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CASE STUDY

Integrated Summary of Safety for an Oncology Multi-trial Data Pooling Study

Case Study Introduction

A biopharmaceutical sponsor needed greater confidence in interpreting safety data for an investigational MEK inhibitor across diverse clinical settings, including neurofibromatosis type 1 (NF1)-related tumours and non-small cell lung cancer (NSCLC). With safety signals requiring careful monitoring across cardiovascular, ocular, and other clinical domains, the sponsor needed a robust Integrated Summary of Safety (ISS) to support evidence-led safety evaluation.

The sponsor was short on statistical programming resource and required an integrated assessment of safety data pooled from four clinical trials. Quanticate supported the sponsor by consolidating and analysing safety data across these trials, spanning early and later development phases, into an ISS designed to inform monitoring strategy and dose considerations.

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Objectives and Key Challenges

The sponsor's objectives were:

  • Deliver an ISS that characterises treatment-emergent safety outcomes for an investigational MEK inhibitor using pooled evidence from four clinical trials.

  • Assess whether key safety patterns differ between disease settings, including NF1-associated PN and NSCLC, and across paediatric and adult contexts.

  • Provide evidence-led input for safety monitoring and dose considerations.

The sponsor faced the following challenges:

  1. Variation in adverse event patterns - Cardiovascular and ocular side effects were observed in preclinical toxicity work and monitored clinically, but their frequency and severity could differ by tumour type, demographic profile, and dosing regimen.

  2. Standardising multi-study safety data - The trials used varied protocols, endpoints, and data capture conventions, creating practical uncertainty in how to align adverse event classifications and safety endpoints.
  3. Synchronising pharmacology data - Integrating pharmacokinetic (PK) and pharmacodynamic (PD) information across differing schedules was essential to interpret safety in relation to dose and exposure.
  4. Ensuring comparable monitoring outputs - Safety relied on multiple assessment modalities, including volumetric magnetic resonance imaging (MRI) for neurofibroma tracking, electrocardiograms (ECGs), ophthalmologic evaluations, laboratory values, and vital signs. 

Need support with an Integrated Summaries?

Quanticate has a wealth of experience in processing integrated summaries of safety and efficacy. If you need analysis from multiple studies to help drive forward your next clinical trial, we are here to help. Contact us today to learn more about our ISS/ISE services.

 

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Strategic Approach and Tailored Solutions

Quanticate’s delivery plan focused on establishing consistent rules for pooling cross-study data, then using those rules to evaluate safety patterns across patient subgroups and dosing regimens. The Statistical Analysis Plan (SAP) defined how safety would be represented, integrated, and quality-checked across the four trials.

1) Endpoint harmonisation using the SAP
The SAP established a structured approach to harmonise and compare safety endpoints across studies, including clear criteria for:

    • Adverse events (AEs)
    • Treatment-emergent adverse events (TEAEs)
    • Serious adverse events (SAEs)

It also set out standards for aligning adverse event definitions and classifications so that analyses would remain comparable despite differing original study designs.

2) Structured integration of pharmacology evidence
To address differences in how studies captured and reported pharmacology measures, the SAP defined a consistent process for pooling and analysing pharmacokinetic (PK) and pharmacodynamic (PD) data. This enabled safety findings to be considered alongside dose and regimen differences, supporting more meaningful interpretation of tolerability.

3) Subgroup analyses to evaluate risk factors
Quanticate supported subgroup analyses to explore whether specific populations showed distinct safety patterns or risk factors. This approach helped the sponsor move beyond an overall pooled estimate and understand where closer monitoring or differentiated dose considerations might be appropriate.

4) Quality checks across key monitoring domains
Rigorous quality checks were applied to safeguard the reliability of integrated outputs and manage variability across data sources. These checks covered major safety and monitoring domains, including:

    • ECG outputs
    • Ophthalmologic assessments
    • Laboratory values and vital signs
    • Consistency and alignment of PK/PD measures

This ensured the pooled analysis rested on standardised, validated inputs.

Successful Client Outcomes

Quanticate delivered a successful ISS that provided the sponsor with a clearer and more consistent view of safety across four trials. The pooled analysis strengthened interpretation of treatment-emergent safety events, including TEAEs and SAEs, while supporting deeper assessment of cardiovascular and ocular safety patterns, subgroup risk factors, and areas requiring careful clinical monitoring.

By integrating PK/PD evidence with safety outcomes, the analysis also helped inform dose and regimen evaluation, supporting strategies intended to balance tolerability with clinical activity. The SAP-led framework provided added long-term value by creating a reusable approach for future integrations, with clear endpoint governance and quality controls to support standardisation across multi-centre studies. 

Conclusion

By bringing together safety evidence from four clinical trials into a single, consistent ISS, Quanticate helped the sponsor strengthen confidence in its safety interpretation across diverse patient populations and disease settings. The work provided a clearer evidence base to support clinical monitoring, dose evaluation, and future integrated safety analyses.

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