Parametric survival analysis and taxonomy of hazard functions for the generalized gamma distribution

The widely used Cox proportional hazards regression model for the analysis of censored survival data has limited utility when either hazard functions themselves are of primary interest, or when relative times instead of relative hazards are the relevant measures of association. Parametric regression models are an attractive option in situations such as this, although the choice of a particular model from the available families of distributions can be problematic. The generalized gamma (GG) distribution is an extensive family that contains nearly all of the most commonly used distributions, including the exponential, Weibull, log normal and gamma. More importantly, the GG family includes all four of the most common types of hazard function: monotonically increasing and decreasing, as well as bathtub and arc-shaped hazards. We present here a taxonomy of the hazard functions of the GG family, which includes various special distributions and allows depiction of effects of exposures on hazard functions. We applied the proposed taxonomy to study survival after a diagnosis of clinical AIDS during different eras of HIV therapy, where proportionality of hazard functions was clearly not fulfilled and flexibility in estimating hazards with very different shapes was needed. Comparisons of survival after AIDS in different eras of therapy are presented in terms of both relative times and relative hazards. Standard errors for these and other derived quantities are computed using the delta method and checked using the bootstrap. Description of standard statistical software (Stata, SAS and S-Plus) for the computations is included and available at http://statepi.jhsph.edu/software.

[1]  R. Prentice A LOG GAMMA MODEL AND ITS MAXIMUM LIKELIHOOD ESTIMATION , 1974 .

[2]  Ross L. Prentice,et al.  Discrimination among some parametric models , 1975 .

[3]  P. Royston,et al.  Flexible parametric proportional‐hazards and proportional‐odds models for censored survival data, with application to prognostic modelling and estimation of treatment effects , 2002, Statistics in medicine.

[4]  E. Stacy A Generalization of the Gamma Distribution , 1962 .

[5]  J W Denham,et al.  A generalized F mixture model for cure rate estimation. , 1998, Statistics in medicine.

[6]  Ronald E. Glaser,et al.  Bathtub and Related Failure Rate Characterizations , 1980 .

[7]  Lee J. Bain,et al.  An exponential power life-testing distribution , 1975 .

[8]  J. Klein,et al.  Survival Analysis: Techniques for Censored and Truncated Data , 1997 .

[9]  Jonathan AC Sterne,et al.  Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies , 2002, The Lancet.

[10]  C. Cox,et al.  Asymptotic confidence bands for generalized nonlinear regression models. , 1995, Biometrics.

[11]  R. Greenblatt,et al.  Patterns of the hazard of death after AIDS through the evolution of antiretroviral therapy: 1984–2004 , 2005, AIDS.

[12]  G. S. Mudholkar,et al.  A Generalization of the Weibull Distribution with Application to the Analysis of Survival Data , 1996 .

[13]  H Putter,et al.  Long‐term survival with non‐proportional hazards: results from the Dutch Gastric Cancer Trial , 2005, Statistics in medicine.

[14]  L Kates,et al.  Regression analysis of censored survival data with the generalized F family--an alternative to the proportional hazards model. , 1986, Statistics in medicine.

[15]  E. W. Stacy,et al.  Parameter Estimation for a Generalized Gamma Distribution , 1965 .

[16]  Paul D. Allison,et al.  Survival analysis using sas®: a practical guide , 1995 .

[17]  T. Holtz,et al.  Time to Sputum Culture Conversion in Multidrug-Resistant Tuberculosis: Predictors and Relationship to Treatment Outcome , 2006, Annals of Internal Medicine.

[18]  Lee-Jen Wei,et al.  The accelerated failure time model: a useful alternative to the Cox regression model in survival analysis. , 1992, Statistics in medicine.

[19]  J. Phair,et al.  The Multicenter AIDS Cohort Study: rationale, organization, and selected characteristics of the participants. , 1987, American journal of epidemiology.

[20]  Joseph Feldman,et al.  The Women's Interagency HIV Study , 1998 .

[21]  J. Sunyer,et al.  Comparison of semiparametric and parametric survival models for the analysis of bronchial responsiveness. , 1996, American Journal of Respiratory and Critical Care Medicine.