Economic evaluations of peritoneal dialysis and hemodialysis: 2004-2012

Introduction

End-stage renal disease (ESRD) is a debilitating condition resulting in death unless treated. Kidney transplantation, dialysis, and conservative therapy supported by palliative care are the three primary treatment options for patients with ESRD^1,2. Although kidney transplantation is the most cost-effective therapy, the supply of donor kidneys is limited³. In addition, patients who are eligible for and choose kidney transplantation usually have to wait months to years for a kidney to become available. During this waiting period, patients are treated with dialysis. The two main types of dialysis are hemodialysis (HD) and peritoneal dialysis (PD). In HD, the removal of wastes and excess fluid is accomplished by circulating blood outside the body through an external filter (dialyzer). HD is usually performed in a hospital or clinic (in-center HD or ICHD), but can also be performed at home (HHD). Conventional HD is typically performed three times per week, with each treatment lasting 3 to 5 hours. In PD, the removal of wastes and excess fluid is accomplished inside the body, in the abdominal or peritoneal cavity. A dialysis solution is placed in the peritoneal cavity, which allows wastes to move from the blood to this solution. After a period of time, the solutions are drained from the body⁴. Unlike HD⁵, PD is usually a continuous therapy, in which dialysis solutions are repeatedly drained from and instilled into the peritoneal cavity so there is a possibility of dialysate dwell (and hence solute removal) up to 24 hours/day 7 days a week⁴. However, some patients are treated with intermittent PD, which is either performed manually (the patient uses gravity to fill and drain the abdominal cavity) through continuous ambulatory PD (CAPD) treatment, or with a cycler (a machine that automatically fills and drains the abdominal cavity, usually while the patient sleeps), in automated PD (APD) treatment⁶.

The prevalence of ESRD (estimated to be 2.8 million globally at the end of 2011⁷) and, consequently, the demand for dialysis, continues to increase due to an aging population, extended life expectancies, the increased prevalence of precipitating conditions such as diabetes⁶. Worldwide, hemodialysis continues to be the most common mode of therapy for individuals with ESRD⁶ and the need to provide dialysis treatments for a large and growing patient population places a heavy economic burden on the global health care system⁸. In the United States, (US), for example, 1.3% of Medicare patients with ESRD accounted for 7.5% of Medicare spending in 2010⁵.

In response to such pressures, initiatives aimed specifically at controlling dialysis-related costs have already been implemented in many countries, including Australia, Portugal, Thailand, United Kingdom (UK) and US^9–14. For example, the Australian government implemented a range of national health reforms in 2012, including a national efficient price (NEP) for hospital services, which was based on the average costs of best practice pathways¹⁴. Similarly, Portugal implemented a bundled payment program for dialysis, bundling dialysis services and products into one rate¹¹. In addition, the Centers for Medicare and Medicaid Services (CMS) in the US enacted an expanded bundled prospective payment system (PPS) for dialysis services in order to control for the unpredictable and escalating costs associated with the provision of dialysis, and to combine pharmaceuticals and lab services that were previously charged separately¹³. These and other initiatives are similar in striving for maintaining healthcare costs and identifying interventions that are less resource intensive and/or cost-effective. Given this changing economic environment, where payers and providers around the world are facing pressure to control healthcare costs while improving patient outcomes, we conducted a systematic review of economic evaluations of PD and ICHD published since 2004. Our purpose was to assess whether the recent literature continues to support the use of PD to be a less resource intensive therapy compared with HD from payer, provider and societal perspectives¹⁵.

Methods

We conducted a systematic literature search for peer-reviewed economic evaluations of dialysis modalities published between January 1, 2004 and March 31, 2012 in the second quarter of 2012. To ensure that we captured articles that might not have been included in the database for the prior literature synthesis which assessed literature from 1996–2006, our literature search included an overlap of three years of inclusion (2004–2012) with the prior literature synthesis. We applied our search strategies in PubMed; EMBASE; Cochrane Collaboration; Database of Abstracts of Reviews of Effects; UK National Health System Economic Evaluations Database; and Health Technology Assessment Database. Medicine indexing terms for dialysis therapies, including renal replacement therapy, peritoneal dialysis, renal dialysis, and hemodialysis units, hospital that linked to the subheading economics, and free-text search terms, including hemodialysis, peritoneal dialysis, renal dialysis, continuous ambulatory peritoneal dialysis, conventional hemodialysis, automated peritoneal dialysis, cost, costs, expenditures, cost analysis, cost effectiveness, cost benefit analysis, pharmacoeconomics, health economics, and economics, were used in the database search.

