Table 1 Summary of mortality analyses of randomised controlled cancer-screening trials
| Trial name | Disease area | Country | Number of participants | Recruitment period | Number of screens | Screening period | Censorship date | Median FU from randomisation | Original analysis | LTFU analysis | No of years from randomisation to mortality reduction* | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Statistical analysis methodology | Final mortality reduction (95%CI) | Statistical analysis methodology (if different) | Final mortality reduction (95%CI) | ||||||||||
| Two county | Breast | Sweden | 162,981 | 1977 | 4 | 1977–1984 | end 1984 | 5.93 years (mean) (29 years? LTFU) | “Mantel-Haenszel” techniques - stratified by county and age | RR = 0.69 (no CI reported; p = 0.013) | Negative binomial regression, robust SEs for cluster randomisation | RR = 0.69 (95% CI 0.56–0.84; p = 0.0001) | ~ 4 years (Figure 1) [14] |
| Malmo | Breast | Sweden | 42,283 | 1976–1978 | 5 | 1976–1986 | end 1987 | 8.8 years (mean) | Relative risk (RR), test based CI | RR = 1.29 (95% CI 0.74–2.25) | No screening effect (no figure in analysis time) [32] | ||
| Gothenburg | Breast | Sweden | 51,611 | 1982–1984 | 4–5 | 1982–1991 | end 1996 | 11.8 years (mean) (~ 14 years LTFU) | RR, Poisson regression. Test based on Likelihood ratio | RR = 0.56 (95% CI 0.31–0.99; p = 0.046) | RR, Poisson regression adjusted for birth cohort | RR = 0.79 (95% CI 0.58–1.08; p = 0.14) | ~ 0 years (Figure 1) [5] |
| Edinburgh | Breast | UK | 54,654 | 1978–1985 | 2–4 (depending on cohort) | 1978–1988 | 1992 | ~ 9 years? 10 years max (12.8 years (mean) LTFU) | Logistic regression modified for cluster randomisation and stratified by age. ITT | RR = 0.82 (95% CI 0.61–1.11) [RR with logistic regression?] | Same | RR = 0.87 (95% CI 0.70–1.06) | ~ 6 years (Figure 2) [33] |
| UK Age Trial | Breast | UK | 160,921 | 1991–1997 | 7 | 1991–2004? | end 2004 | 10.7 years (17.7 years LTFU) | RRs, no detail. ITT | RR = 0.83 (95% CI 0.66–1.04; p = 0.11) | Poisson regression (presumably as before). | RR = 0.88 (95% CI 0.74–1.04; no p-value) | ~ 3 years (Figure 2) [34] |
| ERSPC | Prostate | Europe (7 countries) | 162,387 (in the core age group) | 1991–2003 | up to 3? | 1991–2003 | end 2006 | 9.0 years (13 years LTFU) | Poisson regression to estimate mortality ratio (RR), stratified by centre and age group. ITT |
RR = 0.80 (95% CI 0.65–0.98; p = 0.04). | Same | RR = 0·79 (95% CI 0·69- 0·91; p = 0·001) | ~ 7 years (Figure 2) [31] |
| SCORE | Colorectal | Italy | 34,292 | 1995–1999 | 1 | 1995–1999? | 2006? | 11.4 years | RRs based on average mortality rates (Poisson distribution). ITT | RR = 0.78 (95% CI 0.56 to 1.08) | ~ 5–6 years (Figure 2c) [35] | ||
| NORCCAP | Colorectal | Norway | 98,792 | 1999–2001 | 1 | 1999–2001 | end 2011 | 10.9 years (14.2 years LTFU (mean)) | HRs from Cox model, adjusted for age. ITT | HR = 0.73 (95% CI, 0.56–0.94; p = 0.02) | Same, except primary analysis now has separate estimates for men and women | Men HR = 0.63 (95% CI 0.47-0.83) Women HR = 1.01 (95% CI 0.77-1.33) | ~ 5–9 years (~ 3 years for men) (Figure 2c) [21] |
| PLCO | Prostate | USA | 76,693 | 1993–2001 | 4–6 | 1993–2005? | 2008 | 11.5 years (14.8 years LTFU) | RRs assuming Poisson distribution. ITT. No mention of WLR test and no p value given subsequently | RR = 1.13 (95% CI 0.75 to 1.70) | Same | RR = 1.04 (95% CI 0.87-1.24) | no screening effect (Figure 1) [26] |
| PLCO | Lung | USA | 154,901 | 1993–2001 | 4 | 1993–2005? | end 2009 | 11.9 years | RRs assuming Poisson distribution. Adjusted p for sequential analyses (interim). No mention of how p calculated | RR = 0.99 (95% CI, 0.87–1.22; p = 0.48) | no screening effect (no figure) [20] | ||
| PLCO | Colorectal | USA | 154,900 | 1993–2001 | 2 | 1993–2004 | end 2009 | 11.9 years (15.8 years) | Weighted (0,1) LR test with RRs assuming Poisson distribution. Adjusted p for sequential analyses (interim) | RR = 0.74 (95% CI 0.63 to 0.87; p < 0.001) | Same for RRs though notably no test/p-value | RR = 0.75 (95% CI 0.66–0.85) | ~ 3 years (Figure 2a) [36] |
| PLCO | Ovarian | USA | 78,216 | 1993–2001 | 4–6 | 1993–2005? | 28 Feb 2010 | 12.4 years (14.8 years LTFU) | Weighted (0,1) LR test (one-sided) with RRs assuming Poisson distribution. Adjusted p-value for sequential analyses (interim) | RR = 1.18 (95% CI, 0.82–1.71) CI sequentially adjusted. No p value reported possibly because test was 1-sided? | Same for RRs though notably no test/p-value (also added a Cox model) | RR = 1.04 (95% CI 0.87–1.24) | no screening effect (Figure 1) [37] |
| NLST | Lung | USA | 53,454 | 2002–2004 | 3 | 2002–2007 | end 2009 | 5.4 years (mean) | RRs assuming Poisson distribution. Adjusted p for sequential analyses. Weighted | RR = 0.80 (95% CI 0.73–0.93; P = 0.004) | ~ 1.5 years (Figure 1B) [24] | ||
| UK Flexible Sigmoidoscopy Screening Trial (UKFSST) | Colorectal | UK | 170 034 | 1994–1999 | 1 | 1994–1999 | 31 Dec 2014 | 17·1 years | HRs from Cox model. ITT | HR = 0.69 (95% CI 0.59–0.82; p<0.0001). | Same | HR = 0.59 (95% CI 0.49–0.70) | ~ 3 years (Figure 1G) [17] |
| Canadian National Breast Screening Study (CNBSS) | Breast | Canada | 50,430 | 1980–1985 | 5 | 1980–1985 | end 1991 | 8.5 years (mean) (25 years LTFU) | T test on difference of proportions | RR = 1.36 (95% CI 0.84–2.21) | Cox PHs model | HR = 0.99 (95% CI 0.88-1.12; p = 0.87) | no screening effect (Figure 3) [11] |