Integrated Summary Tips

Quanticate's Medical Writing Team have summarized tips for the preparation of comprehensive, well-written, and focused integrated summary documentation.

Integrated Summary Tips:

Worst practices for producing an integrated summary

• Not providing one!
• Being too brief
• Excluding data that do not support the effectiveness conclusions
• Excluding pertinent safety data
• Pooling data that should not be pooled
• Replying on results from post hot meta analyses
• Discussing experimental endpoints, rather than focusing on primary and co-primary endpoints
• Including datasets without explaining how they were derived

Initial preparation for authors, contributors and reviewers

• Always ensure most up-to-date templates and relevant regulatory guidelines are consulted and used throughout the project life cycle
• Use professional approved style guides, and detail how to cover items not covered in style guides upfront
• Use standardized methods for citation/referencing
• Train authors to write granular documents
• Train reviewers to review electronically

Planning for Lifecycle Management

• Employ methods and tools for information sharing and knowledge management early in the process
• Reviewers need to know what has changed and why
• Consider impact of changes on future documents
• Incorporate best practices for change history

Improved Reviewability

• User effective hyperlinks and bookmarks; all documents from protocol through to summary should be hyperlinked and bookmarked at time of preparation rather than at the end
• Write with electronic review in mind – FDA Good Review Practices
• Create an efficient work flow
• Produce submission-ready documents at all stages – employ a consistent QC checklist to make this happen

Get the Basics Right - Writing

• Clear, concise, objective statements
• Acceptable grammar and punctuation
• Consistent writing style and Quality Control (QC) checklists to ensure intra and inter document consistency
• Accurately crafted key messages; no mixed messages; same message throughout; focus on label claims
• Ensure scientific interpretation, not regurgitation
• Easy-to-read layout: 100% zoom, 12 pt font, Times New Roman
• Easy to navigate - sufficient and accurate hyperlinks and bookmarks
• Find the right balance between content re-use and avoid redundant repitition. Content does not mean simply copying and pasting from one document to another
• Avoid repeating detail already given in the individual summaries of clinical trials; Don't cut and paste - hyperlink instead
• For legacy trials, use the body of the Clinical Study Report (CSR) as the source, not the CSR sypnosis

Get the Basics Right - Statistics

• Don't use secondary data unless they support label claims or reveal an issue
• Provide comprehensive, detailed, in-depth analysis of results in aggregate with a clear rationale for the methods used
• Utilise both positive and negative trials
• Compare trials of similar designs: Weighting of sample size; Examine by common covariates or stratifications; Consider controls, durations, parent populations, endpoints, dropouts, statistical analyses
• Consider inconsistencies in the data
• Consider areas needing further exploration

Safety Summaries

• Choose a single dictionary, and include dictionary and version in the methods. If older dictionaries used and re-coding is not possible, include details and/or a footnote to explain
• Consistent terminology (e.g., If presenting >5% common adverse events [AEs], use this cut-off throughout)
• Reference Quantitiative Satefy Analysis Plans (QSAPs) where applicable 
• Discuss statistical issues with AEs; search the database for related AEs
• Always show gender specific denominators
• Mention denominator over time
• Graph representation is good
• Present clinically significant criteria for laboratory, ECGm vital signs and AEs; where applicable, referencing most current criteria
• Multiple labs - ensure reference ranges in same unit of measure (applying conversions, where necessary)
• Lab ranges and lab cut-offs often come up when reviewing

Efficacy Summaries

• Mention limitations of sample size
• Age, sex, race and geographic location; clinically relevant demographic factors
• Consider US versus non-US - Does this have an impact on efficacy? Describe regional differences
• Deal with the drop outs - planned versus actual
• Consider and discuss risk benefit
• Analyse postive and negative findings
• Focus on pre-specified endpoints
• Consider sub-populations
• Use graphical representations such as Forest Plots
• Data format is important (e.g., convert to the same unit of measure)
• Use tables to combine and present data. All cells should have something or it may be construed as missing; use consistent footnote symbol order for every table
• When pooling data, discuss and present selection process
• State and discuss problems; it provides a more credible analysis
• Include clinical information relevant to dose recommendations and individual dose responses
• Listings are not required anymore by FDA; SAS viewer is used

Related Blog Posts

• Integrated Summaries of Safety & Efficacy for Regulatory Submissions
• Using CDISC SDTM to Improve Cost and Quality in Integrated Summaries

Authors note: This blog was originally published on 05/04/2012 and has since been updated.