Our search identified 498 publications (Figure 1). Two investigators (FXL and TPQ) screened 40% of all the found abstracts independently based on our research objective. With 96% of the selected articles matched, one investigator (TPQ) continued the remaining selection. Articles were excluded (n=444) if they were of the following publication types: Editorial, Letter, Case Report, Comment, Interview, Lecture, News, Newspaper Article, or Patient Education Handout, or if the title/abstract did not suggest that a comparison was made between the costs of at least one sub-modality of PD to at least one sub-modality of ICHD. Articles were included (n=54) if they were original research studies with text in English, and if they compared costs and/or cost effectiveness associated with PD and ICHD or subtypes of PD and ICHD. To be comprehensive, additional articles (n=15) were identified through a review of references from the selected papers. These 69 articles were subjected to full-text review and further inclusion criteria were applied. Studies that did not focus on an economic evaluation of dialysis, or did not differentiate between the costs of PD and ICHD (or their subtypes) were excluded, as were review articles with no original data. Twenty-four articles (18 cost studies and 6 cost-effectiveness studies) met all of these inclusion criteria. Relevant study data were manually extracted (TPQ) and cross-checked for accuracy (FXL).

Figure 1. Flow chart of study selection.

Results

The 24 articles included in our review provide economic and cost-utility data from 13 high-income (Australia, Austria, Finland, France, Greece, Italy, Japan, New Zealand, Singapore, Spain, Switzerland, UK, US), three upper-middle income (Chile, Malaysia, Mexico), and six lower-middle income (China, Columbia, India, Romania, Thailand, Turkey) countries. Designations of high, upper-middle, and lower-middle income countries are based on World Bank definitions whereby economies are divided according to the 2011 gross national income (GNI) per capita, which is calculated using the World Bank Atlas method. Defined groups are: low income, $1,025 or less; lower-middle income, $1,026–$4,035; upper-middle income, $4,036–$12,475; and high income, $12,476 or more¹⁶. Table 1 outlines the costs of ICHD and PD found in 19 countries from our 18 cost studies.

Cross-country comparisons of economic data are challenging to perform well under the best of circumstances, but perhaps especially in the case of dialysis, where ICHD-related costs are comprised primarily of labor and capital expenses, whereas PD-related costs are associated primarily with disposables, such as dialysate solutions and supplies. In this review, the usual concerns were compounded by the variability of the data compared within individual studies and by incomplete transparency within individual reports. Cost perspectives, where specified, ranged from patients, service providers, and payers to government health systems. With different perspectives, different costs are considered relevant and different methods of apportioning direct and overhead expenses may influence the reported results¹⁷. The currency years reported in these studies, where specified, spanned more than a decade (1997 to 2010), demanding significant assumptions to adjust for price inflation, international currency valuations, and purchasing power parity in order to arrive at a common-currency metric. Furthermore, differences in provider payment and healthcare financing systems, variation in rates of HD versus PD use affecting economies of scale across different countries, and potential differences in treatment settings intensify the challenges for cross-country comparisons of these studies. Data sources were similarly varied, including literature-derived secondary sources, hospital records, insurance information, disease registries, government publications, expert opinions, surveys, and semi-structured interviews. Finally, the 19 countries from which dialysis costs were reported are at different levels of economic development. As such, they have widely varying infrastructures available to support dialysis services, as well as different barriers to the use of each dialysis modality^18,19. Each of these factors further magnify the danger of cross-country comparisons²⁰. Nevertheless, the data shown in Table 1 remain valuable insofar as they highlight the magnitude of dialysis costs and the relative (not absolute) cost differences between the dialysis modalities across countries. Ratios of costs for ICHD compared to PD are included in Table 1 to assist with this exercise. Ratios less than 1.00 (parity) denote lower cost of ICHD compared to PD.

