Expert Insights

Expert Insights

Identifying The Three Leading Ways Your ISS and ISE Can Derail Your Study

Identifying The Three Leading Ways Your ISS and ISE Can Derail Your Study
10 March 2020

Compiling and submitting the ISS and ISE are a vital part of a successful new drug application submission to gain approval from the FDA. However, they each involve integrating the culmination of years of clinical development data to show the drug’s safety and efficacy. Building these integrated datasets can be challenging, to say the least. From making sure structures and formats are consistent, while also ensuring that each dataset is CDISC-compliant, to anticipating issues that can arise—developing the integrated summaries is a multi-faceted process.

How can you anticipate potential issues in the integration before they arise? Below are the top three areas where the ISS and ISE can begin to go awry.

Data Integration

Producing the integrated datasets is the most challenging and time-consuming part of the ISS/ISE process. Because of this, we advise that drug developers get started as early as possible.

Errors in the integrated datasets are among the most common causes for ‘refusal to file’ responses from the FDA. Additionally, if the data is integrated incorrectly, the results of analysis may be incorrect and not represent the true features of the study drug. Efficacy may look better or worse than the reality.

Numerous types of data and steps are typically required to get the data ready for integration. These include:

  • Assessing lab data
  • Up-coding: MedDRA, WHODrug, CTCAE
  • Performing CDISC conversion
  • Assessing derived variables to ensure consistency
  • Performing consistency checks
  • Making treatment group determinations (e.g., whether or not to combine placebo groups with varying dosing schedules)

Timeline Issues

Timeline issues are also common in integrations. Typical issues that might occur here include:

  • The timeline for Phase III studies may change, affecting your timeline for integration.
  • It may be that you originally decide to integrate at the ADaM level only to find out that data issues are prohibiting integration and the dataset integration needs to start at STDM, with ADaM datasets being created after STDM.
  • Integrated data output (mainly tables and figures) that are poorly designed can make writing the ISS and ISE difficult for medical writers, causing delay in delivery time for review which will impact submission timelines.

Resource Issues

Resource issues can result when:

  • Enrollment, or other aspects of the trial, occur faster than planned and there are not enough resources to accommodate integration work earlier than expected.
  • More commonly, if Phase III studies take longer than expected, this may delay the integration process, and integration teams that are already committed to another project may be constrained on their ability to help during this later timeframe.

These are just a few of the issues that can surface while developing the integrated datasets. As a result drug developers need to start early; develop and stick to a plan, and capitalize on frequent communications.

Overcoming These Top Issues and More

To learn more about planning for an ISS and an ISE and how to solve these common or other unforeseen issues, please read our checklist: Planning for ISS/ISE Integration: 4 Critical Steps to Get Started. Or Contact us today to find out how we can facilitate your next submission.

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