Kestrel
Abbreviated Data Lifecycle Plan
Demography
Version 0.x
Author:Kestrel Consultants, Inc.
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Data Lifecycle Plan
Abbreviated Demography
Version 0.0
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Table of Contents
Table of Contents
Document Revision History
1.domain rationale
1.1Data Purpose
1.2Data Overview
1.3Additional Considerations
2PROTOCOL contents
2.1Protocol Description
3Clinical Study Report
3.1Report Description
4statistical Analysis Plan Considerations
4.1Considerations for Statistical Analysis Plan
5Reporting Data displays
5.1Reporting Data Listings
5.2Summary and Analysis Tabulations
5.3Graphical Displays
6capture AND reporting datasets
6.1Dataset Descriptions
6.2Derivations
7Data capture
7.1Case Report Form Layout
7.2CRF Completion Instructions
7.3CRF Annotations
8Data Review
8.1Data Review Listings
8.2Monitoring Guidelines
8.3Computerized Checks
8.4Ongoing Medical Review
9Regulatory requirements
10external and internal references
11rationale for key decisions
APPENDIX 1: CODE/DECODE LISTS
APPENDIX 2: SAMPLE data displays
A2.1.CSR In-Text Table Examples
A2.2. Reporting Data Listing Examples
A2.3. Summary Tabulation Examples
APPENDIX 3: SURVEYS/WORKSHEETS
APPENDIX 4: [defined as needed]
Document Revision History
VERSION / DATE / UPDATED BY / REVISION HISTORY1.domainrationale
1.1Data Purpose
Data Purpose
The Demography Data Lifecycle Package incorporates core Demography data, as specified by CDISC, e.g., sex, race and age (derived from date of birth).
Demography data are used to characterize the subject population to determine whether a similar distribution was seen across treatment groups and analysis populations. Key safety and efficacy parameters should summarized by demography variables to determine if different responses are seen in different populations.
…
1.2Data Overview
The use of this DLP isrequired for all Phase 1, 2 and 3 studies. It may be required for Phase 4.
1.2.1Variation1: Default DLP
# / DATA / REQUIRED OR OPTIONAL / CAPTURED, DERIVED, PRESET / USAGE CONSIDERATIONS1 / Date of Birth / Required / Captured / Required unless replaced by Reported Age or Gestational Age.
2 / Sex / Required / Captured
1.3Additional Considerations
Examples in the full edition of the Demography DLP. They include a discussion of the application of the FDA Race and Ethnicity guidance.
2PROTOCOL contents
2.1Protocol Description
2.1.1Variation 1: Default DLP
Line # / content1 / Date of Birth / Age: specify any eligibility requirement with respect to age. Present rationale for upper and lower age limits
2 / Sex: specify any eligibility requirement with respect to sex. Present rationale for exclusion of any groups.
3 / Define when the date of birth and sex should be collected
4 / Define any planned stratification or analysis of subpopulations based on demographic or baseline characteristics.
5 / Specify the analysis sets (and their complement) for which summaries of demographic data will be generated
6 / Specify which (if any) age groups will be used for presentation purposes (e.g. 18 to 44, 45 to 64, 65 to 74, and 75 and over)
7 / Specify whether p-values will be computed to compare demographic variables across treatment groups:
- specify which statistical tests will be used
- specify how the p-values will be interpreted an what (if any) action will be taken based on the results observed
3Clinical Study Report
3.1Report Description
Demographic information is presented for all subjects in all clinical trials. The sponsor is expected to look for trends based on demographic effects in every aspect of study results (extent of exposure, efficacy assessments, safety assessments, center effects, etc) and assess any observation for its possible effect on study outcomes.This assessment must occur regardless of whether there is any predefined, formal statistical test for effects based on demography. Since this DLP focuses on the demographic data themselves, further consideration and examples of data presentations are included in other DLPs.
Note that formal analysis of demographic subgroups is moretypically done, notat the study level, but rather at the submission level where the population is more likely to be large enough for robust statistical comparison.
3.1.1Variation 1: Default DLP
# / ELEMENT / SECTION CONTENT1 / Synopsis / Summarize the high-level demographic characteristics of the study population. State whether or not any important differences were observed between treatment groups.
