Review by Joseph Ross – 07/27/2017 – 7:19am

Data Request Number: 2017-1856 Is the scientific purpose of the research proposal clearly described?: Yes Will request create or materially enhance generalizable scientific and/or medical knowledge to inform science and public health?: Yes Can the proposed research be reasonably addressed using the requested data?: Yes, or it’s highly likely Please use this space to provide any comments, feedback or concerns (optional):

This is an interesting request to use data to examine the safety and efficacy of biologic therapy for inflammatory bowel disease. This is an important project, but would benefit from further clarification prior to approval.
First, the request suggests that patients older than 60 will be defined as “cases”, those under 60 as “controls”. What remains unclear is how the full cohort of all trials are being included analyses: What about patients who were assigned to placebo therapy? Are only patients who were assigned to biologic therapy being included in analyses? A stronger study design would meta-analyze all trials, all patients, and examine for interaction effect by age, to determine whether the benefit in comparison to placebo is significantly different (either larger or smaller) for patients older than 60 when compared to those under 60.
Second, what meta-analysis methods are being used to analyze the 12+ trials on an aggregate level? The authors suggest that they are using multivariable logistic regression methods – this seems crude. More advanced methods are necessary to account for clustering of patients within trials, differences across the trials, which therapies were used in the trial, what clinical condition patients were being treated, and so forth.
Finally, the title of the study suggests that safety is an important focus of the study, but no safety outcomes are defined.

Recommendation for this data request: Not Approve

Please see comments above. These should be addressed and the proposal re-reviewed prior to approval.