Use of surrogate endpoints in health technology assessment and reimbursement of treatments for the management of chronic kidney disease

Abstract

The judicious use of surrogate endpoints as substitutes for patient relevant target outcomes can substantially reduce the size and duration of clinical trials, thereby driving down research and development costs and driving faster patient access to innovative therapies. Whilst increasingly used by regulators over the last two decades, health technology assessment (HTA) agencies and payers have been more sceptical in acceptance of surrogates in their reimbursement decisions. Central to acceptance is scientific validation and demonstration of the association in the treatment effect on the surrogate endpoint and target outcome. This review summarises the validity and utility of glomerular filtration rate (GFR) slope as a 'first in class' surrogate with robust evidence of a strong treatment effect association (i.e., R2 trial of 97%) with clinically meaningful kidney target outcomes including dialysis and kidney transplantation. Given the likely continued challenges in the use of surrogate endpoints in future healthcare policy making, we conclude this review with the opportunities for stakeholders-healthcare industry, regulators and payers, clinicians and trialists, and patients and the public-to leverage the future appropriate use of surrogates.