Health Economic Evaluations of Endoscopic Vein Harvesting Compared to Open Vein Harvesting for Coronary Artery Bypass Grafting

Transcription

1 Medicine with Industrial Specialization Medical Market Access Aalborg University Fall 2011 Health Economic Evaluations of Endoscopic Vein Harvesting Compared to Open Vein Harvesting for Coronary Artery Bypass Grafting Group 705 Line Blindbæk Jenny F.A. Mathiesen Anne S. Vestergaard Páll Jóhannesson

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3 Title: Health Economic Evaluations of Endoscopic Vein Harvesting Compared to Open Vein Harvesting for Coronary Artery Bypass Grafting Project period: September 2nd - December 20th, 2011 Project group: 705 Participants: Anne S. Vestergaard Jenny F. A. Mathiesen Line Blindbæk Páll Jóhannesson Supervisor: Karin Dam Petersen Co-Supervisor: Lars Oddershede Circulations: 7 Number of pages: 59 Appended on CD-ROM: Copy of the report, articles consulted, calculation in spreadsheets Finished: December 20nd, 2011 Abstract: Objective: In this report health economic evaluations are performed in order to clarify, which procedure to give greater priority to when considering endoscopic vein harvesting and open vein harvesting for coronary artery bypass grafting. Methods: The health economic evaluations consist of a cost-utility and cost-effectiveness analyses. Evidence based data and material has been utilized to fulfill the evaluations. The economical analyses were conducted in accordance to international guidelines, while focusing only on the incremental costs and effects between the endoscopic vein harvesting procedure and open vein harvesting procedure. Outcomes were qualityadjusted life-years gained, as well as avoided infectious and non-infectious leg wound complications. Costs were calculated in Danish kroner. A sensitivity analysis has been performed to investigate the uncertainties of the primary analysis and the susceptibility of the results achieved. Results: The cost-utility analysis resulted in DKK per QALY gained, if utilizing endoscopic vein harvesting instead of open vein harvesting. Additionally, the costeffectiveness analyses showed that the cost per avoided non-infectious leg wound complication is DKK and DKK per avoided infectious leg wound complication. Willingness to pay analyses have to be conducted of the two effect outcomes, avoided non-infectious leg wound complications and avoided leg wound complications, to investigate whether this is an acceptable price to pay to avoid these complications. The content of the report is freely available, but publication (with references) may only be performed in agreement with the authors.

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5 Contents Contents 5 1 Preface Foreword Reading Guidance Literature Search Introduction 3 3 Problem Analysis Bypass Surgery Vein Harvesting Procedures Open Vein Harvesting Endoscopic Vein Harvesting Comment on Existing Literature Problem Statement 11 5 Methods Economic Evaluation Methods Cost-Utility and Cost-Effectiveness Analyses: A theoretical Overview Cost-Effectiveness Analysis Cost-Utility Analysis Discounting Policy Implementation Costs Operative Time Endoscopic Vein Harvesting Equipment Length of Hospital Stay Visits from Home Care Nurse and GP Early Readmissions to Hospital Late Readmissions to Hospital Learning Curve of Endoscopic Vein Harvesting Utilities Pain Mobility Effectiveness Sensitivity Analysis

6 6 CONTENTS 6 Results Cost-Utility Analysis Results Cost-Effectiveness Analysis Results Sensitivity Analysis Results Discussion 31 8 Conclusion 35 9 Abbreviations and Glossary 37 Bibliography 39 A Calculations 45 B Consulted Literature 49

