CORRESPONDENCE

Re: Is Patient Travel Distance Associated With Survival on Phase II Clinical Trials in Oncology?

Alvaro Muñoz, Jonathan Samet

Affiliation of authors: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Correspondence to: Alvaro Muñoz, PhD, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe St., Rm. E-7008, Baltimore, MD 21205 (e-mail: jvaldez{at}jhsph.edu)

We read with interest the report by Lamont et al. (1) and the accompanying editorial by George (2). Although at first glance the results appeared to include a complete multivariable analysis, on close examination there may be major conceptual and methodologic flaws in the analysis. In the presence of only a modest sample size (n = 110), regression methods cannot be expected to correct for the very strong differences between patients living more than 15 miles from the treatment center and those living closer to it. Table 3 shows striking differences in race, income, educational level, and the proportion of laryngeal cancer cases between the two groups of patients. This tight linkage of patient characteristics to distance from the treating institution precludes the independent assessment of the effect of distance, even if a multivariable model is used.

The manuscript omitted data essential for the reader to fully assess the complex interactions among the variables analyzed. Specifically, the number of deaths was not reported and the univariate hazard ratio for more than 15 miles to 15 miles or less and the corresponding Kaplan-Meier curves were not presented. Under the premise that those living within 15 miles are at a higher hazard of death, and given that African Americans accounted for 77% of those living within 15 miles of the treatment center but only 9% of those living more than 15 miles from it [OR = (77/23)/(9/91) = 33.8 for the association between close distance and being African American, using data in Table 3], it would be expected that African Americans would have a higher hazard of death relative to whites. What was the univariate association between race and outcome?

Before showing the results of the full multivariable model, a stratified analysis according to variables in Table 3 providing the hazard of death among those living more than 15 miles from the treating center relative to those living within 15 miles should have been presented. For example, among white individuals, what was the hazard of death for those living more than 15 miles away relative to those living 15 miles or less? What about the corresponding hazard ratio among African American individuals?

In the presence of the very strong association (OR = 33.8) between short (<=15 miles) distance traveled for treatment and African American race, the surprising finding from the multivariable model presented in Table 4, that living more than 15 miles from the treatment center and being African American were both associated with a similarly reduced hazard of death (hazard ratios [HRs] = 0.32 and 0.30, respectively), reveals a possibly very complex qualitative interaction between distance and race. The likely scenario of white race being a strong risk factor if distance is 15 miles or less but protective if distance is more than 15 miles may illustrate the complex social dynamics of neighborhoods rather than a simple effect of distance to the treatment center. Alternatively, the data presented in Table 4 could reflect a miscoding of race; if there is miscoding, then the text and discussion about the unexpected association of African American race with reduced risk are incorrect.

The article has several other methodologic flaws: 1) There are inconsistencies in the data: Table 2 reports 74 individuals of white race but the data in Table 3 yield only 71. 2) The shape of the distribution of income called for that variable to be categorized rather than treated as a continuous variable. 3) For the square terms of age and income in Table 4, hazard ratios should not have been presented because the antilogarithms of their regression coefficients do not compare any two groups. 4) There were 11 parameters in the multivariable model, leaving only an average of 10 individuals, some possibly with unobserved time to death, for the estimation of each parameter.

We were motivated to explore this article because of its extremely strong findings in the face of a relatively modest sample size. We found the presentation of data in this study to be incomplete and its methods to have apparent flaws. The study's conclusions are therefore suspect, absent reassessment of the findings in light of our concerns.

REFERENCES

1 Lamont EB, Hayreh D, Pickett KE, Dignam JJ, List MA, Stenson KM, et al. Is patient travel distance associated with survival on phase II clinical trials in oncology? J Natl Cancer Inst 2003;95:1370–5.[Abstract/Free Full Text]

2 George SL. Selection bias, phase II trials, and the FDA accelerated approval process. J Natl Cancer Inst 2003;95:1351–2.[Free Full Text]



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