2 / Investigational Plan / Specify the demography-related criteria that needed to be satisfied in order for subjects to be eligible to participate in the study. Describe any stratification or analysis of subpopulations for efficacy or safety evaluation that was performed based on demographic characteristics.Restate the criteria as included in the protocol, and identify any deviations. If applicable, describe any changes in protocol-defined methodology that were made during the study with rationale.Describe any statistical adjustments made based on demographic variables if appropriate.If race or other demographic categories were mapped or collapsed, define how this was done.
3 / Safety Evaluation / Summarize the high-level demographic characteristics of the overall study population. Discuss critical demographic characteristics, and for studies that are large enough and for all Phase III studies compare treatment groups for each relevant characteristic. Discuss any factors that could affect response to study treatment.
Similarly, summarize and compare every additional study population that has been assessed for either safety or efficacy. Also assess comparability of the complementary excluded subgroup.
If the size of the study permits, assess and discuss demographic subgroups for unusually large or small safety-related treatment effects (eg, AEs, lab values, vital signs, and other protocol-specified observations).
4 / Efficacy Evaluation / See Safety Evaluation above for additional points.
Refer to the CSR section in other DLPs for description of how demographic groups should be compared by treatment group and discussed in light of:
- Extent of exposure
- Safety parameters (AE, physical exam, laboratory values, vital signs, etc)
- Serious adverse events and other significant AEs
5 / Discussion and Overall Conclusions / If applicable, assess possible impact on study results of any pattern observed, either in overall demographics or in demographic differences between treatment groups. Discuss the significance of these patterns.
6 / In-Text Data Display / Tabulation by treatment group of subject demographics
7 / Appendices / N/A
See DLP Appendix 2 for examples of the above data displays.
4statistical Analysis Plan Considerations
4.1Considerations for Statistical Analysis Plan
The points below are statistical considerations that are specific to this DLP. They supplement the methodologies presented in the general Statistical Methodology document.
4.1.1Variation 1: Default DLP
# / content1 / Define any assumptions used to impute missing parts (day, month) of the date of birth in order to compute age
2 / Define how age has been be calculated (preferred is “Age at RFSTDTC”; “Age on entry” may also be used)
5Reporting Data displays
5.1Reporting Data Listings
Unless otherwise specified, the displays described are the minimum recommended for inclusion in the study report. By default all displays are organized by treatment group.
5.1.1Variation 1: Default DLP
5.1.1.1Reporting Data Listing Shells
Examples of each listing can be found in Appendix 2.
# / Listing Name / Description / assumptions & rules1 / Listing of Demographic Characteristics by Subject / Listing of all demographic variables (columns) for all subjects (rows), organized by treatment group
This is the basic listing, and should always be included.
Key baseline characteristics can be added to this listing if they are few enough not to make the listing unreadable
5.1.1.2Reporting Data Listing Parameters
# / Parameter / Description / Default & Alternative values1 / By Group Processing / Group like subjects together, e.g., display by sex / Default: None
Alternative: By sex
2 / Sorting / Define how the records should be sorted, including order within which treatment group is presented. / Default: by treatment group (listing), by subject number (row)
Alternative: none
3 / Subsetting / Include only a portion of the subjects based on some shared characteristic / Default: none
4 / Flags / Set flags to identify subjects and values that meet specified criteria / Default: none
Alternative: flag subjects who did not take study treatment
5.2Summary and Analysis Tabulations
5.2.1Variation 1: Default DLP
5.2.1.1 Tabulation Shells
Examples of each tabulationcan be found in Appendix 2.
# / tabulation Name / Description / Assumptions & rules1 / Summary of Subject Demographics (Option with p-value) / Includes required data capture fields, plus additional derived data fields. Includes p-values comparing treatment groups / Age column can be Age, Reported Age or Gestational Age
2 / Summary of Subject Demographics (Option without p-value) / Includes required data capture fields, plus additional derived data fields. Omits p-values / Age column can be Age, Reported Age or Gestational Age
5.2.1.2 Tabulation Parameters
# / Parameter / Description / Default & Alternative values1 / Summary Statistics / Specify the summary statistics that will be presented and the order and precision in which they will be listed. / Summary #1:
Default:
Alternative:
2 / By Group Processing / Group like subjects together, e.g., display by sex. The tabulations may be split by the values of the specified field. / Default: none
Alternative: a categorical variable of interest (e.g. sex)
3 / Sorting / Define how the records should be sorted, including order within which treatment group is presented. / Default:
Alternative:
Treatment group in general should be presented with active first and then placebo or in ascending order of dose but ultimately depend on study design.
