High hospital research participation and improved colorectal cancer survival outcomes: a population-based study

Abstract

Objective: In 2001, the National Institute for Health Research Cancer Research Network (NCRN) was established, leading to a rapid increase in clinical research activity across the English NHS. Using colorectal cancer (CRC) as an example, we test the hypothesis that high, sustained hospital-level participation in interventional clinical trials improves outcomes for all patients with CRC managed in those research-intensive hospitals.

Design: Data for patients diagnosed with CRC in England in 2001-2008 (n=209 968) were linked with data on accrual to NCRN CRC studies (n=30 998). Hospital Trusts were categorised by the proportion of patients accrued to interventional studies annually. Multivariable models investigated the relationship between 30-day postoperative mortality and 5-year survival and the level and duration of study participation.

Results: Most of the Trusts achieving high participation were district general hospitals and the effects were not limited to cancer 'centres of excellence', although such centres do make substantial contributions. Patients treated in Trusts with high research participation (≥16%) in their year of diagnosis had lower postoperative mortality (p<0.001) and improved survival (p<0.001) after adjustment for casemix and hospital-level variables. The effects increased with sustained research participation, with a reduction in postoperative mortality of 1.5% (6.5%-5%, p<2.2×10^-6) and an improvement in survival (p<10^-19; 5-year difference: 3.8% (41.0%-44.8%)) comparing high participation for ≥4 years with 0 years.

Conclusions: There is a strong independent association between survival and participation in interventional clinical studies for all patients with CRC treated in the hospital study participants. Improvement precedes and increases with the level and years of sustained participation.

Keywords: CLINICAL TRIALS; COLORECTAL CANCER; HEALTH SERVICE RESEARCH.

Figure 1

Trust average research participation rates (the numbers of patients enrolled in interventional colorectal cancer (CRC) trials divided by total number of new patients with CRC) over the whole 8-year period expressed as percentages by Trust.

Figure 2

HR and p value plots showing the effect of an increasing sustained rate of Trust-level research participation in CRC studies on 5-year survival. Cox multivariable analysis was performed using the explanatory variables listed in the text. The additional variable was a composite score derived from the number of years for which the research participation rate met and exceeded the % cut-off, giving the number of years the rate of participation was sustained above the percentage shown. The HR shown is for each year where the rate was sustained above that percentage. The associated p value is also shown, plotted on a log scale. (A) Includes adjustment for Experimental Cancer Medicine Centre (ECMC) status while (B) excludes adjustment for ECMC status. Where 3% of patients participate in clinical trials there is a significant (p<0.01) impact on 5-year survival. There is a rapid increase in the p value as the percentage research participation increases up to 7% (p<10¹¹) and then a slower increase to a peak or peaks between 16% and about 30%. After this the p value decreases, as the number of Trusts achieving such high levels of research participation becomes smaller. The same pattern is seen for both analyses (with and without ECMC status).

Figure 3

Adjusted survival curves for patients treated in institutions with high research participation. It shows the cumulative survival for patients treated in institutions that have ≥16% participation in interventional clinical trials for 0, 3 or ≥4 years. At the scale of this graph the results for 1 and 2 years are superimposable over that for 0 years. The curves are highly significantly different and show that the separation occurs principally in the first year of follow-up. Survival is adjusted for primary procedure, index admission, Dukes’ stage, age, deprivation and Experimental Cancer Medicine Centre status.