7 Chapter 1 Preface 1.1 Foreword This report is written by group 705 studying Medicine with an Industrial Specialization at the Department of Health Science and Technology, Aalborg University. The report is the product of a project on the 7th semester, the first semester of the master program Medical Market Access, and has been written in the period between 2nd of September 2011 and 20th of December The academic level of this project is intended for students that have completed the 7th semester of the education Medicine with Industrial Specialization, others with the same qualifications, or persons with an interest in the field of medical market access. The project has been conducted under the supervision of Karin Dam Petersen and co-supervision of Lars Oddershede, whom we wish to thank for their helpful guidance. In addition, we also wish to thank the Department of Cardiothoracic Surgery at Aalborg Hospital and Annette Kirkegaard Pedersen for the opportunity to observe coronary artery bypass grafting. Furthermore, we wish to thank the Department for Human Resources, Salary, and Personnel at the Region of Northern Jutland for helpful assistance in retrieving informations regarding costs. 1.2 Reading Guidance In this report the different chapters are numbered according to the following principle; 2; 2.1; Figures and tables are numbered in chronological order within the chapter they belong. A glossary is found in chapter 9, with the words included marked in italics the first time they appear. Abbreviations are shown in parenthesis when these are introduced and can also be found in chapter 9. The Vancouver system of referencing is used to refer to documents consulted, books, and images reproduced in the creation of this report. The list of references provides all necessary information regarding the concerned sources. In the list of references the sources are arranged numerically. A CD-ROM is enclosed with this report, on which a copy of the report, articles consulted, and documentation on calculations can be found. 1

8 2 CHAPTER 1. PREFACE 1.3 Literature Search The literature used in this study represents the best currently available evidence in accordance with international guidelines. [1] Numerous sources were used to search for literature investigated in the creation of this report, including medical databases such as Scopus, Pubget, and PubMed. The authors of this report will aim to use articles from year 2000 until The quality of articles is prioritized in accordance with international guidelines with respect to the classical hierarchy of evidence to be either metaanalyses, reviews, randomized controlled trials, etc. [1, 2]. Furthermore, the reference lists of the examined literature have been studied. The literature has been found by combining search-words appropriately when exploring different topics, relevant to this report. If retrieving many papers on a particular subject, their importance has been evaluated according to the evidence hierarchy and date of publication. In some cases newer papers carries more weight than older studies due to updated information or procedures carried out in the health care sector, but if the study design and method is of higher quality and reliability in an older study compared to a newer one, the older study is favored. The following combinations of words were used in the initial proces of literature search: Endoscopic + open + vein harvesting + CABG, endoscopic + CABG, saphenous vein + open + endoscopic, CABG + open + endoscopic + complications, CABG + infections, leg wound infections + CABG, randomized controlled trials + CABG. These combinations resulted in papers presenting a general overview of the topic CABG and the use of endoscopic and open harvesting techniques, as well as infection rates. Later in the process, other combinations of words were applied: Short- and long-term complications + EVH + OVH, long-term complications + OVH + EVH, personnel training + EVH, late readmission + CABG, late readmission + EVH + OVH, graft patency + CABG, learning curve + EVH, mobility + OVH + EVH, district nurse + CABG + EVH + OVH, home care + CABG + OVH + EVH, GP visits + CABG, post discharge care + CABG, post-operative pain + OVH + EVH, discomfort + OVH + EVH. The aim of this search was to retrieve literature on selected topics and to find studies concerning more specific outcomes in reference to the post-operative complications and discomfort for the patients. When using different search databases, the number of citations of the different papers has been used as an indication of their scientific importance. This has been evaluated with respect to their publication date, as newer studies tend to have few citations or may not have been cited yet. Furthermore, the credibility of the evidence presented in the investigated papers has been evaluated and, if possible, the authors approach to the topic in question has been determined.

9 Chapter 2 Introduction Coronary artery bypass grafting (CABG) surgery was introduced in 1960 to alleviate the symptoms and deaths of ischaemic heart disease, by revascularization of the myocardium. The procedures to procure the bypass graft include among others an open vein harvesting (OVH) procedure and an endoscopic vein harvesting (EVH) procedure, with the great saphenous vein from the leg as the most commonly used graft. The EVH procedure was put into practice in 1996 in the hope of reducing post-operational pain, morbidity, mobility disturbances, and wound healing complications associated with the OVH procedure. [3, 4, 5, 6] The EVH technique is widely used in the USA, where it accounts for 80 % of all saphenous vein grafts used in CABG [7]. Only few studies have, however, actually investigated whether EVH is more cost-effective when considering patients well-being post-operatively, just as there is some uncertainty of its effectiveness in avoiding wound healing complications [8]. The only noticeable study on the cost-effectiveness of EVH and OVH, conducted by Rao et al. [9], consists of a cost-utility analysis (CUA), with no other effect goals than quality-adjusted life-years (QALYs) gained. The study showed that EVH was cost-effective in comparison to the OVH method. The association between the EVH method and long-term morbidity and mortality has been called into question by a study from 2009, as higher rates of mortality, myocardial infarction, and repeated revascularization was found three years after primary CABG with EVH compared to CABG with OVH [10]. In contrast, studies from 2005 and 2011 have found no difference in long-term mortality and morbidity [11, 12]. Based on the study by Grant et al. [11] from 2011, the EVH intervention has recently been re-accepted as a safe procedure when performing CABG at Aalborg Hospital [13]. 3

