Kidney Diseases. Friedrich K. Port, MD, MS, and Garabed Eknoyan, MD

Transcription

1 AJKD American The Official Journal of the National Kidney Foundation Journal of Kidney Diseases The Dialysis Outcomes and Practice Patterns Study (DOPPS) and the Kidney Disease Outcomes Quality Initiative (K/DOQI): A Cooperative Initiative to Improve Outcomes for Hemodialysis Patients Worldwide Friedrich K. Port, MD, MS, and Garabed Eknoyan, MD Two initiatives were launched in the closing years of the past century with the goal of improving the treatment outcomes of patients with kidney failure: the Kidney Disease Outcomes Quality Initiative, which formed expert panels to develop evidence-based clinical practice guidelines, and the Dialysis Outcomes and Practice Patterns Study (DOPPS), which now gathers data on practice patterns in dialysis facilities in 12 countries, including the United States. Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) program was established to promote worldwide coordination and integration of initiatives to develop and implement clinical practice guidelines and provides new opportunities of cooperation with the international scope of the DOPPS. Collaboration between the DOPPS and KDIGO will lead to broader dissemination of relevant information to nephrologists, health care providers, and patients. Linking the DOPPS scope of work with the KDIGO goals will help develop continuous quality improvement programs and the provision of direct feedback to participating dialysis centers throughout the world. This will establish an essential component in the translation to clinical practice of evidence-based guidelines worldwide. Am J Kidney Dis 44(S2):S1-S by the National Kidney Foundation, Inc. INDEX WORDS: Hemodialysis; Dialysis Outcomes and Practice Patterns Study (DOPPS); Kidney Disease Outcomes Quality Initiative (K/DOQI); evidence-based guidelines; observational studies; clinical performance measures. HEMODIALYSIS, BEGUN as exploratory attempts to sustain life in the 1950s, now provides life-saving therapy to millions of individuals worldwide. Unfortunately, despite significant advances in dialysis technology and in the management of its complications, wide disparities in the clinical care and outcomes of dialysis patients persist throughout the world. Several important initiatives for the care of dialysis patients were launched in the past decade on the strength of data showing that rigorously developed and evidence-based clinical practice guidelines (CPGs) reduce variability in quality of care, improve patient outcomes, and benefit the efficiency of health care. The National Kidney Foundation launched the first of these, the Dialysis Outcomes Quality Initiative (DOQI) in The initial set of CPGs developed by DOQI on hemodialysis VOL 44, NO 5, SUPPL 2, NOVEMBER 2004 adequacy, peritoneal dialysis adequacy, vascular access, and anemia were issued in 1997 and updated in Their favorable impact on From the University Renal Research and Education Association, Ann Arbor, MI; and Renal Section, Department of Medicine, Baylor College of Medicine, Houston, TX. The Dialysis Outcomes and Practice Patterns Study is supported by research grants from Amgen and Kirin without restrictions on publications. The NKF gratefully acknowledges the support of Amgen, founding and principal sponsor of K/DOQI. The publication of this supplement was supported by the DOPPS. Address reprint requests to Friedrich K. Port, MD, MS, University Renal Research and Education Association, 315 W. Huron Street, Suite 260, Ann Arbor, MI dopps@urrea.org 2004 by the National Kidney Foundation, Inc /04/ $30.00/0 doi: /j.ajkd American Journal of Kidney Diseases, Vol 44, No 5, Suppl 2 (November), 2004: pp S1-S6 S1

