Pooling Clinical Data - a medical writer's perspective

Pooling Clinical Data - a medical writer's perspective

Pooling of data is used by all companies involved in submitting clinical trial data. There are various reasons to pool data including the production of documents for Development Safety Update Reports (DSURs), publications and parts of an NDA submission.

One of the hurdles a project team (including the medical writer) face is the decision on how to best pool or not pool clinical trial data for submission to regulatory authorities. The first approach to pooling clinical data is planning. A plan should be developed to identify which studies and which data should be pooled for any given deliverable from both an efficacy and a safety perspective.1,2

The role of a medical writer is to tie the pooled datasets and analyses together into the final submission document. Medical writers are required to work closely with biostatisticians to understand what is expected of regulatory authorities.

A key consideration that needs to be discussed between the medical writer and project team is the differences between studies, which can affect the ability to interpret pooled analyses.  These differences include but are not limited to:3

  • Important demographic or disease characteristics (e.g., severity, previous treatment, concomitant diseases and treatments, prognostic or predictive biomarkers).
  • Methods of assessing efficacy/performance and/or specific test procedures (e.g., measurements of biomarkers and clinical endpoints).
  • Study design features (e.g., population, study duration, doses administered).

Other considerations include justifying pooling or not pooling clinical data from specific studies or subsets of patients.  For example, pooling safety data from healthy volunteers with data from patients with the indicated disease or condition may be acceptable in looking for possible unexpected or uncommon adverse effects of the drug. In other cases, the data pooling would weaken the overall safety profile to be presented and mislead the reviewer.3 With sizeable amounts of data to analyse, pooling clinical data can be a complicated task and becoming lost amongst the data is a common scenario for many.3 The clinical data presented must be clear, efficient, and meet regulatory requirements.  This is where a medical writer can assist identify solutions that will cope with thorough reviews, both internally and by regulatory authorities.

Although ICH guidelines discuss the integration of data across trials, there are rarely any fixed guidelines to adhere to. However, as guidances are updated over time, it is vital that the medical writer as well the project team are up-to-date with latest industry information.

 


1 Yeh, A., Zhang, Z.G, Wang, S. Pooling Clinical Data.

2 Gerlach, J.R, Bowen, J.C. Facilitating Data Integration for Regulatory Submissions. SCSUG 2010.

3 Sibley, S. The Roundtable: Out Thoughts about Model Based Drug Development. Diving into Best Practices for Pooling Clinical Data. 2016.