, we combine the information of qualifier variables and TESTCD value to create a unique PARAMCD value. In this example, a paramcd value of SISBP can be used to indicate the sitting systolic blood pressure and STSBP can be used to indicate the standing systolic blood pressure.
Clinical trial is a scientific investigation that examine and evaluate the safety and efficacy of new drugs or therapeutic procedures using human subjects.
Randomization is the process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments
The process of deliberately keeping the subjects and trial personnel unaware of the treatment being received is called blinding.
A blinded study in which only the subject is blinded to the treatment is called a single-blinded study.
A blinded study in which both the subject and investigator are blinded to the treatment is called a double-blinded study
An open-label clinical trial is the one in which both the subject and trial personnel are aware of the treatment being administered.
A parallel arm study is the one in which a clinical trial subject is randomized to one of the multiple arms of the study and will only receive the treatment corresponding to that arm of the study, where as in a cross-over study a subject will be randomized to a treatment sequence in which the subject will receive more than one treatment in the specified sequence.
A cross-over study is the one in which a clinical trial subject is randomized to a treatment sequence and the subject is exposed to a sequence of treatments over different treatment periods.
In these studies, there will be two treatment periods. 1) Double-blind period: in this period subject will be exposed one of the possible treatments in a double blind manner. 2) Open-label extension period: Once a subject completes the double-blind treatment period, subject may choose to enter into open-label extension period in which all the subjects will be provided with an active medication.
When a point of view prevents impartial judgment on issues relating to the subject of that point of view. In clinical studies, bias is controlled by blinding and randomization.
The ability of a drug or treatment to produce a beneficial result. A drug demonstrates efficacy if it is effective at the dose tested against the illness for which it is prescribed.
Overall outcome that the protocol is designed to evaluate.
In a clinical trial, a subject will be exposed to either investigational treatment or control treatment. Any other medications administered to the subject are called concomitant medications.