2 S2 the quality of care delivered to dialysis patients has been documented. 2 In the process of developing DOQI guidelines, it became evident that in order to actually improve outcomes it was essential to improve the health status of patients who are initiated on dialysis, and that therein existed an even greater opportunity to improve outcomes for all individuals with chronic kidney disease. To reflect this more ambitious phase, in which guideline development would encompass the entire spectrum of chronic kidney disease, reference to dialysis in DOQI was changed to disease and a new initiative termed Kidney Disease Outcomes Quality Initiative (K/DOQI) was launched in At the same time, several organizations in different countries had begun their own guideline development processes. Although in general the recommendations of these guidelines were similar to those of the K/DOQI, there were differences in the targets recommended and the rating system of the strength of the evidence among the various guidelines. Consequently, it became evident to those developing guidelines that there was a need for a more uniform and global approach to the process. It was on this basis that after initial exploratory and consultative meetings a new initiative, the Kidney Disease: Improving Global Outcomes (KDIGO) was launched in 2003, with the stated mission to improve the care and outcomes of kidney disease patients worldwide through promoting coordination, collaboration and integration of initiatives to develop and implement clinical practice guidelines. 3 Reference to implementation in the mission statement of KDIGO is vital. There is no evidence that the passive dissemination of CPGs, no matter how rigorously developed, results in changes in clinical practice. It is the difficult and costly task of implementing CPGs that makes them the best tools now available to close the gap between actual and evidence-based clinical practice. The implementation of rigorously developed CPGs has been said to lead to even greater improvements in patient care than the introduction of some new technologies. 4 Among implementation strategies, the linkage of guideline recommended targets to actual data gathered on site and its feedback to providers is the best available tool, particularly when this is linked to PORT AND EKNOYAN continuous quality improvement programs and their evaluation through clinical performance measures. It is the first component of this goal, data gathered on site, which prompted the launch of another initiative, the Dialysis Outcomes and Practice Patterns Study (DOPPS) in COMMON GOALS FOR THE K/DOQI AND THE DOPPS During the mid-1990s, when the DOQI was initiated, the DOPPS was conceived with the goal of increasing the longevity of hemodialysis patients by evaluating practice patterns in dialysis facilities. The goals of the DOQI were to establish practice guidelines for dialysis through consensus of expert panels based on all available medical evidence. Thus, the goals of the DOQI and the DOPPS were remarkably similar; yet their approaches were different. The DOQI and later the K/DOQI sought to develop evidencebased guidelines or, when evidence was lacking, offer guidelines based on expert opinion, available as findings in the published peer-reviewed literature. The DOPPS investigates a large number of practice patterns to detect new evidence for modifiable treatment factors that are associated with improved outcomes. This supplement focuses on areas that show the complementary nature of these 2 entities. Many of the articles in this supplement describe practices and other parameters that have been shown in the DOPPS to be associated with better outcomes and to document the degree of deviation in actual practice from K/DOQI guidelines in delivering care to hemodialysis patients. Additionally, the DOPPS evaluates trends in adherence to these new guidelines over the last few years, using both US and international data. WHY GUIDELINES? Only a couple of generations ago, the commonly used evidence in medicine was the personal experience of a senior physician, and one generation ago, it was the consensus of several of them. In more recent years, clinical evidence has been based on systematic reviews of prospectively collected data and meta-analyses. These extremely valuable tools distill and analyze the evidence in the literature but do not always make necessary recommendations for clinical practice and, more importantly, are not linked to imple-

3 DOPPS AND K/DOQI COLLABORATION mentation tools. On the other hand, the practical specificity of well-defined guideline statements, which are based on the same evidence, allows for the development of implementation tools and facilitates their translation into evidence-based clinical practice. That has been the purpose of the K/DOQI. The guiding operative principles of K/DOQI CPGs are that they be interdisciplinary, evidencebased, scientifically rigorous, and open to review. The guidelines are based on a comprehensive literature review and preset criteria for the selection of articles for structured analysis used in developing the evidence report that are supplemented by the clinical judgment and expert opinion of the independent work groups charged in developing guidelines. The guidelines undergo an extensive review process, which exposes the chain of reasoning for each guideline to open debate; the final product consequently reflects a broader consensus of health care professionals, providers, patients, managers, and organizations. Each guideline statement incorporates a detailed, referenced rationale and evidence tables, allowing practitioners to evaluate the evidence and determine how to apply recommendations to the distinct needs of individual patients. In addition, the specificity of the guideline statements allows for their use in developing clinical performance measures. Perhaps the best example of this has been the use of K/DOQI guidelines in developing clinical performance measures by the Centers for Medicare and Medicaid Services, which have been instrumental in improving the level of care being delivered in the United States. 5 The broader applicability of such an approach at the international level should improve the delivery of dialysis care worldwide. The data gathered by the DOPPS allow for the initiation of such an international approach. A key feature of the DOPPS is its sampling approach to obtain nationally representative samples of dialysis facilities and hemodialysis patients in different countries. In another article in this supplement, Pisoni et al 6 describe the methods of data collection and analysis for the DOPPS. LEVELS OF EVIDENCE In developing clinical performance measures, guidelines selected for implementation must be identified judiciously and be strictly evidence S3 based. Well-conducted randomized controlled trials are the gold standard of evidence because they can make all else equal and thus allow assumption of causality. This requires a welldesigned and strictly enforced randomization process of a sufficient sample size. Unfortunately, there is a dearth of such studies in dialysis. A review of all such trials in the last 20 years 7 highlights 2 problems: first, compared with other areas of medicine, such trials are particularly rare in nephrology; second, about one half of randomized trials were not analyzed by the original assignment but rather as correlations. Analyses that deviate from the random assignment invalidate the design and result in the same limitations as those that apply to observational studies. The first major randomized dialysis trial, the National Cooperative Dialysis Study, may serve as an example. It was designed to test 2 hypotheses: whether dialysis treatment time (long or short) and time-averaged blood urea nitrogen concentration (high or low) influence outcomes of morbid events. 8 A subsequent analysis by Sargent and Gotch 9 has become famous for developing the concept of Kt/V and associated outcomes. However, their analysis was not based on the initial randomization but rather on the observational data from all study patients. Observational studies are often generating new hypotheses that can be tested more rigorously in randomized controlled clinical trials, as was done in the HEMO Study for Kt/V. Table 1 shows the strengths and limitations of observational studies and randomized controlled trials. The advantage of being able to imply causality makes randomized trials highly desirable despite their high cost and limited number of hypotheses that can be tested. Additionally, in clinical practice, there are many areas in which a trial cannot be performed because of ethical constraints. For example, one cannot conduct a study that randomizes patients into a group with poor phosphorus control or low dialysis dose. The HEMO Study overcame such ethical concerns by studying high dialysis dose compared with standard dose, but it could not study patients receiving a lower than the K/DOQIrecommended standard dialysis dose. Guidelines describe this problem by specifying the level of evidence in support of each recommendation; observational studies such as the DOPPS do not

