Censoring in clinical trials: Review of survival analysis techniques

Medical and epidemiological studies are mostly conducted with an interest in measuring the occurrence of an outcome event. Studies conducting survival analysis, however, are focussed toward measuring time to event or outcome. Time to event could vary from time to fatal event i.e. death, or time to occurrence of a clinical endpoint such as disease, or attainment of a biochemical marker. Survival analysis studies originated with the publication of John Graunt’s Weekly Bills of Mortality in London. First life table was prepared by Healy.(1) Survival analysis is also known as lifetime data analysis, time to event analysis, reliability and event history analysis depending on focus and stream where it is used. However, survival analysis is plagued by problem of censoring in design of clinical trials which renders routine methods of determination of central tendency redundant in computation of average survival time. The present essay attempts to highlight different methods of survival analysis used to estimate time to event in studies based on individual patient level data in the presence of censoring. Section 2 highlights types of censoring encountered in a clinical trial, its types and potential statistical solutions. Survival analysis techniques, its assumptions and suitability of methods under different data conditions are illustrated in sections 3 and 4. The next section 5 discusses the importance of techniques to extrapolate estimate of life expectancy derived over a period of time exceeding the duration of trial follow-up. Lastly, section 6 cites limitations and advantages of different methods and finally concludes by indicating possible future areas of research and practice for health economists and public health professionals. We reviewed articles published in PubMed, Science Direct and Ovid search engines using “censoring in clinical trials”, “survival analysis” and “Kaplan Meier method” as key words. After a total of 213 articles retrieved, articles focussing only on methodology aspect were considered for the present review. Original articles were preferred following by subsequent discussion articles, which added substantially to the methodology.