4 / Subsetting / Include only a portion of the subjects based on some shared characteristic / Default: none
Alternative: none
5 / p-value / Calculate p-value of change / Default: none
5.3Graphical Displays
Description and Purpose
No graphical displays are generated for these data.
5.3.1Variation 1: Default DLP
5.3.1.1 Graph Shells
# / Graph Name / Description / assumptions & rulesN/A
5.3.1.2 Graph Parameters
# / Parameter / Description / Default and Alternative ValuesAbbreviated Demography DLPPage 1 of 22
Data Lifecycle Plans® Used with permission from Kestrel Consultants, Inc. ©2007-2009, all rights reserved
6capture AND reporting datasets
Identifier variables are not included in the data capture and reporting datasets, and are defined in the General DLP.
6.1Dataset Descriptions
Capture Dataset Name: DMC
Reporting Dataset Name: DMR
Key fields: None (only one record per subject)
6.1.1Variation 1: Default DLP
REQ / OPT# / FIELD NAME / type (length) / field label / CODE LIST / CAP / REP / comment
1 / BRTHDTD / Num (2) / Date of Birth Day (DD) / R / O / Permits partial dates to be stored; required unless privacy considerations prevent its collection
2 / BRTHDTM / Char (3) / Date of Birth Month (MMM) / R / O / Permits partial dates to be stored
3 / BRTHDTY / Num (4) / Date of Birth Year (YYYY) / R / O / Permits partial dates to be stored
4 / BRTHDT / Date (9) / Date of Birth / O / R
5 / SEX / Char (16) / Sex / SEXL / R / R / Responses of 'Male' and 'Female' must be present on CRF; responses of 'Unknown' and 'Undifferentiated' are optional.
7 / AGE / Num / Age in AGEU at RFSTDTC / O / O / CDISC SDTM variable; length depends on AGEU
8 / AGEEN / Num / Age in AGEU on entry / O / R
9 / AGEU / Char (6) / Age Units / AGEUL / R / R
12 / DMDT / Date (9) / Date of Collection / O / O / Permits collection of Date of Visit where useful
13 / DMDY / Num (3) / Study Day of Collection / O / O
Bolded and Italicized Field Names indicate derived fields. Derivations can be found in Section 6.2
Date (9) indicates a date stored as DDMMMYYYY (e.g. 16OCT2007)
Time (5) indicates a time stored as HH:MM (e.g. 18:31)
Abbreviated Demography DLPPage 1 of 22
Data Lifecycle Plans® Used with permission from Kestrel Consultants, Inc. ©2007-2009, all rights reserved
6.2Derivations
6.2.1Variation 1: Default DLP
Note: RFSTDT is the CDISC-defined reference date, usually either date of screening or date of first study treatment
# / derived FIELD NAME / derived field label / algorithm for derivation / Rounding (precision) / BLANK ELEMENTS / COMMENT1 / BRTHDT / Date of Birth / Concatenate BRTHDTD, BRTHDTM and BRTHDTY to a single date / See comment / Default: not derived if any date component is blank; Alternative: derived by convention (conventions must be clearly documented)
2 / BRTHDTFV / Date of Birth (completeness flag, coded) / set to 2 if BRTHDTD is missing and BRTHDTM is present
set to 3 if BRTHDTD is present and BRTHDTM is missing
set to 4 if BRTHDTD is missing and BRTHDTM is missing
set to 1 otherwise / Assumes Year (BRTHDTY) is present
3 / AGE / AGE in AGEU at RFSTDTC / (RFSTDT – BRTHDT) / 365.25 / Truncate (xx) / See comment / Derived only when BRTHDT is complete either by collection or convention; RFSTDT should be defined and documented; AGEU = Years
3a / (RFSTDT – BRTHDT) / 30.42 / Default: Truncate (xx.x); Alternative: Round(xx.x) / See comment / Derived only when BRTHDT is complete either by collection or convention; RFSTDT should be defined and documented; AGEU = Months
6 / DMDY / Study Day of Collection / DMDT - RFSTDT +1 if DMDT is on or after RFSTDT,
DMDT - RFSTDT if DMDT precedes RFSTDT / RFSTDT is the CDISC-defined reference date, usually either date of screening or date of first study treatment
Additional rows in full DLP.