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11 Chapter 3 Problem Analysis 3.1 Bypass Surgery Several treatment options exist to alleviate the symptoms of ischaemic heart disease; both invasive, pharmacological, and life style interventions may constitute preferable options. Invasive treatment includes percutaneous coronary intervention (PCI) and CABG. In CABG, harvested veins or arteries provide bypasses for the provision of blood and nutrients to the myocardium past coronary arteries affected by coronary artery disease. This way, it provides protection from further occlusion of coronary arteries and consequent ischaemia which otherwise could become fatal. [6] According to Patel et al. [5], coronary revascularization is recommendable if the benefits expected in terms of survival and well-being, e.g. reduced symptoms and improved functional status, outweigh the inherent risks of the operation. CABG may be considered as treatment, if the patient has certain symptoms, which amongst other include stable and unstable angina pectoris, myocardial infarction (MI), multivessel disease, and ventricular arrhythmias concomitant with coronary stenoses, which can be treated by revascularizing surgery. Appropriate coronary anatomy allowing for revascularization is needed. In many cases PCI is the better treatment option; there are, however, cases in which CABG is still first choice: Left main stenosis, multivessel disease, if stenoses are not clearly defined, if there is dysfunction of the left ventricle, or if the patient is diabetic. [5, 14] Due to increasingly efficient pharmacological treatment and PCI surgery, the number of CABGs performed in Denmark has declined over the years. This is illustrated in figure 3.1 on the following page, in which numbers of CABG performed declined from 3353 operations in 2003 to 2130 operations in 2009, from which Aalborg Hospital performed 270. [14, 15, 16, 17] As seen in figure 3.2, men are more often recommended for CABG than women; as of 2009 men accounted for more than 4/5 of all CABGs performed in Denmark. Furthermore, the greater part of the CABGs are performed on elderly people; thus, more than 1/3 of CABG patients have reached 70 years of age. Statistics further show, that approximately 1/5 of all CABG patients are diabetic. A large part - close to 3/4 - also suffers from hypercholesterolemia and hypertension. [10, 11, 14, 15, 18] 5

12 6 CHAPTER 3. PROBLEM ANALYSIS Figure 3.1: Total number of CABGs performed in Denmark from 2003 to CABG: Coronary artery bypass grafting. Numbers are from [14, 15, 16, 17]. Some health state factors are known to slow wound healing; it is documented that age, diabetes, smoking, and peripheral vascular disease disturb the healing process, primarily due to insufficient blood supply. Gender also is of importance, as females have a larger percentage of subcutaneous fat, which increases the risk of poor wound healing compared to males. Overweight and obesity are also determinants of recovery time; the loose fat around thighs has a tendency to lead blood towards the adipose tissue and create hematomas, which has a negative impact on leg wound healing. [3, 4, 11, 19] Men Women Number per Age Figure 3.2: Number of coronary artery bypass graftings performed in Denmark per inhabitants in different age groups. Numbers are from a report published in Modified from [14].

