Hazard ratios in cancer clinical trials--a primer

Abstract

The increase and diversity of clinical trial data has resulted in a greater reliance on statistical analyses to discern value. Assessing differences between two similar survival curves can pose a challenge for those without formal training in statistical interpretation; therefore, there has been an increased reliance on hazard ratios often to the exclusion of more-traditional survival measures. However, because a hazard ratio lacks dimensions it can only inform the reader about the reliability and uniformity of the data. It does not provide practitioners with quantitative values they can use, nor does it provide information they can discuss with patients. Motivated by a non-scientific poll of oncologists in training and those with board certification that suggested only a limited understanding of the derivation of hazard ratios we undertook this presentation of hazard ratios: a measure of treatment efficacy that is increasingly used and often misused.

Figure 1 |

The use of the term hazard ratio in abstracts. a | The increase in the use of the term hazard ratio in the abstracts of journal* articles reporting cancer clinical trial data over time. b | Abstracts reporting clinical trials* that included a hazard ratio and published in January, February and March of 2011 were examined. Both the hazard ratio and the relevant times were presented in 57% of these abstracts, whereas only a hazard ratio without reference to the absolute values in time could be found in 43% of abstracts. *Journals assessed: Annals of Oncology, Clinical Cancer Research, European Journal of Cancer, Journal of Clinical Oncology, Lancet, Lancet Oncology, New England Journal of Medicine.

Figure 2 |

Kaplan–Meier plot of hypothetical clinical trial. The data for this plot are tabulated in Tables 1 and 2.

Figure 3 |

Kaplan–Meier plot of two studies that led to registration of the respective drugs in renal cell carcinoma. a | sorafenib and b | sunitinib. Permission obtained from Massachusetts Medical Society part a © Escudier, B. et al. N. Engl. J. Med. 356, 125–134 (2007) and part b © Motzer, R. J. et al. N. Engl. J. Med. 356, 115–124 (2007).

Figure 4 |

Graphical presentation of hypothetical clinical trial data (Table 3) demonstrates how the hazard rate is calculated and how this rate can be used to calculate the hazard ratio. a | Kaplan–Meier plot for the two arms of the hypothetical study (control and experimental). b | The hazard rate can vary over time and this variation can disproportionately affect one arm of the trial at different time points.