Introduction
Integrated Summaries of Safety (ISS) and Effectiveness (ISE) bring together data from across clinical trials to give regulators a clear picture of a treatment’s risk and benefit profile. While the Common Technical Document (CTD) format provides clinical summaries of efficacy and safety (SCE and SCS), US regulations still require detailed ISE and ISS documents, which offer deeper analyses and greater regulatory detail. [1] This blog will explore the real-world challenges sponsors face when delivering an ISS, and practical strategies for overcoming them.
While every development program is different, common themes and challenges emerge across therapeutic areas.
Challenge 1: Multiple studies, multiple standards
Different clinical trials are often designed years apart, using varied data standards and collection methods. Bringing these datasets into alignment for a single ISS is a major hurdle.
Solution: Establish consistent data standards early in development, and use robust programming workflows to ensure harmonization across trials.
Challenge 2: Last-minute SAP changes
Regulatory interactions frequently lead to revised SAPs. When these come late in the process, teams must re-run analyses under significant time pressure.
Solution: Build flexible programming approaches that can adapt quickly, and maintain proactive communication between statisticians, programmers, and regulatory teams.
Challenge 3: Limited time for delivery
The ISS often comes at the very end of a program, leaving limited time before submission. Any missteps can cause delays that impact approval timelines.
Solution: Start integration planning early, ideally while late-phase trials are ongoing, so that preparation runs in parallel with data collection.
Challenge 4: Data consistency and credibility
Regulators expect a seamless story across the ISS. Any inconsistencies between study-level outputs and integrated analyses undermine confidence.
Solution: Implement rigorous QC processes and involve specialist biometrics and data science experts to ensure all outputs are aligned and defensible.
Conclusion
Delivering an ISS requires foresight, collaboration, and technical expertise. By recognizing the most common pitfalls and investing in the right people and processes, sponsors can ensure their ISS not only meets regulatory requirements but strengthens the overall submission package.
At Phastar, our specialist biometrics experts have deep experience in aligning complex datasets, managing evolving SAPs, and delivering regulatory-ready outputs.
References:
- Schwartz, D.N., Umen, M.J., Nomides, K. et al. Understanding the Differences and Effectively Transitioning between the US Integrated Summaries of Effectiveness and Safety (ISE/ISS) and the CTD Summaries of Clinical Efficacy and Safety (SCE/SCS). Ther Innov Regul Sci 44, 641–648 (2010). https://doi.org/10.1177/009286151004400511
