Chassany O, Knoll S, Manson S, Stull D. Understanding and addressing potential bias in patient-reported outcomes from clinical trials. Presented at the ISPOR 21st Annual European Congress; November 13, 2018. Barcelona, Spain.


PURPOSE: We will share a variety of novel trial design and analytic techniques to understand or minimize bias in PRO data, with implications for understanding treatment effects and optimizing HTA and regulatory submissions.

Bias within PRO data collected in trials has been a longstanding issue, which can confound conclusions drawn from such data. Certain diseases with event driven data collection (e.g. oncology) and trial designs (e.g. open label and single arm trials) have the potential for higher levels of bias. We will first discuss trial design including examples of how to optimize trial design in different situations, e.g. where it is not possible to have a double blinded study or when symptoms aren’t expected to coincide with planned site visits. We will also discuss approaches for minimizing the amount of missing PRO data including technology and effective site communication.

We will discuss a variety of analytic techniques that can be used to better understand PRO data, particularly in situations with large amounts of potentially informative missing data. A few examples will be shared to best understand these data, including pattern mixture models and extended pattern mixture models. In addition, more complicated (i.e., indirect/mediated) relationships often exist between treatment and PRO outcomes, but traditional analyses often don’t capture them. We will describe alternative approaches and present recent examples from oncology clinical trials.

Finally, we will discuss the importance of minimizing bias and missing data from an evaluator’s perspective: how can we anticipate or at least identify potential biases, and analyze, interpret and present results in a submission dossier for optimizing a submission for drug approval or reimbursement? There will be polling throughout this workshop to ask the audience their priorities in terms of approaches to minimizing bias, the pros/cons of different approaches, and an opportunity for questions at the end.

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