Recent breakthroughs in anticancer therapies such as small-molecule drugs and immunotherapies have made improvements in Health-Related Quality of Life (HRQOL) possible among cancer patients over the course of treatment. In a recent paper published in the Journal of Clinical Epidemiology, Cottone and colleagues are the first to propose the framework for assessing the change in HRQOL over time in these patients: Time to HRQOL Improvement (TTI), and Time to Sustained HRQOL Improvement (TTSI).
In the proposed framework, TTI is based on the time to the “first clinically meaningful improvement occurring in a given scale or in at least one among different scales” – for instance, a minimal important difference (MID) of 5 points on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire – Core 30 (QLQ-C30). The authors suggest utilizing the first posttreatment score as the baseline measurement for monitoring improvements over time. “Sustained improvement” was defined as the first improvement that is not followed by a deterioration that meets or exceeds the MID.
The use of Kaplan-Meier curves and Cox proportional hazards is inappropriate for these outcomes, the authors argue, as it does not allow for possible competing events, such as disease progression, toxicity, or the possibility of an earlier improvement in another scale when multiple scales are used. They propose the use of the Fine-Gray model for the evaluation of TTI and TTSI and pilot it with a case study of 124 newly diagnosed chronic myeloid leukemia patients undergoing first-line treatment with nilotinib.
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| Time To Improvement (TTI) and Time to Sustained Improvement (TTSI) can be used to elucidate differences in HRQOL responses to treatment based on baseline characteristics. Here, the figure shows TTSI in fatigue scores based on hemoglobin level at baseline. Click to enlarge. |
Using this model, the authors found that improvements in fatigue scores appeared more quickly than those in physical functioning when measuring scores from baseline (pre-treatment), but upon using first post-treatment score as the baseline, the differences between improvement rates in fatigue and physical functioning diminished. Additionally, a lower baseline hemoglobin level was associated with earlier sustained improvements in fatigue.
While the proposed method of evaluating TTI and TTSI has some limitations, such as lower statistical power than other ways of tracking changes in HRQOL over time, it also has notable strengths. In particular, this method can be used to elucidate differences between treatment approaches that show similar survival outcomes so that the approach with shorter TTI and TTSI can be favored.
Cottone, F., Collins, G.S., Anota, A., Sommer, K., Giesinger, J.M., Kieffer, J.M., ... & Efficace, F. (2020). Time to health-related quality of life improvement analysis was developed to enhance evaluation of modern anticancer therapies. J Clin Epidemiol 127:9-18.
Manuscript available from publisher's website here.