13 3.2. VEIN HARVESTING PROCEDURES Vein Harvesting Procedures The great saphenous vein accounts for 70 % of all grafts in the UK [11]. An alternative harvest site is the forearm where the radial artery can be used as graft. Furthermore, surgeons may opt to utilize the right or left internal mammary artery as graft. In this study, only the two methods concerning the saphenous vein harvesting procedure will be examined. [6, 11, 20, 21] Open Vein Harvesting OVH of the saphenous vein is performed by making a continuous, longitudinal incision proximally to the medial malleolus towards the knee, or from the groin and extending distally. The vein can either be harvested from the calf or thigh depending on the incision site at the knee, with the calf as the most common harvest site. If the required length of the vein is longer than can be obtained either below or above the knee area, the incision can be extended either proximally or distally to the knee. [22] The exposed vein is released from side branches by means of ligating clips and/or ligatures of vicryl. When the vein is free and has been removed the incision wound is closed. The vein is immediately rinsed and carefully distended with a solution containing 20 ml blood from the patient, 100 ml heparin, and 2 ml papaverine. The vein is kept in this solution at room temperature until it is needed. [18, 22] OVH is a relatively simple procedure, meaning that there is no need for special equipment in order to perform the excision, other than standardized surgery equipment. OVH follows a traditional no-touch strategy in order not to damage or disrupt the vessel wall of the graft, so despite that the patient contracts a large wound, the graft should be relatively intact. [3, 23, 24] Unfortunately, due to the large wound, the risk of contracting infections and wound complications are relatively large compared to smaller incisions [4, 18]. Such large wounds also inevitably cause scarring and discomfort for the patient; especially post-operational pain is relevant, as it may immobilize patients [3]. Due to the health state of CABG patients in general, it is expectable that a large part suffers from a prolonged healing process, increasing discomfort related to the vein excision Endoscopic Vein Harvesting When performing EVH of the saphenous vein an endoscopic operating system is needed. Firstly, an entry point has to be made for the equipment, with a 2-3 cm long skin incision on the medial side just above or below the knee avoiding the knee flexion area, see figure 3.3 on the next page. The saphenous vein is dissected to create a pocket along the vein for the endoscope which makes it possible to visualize the vein and its surrounding area on a video monitor. Some surgeons make a second incision either in the groin or near the ankle, depending on the first incision, to fixate the other end of the vein. If additional length of the vein is required from the upper or lower leg, the initial access incision is used to insert the instruments and the vein is followed distally or proximally.

14 8 CHAPTER 3. PROBLEM ANALYSIS A B Figure 3.3: Incision sites for endoscopic vein harvesting. A: The proximal two thirds of the vein, B: The distal two thirds of the vein, C: Excision of the entire saphenous vein. Modified from [25]. C CO 2 is insufflated at a maximum pressure of 15 mmhg to make a tunnel in which the endoscope can operate and the surgeon can orientate. [18, 25, 26] Using an endoscopic dissector the vein is released from soft tissue as well as side branches of the vein. When sufficient vein length is liberated, a second incision can be performed on the thigh or lower leg depending on whether the first incision is proximal or distal to the knee area. It is, however, possible to cut the vein completely free and retrieve it via the first incision and the wound is subsequently sutured. Further preparation and use of the vein is similar to the OVH procedure. The procedures are not always the same because of modifications in order to improve the technique, thus, sometimes the second incision is eschewed to avoid scarring and the risk of wound complications. Furthermore, the harvesting site can differ between lower leg, upper leg, or the entire length of the leg, but traditionally EVH has been performed on the thigh. [18, 22, 27] EVH has been introduced to decrease infection rates, length of hospital stay (LOS), patient discomfort, and pain related to the OVH. Evidence supports that the introduction of EVH has decreased wound complication rates, and some studies indicate that there is a tendency to shorter hospitalizations and less patient discomfort related to the vein excision compared to OVH. [18, 28] Although EVH has proved a useful harvesting technique it has not fully superseded OVH; possibly due to the fact that EVH requires the investment in relatively expensive endoscopic equipment, both disposable and non-disposable, which also requires training of personnel in its correct use [28, 29]. The superiority of EVH compared to OVH has not been established on all areas; thus, there is still some uncertainty whether EVH actually increases patient satisfaction and if it decreases the length of hospitalizations [28, 29]. An issue of great concern in recent years, is the question whether the rougher treatment of the vein in EVH may provide grafts of inferior quality, compromising their long-term durability [10, 22]. Thus, in 2011 the National Institute for Health

