Assessing the impact of restricted follow-up and small sample sizes on survival estimations in prostate cancer using registry data.

294 Background: Economic evaluations in oncology aim to assess the value of new therapies in the long term based on clinical trial data that often have restricted follow-up times (< 5 years) and small sample sizes (< 500 patients). This requires the use of extrapolation assumptions on long-term survival that go beyond the observed data. In this analysis, differences in survival extrapolation methods are tested in samples of sizes and follow-up reflecting typical clinical trials against a background of known survival in prostate cancer from a US based cancer registry.

METHODS: Data from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) registry on long-term survival in patients with stage IV prostate cancer were employed. The data set comprised those patients diagnosed between 1988 and 2003, with follow-up data available until 2012. Additional survival for those who received surgery (compared to those who did not), was estimated based on extrapolations using standard parametric statistical models (exponential, Weibull, log-logistic, log-normal, Gamma) fitted to the observed data. Survival analyses were run for 5 sample size scenarios (n = 27,670, 1000, 500, 200, 50) and 6 follow-up scenarios (follow-up years = 25, 20, 10, 5, 2, 1) yielding 30 combination scenarios. Performance of the methods was tested relative to the maximum follow-up, maximum sample size scenario (i.e. reference case) from the SEER registry.

RESULTS: Log-logistic and log-normal models were associated with flat tails which led to inflated survival estimations. For scenarios with smaller sizes, gamma models often did not converge. Exponential models were the most frequently reported as best model fit (in approximately 50% of scenarios). Also, gains in OS were consistent when exponential models were selected, and closely matched gain in OS from the reference case.

CONCLUSIONS: Since clinical trials in oncology are often associated with small patient sample sizes and restricted follow-up, selecting an exponential model may lead to the most consistent and stable results based on the experiment constructed here. Further research should confirm these results for other types of cancer.