Assessing pharmacological interventions for bone metastases: the need for more patient-centered outcomes

Abstract

Bone metastases are associated with a broad spectrum of clinical sequelae. Pain, reduced mobility, skeletal complications and treatment-related events reduce quality of life. Numerous randomized controlled trials have evaluated pharmacological interventions to treat bone metastases. The primary outcomes used have evolved over the past 25 years; from improvement in pain to time to first skeletal-related event (SRE). In the current definition, a SRE consists of pathological fracture, spinal cord compression or the need for radiotherapy or surgery to the bone. Currently used outcomes can detect small differences between interventions. However, there are several limitations to SRE-related outcomes. In this article we illustrate the evolution of outcomes used in randomized controlled trials, critically appraising current outcomes used and proposing that more patient-centered outcomes are needed.

Keywords::

• bisphosphonates
• bone metastases
• denosumab (Xgeva^®)
• multiple-event analysis
• randomized controlled trial
• skeletal-related events
• time-to-event analysis

Disclaimer

The views expressed in this paper are those of the authors and not necessarily those of the Chief Scientist Office or the NIHR HTA Programme. Any errors are the responsibility of the authors.

Financial & competing interests disclosure

The Health Services Research Unit, University of Aberdeen was commissioned by the NIHR HTA Programme on behalf of NICE to undertake a systematic review of the clinical effectiveness and cost–effectiveness, and economic evaluation of denosumab for the treatment of bone metastases from solid tumors, of which J Ford, G Mowatt and R Jones are authors. The Health Services Research Unit, Institute of Applied Health Sciences, University of Aberdeen is core-funded by the Chief Scientist Office of the Scottish Government Health Directorates. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.