Comparison of absolute benefits of anticancer therapies determined by snapshot and area methods.

BACKGROUND: Reporting of relative risk reduction as the measure of treatment effect in randomized clinical trials (RCTs) may be difficult to understand. Here, we compare two methods for assessing absolute benefits of anticancer therapies. MATERIALS AND METHODS: We searched PubMed for RCTs comparing therapies for breast and colorectal cancers published 1975-2009 (adjuvant setting) and 2000-2010 (metastatic setting). Eligible trials reported statistically significant differences. Kaplan-Meier curves were assessed for absolute differences in time-to-event end points at a single point (snapshot method) and as the area between curves (area method). Pooled absolute benefits determined by both methods were compared by the Pitman-Morgan test. RESULTS: Eighty-three and 39 paired curves were assessed in the adjuvant and metastatic settings, respectively. In trials of adjuvant therapy, absolute benefits were larger and more variable when assessed at different time points by the snapshot compared with the area method (median and ranges for 60-month difference in overall survival: 7.6% [2.5%-28.4%] and 4.5% [1.8%-13.6%]; P = 0.002, respectively). For metastatic disease, both methods were within 0.5 month of each other in 62% of trials. CONCLUSIONS: The area method provides an alternative measure of absolute treatment effect, which uses all of the available data and is less dependent on the shape of survival curves.

Absolute benefits of medical therapies in phase III clinical trials for breast and colorectal cancer.

BACKGROUND: Phase III randomized clinical trials (RCTs) have become larger and are powered to detect small absolute benefits. Temporal changes in absolute benefits of experimental medical therapies reported in RCTs are unknown. METHODS: We identified all RCTs with sample size > or =200 evaluating experimental medical therapies for breast and colorectal cancer published from 1975 to 2007. We assessed changes over three decades in absolute differences in time-to-event end points between experimental and control arms by (i) the usual method (i.e. at one point) and (ii) as the area between time-to-event curves up to a predefined time. RESULTS: We identified 236 eligible RCTs of which 57% (N = 135) evaluated adjuvant treatments. Experimental treatments became more often compared with active treatments (48% versus 59% versus 81%; P < 0.0001). Median absolute benefits of experimental adjuvant treatments decreased but outcomes in control arms improved with time. For RCTs evaluating metastatic disease, there were no changes in absolute benefit over time but incremental monthly costs of new approved treatments increased with time by 100-fold (P < 0.0001). CONCLUSION: In RCTs of breast and colorectal cancer, new effective adjuvant treatments show decreasing absolute benefit, while new treatments of metastatic disease show unchanging levels of benefit at rapidly escalating costs.

Global drug development in cancer: a cross-sectional study of clinical trial registries.

BACKGROUND: Drug development in cancer is costly and may be directed toward 'profitable' cancers of the more developed regions (MDR) as compared with those of the less developed regions (LDR) of the world. Here, we describe drug development in relation to cancer type and geographic location. MATERIALS AND METHODS: We reviewed phase II and III clinical trials evaluating new cancer drugs, which were registered from January to June 2008. Correlations were sought between the number of clinical trials and incidence, mortality and prevalence of the cancers studied (obtained from GLOBOCAN 2002) and stratified by region of the world. RESULTS: We identified 399 newly registered trials. Most trials (N = 229, 57%) were sponsored by industry. The most common types of cancer studied were breast 73 (18%), lung 57 (14%), prostate 44 (11%) and colorectal 28 (7%). In MDR, incidence, mortality and prevalence correlated significantly (Pearson r = 0.80, 0.73 and 0.63; P < or = 0.01) with the number of all registered clinical trials, whereas in LDR, only prevalence showed significant association (Pearson r = 0.55; P = 0.03) with the number of trials for a given type of cancer. CONCLUSION: Lethal cancers that are common in the LDR (e.g. stomach, liver and esophageal cancers) deserve greater emphasis for drug development.