Ensuring the quality of data submitted to regulatory agencies like the FDA (CBER and CDER) is vital in the Life Sciences industry. For nonclinical studies, the standard format is SEND (Standard for the Exchange of Nonclinical Data). SEND provides a standardized structure for submitting data, and adherence to its implementation guides (like IG 3.1.1, with IG 4.0 on the horizon) is mandated for various study types.
However, achieving complete SEND conformance and ensuring data accuracy presents significant challenges for many sponsors and CROs.
The Critical Challenge: Traceability and Accuracy
The FDA’s technical conformance guide emphasizes that study data validation is crucial to ensure data is compliant, useful, and supports meaningful review and analysis. A key requirement highlighted by the FDA is that each study data set must be 100% traceable to the final study report.
This is where many standard validation processes fall short. Traditional methods often rely on spot checks of data, reviewing only a small percentage of subjects or data points within a domain. In a standard repeat dose toxicity study, this could mean checking as little as 1% or of the actual data points.
Why is this a problem? Spot checks leave plenty of room for errors. These can include:
- Data points missing due to deviations
- Data points that are out of range
- Observations with comments that are missed
- Data entry errors, including typographical mistakes during initial collection or SEND transformation
Reviewer experience shows that establishing traceability is one of the most problematic issues associated with any data conversion. When data in the SEND dataset doesn’t align 100% with the final study report, it can significantly impact the review process, even if it doesn’t trigger an outright technical rejection.
SEND-ASSURE: PointCross’s Solution for Enhanced Quality
PointCross Life Sciences has served the Life Sciences industry since 2009, and is actively participating with CDISC, PhUSE, and have worked closely with the FDA as a contracting partner. PointCross has helped both small, and large sized biotechs with nearly 10,000 studies processed and brought to market our SEND-ASSURE service. SEND-ASSURE is an enhanced QC check specifically designed to address FDA comments around traceability and ensure the reliability of your SEND submissions.
SEND-ASSURE is part of PointCross’s Data Standardization services for nonclinical studies, which also include SEND Generation, Interim Study Monitoring, and study repository services that are all built on the Xbiom platform.
The SEND Assure Process: Going Beyond Spot Checks
What sets SEND-ASSURE apart is its commitment to full reconciliation. It’s an in-depth, detailed QC check performed after your SEND creation but before submitting to a regulatory agency. The process involves checking every single data point that will be submitted within your SEND data set.
SEND Assure checks against multiple sources:
- The final PDF study report (or a draft report)
- Study metadata
- Tabulated study data
- Released validation and conformance rules (FDA business rules, FDA validator rules, FDA technical rejection criteria, PMDA validation rules, CDISC conformance rules)
- Implementation guides and best practices
The process involves digitizing tables and figures from the study report and then using the SEND data to recreate these digitized elements. For quantitative data, this means comparing elements like mean, standard deviation, standard error, and count. If even one of these elements doesn’t match, a “not match” flag is raised, requiring review. Qualitative data is checked for the presence and count of values. Data not suitable for tabular comparison is visually inspected.
Any mismatches or discrepancies found during this reconciliation are documented in the SEND Assure report.
PointCross offers two service options: the traditional service which provides the detailed reports, and an optional service that includes corrections made directly to your SEND data sets (XPT files, nSDRG, define.xml). This is particularly helpful if your original SEND preparer is unavailable or if you need to standardize acquired study assets.
What Kind of Issues Does SEND-ASSURE Find?
Even studies considered “pretty good” often have issues when undergoing a full review. PointCross has found that 100% of reviewed studies had issues that would have impacted the review, ranging from incomplete data sets to misrepresentations between the report and SEND data.
Common findings include:
- Missing Trial Summary (TS) parameters indicated in the report
- Issues with data modeling (e.g., how wash-out periods are represented)
- Failure to include data requiring custom domains (like ADA, immunogenicity, or gene-tox data)
- Missing fasting or baseline flags when indicated in the report
- Missing required variables like PCDY and PCDTC needed for calculations
The final deliverable, the SEND-ASSURE report, is a detailed spreadsheet categorized into three levels of findings:
- Must be changed: Findings requiring changes based on conflicting evidence from standards documentation, conformance rules, or differences from the final report.
- Should be documented: Items causing errors that may not have a single “right” way to fix according to guides/rules, often related to complex studies. These findings (including common false positives like consistency of origin warnings when using pool IDs) should be documented in the nSDRG or define.xml.
- Suggestions: Information present that could be added or changed in the SEND data set, like including a principal investigator or test site in a findings domain.
The report details the issue type, location, variable names, description, suggested correction, and the source of the citation (report, IG, validation report). PointCross uses its own eDataValidator, which includes FDA, CDISC, PMDA, and PointCross-specific rules, integrated into the process.
The PointCross Advantage: Guaranteed Quality and Confidence
PointCross offers significant benefits:
- Guaranteed 100% reconciliation of your data set.
- Guaranteed zero technical rejections.
- Provides a full, detailed report on the conformance of your data set.
- Offers a more cost-effective solution compared to getting a full SEND data set prepared from scratch, estimated at approximately 50% less than some other preparers.
- Allows you to submit your study with confidence.
Leveraging their proprietary validator and Xbiom platform for data creation and revision allows PointCross to stand behind these guarantees.
Get Started with SEND Assure
Nonclinical researchers often lack the time and expertise required for detailed SEND validation. The SEND-ASSURE service provides the necessary expertise and thoroughness.
To learn more about SEND-ASSURE or to get a quote, please reach out to us at dsservices@pointcross.com.PointCross offers an automatic SEND quote generator. This tool provides a baseline quote for budgetory purposes for both SEND generation and the SEND Assure process