Abbreviated Demography DLPPage 1 of 22
Data Lifecycle Plans® Used with permission from Kestrel Consultants, Inc. ©2007-2009, all rights reserved
7Data capture
7.1Case Report Form Layout
CRF layouts in the DLPs are representative of the templates that are used in studies. CRFs will be modified as necessary to address specific requirements.
7.1.1Variation 1: Default DLP
7.1.1.1. Default CRF with required fields
7.1.1.2. Default CRF with optional fields
Examples in the full edition of the Demography DLP
7.2CRF Completion Instructions
7.2.1Variation 1: Default DLP
# / data / instructions1 / Date of Birth / Enter subject’s date of birth in DD-MMM-YYYY format using the three character English abbreviation for the month. Remember to record the subject’s birth year, not the current year.
2 / Sex / Record the subject’s self-reported sex.
7.3CRF Annotations
These annotations serve to link the CRF layout to the database structure, as defined in the DLP.
7.3.1Variation 1: Default DLP
7.3.1.1. Annotated CRF with required fields
7.3.1.2. Annotated CRF with optional fields
Examples in the full edition of the Demography DLP
Abbreviated Demography DLPPage 1 of 22
Data Lifecycle Plans® Used with permission from Kestrel Consultants, Inc. ©2007-2009, all rights reserved
8Data Review
These checks are the basic ones expected for every study. Additional checks can be defined as appropriate.
8.1Data Review Listings
The sponsor should decide the frequency with which each listing should be reviewed and the functional areas who should participate. It is strongly recommended that there be medical monitor, statistical and data management input on each review.
8.1.1Variation 1: Default DLP
# / listing name / description / Instruction1 / Review of Entries of “Other” Races / Purpose / To review entries recorded in the “Other, specify” field:
- To identify unacceptable entries (illegible, nonsense, non-specific, etc.)
- To identify entries that should be re-classified to one of the entries on the code list RACEL (if documented in the data management plan, changes can be made by self-evident correction; no query needed)
Columns / Column 1: Subject ID
Column 2:“Other, specify” entry
Column 3: Blank column to record any action
needed (optional)
The listing should be restricted to only those subjects for
which Race is ‘Other’ or “Other, specify” is not blank
Reviewing Functions / (minimally medical monitor, statistical and data management)
Reviewer Guidance / Review the entries on the listing:
- Flag any unacceptable entries for querying
- Flag any entries that should be re-classified, and the code list value to which they should be re-classified
Comment / When considering entries for reclassification, the use of the Race vocabulary table located within Health Level Seven’s Reference Information Model Structural Vocabulary Tables is recommended. This table can be used as an initial reference, stored centrally within CDM, and added to as necessary when entries are reclassified, thus maintaining a single, centrally administered, internally consistent code list for the classification of race.
8.2Monitoring Guidelines
8.2.1Variation 1: Default DLP
# / field / guidelines1 / General /
- Use the CRF completion guidelines to supplement these Monitoring guidelines.
- Demography information must be present for all subjects who have been either randomized and given study treatment, or have been dropped from the study following randomization without receiving study treatment.
2 / Date of Birth / Ensure that subject’s age satisfies eligibility criteria; if there are no eligibility criteria, ensure age is reasonable for the study (e.g. between 18 and 90 for a typical adult study)
3 / Sex / Ensure subject’s sex satisfies eligibility criteria.
8.3Computerized Checks
8.3.1Variation 1: Default DLP
# / type of check / fields included / details / action1 / Missing value / Sex / Query
2 / Missing value / Date of Birth / Query unless Date of Birth is missing only those parts included in approved documentation (to protect subject confidentiality)
3 / Missing value / Date of Collection / Query
4 / Code list / Sex / See code list SEXL / Query
5 / Code list / Date of Birth Month (MMM) / JAN, FEB, MAR, APR, MAY, JUN, JUL, AUG, SEP, OCT, NOV, DEC / Query
6 / Range / Date of Birth Day (DD) / Must be a valid value in relation to the Date of Birth Month (MMM) / Query
7 / Range / Age in AGEU on entry / Must be within range specified in protocol (if no range given, specify range reasonable for population being studied) / Query
8.4Ongoing Medical Review
All additional consistency checks are performed either during monitoring or by data management and duplication by the medical monitor is unnecessary. Note that these checks can be performed on CRF data or using specialized computerized listings
8.4.1Variation 1: Default DLP
None.
Abbreviated Demography DLPPage 1 of 22