4 S4 PORT AND EKNOYAN Table 1. Comparison of Key Features Between Randomized Controlled Trials and Observational Studies Feature Controlled Trial: HEMO Study Observational Study: DOPPS Number of hypotheses Usually only 1 or 2 Many Cost per hypothesis Very high Low to moderate Sample size Often marginal Less restricted Study of poor treatment Ethically not feasible Feasible via representative sample study Study of medications Ideally suited Confounding by indication* Study of trends Limited Feasible Causality Yes (for positive findings) Correlation, suggestive only Representativeness Limits due to selection criteria Feasible Statistical adjustment Usually not required Always required *Results showing benefit associated with medication use despite this confounding are of great interest. Negative findings may be difficult to interpret because high cost usually limits the sample size. have such ethical limitations but require appropriate statistical adjustments and analysis. On the example of the evidence from the DOPPS, one can describe different levels of analytical approaches that attempt to simulate randomized controlled trials. First, DOPPS analyses try to make all else equal through adjustment for a large number of factors, including many comorbid conditions. Such adjustments include demographic factors, about 15 comorbid conditions based on responses to 50 questions collected at study entry, numerous laboratory values, and medication use; these adjustments are supplemented by a variety of quality of life parameters based on an expanded Kidney Disease Quality of Life Short Form (KDQOL). These baseline data allow assessment of outcomes by an intention-to-treat approach, which is also used in randomized trials. For some questions, it may be important to consider an as-treated approach that allows patients to change their treatment assignment over time. Second, facility-based analyses of practice patterns and outcomes reduce issues of patient selection. For example, patients with low hemoglobin or low urea reduction ratio (URR) may be patients who are sicker or have unstable dialysis sessions. In these cases, their higher mortality risk may result from factors other than hemoglobin or URR. Analyses of the percentage of patients in each facility who have a low hemoglobin level or a low URR point more clearly to practice patterns so that associated worse outcomes are less likely to be related to patient selection. Such analyses can adjust for both patient factors and for facility characteristics and may simulate a randomized trial. Third, one can imply causality of findings more directly if an observational study can show that changes in treatment over time are associated with corresponding changes in outcomes. For example, analyses of US dialysis facilities showed that the adherence to the K/DOQI anemia guidelines varied by facility. Those that improved adherence levels the most over 4 years showed the greatest improvement in their patients mortality risk and those with little change in adherence levels showed no such improvement. 10 This statistically significant finding provides stronger incentives than other observations; however, it does not necessarily establish causality and might still be related to other changes in facility practices. An additional analysis grouped facilities similarly by changes in adherence to the K/DOQI dialysis dose guidelines using the percentage of patients with URR 65% as an indication for improvement in this practice over time. The results showed again that those facilities with greatest improvement in adherence to URR guidelines had the greatest improvement in their patients mortality risk and those with no change over time had essentially no improvements in outcomes. Improvement in mortality risk was associated independently with facility improvement in adherence to each of these guidelines. 10 This adjusted analysis overcame many potential confounders and provided substantial evidence toward implied causal mechanisms of better anemia control and better dialysis dose for the better patient survival.

