One day, I need to validate a SPM related files and ADSPM in a hematology study, I communicated with an experienced colleague many times and finally got the work done. Since each study has different data structure, there is no standard SPM process available for all. I will share my experience with SPM work, hopefully it is helpful in some way.
SPM (Second Primary Malignancy) is a good indication to access safety analysis in hematology studies. In addition, it reflects the disease progression. SPM, such as DNA damage, cytotoxic chemotherapy agents, may occur months/years after the original (primary malignancy ) was diagnosed and treated.
In Hematology studies, such as newly diagnosed multiple myeloma trials(NDMM), if an increased frequency SPM were reported in studies, we will generate an ADSPM dataset from multiple sources (AE, Death, Drug safety database)to capture the info.
Key point: SPM sequence
Since the SPM collected from multiple sources(AE, Death, SPM Safety track, MSAE) linked and combined, we need Clinical Scientist, Statistical programmer, and statistician closely work together.
SPM Related Work Process Flow:
Database Lock -> Study Analysis datasets(SPM Process)-> SPM Sequencing and Data Derivation -> ADSPM ->SPM TLG Development QC and Review
SPM TLG could include, but not limited to:
Tables: risk factor, univariate and multivariate, odds ratio, SPM free survival,
SPM survival, time-dependent covariates
Listings: Medical History, prior cancer history
Figures: Competing risk, KM, forest plot, piecewise Cox regression
Source Data: ADSL, ADAE, Death Data, SPM Unique preferred term sheet, Reconcile File
Key variables: STUDY, SUBJID, AESEQ, SPMFL,EXCLRN,SPMPD, PTNM,SOCNM,CAT, CAT1, CAT2, CAT3
AESEQ: SPM reconcile sequence (from AE) AESTDT: AE start date SPMFL: SPM flag (yes, no) EXCLRN: SPM excluded reason SPMPD: SPM recurrence/progression (Yes, No, missing) PTNM: SPM preferred term SOCNM: SPM system organ class CAT: SPM category CAT1: SPM category level1 CAT2: SPM category level1 CAT3: SPM category level1
- Select ADSL safety population
- Select SPM category and AEDECOD from ADAE
- Import SPM related excel sheet (unique preferred term, reconcile file) as SPM
- Merge ADSL with SPM by subject ID
- Modify the variable SPM Sequence
- Repeat step 3-5 for Death and SPM AE
- Merge three data (Death, AE, SPM AE) together
Sample ADSPM Output:
Thanks very much to Jason Zhang for guiding me through the process and sharing the precious SPM materials.
Allan JM, Travis LB Mechanism of therapy