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Are you planning a regulatory submission and need to include an Integrated Summary of Safety (ISS) and Integrated Summary of Efficacy (ISE) within your Common Technical Document (CTD)?

Due to the unique nature of each submission, understanding the best way to plan your integrated summaries can be difficult. Challenges arise when combining multiple studies to review the safety and efficacy of an IND/NDA. Standardization across data is mandatory as regulatory bodies seek CDISC standards within your submission.

Free Guide: How to Plan a Successful ISS/ISE

Citrine Healthcare has long legacy of producing Integrated Summaries for a wide range of clients over the years. As a data-focused CRO, Citrine Healthcare has the programmers and statisticians to provide expert advice on the best way to combine data for an ISS/ISE, including help in identifying how ‘time to approval’ can be reduced by careful up-front planning.

An ISS or ISE are both important tools - as the larger sample size of data allows for easier identification of any correlations and trends. This allows for better-presented and unbiased data for regulatory submissions as the regulatory authorities state ISE and ISS are critical components of a submission. After combining data for an ISS/ISE, support in the ISS/ISE preparation within the CTD can be provided by our medical writing department.

Integrated Summary of Safety (ISS)

Within ISS, the safety results of different studies on the same compound are pooled together.

Advantages of an ISS include:

  • Identification of common related adverse events (AEs)
  • Identification of common serious adverse events (SAEs)
  • Identification of safety concerns that may not be apparent from a single study
  • Allowing an assessment of safety in subgroups if sample sizes are sufficiently large
Integrated Summary of Efficacy (ISE)

Within ISE, the efficacy results from different studies conducted on the same compound are combined.

The advantages of ISE include:

  • Enable the assessment of efficacy in subgroups (e.g. paediatrics)
  • Enable the assessment of the efficacy of secondary endpoints, which may have been under‑powered in individual studies
  • Allow detailed comparison of results versus a comparator drug
  • Allow assessment of the efficacy of repeat doses
  • Enable the dose-response profile to be more accurately estimated
  • Allow any changes that may have occurred in efficacy over the lifetime of the drug development to be investigated
  • Help to address why results for a particular study may be inconsistent with the results of other studies
  • Enable the assessment of the sensitivity of results to different methodologies for defining endpoints, or different methodologies for handling missing data