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Research:
Justin A. Ezekowitz, Carl van Walraven, Finlay A. McAlister, Paul W. Armstrong, and Padma Kaul
Impact of specialist follow-up in outpatients with congestive heart failure
CMAJ 2005; 172: 189-194 [Abstract] [Full text] [PDF]
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Justin A Ezekowitz   (22 March 2005)
[Read eLetter] Impact of Specialist Follow-up in outpatients with heart failure
Murray M Finkelstein   (7 February 2005)

Response 22 March 2005
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Justin A Ezekowitz
Uinversity of Alberta

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justin.ezekowitz{at}ualberta.ca Justin A Ezekowitz

Dear CMAJ,

We thank Dr. Finkelstein for his letter. Dr. Finkelstein is appropriately concerned about the inclusion of post-event outcomes in the regression model. Such an incident results in biased associations – namely, one being unable to determine if the predictive factor resulted in the event or if the event resulted in the predictive factor. This has been called “survivor-treatment selection bias”(1) or, more generically, “time-dependent bias” and is relatively common even in highly cited medical journals. In a recent systematic review, we found that 18.6% (95% CI 15.8 to 21.8%) of studies with a survival analysis contained a time- dependent factor and that 40.9% [32.3 to 50.0%] of these studies were susceptible to time-dependent bias. (1)

However, we strongly disagree that our Cox model is done incorrectly, as it corrects for this bias. As we state in the methods section, we adjust for the appropriate time-dependent variables and have a variable expressing ‘time spent in hospital up to that time’. (3) The results section summarizes the findings. The phrase ‘within 1 year after discharge’ stated in the results section refers to the censoring time that we used for all analyses in the study. We do not use ‘future information’ as stated by Dr. Finkelstein, and our methodology is robust.

We state clearly in our Methods section that we performed a sensitivity analysis using all outpatient visits rather than cardiovascular visits to define our groups; however, this analysis was truncated by the journal due to space limitations. Using the same variables as in Table 3 but using all visits rather than cardiovascular visits, we found similar results: compared to those without any outpatient visits, patients seen by a family physician (OR 0.80 [95%CI 0.64 to 0.96]) or a specialist and family physician (OR 0.48 [95%CI 0.40 to 0.58]) had lower mortality rates. Furthermore, similar results were obtained with the Cox model using all visits instead of cardiovascular visits: seeing a specialist (HR 0.95 [95%CI 0.94 to 0.96]) was associated with lower mortality.

Regards,

Justin A. Ezekowitz, MBBCh MSc Carl Van Walraven, MD MSc Finlay A. McAlister, MD MSc Paul W. Armstrong, MD Padma Kaul, PhD

1. Glesby MJ, Hoover DR. Survivor treatment selection bias in observational studies: examples from the AIDS literature Ann Intern Med 1996;124:999–1005.

2. van Walraven C, Davis D, Forster AJ, Wells GA. Time-dependent bias was common in survival analyses published in leading clinical journals. Journal of Clinical Epidemiology 2004; 57: 672-680.

3. Ezekowitz JA, van Walraven C, McAlister FA, Armstrong PA, Kaul P. Impact of specialist follow-up in outpatients with congestive heart failure. CMAJ 2005;172(2):189-94.

Conflict of Interest:

None declared
Impact of Specialist Follow-up in outpatients with heart failure 7 February 2005
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Murray M Finkelstein
Family Medicine Centre, Mt Sinai Hospital

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Re: Impact of Specialist Follow-up in outpatients with heart failure

murray.finkelstein{at}utoronto.ca Murray M Finkelstein

Ezekowitz and colleagues have concluded that patients with congestive heart failure followed by specialists and Family Physicians (FP) have better survival than patients followed by FPs alone. Their analysis is, however, not internally consistent. In the methods section they state, quite appropriately, that "a time dependent analysis is essential when examining the effect of physician follow-up because patients' outcomes can determine their exposure". Nevertheless, apart from a brief paragraph at the end of the results section, all of their findings (Tables 2, 3, and Figure 1) are presented in terms of an inappropriate time-independent analysis which ignores any change in the provision of care during follow- up.

All patients, at the moment of discharge, will have had no cardiovascular follow-up, and they will remain in that category until the first physician visit, at which time their status will change. Should that visit be to an FP, they will, at that time, move into the FP only category. Should they subsequently visit a specialist, they will move from the FP only to the FP and specialist category. From a methodological point of view, they will leave behind the days at risk they experienced while in each of the preceding categories. A time dependent Cox regression will assign them to the appropriate category in the risk set formed at the time of each death in the cohort. Neither the log-rank analysis of Figure 1, nor the multiple logistic regression analysis of Table 3, make this correct comparison.

It is also not clear that the Time dependent Cox analysis mentioned in the last paragraph of the results section has been done correctly. The authors state that the model was adjusted for "cumulative days spent in hospital within 1 year after discharge". In a Cox analysis, one compares the characteristics of subjects who die with the characteristics of those subjects still alive at the time of death. The relevant variable, would then be time spent in hospital UP TO THAT TIME. Use of cumulative days within 1 year of discharge requires the use of FUTURE INFORMATION. This is logically untenable.

I conclude that the authors results cannot be accepted at face value because their methodology was not appropriate for their study design. I would encourage them to compute the appropriate time dependent models to answer this important question about management of congestive heart failure.

Sincerely,

Murray Finkelstein PhD MDCM CCFP Family Medicine Centre Mt Sinai Hospital

Conflict of Interest:

None declared