The findings from our review demonstrate that ICHD costs, whether they are medical direct-, total medical-, or total medical plus indirect costs, are generally (but not always) higher than PD costs. A 2009 Finnish study²¹ of the total medical costs (payer perspective) of PD and ICHD reported that the cost of ICHD tended to be about 25%–38% higher than the cost of PD (ICHD:PD ratio = 1.25-1.38). In contrast, a 2007 study evaluating the direct costs of PD and ICHD (payer perspective) in Japan²², found that the cost of ICHD tended to be about 86% of the cost of PD (ICHD:PD ratio = 0.86). Nevertheless, data from 82% (9/11) of the high-income, 50% (1/2) of the upper-middle income, and 83% (5/6) of the lower-middle income countries represented in our review show the cost of ICHD to be more than that of PD. Figure 2 arrays the country-specific cost ratios for ICHD compared to PD.

Figure 2. PD (peritoneal dialysis): ICHD (in-center hemodialysis) cost ratios in 19 countries.

Six of the 24 studies in our review were cost-effectiveness or cost-utility studies; that is, they considered the outcomes of each dialysis modality in terms of patient life-years, and/or healthy life-years (typically measured as quality-adjusted life years) in addition to costs. Despite wide variability in methodologies, outcome measures, perspectives, time horizons, costs, and analytic approaches used in these six studies, each came to a similar conclusion: the cost-effectiveness of PD is equivalent to (1 study), or better than (5 studies) the cost-effectiveness of ICHD (Table 2).

The 24 economic analyses reviewed in the context of this study were of variable quality. This is a particular concern because the individuals who need to use these analyses to guide decisions may not be experts at evaluating them²³. To document the quality differences between studies in the context of this review, we characterized the reports using criteria adapted from the Quality of Health Economics Studies (QHES) instrument²³, which was specifically developed to emphasize appropriate methods; and valid, transparent, and comprehensive results reporting in health economic analyses²³.

Characteristics of high-quality studies not only clearly specified the objective, perspective, and data source, but also included a detailed description of the study methodologies; total direct, non-direct, indirect, and intangible medical costs; and addressed both limitations and biases. While the majority of cost-effectiveness studies clearly described study objective, perspective, and study estimates (83%–100%), fewer studies addressed the validity of outcome measures and biases (67%). Similarly, cost studies frequently reported study objective and direct medical costs, but none of the cost studies included intangible costs and only a few studies (17%) included indirect costs. Intangible costs may be difficult to assess well in the context of dialysis due to the lack of a firm value and the challenge in quantifying pain and suffering within a heterogeneous population.

Discussion

We conducted a systematic search for peer-reviewed economic evaluations of dialysis modalities published between January 2004 and March 2012, with the goal of evaluating the economic literature within the context of recent global dialysis payment policies encouraging greater use of PD, while building on an earlier systematic review of the literature¹⁵ that was published between 1996 and 2006. The results of our review reiterate that ICHD is generally more costly, and less cost-effective than PD in the majority of studies and countries that examined costs and/or cost effectiveness associated with the different dialysis modalities. These results are consistent with previously published systematic reviews of the literature^15,24. In fact, there is a growing body of evidence suggesting greater use of PD or the use of PD as first treatment modality for appropriate ESRD patients^25–27. Our findings show that existing reimbursement incentives for delivering dialysis therapies have implications for both clinical practice and health policy. The burden of rising healthcare costs globally, coupled with competing economic priorities, highlight the importance of establishing policies that encourage the use of PD over ICHD, whenever feasible and clinically appropriate.

There are exceptions where PD has been reported to be more costly than ICHD; these are noted in Table 1. The reasons behind these exceptions are myriad, but chief among them may be methodological differences between studies, as well as variations in practice patterns, cost estimations, and the inclusion/exclusion of specific cost elements. For example, a study conducted in Spain²⁸ included staff wages for direct PD-related medical costs, whereas ICHD costs excluded these costs in the calculation of direct medical costs. In effect, this particular study reported PD to be more costly than ICHD.