15 3.2. VEIN HARVESTING PROCEDURES 9 and Clinical Excellence (NICE) has issued a warning, that surgeons should exercise caution if performing EVH instead of OVH due to the contemplation that EVH may cause more long-term complications than OVH [22] Comment on Existing Literature When implementing new medical technology, evidence of its safety is critical, and often there is an impressive multiplicity of papers on its efficacy, safety, and often also superiority compared to older technology. This is also the case for EVH, which has been examined vigorously in order to establish its effectiveness and superiority compared to OVH. However, when reviewing the existing literature on the subject, lacks, flaws, and deficiencies are numerous. To fully understand the implications of using one method instead of another, a revision of the best, currently available literature is appropriate. Authors often fail to describe under what circumstances their studies have been conducted; they often do not openly express the time frame of their studies and fail to do long-term follow-up studies on the effect of EVH compared to OVH. This may provide uncertainty, which of the excision methods may be superior over time, regarding e.g. infection rates, readmissions, etc.. Furthermore, though having expressed a certain time frame, some authors do not report at what point on the timeline of their study certain outcomes have occurred, e.g. whether infections occur before or after discharge from hospital. [4, 8, 20, 26, 30] Due to the speciality of these procedures, the populations in trials are often relatively small, producing debatable results. Well-designed studies with small populations may produce good and credible results; however, many studies do not present high-quality evidence with respect to the evidence hierarchy, by e.g. using randomization [1]. This may be due to the fact that medical professionals should at all times provide the best possible care; anything else would be unethical. The lack of randomization might, furthermore, be a result of restricted resources and time. From a research related point of view, however, the lack of solid evidence only provide uncertainty regarding the results presented. [8, 10, 20] EVH has been introduced with one of the main grounds being to reduce patient discomfort and pain. For this reason, it is surprising that only few studies use the patient experienced pain and mobility restriction as effect goals. Instead, many of the studies published on the subject concern effectiveness of the two excision methods referring to differences in numbers of infections, readmissions to hospital, and length of hospitalization, etc. between the two methods. When only focusing on the effects of implementing EVH and ignoring the costs related to it, these analyses do not provide an appropriate description of the harvesting methods for a decision maker to decide what surgery method to use. [1]

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17 Chapter 4 Problem Statement Despite the fact that EVH is widely introduced both in the USA and Europe, only one health economic evaluation has compared costs and outcomes in correlation with the patients well-being post-operatively. The full economic evaluation has been chosen as an appropriate investigation method of whether OVH or EVH may be the best choice of methods: In this report health economic evaluations are performed to investigate whether endoscopic vein harvesting should be more costeffective than open vein harvesting. This is done by conducting two cost-effectiveness analyses of cost per avoided infectious and non-infectious leg wound complication and a cost-utility analysis of quality-adjusted life-years gained when using endoscopic vein harvesting instead of open vein harvesting. New evidence has questioned the long-term viability and patency of veins excised by EVH [10, 20, 22]. If EVH grafts are of inferior quality compared to those excised by OVH, it may affect the long-term outcome due to an increased rate of late complications, such as stenoses, unstable angina pectoris, and death. Though literature findings are inconsistent, an evaluation of survival and complication rate thus seems pivotal. For this reason, the time frame of this cost-utility analysis is wide to include all currently available information concerning long-term outcomes from both OVH and EVH. 11

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19 Chapter 5 Methods 5.1 Economic Evaluation Methods The costs of health care systems have become an increasing burden on national economical systems. As a greater percentage of the gross national product of western countries is used on health care, there is an increasing need to focus on evidence based medicine when prioritizing decisions [31]. Health economic evaluations are methods to help prioritize in a world with limited resources. The criteria for optimal decision making is maximum value for money. Economic evaluations are useful tools when making evidence-based decisions. Two types of economics evaluations exist; the partial and full evaluations. The partial evaluation only focuses on consequences of one program or service e.g. cost of illness in contrast to the full economic evaluation, which compares the cost and outcome. The different types of full health economic evaluations are cost-benefit (CBA), cost-effectiveness (CEA), and cost-utility analyses (CUA), differing via their outcome. [1, 31] The CBA values cost and benefits in monetary units. Due to the outcome unit it is possible to compare results across societal sectors for what reason, it is often considered the most powerful evaluation technique compared to other economic evaluations. The CBA is extensive, including all factors, which may be affected by the intervention investigated. Thus, it also includes non-health related benefits and costs in other sectors, not directly related to the intervention, such as time spent by relatives, lost earnings, sickness benefits, etc.. Furthermore, the analysis can be used when only one technology has to be evaluated. Due to the extensiveness of the CBA, for the investigation of some interventions it may be unnecessarily complex to perform compared to the information needed. [1] The two remaining analyses, the CEA and the CUA, are very similar to each other, as they share many features and qualities. In the following section, the theoretical base of the two evaluations is outlined Cost-Utility and Cost-Effectiveness Analyses: A theoretical Overview The availability of high quality evidence on the effectiveness of the options compared is essential for the economic evaluation analyst in order to draw 13

