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# Statistical Principles Addendum Issues Raised
- URL: https://www.fdaweb.com/statistical-principles-addendum-issues-raised/
- Published: 2018-05-01T12:00:00.000Z
- Updated: 2026-09-15T00:01:59.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5141344

Commenting on an International Council on Harmonization draft guidance on statistical principles for clinical trials addendum on estimands and statistical analysis in clinical trials, Pharmaceutical Research and Manufacturers of America (PhRMA) [says](https://www.regulations.gov/document?D=FDA-2017-D-6113-0019&ref=fdaweb.com) that additional clarity is needed in several areas to help reduce clinical trial complexity and increase clarity in product labeling. PhRMA raises these five points: 

- industry should have an opportunity to provide feedback on case studies that are to accompany the guidance before the final version of the addendum to ensure that it includes studies that are most helpful in applying the statistical principles for clinical trials;
- case studies should provide sufficient detail on how to choose an estimand strategy that is aligned with the question of interest and also explores how to choose a particular estimation approach for the primary analysis;
- the guidance should include details of alternative estimation approaches that might be required as sensitivity analyses and a clear example of supplementary analyses that would be helpful in answering a different question of interest;
- FDA should include examples of how to best summarize the statistical approach used in the clinical trial to guide development of concise and easily understood professional and patient labeling; and
- FDA should update disease-specific guidances in a timely manner and include clarity on estimand approaches that may be acceptable in particular situations.

PhRMA also says it believes the draft could be improved by streamlining the language and shortening the document in some areas, providing additional details in other areas and adding more helpful examples to instruct sponsors.

AstraZeneca [tells](https://www.regulations.gov/document?D=FDA-2017-D-6113-0018&ref=fdaweb.com) FDA that attention should be paid to the PhRMA five points. “If the points are not addressed,” it says, “there is a risk that the estimand framework will not improve the evaluation and reporting of clinical trials used for regulatory decision making. Indeed, in the short term there is a danger that the situation will get worse due to the lack of clarity on how to implement the outlined framework. Also, how estimands are described in drug labels needs urgent attention in order to clearly and accurately communicate the results of clinical trials to prescribers and patients.”