Most of the studies in our review consider only direct medical and non-medical costs in their analyses. Direct medical costs include physician and other staff costs (fees; salaries); capital costs of hemodialysis machines and PD cyclers; costs associated with establishing and maintaining vascular access; ongoing use of dialysis-related supplies such as solutions, medications, and tubing; as well as costs associated with radiology, laboratory and hospitalization. Direct non-medical costs include overheads for administering and maintaining buildings and facilities but they may also include patients’ travel to a dialysis center or physician’s office. It is important to keep in mind that PD and ICHD rely on very different direct cost components. The direct cost of ICHD is driven primarily by the cost of staff, buildings, infrastructure, and capital equipment (i.e., fixed costs), whereas the direct cost of PD is driven primarily by the supply costs of dialysis solutions, tubing and other disposables (i.e., variable costs). Thus, it is not enough to compare dialysis modalities based on differences in one or two cost components. Rather, cost comparisons of PD and ICHD must be based on the total costs of therapy, as direct medical costs alone do not have the same relevance from all economic perspectives. For instance, in the developing world where labor is relatively inexpensive and the cost of imported dialysis solutions and supplies is high, it is easy to perceive PD as being more expensive than ICHD²⁹. The reverse may be true in developed economies where labor is relatively more costly than disposable supplies.

Indirect costs, or productivity losses of patients and caregivers were rarely included in the studies we reviewed, even in the four studies focusing on six countries for which the stated perspective of the analysis was societal^30–33. Of these, the most comprehensive array of indirect costs is represented in a Thai study that considers all resources used by dialysis patients and/or caregivers, including capital, labor and materials costs of health-care providers, as well as the real and opportunity costs associated with patient treatment time, informal patient care, and sick leave³¹. Of course, the inclusion of indirect and/or productivity costs will substantially increase the reported cost of any dialysis modality, but these costs have a particular impact on the cost of ICHD which requires regular, lengthy, dialysis treatments that are provided outside of patients’ homes.

Intangible costs denote those consequences of an intervention that are particularly challenging to measure, such as the value of improved health per se, or the pain, suffering, and impairment in quality of life associated with treatment. Only five^{30,31,34–36} of the 24 studies included in our review considered intangible costs, all of them via the utility scores used to arrive at quality-adjusted life years.

Our review has several limitations. First, our review focused on economic evidence comparing PD and HD; articles comparing the clinical and patient outcomes associated with PD and HD were not included in this review. Second, we included all articles we found that compared the costs and/or cost effectiveness of PD vs. ICHD. These articles are of varying quality and our report did not differentiate the quality of these findings. As such, it is difficult to make generalizations about the published literature of dialysis economics owing to the limited number of studies available and differences among them in terms of study methods, geography, scope, and quality. Some studies rely on decades-old data that may not be relevant to present-day economies; other studies fail to indicate the currency-year used in analysis. Between-country differences in economic development, practice patterns, reimbursement structures, provider payment, healthcare system financing, and social norms often make it difficult to interpret the findings from one country in the context of another country. In addition, the proportion of patients on HD vs. PD and the treatment settings (provider demographics such as freestanding/satellite vs. hospital-based dialysis clinics) vary across countries. Even studies that report ‘direct costs’ may include/exclude different components of direct cost and, thus, may not necessarily produce comparable results. Further, some authors clearly specify the perspective taken in their analyses (e.g., societal, payer, provider); in other papers the perspective is only implied. Reported study methods, too, may be insufficiently transparent to evaluate study quality; for example, the calculations used to derive costs or the elements of costs (e.g., frequency of dialysis, prescription drug use) are often lacking or unclear. Data sources may vary among studies as well; data sources may include disease registries; hospital, insurer, or government databases; secondary literature; government publications; dialysis product distributors; dialysis center data; and/or individual patient interviews. Just one of these between-study differences introduces uncertainty when drawing comparisons among study results. Because published studies of the economics of dialysis often vary on many of these parameters, specific, robust between-study comparisons cannot be made.

Despite the methodological differences and variable quality across the studies within our review, ICHD clearly emerged as a more expensive modality than PD in most of the 19 countries represented in our review. These results are consistent with earlier systematic reviews of the dialysis literature^15,37. Similarly, the cost-effectiveness studies presented in Table 2 begin to show a nascent picture of cost-savings related to PD; the limited number of cost-effectiveness studies and the methodological differences between them (e.g., differences in the variables considered within each modelled analysis) preclude the drawing of specific conclusions.

Conclusion

The magnitude of costs associated with providing dialysis therapies globally is large and growing. Our findings echo those of prior published reviews and add to the growing body of evidence finding PD is significantly cost-saving compared to ICHD therapy in most developed countries and some developing countries. Additionally, evidence continues to suggest that PD is a cost-effective strategy relative to ICHD. Therefore, it appears that increasing the use of clinically-appropriate PD would substantially reduce healthcare costs and help health systems meet ever-tightening budget constraints.