20 14 CHAPTER 5. METHODS well-informed conclusions. When assessing a new technology in contrast to another it may be possible to use results from former studies concerning the complementary technology to perform a fair comparison of the technologies. Using already published studies provides a larger set of data and may help in assessing whether the new technology is superior to the existing. Data quality, relevance, and comprehensiveness are important issues to consider. One of the most important methodical qualities is the random selection of participants to intervention groups. The best results when examining intervention effects may, however, come from the compilation of studies with several different study designs. Secondly, the relevance of studies has to be taken into account. It is important to consider whether the clinical setup presented in the investigated studies can actually be compared. The third issue is comprehensiveness which is questioning whether the used clinical data represents the topic in question correctly. For that reason, it is important to consider the homogeneity and quality of the primary studies before an overall estimate of the intervention effect is performed. [1] Cost-Effectiveness Analysis The CEA is helpful when evaluating two or more technologies with similar outcomes, e.g. life-years gained, avoided infections, decrease in blood pressure, number of symptom-free days, etc.. Outcomes may, however, differ between programs. For this reason CEAs cannot be used for comparison of all interventions within the health sector; thus a CEA with avoided infections as its outcomes cannot be used in a comparison of cost-effectiveness of another intervention, if its effectiveness is measured in bed days reduction or the like. In spite of this, the CEA is of importance for the administration of hospitals and health care personnel because it provides information on tangible outcomes. [1] Cost-Utility Analysis The CUA focuses on health care programs or treatments with particular attention to health-related quality of life (HRQoL) produced or lost within the programs. In CUA, the incremental cost of an intervention from a certain viewpoint is compared to the incremental health improvement referable to that intervention. The health improvement is most often stated in QALY, which results in a conclusion of the analysis in cost per QALY gained. This universal outcome is applicable within the entire health sector and hence it is possible to compare different interventions. QALY provides a currency, which can be utilized in CUAs of similar intervention methods to provide a common frame of reference between the different intervention options. Furthermore, any impact on HRQoL through different, dissimilar interventions can be found; even if the interventions do not have the same aim. Roughly speaking, a measurement of QALYs gained though e.g. hip replacement operations can be compared to those gained by e.g. CABGs. This makes QALY a useful measure when attempting to quantify HRQoL gained by different interventions in CUAs. [1, 32] QALY takes into account quantity of life - the life expectancy - and quality of life. NICE defines QALY as a measure of a person s length of life weighted by a valuation of their health-related quality of life. That is, one life year is weighed according to the health state in that year: This way, one year of

