Within trial comparison of survival time projections from short‐term follow‐up with long‐term follow‐up findings

Abstract

Abstract Aims Data on long‐term treatment effects are scarce, despite the intent to use new therapies for many years and the need of patients, physicians and payers to have a better understanding of the lifetime benefits of treatments. The restricted mean or median survival time (RMST) calculated using age instead of time, hypothetically enables estimation of long‐term gain in event‐free or overall survival from the short‐term (within‐trial) effects of an intervention, compared with its control. Tha aim of the study is to use trials with long‐term follow‐up available through extension studies to compare the long‐term projections estimated using RMST from within‐trial follow‐up data with the actual long‐term outcomes in the extension studies. Methods and results We estimated the median long‐term survival time using age instead of follow‐up time and compared these model‐based projections with the actual long‐term estimates in the (i) SCD‐HeFT trial vs. SCD‐HeFT long‐term outcomes; (ii) SOLVD trial vs. SOLVD 12 year follow‐up; (iii) STICH trial vs. STICHES; and (iv) ACCORD study vs. ACCORDION. In the long‐term follow‐up of SCD‐HeFT, gain in survival with ICD vs. placebo over a median of 11.0 years was +1.4 years of life. The RMST model‐derived survival projection from the within‐trial data (median follow‐up of 3.4 years) gave an estimated survival gain of +1.2 years. In STICHES, over a median follow‐up of 9.8 years, coronary artery bypass grafting (CABG) vs. medical care led to a survival extension of +1.4 years in favour of CABG. RMST projections using within‐trial data from STICH (median follow‐up of 4.9 years), gave an extended survival of +2.4 years in favour of CABG in younger patients. In the long‐term follow‐up of SOLVD, enalapril vs. placebo led to a survival gain of +0.8 years over a median follow‐up of 12.1 years. The RMST projections from the within‐trial data (median follow‐up of 2.8 years) gave a survival extension of +0.3 years in favour of enalapril. In the long‐term follow‐up ACCORDION study, with a median follow‐up of 8.8 years, intensive vs. a standard anti‐hyperglycaemic treatment did not influence long‐term survival, which was concordant with the RMST projections from the short‐term ACCORD study with median follow‐up of 4.9 years. Conclusions Age‐based survival projections using within‐trial data generally provided concordant results with the actual survival measured in long‐term follow‐up extension studies. Our findings suggest that age‐based lifetime projections may be used as means to assess the long‐term treatment effects.

Keywords

• Restricted mean survival time
• Long‐term follow‐up
• Survival estimates
• Randomized controlled trials