Study Start Date in SDTM – Why Getting It Right Matters

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Study Start Date in SDTM – Why Getting It Right Matters

Study Start Date in SDTM – Why Getting It Right Matters

The Study Start Date (SSTDTC) is a crucial element in the submission of clinical trial data, especially in meeting regulatory requirements. Since December 2014, the FDA has provided explicit guidance on defining and utilizing this data point, but many sponsors and service providers face challenges in its consistent application. Missteps in defining the Study Start Date can lead to technical rejection during submission reviews, delaying the regulatory process. This article explores the definition, importance, and proper implementation of the Study Start Date in SDTM (Study Data Tabulation Model) submissions, based on regulatory guidance and best practices.

FDA’s Definition of Study Start Date

The FDA, in its 2014 guidance, clarified that the Study Start Date for clinical trials is the earliest date of informed consent for any subject enrolled in the study. This approach ensures a data-driven, verifiable measure, using clinical trial data captured in the Demographics (DM) domain of SDTM. By anchoring the Study Start Date to the earliest informed consent, the FDA avoids manipulation of study timelines and enforces adherence to accepted data standards during study execution.[1]

Why is the Study Start Date Important?

The Study Start Date serves as a cornerstone in the clinical trial submission process. It plays a critical role in:

  • Compliance: The Study Start Date is used as a benchmark to assess the trial’s adherence to FDA’s data standards catalog. Standards implementation is tracked based on this reference date.
  • Consistency: A well-defined Study Start Date ensures uniformity across various study data elements, including SDTM domains, analysis datasets, and associated regulatory documentation.
  • Avoiding Rejections: Incorrect or inconsistent assignment of the Study Start Date can lead to technical rejection by the FDA during submission. Rule 1734, for instance, mandates that the Study Start Date be recorded in the Trial Summary (TS) domain, and failure to meet this criterion can result in a rejection of the submission package.[1]

Where to Record the Study Start Date

Accurate recording of the Study Start Date is essential for successful regulatory submissions. This date must appear in two key sections of the eCTD (electronic Common Technical Document) that are submitted to the FDA:

  1. SDTM TS Domain: The Study Start Date is stored in the variable TS.TSVAL where TSPARMCD = 'SSTDTC'. It must adhere to the ISO 8601 date format (YYYY-MM-DD).
  2. Study Data Standardization Plan (SDSP): The Study Start Date is also included in the SDSP, which contains metadata about the study, along with other relevant details such as the use of FDA-endorsed data standards.[1]

Challenges in Defining the Study Start Date

One major challenge in defining the Study Start Date arises from the varied interpretations among stakeholders. For example:

  • Data Managers may consider the go-live date of the data collection system as the Study Start Date.
  • Safety Teams might prioritize the first dose date of the investigational product.
  • Clinical Operations could focus on the date of the first patient visit at the clinic.

However, the correct interpretation, as per FDA guidance, is the earliest informed consent date, ensuring a consistent and regulatory-compliant approach.[1]

How to Verify the Study Start Date

Verifying the Study Start Date requires careful examination of clinical data. The following steps can help:

  1. Examine the DM Domain: The DM.RFICDTC variable (date of informed consent) is cross-checked against the protocol and Statistical Analysis Plan (SAP) to ensure it aligns with enrolled subjects.
  2. Exclude Screen Failures: Screen failures must be excluded from the analysis as they do not contribute to the Study Start Date. Only enrolled subjects should be included in this determination.
  3. Programmatic Check: The following SAS code can be used to programmatically select the earliest informed consent date for the enrolled subjects: 
    proc sql noprint;
   select min(rficdtc) from SDTM.DM
   where rficdtc is not null and armcd in ('TRTA', 'TRTB');
quit;

Global Considerations

While the FDA’s definition is clear, other regulatory authorities such as the PMDA in Japan and the NMPA in China have slightly different approaches. For example, the PMDA evaluates standards based on the submission date rather than the Study Start Date. As more global regulators adopt machine-readable clinical data standards, alignment with FDA guidance may serve as a reference point for future harmonization efforts.[1]

Multiple Ways to Derive Stusy Start Date (SSTDTC) in SDTM

Several SAS-based methods can be used to derive the Study Start Date (SSTDTC) in SDTM. Below are a few approaches:

1. Using PROC SQL

PROC SQL can compute the minimum date directly from the dataset:

proc sql noprint;
    select min(rficdtc) into :mindate
    from SDTM.DM
    where rficdtc is not null and armcd ne 'SCRNFAIL';
quit;

2. Using DATA STEP with RETAIN

This approach retains the minimum date as the dataset is processed:

data earliest_consent;
    set SDTM.DM;
    where rficdtc is not missing and armcd ne 'SCRNFAIL';
    retain min_consent_date;
    if _N_ = 1 then min_consent_date = rficdtc;
    else if rficdtc < min_consent_date then min_consent_date = rficdtc;
run;

proc print data=earliest_consent(obs=1);
    var min_consent_date;
run;

3. Using PROC MEANS

PROC MEANS can be used to calculate the minimum date:

proc means data=SDTM.DM min noprint;
    var rficdtc;
    output out=min_consent_date(drop=_type_ _freq_) min=MinRFICDTC;
run;

proc print data=min_consent_date;
run;

4. Using PROC SORT and DATA STEP

This approach involves sorting the dataset and extracting the first record:

proc sort data=SDTM.DM out=sorted_dm;
    by rficdtc;
    where rficdtc is not missing and armcd ne 'SCRNFAIL';
run;

data min_consent_date;
    set sorted_dm;
    if _N_ = 1 then output;
run;

proc print data=min_consent_date;
    var rficdtc;
run;

Conclusion

Accurately defining and recording the Study Start Date is essential for compliance with FDA regulations and avoiding submission rejections. Ensuring consistency across study data and metadata is key to a successful clinical trial submission process. Various methods in SAS, including SQL-based and procedural approaches, offer flexible options for deriving the study start date (SSTDTC) in SDTM.

References

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