Considerations for the Development of Treatment Efficacy/Benefit Attributes and Levels in Patient Preference Studies

OBJECTIVES: Attributes reflecting efficacy/benefit can be key towards informing healthcare decisions with various stakeholders. However, inclusion in patient preference (PP) studies presents unique challenges. Common challenges are outlined alongside recommendations with respect to constructing ‘fit-for-purpose’ treatment efficacy/benefit attributes.

METHODS: Best practice methodological guidance relating to expression of efficacy data in PP studies were reviewed and critically-evaluated. Review outputs informed recommendations and considerations to optimize expression of efficacy/benefit data in PP studies, which may support methodological robustness and mitigate risk of confounding effects.

RESULTS: Efficacy endpoints in clinical trials may include assessments of clinical events (e.g., mortality), patient-reported symptoms (e.g., pain), functioning (e.g., ability to walk), or relevant surrogates. Trials often examine the effect of treatment on multiple endpoints. Supportive data for endpoints may vary (e.g., time-to-event, proportion of responders, mean change in scores). Likewise, endpoints may be analyzed via various statistical techniques. Critical considerations relevant to bolstering generalizability of PP findings include a) prioritization, selection, and communication of efficacy attributes [in a manner that is reflective of trial data], b) ensuring content is comprehendible to target participants, and c) efforts to minimize potential bias when corresponding to real-world treatments. Endpoints may need to be prioritized or become composite attributes to minimize design complexity and enable comparison across diverse treatment profiles. Deviations from endpoint definitions should be evidence-based, particularly in regulatory contexts. Certain studies may permit holding efficacy constant if efficacy outcomes across therapies are equivalent/non-differentiating, or to further-explore other differentiating attributes. Attribute/level wording and presentation must be adequately pre-tested in the specific population of interest (via in-depth qualitative interviews) to support appropriate framing and consistent understanding/interpretation.

CONCLUSIONS: Efficacy attributes in PP studies must be evidence-based and appropriately framed as informed via in-depth qualitative pre-testing. Such approaches can ensure efficacy is communicated to patients in an appropriate, clinically accurate, and ethical manner.