21 5.1. ECONOMIC EVALUATION METHODS 15 perfect health corresponds to one QALY, whereas if the health state is less than perfect, the year is worth less than one QALY. Calculation of QALY can be demonstrated by the following example; four years with a valuation of the health state to 0.75 only correspond to three QALYs and one year with a health state valuated to 0.5 only corresponds to 0.5 QALY. [1, 32] When measuring quality of life, factors influencing it are countless. Even when only measuring HRQoL, restrictions on what dimensions are taken into account are extremely relevant. For QALY, the preferred option of valuating the HRQoL is the EuroQol 5-dimension (EQ-5D) measure of health related quality of life - which is also put into practice in this report though other options are available. The EQ-5D is multiple-choice questionnaire with five questions including three options each. The three options can be simplified to severe problems (EQ-5D option 3), some problems (EQ-5D option 2), and no problems (EQ-5D option 1); it gives a simplified version of a person s health state, but has shown itself useful when assessing different patient populations. The five questions deal with five health dimensions, which are used to valuate the general health state: Mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. [1, 32] Normally when measuring HRQoL by QALY, death corresponds to zero. Some health states, however, may be considered worse than dead for which reason QALY scores may actually be negative, due to the method of calculation used in the EQ-5D [1] Discounting Policy An important factor to consider, when performing health economic evaluations on programs that may have effects and costs allocated over multiple years, is the discounting policy. In general, costs have to be discounted to present values. There is some dispute, however, whether utility and effectiveness should be discounted or not [1]. Arguments given for not discounting are that discounting years of life or effectiveness will favor the present population or effect compared to the future one. This is reasonable in relation to resources where it is expected that future generations are wealthier, but it does not make sense in the context of health. However, this statement is also problematic since some expect future generations to have improved the health technology. In contrast to these problematic aspects there are arguments favoring discounting. [1] It has been documented that the conclusion might be misleading, if leaving the effects undiscounted while the costs are discounted or if the costs and effects discounted at different rates. If the effect remains undiscounted it will appear to be cheaper to make the investment in a health care intervention or building a hospital in the future compared to present time; if not discounting the value of expenditure, meaning the utility or effect, it would appear that next year the same amount of effect could be gained for less, the discounted, money. Contrary, when discounting at the same rate as the costs, the present value of expenditure will be equally lower next year. This way it is avoided that the value of the expenditure appears to increase in value, which would happen otherwise, if only costs are discounted. In practice, the discount rate is normally set to 3 or 5 % for both costs and effects. These rate can be used if there is no official guidance on discounting. [1]

22 16 CHAPTER 5. METHODS Sensitivity analyses may be carried out to illustrate the consequences of using alternative discount rates and different assumptions regarding the clinical data. [1] 5.2 Implementation The analyses in this report is written from a health sector view, and include information from hospitals from primary admission with post-operative care related to the leg wound, but also readmissions due to early complications, as well as visits at a general practitioner (GP) and from home care nurses, where the information has been obtainable and credible. The authors of this report have attempted to be impartial regarding the two harvesting methods. However, when assumptions have been made the results favoring EVH the least have been chosen for further investigation. This is furthermore the case if more results have been available on the same topic. Ideally the health economic evaluations should proceed until death of all patients included in the studies to include all potential late complications, either related to the leg incision or the graft. Most of the studies investigated, however, only provide follow-ups of a certain time span; the longest being five years. To perform the full economic evaluations, documentation on cost, utility, and effectiveness will be presented below, ending with a rudimentary sensitivity analysis, investigating the uncertainties of the calculations. 5.3 Costs Cost calculations are in this section presented with the assumptions that have been made to perform the analysis. The amount of evidence is not convincing on all topics, since not much attention has been paid to all areas. Discounting has been deemed appropriate as this analysis uses resources over the course of several years. The discounting rate is set to 3 % in accordance with international guidelines [1]. All prices are given in Danish kroner (DKK) in Prices from 2010 or earlier are corrected for inflation by inflation rate from statistics Denmark [33]. Since no inflation rate can be obtained from 2011, a mean inflation rate of 2 % is applied. Exchange rates for foreign currency is obtained from an average rate given by the National Bank of Denmark [34]. All details on cost calculations are found in appendix A. Furthermore, an overview of the literature investigated can be seen in appendix B in table B.1. Consumption of resources is seen in table 5.1 and costs of resources can be seen in table 5.2 on page 21. Since an incremental analysis only includes cost that differ between the two interventions, costs that are the same in the two harvest methods are not included, e.g. OVH surgery training, the CABG operation, and diverse disposable equipment. Resource consumptions deemed appropriate for investigation from the health sector view are operative time, surgical EVH equipment, LOS, home care and GP need, early and late readmissions, as well as EVH procedure training.

