Title: Development and application of innovative survival methodologies: advancing understanding of the pathways between diagnostic route and cancer survival
Funder: Cancer Research UK

Abstract: Background: For many cancers, survival remains lower in the UK than in other developed countries. Late diagnosis appears to be a significant driver of these poorer outcomes. Findings from international comparative studies have stimulated strategic reforms, including introduction of the urgent referral route to diagnosis (RTD) (i.e. 2-week wait pathway). Analyses of English data consistently suggest that RTD - the route a cancer patient follows to the point of diagnosis - is associated with their subsequent survival. However, the mechanisms by which RTD influences survival remain unclear; whether RTD has a direct effect on survival, or whether the effect is indirect and mediated by other factors, such as stage, treatment or caseload, is unknown. Improved understanding of these mechanisms is needed if further advances in cancer survival in the UK are to be achieved, but traditional survival analysis approaches reveal little about mechanisms. Aims: This project aims to (i) refine, extend and promote an innovative survival methodology which allows assessment of direct, indirect and mediation effects and (ii) apply this to advance understanding of the potential causal pathways between RTD and cancer survival in England. Methods: We have developed an innovative Structural Equation Modelling-based method for survival analysis. Phase 1 will involve refining and extending the method to address limitations and accommodate features of cancer data (e.g. refining how the survival outcome is modelled, accounting for hierarchical data). Phase 2 will involve analysis of RTD and survival for cancers of the breast, prostate, lung and colorectum diagnosed in England in 2006-2014. For each cancer, theoretical models of how 2-week wait and other major diagnostic routes (emergency presentation, standard GP referral) influence survival will be developed from theory, literature, and PPI and clinical consultation. These will be tested using the refined statistical approach, quantifying direct and indirect effects of diagnostic route on survival. Statistical code will be made freely available to promote use of the approach in the cancer registration and epidemiological communities. Analysis results will be disseminated through scientific conferences and journal papers and summaries for patients, health professionals, service providers and Commissioners, and policy-makers. How the results will be used: The findings will inform (i) which patient groups and/or aspects of the cancer pathway policy should focus on, and (ii) the types of services developments or other interventions that might be needed, to improve cancer survival in the UK. The results may inform priorities for the next Cancer Strategy.

Lay abstract: Background: For many cancers, survival remains lower in the UK than in other developed countries. Late diagnosis appears to be a significant driver of these poorer outcomes. Findings from international comparative studies have stimulated strategic reforms, including introduction of the urgent referral route to diagnosis (RTD) (i.e. 2-week wait pathway). Analyses of English data consistently suggest that RTD - the route a cancer patient follows to the point of diagnosis - is associated with their subsequent survival. However, the mechanisms by which RTD influences survival remain unclear; whether RTD has a direct effect on survival, or whether the effect is indirect and mediated by other factors, such as stage, treatment or caseload, is unknown. Improved understanding of these mechanisms is needed if further advances in cancer survival in the UK are to be achieved, but traditional survival analysis approaches reveal little about mechanisms. Aims: This project aims to (i) refine, extend and promote an innovative survival methodology which allows assessment of direct, indirect and mediation effects and (ii) apply this to advance understanding of the potential causal pathways between RTD and cancer survival in England. Methods: We have developed an innovative Structural Equation Modelling-based method for survival analysis. Phase 1 will involve refining and extending the method to address limitations and accommodate features of cancer data (e.g. refining how the survival outcome is modelled, accounting for hierarchical data). Phase 2 will involve analysis of RTD and survival for cancers of the breast, prostate, lung and colorectum diagnosed in England in 2006-2014. For each cancer, theoretical models of how 2-week wait and other major diagnostic routes (emergency presentation, standard GP referral) influence survival will be developed from theory, literature, and PPI and clinical consultation. These will be tested using the refined statistical approach, quantifying direct and indirect effects of diagnostic route on survival. Statistical code will be made freely available to promote use of the approach in the cancer registration and epidemiological communities. Analysis results will be disseminated through scientific conferences and journal papers and summaries for patients, health professionals, service providers and Commissioners, and policy-makers. How the results will be used: The findings will inform (i) which patient groups and/or aspects of the cancer pathway policy should focus on, and (ii) the types of services developments or other interventions that might be needed, to improve cancer survival in the UK. The results may inform priorities for the next Cancer Strategy.

Research activity codes: 4.3 INFLUENCES AND IMPACT;7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT)
Health categories: CANCER AND NEOPLASMS