MRC/CSO Social and Public Health Sciences Unit

SPIRIT|CONSORT-SURROGATE

This project aims to develop consensus-driven reporting guidelines for Randomised Controlled Trials and protocols that use surrogate primary endpoints. This will be achieved by developing consensus-driven extensions to the SPIRIT and CONSORT checklists: SPIRIT-SURROGATE and CONSORT-SURROGATE (see lay summary on the Patient and Public Involvement page).

Well designed, conducted, and reported randomised controlled trials (RCTs) provide rigorous scientific evidence for evaluating health interventions. However, RCTs can be time and resource intensive.  To make them more time and resource efficient, surrogate endpoints are used as substitutes for patient relevant outcomes (e.g., hospitalisation, death). Traditionally, surrogate endpoint use has focused on the regulatory setting for pharmaceuticals and whether biomarkers are “likely to predict” patient-centred outcomes of interest (e.g., systolic blood pressure for cardiovascular events, low density lipoprotein cholesterol for myocardial infarction, and HIV viral load for development of AIDS).  Nevertheless, it is important to acknowledge a more wider application in RCTs of intermediate outcomes that are believed to capture the causal pathway through which pharmaceutical, surgical, organizational or public health interventions impact the ultimate patient-relevant outcome: for example, hospice enrolment for mortality with an intervention aimed at improving end of life care or fruit and vegetable consumption for cardiovascular events for a behavioural intervention aimed at reducing cardiovascular risk.

Despite the efficiency offered by surrogate endpoints,  there are concerns about their limitations, such as overestimating health benefits and possible failure to predict true benefits of interventions resulting in the roll out of interventions with no health benefit or even harmful. Therefore, design and reporting of RCTs using surrogate endpoints should clearly convey the uncertainty and risks associated with their use if critical. However, this has not been the case.  For instance, an analysis of 626 RCTs found that 17% used a surrogate primary endpoint and of these, only 35% discussed whether the surrogate was a valid predictor of patient-relevant outcomes. Reporting guidelines can guide design and improve the reporting of RCTs at both the protocol and report stages. However, there is no consensus-driven guideline to report RCTs using surrogate primary endpoints. Our working definition of a surrogate endpoint is: ‘a biomarker or intermediate outcome used to substitute and predict for a final patient relevant outcome (i.e., characteristic or variable that captures how a patient feels, functions, or how long they survive, such as the outcomes of mortality or health-related quality of life)’.

Aims and phases of research

Therefore, this project aims to develop and disseminate CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) extensions to improve reporting of trials and protocols with surrogate primary endpoints.

To achieve this aim, published guidance on development of health research reporting guidelines will be used. Based on this guidance, the project will have four phases:

• Phase 1 (Literature reviews) to identify items to be included in extensions and participants for a Delphi study;
• Phase 2 (Delphi study) to rate the items identified in Phase 1;
• Phase 3 (Consensus meeting) to ratify on rated items and agree on final items for inclusion in extensions;
• Phase 4 (Knowledge translation) to disseminate the project outputs through various strategies such as publications, key partners, and stakeholder engagement. The project activities will be conducted over 18 months starting from January 2022, (see Figure below).

Engage with us

Contact us: consort-surrogate@glasgow.ac.uk
Follow us on Twitter @Consort_surr

Register your interest to participate in the project using the following link: https://forms.office.com/r/1UuDCBU8bc

Take part in the Delphi survey

Glossary of terminology

SPIRIT checklist

SPIRIT Privacy Notice

Comments for each definition WORD 

Comments for each rated item WORD 

Cover letter summary and Round 1 feedback WORD 

Endorsement & Funding

The project funding application was endorsed by Medical and products Regulatory Agency (MHRA) and the National Institute for Health and Care Excellence (NICE). The project is funded by the Medical Research Council Better Methods for Better Health.