5 DOPPS AND K/DOQI COLLABORATION These discussions of adjustments and of patient-based versus facility-based analyses are necessary for any observational study to consider arguments in favor of implied causality. For patient-based analyses, the DOPPS adjusts for clustering of patients in facilities. Additionally, international DOPPS analyses adjust for countries through stratification to search for consistent patterns in all DOPPS countries. Both the DOPPS and the K/DOQI have established several levels of evidence. The K/DOQI has done so with a formal establishment of rules of reporting of levels of evidence. 1 The DOPPS does so by reporting the details of adjustment and by usually offering results using different levels of adjustment. If results change with different levels of adjustment, the findings lead to further understanding of the role of the adjustors; if there is little change, it suggests the stability, robustness, and consistency of the results. DOPPS, K/DOQI, AND KDIGO: A COOPERATIVE, INTERACTIVE INITIATIVE Dissemination of information and feedback to health care providers are necessary for guidelinedriven, evidence-based practices in dialysis facilities to improve the lives of dialysis patients. K/DOQI guidelines are instrumental in education and establishing targets. DOPPS has used these targets and provided survival data based on achieved targets in support of the guidelines. To reach professionals and patients in dialysis facilities more broadly, the National Kidney Foundation Best Practices Newsletter was launched in This newsletter will feature new findings from the DOPPS in each issue. An important component of this project is using DOPPS data to document adherence with or deviation from the K/DOQI guidelines. Detected deviations point to opportunities for improved patients care and outcomes. The DOPPS recently received support to expand its data gathering to include additional parameters that allow better understanding on how some dialysis facilities accomplish better adherence than others. This new DOPPS III will be designed to look into the how-to of achieving K/DOQI targets and provide new understanding of dialysis practices. At the same time, DOPPS III will continue the study s work of associating practice patterns with outcomes and to expand on not only longer life but also better S5 life. DOPPS III will help identify obstacles to improving patient care while continuing to collect data that can be used in further refining K/DOQI recommendations and goals. The international scope of DOPPS data and the worldwide commitment of KDIGO suggest a natural overlap and opportunity for collaboration; the linkage of the 2 projects will provide a missing link in the successful implementation of CPGs worldwide. To this end, KDIGO has initiated an electronic, interactive web-based clearinghouse of available CPGs, including implementation tools and clinical performance measures currently in effect. This will provide for the direct comparison of recommended targets in different guidelines with the rationales for their differences. It will also incorporate in tabular form DOPPS data on actual targets achieved in different countries. One derivative of this effort will be the ultimate reconciliation of different targets given in various guidelines. Two other derivatives expected are direct feedback to centers providing data to the DOPPS and educational materials that can establish and track quality improvement programs in achieving CPG targets. It is hoped that these efforts can fulfill the requirements of the best tool to translate guidelines into clinical practice to improve outcomes for hemodialysis patients worldwide. The ultimate success of all these cooperative initiatives presents problems and challenges. Much has been achieved since the K/DOQI and the DOPPS were launched. The lessons learned should pave the way for cooperation with KDIGO. Clearly, there is much more that can be done to make lives better for dialysis patients worldwide. These cooperative initiatives are committed to make the future better than the present. ACKNOWLEDGMENT The authors gratefully acknowledge the collegial support of Kerry Willis and the editorial leadership of Miles P. Finley, with editorial assistance from Tom Bowden and Caroline Shevrin, for this supplement. REFERENCES 1. Implementation of the National Kidney Foundation- Dialysis Outcomes Quality Initiative Guidelines. Adv Renal Repl Ther 6:3-74, Collins AJ, Roberts TL, St Peter WL, et al: United States Renal Data System assessment of the impact of the National Kidney Foundation-Dialysis Outcomes Quality Initiative guidelines. Am J Kidney Dis 39: , 2002

6 S6 3. Eknoyan G, Lameire N, Barsoum R, et al: The burden of kidney disease: Improving global outcomes. Kidney Int (in press) 4. Weingarten S: Using practice guideline compendiums to provide better preventive care. Ann Intern Med 130: , Sugarman JR, Frederick PR, Frankenfield DL, et al: Developing clinical performance measures based on the Dialysis Outcomes Quality Initiative Clinical Practice Guidelines. Am J Kidney Dis 42: , Pisoni RL, Gillespie BW, Dickinson DM, et al: The Dialysis Outcomes and Practice Patterns Study: Design, data elements, and methodology. Am J Kidney Disease 44:S7- S15, 2004 (suppl 2) PORT AND EKNOYAN 7. Strippoli GF, Craig JC, Schena FP: The number, quality, and coverage of randomized controlled trials in nephrology. J Am Soc Nephrol 15: , Parker TF, Laird NM, Lowrie EG: Comparison of the study groups in the National Cooperative Dialysis Study and a description of morbidity, mortality, and patient withdrawal. Kidney Int Suppl 13:S42-S49, Gotch FA, Sargent JA: A mechanistic analysis of the National Cooperative Dialysis Study (NCDS). Kidney Int 28: , Hulbert-Shearon TE, Ashby VB, Wolfe RA: Improvements in dialysis patient mortality are associated with improvements in URR and hematocrit, J Am Soc Nephrol 14:267A, 2003 (abstr)