Functional Data Analysis Applied to a Randomized Controlled Clinical Trial in Hemodialysis Patients Describes the Variability of Patient Responses in the Control of Renal Anemia

Abstract

The achievement of desirable hemoglobin levels in renal anemia that is treated with epoetins is often incomplete and subject to much variation of outcome values and applied dosage. The further development of clinical decision support for renal anemia requires the characterization of patient responses and an analysis of the dynamics of the dosage and response variables. In this methodologic article, the extended data of a randomized, controlled clinical trial comparing two epoetins were examined by the techniques of functional data analysis to establish how precisely the patterns of treatment response might be described and analyzed. The description of the trajectory of hemoglobin values in each patient as a mathematical function allowed the characterization of individual responses, with a wide variety of patterns being revealed. An analysis of the degree of system control in the management of the anemia was then possible through phase plotting. The analysis also allowed an expression of the dynamic characteristics of the entire experimental system, analyzed in summary group waveforms with standard statistical properties. In addition, a quantification of the notional instability of patient responses enabled the determination of a subset of patients for whom control might be improved in a modified management system. It is concluded that functional data analysis does provide the basis for further characterization and experimental study of the control of renal anemia.

Randomized Trial of Model Predictive Control for Improved Anemia Management

“…We show that this approach resulted in fewer Hb measurements Ͼ13 and Ͻ9 g/dl. Other work in this area and tested in clinical trials has concentrated on the computer implementation of paper algorithms (15). At this time, MPC is limited to intravenous EPO in hemodialysis patients.…”

Hemoglobin Variability in Anemia of Chronic Kidney Disease

“…21 Different methods have been used to quantify the degree of hemoglobin variability (Box 1), including the conventional SD; the coefficient of variation, that is, the ratio of the SD to the mean; the proportion of time outside certain thresholds (Figure 2), on the basis of either actual hemoglobin measurement or rolling averages of hemoglobin measurements 17 ; the magnitude of the residual SD or the average of the absolute SD changes 25 ; and the absolute value of the rate of hemoglobin change or trajectory (calculated from curve-fitting computer algorithms) measured in g/dl per month. 26 As depicted in Figure 3, however, the linear regression slope may not discriminate between the inter-patient variance, which implies the population level variability, and the intra-patient variability; that is, the variability at the individual level, which is the relevant metric to study hemoglobin variability. More sophisticated repeated measure models may be required to decompose the variability slope into its different individual patient-and population-based components.…”

Hemoglobin Variability in Nondialysis Chronic Kidney Disease

“…Furthermore, CKD studies to date have been primarily restricted almost exclusively to hemodialysis patients who were receiving erythropoiesis-stimulating agents (ESA) (1)(2)(3)(4)(5)(6)(7)(8) Debate exists on which factors may influence the severity and frequency of Hb variability. Identification of these factors is necessary if manipulation of Hb variability in experimental or clinical settings is a goal (3,4,8,10,11,12). There are some data to suggest that physician prescribing patterns of ESA and the type of ESA affect variability; however, because both may be confounded by other factors, the specific contribution of these and other factors to Hb variability remains uncertain (3,4,10,11,12).…”

“…Identification of these factors is necessary if manipulation of Hb variability in experimental or clinical settings is a goal (3,4,8,10,11,12). There are some data to suggest that physician prescribing patterns of ESA and the type of ESA affect variability; however, because both may be confounded by other factors, the specific contribution of these and other factors to Hb variability remains uncertain (3,4,10,11,12). The goal of this analysis was to assess the presence of anemia and Hb variability within a culturally diverse, nondialysis CKD population that included patients who were not receiving ESA therapy.…”