23 5.3. COSTS Operative Time A meta-analysis from 2005 documents a longer operative time with EVH of approximately 15 minutes compared to OVH [12]. This analysis is supported by a systematic review from 2006 reporting longer harvesting times in EVH procedures [28]. Furthermore, a prospective randomized trial from 2008 documented a total surgery time of 232 min with the use of EVH and 216 min for the use of the OVH method, resulting in a difference of 16 min [18]. In contrast to these findings, in a meta-analysis from 2010 by Markar et al. [29] no significant difference was found in vein harvest time. Due to the validity of the study design and novelty of the study by Markar et al. [29], it is concluded that no difference in total operative time exists between the two interventions. This variable will therefore not be included in further cost calculations, other than in the sensitivity analysis Endoscopic Vein Harvesting Equipment The investment in non-disposable medical equipment used in the endoscopic system has been corrected for inflation and is discounted with a rate of 3 % with a 10 year write-off period, due to the expected clinical service life of the endoscopic equipment. Details on discounting can be seen in appendix A, equation A.1 and A.2. The Guidant VasoView R Endoscopic Harvesting System has been the chosen brand from which the costs are calculated due to the fact that this system is preferred for CABGs at Aalborg Hospital. Details on equipment included in cost calculations in this report are seen in table 5.1; the list of equipment includes the necessary tools and specific materials that must be taken into account when operating with the endoscopic operation system. [13] Equipment costs should furthermore be allocated to all patients whom the equipment is used upon. At Aalborg Hospital 270 CABGs are performed per year Length of Hospital Stay In Denmark it is desirable to shorten hospitalizations in order to cut down waiting lists [35, 36]. A meta-analysis from 2004 found a reduction of one day in LOS within the patient group undergoing EVH compared to the OVH group [37]. This is supported by another meta-analysis from 2005 showing an average reduction in LOS of 0.85 days in an EVH group compared to an OVH group [12]. However, a meta-analysis of randomized controlled trials from 2010 showed no statistically significant difference in LOS between the two harvesting methods, but a tendency in favor of EVH of 0.26 days longer stay for patients undergoing OVH [29]. Based on the literature, it is concluded that EVH reduces LOS compared to OVH. Representing the newest evidence, the numbers from the 2010 metaanalysis will be used for further investigation of difference in costs [29]. To estimate hospital costs, a tariff on DKK per day composes the base for the calculations [38], see 5.1 and 5.2. This rate compensates for basic expenses concerning the stay at the hospital e.g. labor costs and materials. Calculations can be seen in appendix A; A.3 and A.4.

24 18 CHAPTER 5. METHODS Visits from Home Care Nurse and GP An early study of EVH and OVH from 2001 involving 60 patients illustrates that a significantly higher number of the 30 OVH patients needed visits to the GPs and from community nurses than the EVH group at six weeks follow-up. More precisely eight patients from the OVH group visited the GP and 13 had visits from a community nurse, whereas only one patient from the EVH group visited the GP and one had visits from the community nurse [24]. The same significant tendency is reported in a study from 2004 involving 108 patients (56 OVH patients, 52 EVH patients) in a six weeks follow-up, where nine times as many OVH patients visited the GP as EVH patients. Furthermore, the district nurse visited 12 times as many patients from the OVH group as from the EVH group [3]. These two studies show that the need of home care and GP is substantially higher for OVH patients, but do not report how many visits were needed per patient. For this reason, the studies cannot be utilized for further cost calculations. Andreasen et al. [18] document that OVH patients on average visits the GP 0.71 times post-operatively, whereas EVH patients on average only visited the GP 0.03 times. The same tendency is seen in the need of home care; the OVH patients on average are visited 0.48 times by a home care nurse, whereas the EVH patients are not visited at all [39]. The costs related to home care is calculated on the basis of the time rate for a home care nurse of DKK [40]. This labor cost includes all aspects of an infection cleaning session ; administration, medical record-keeping, transport time, materials, and treatment of the patient. The average duration of a visit is 0.75 hour [40]. Based on the findings by Andreasen et al. [18] it is assumed, that the EVH group does not have any visits from the home care nurse, for what reason the calculations are only made for the OVH group. See calculations in appendix A; A.7 - A.9 and results in table 5.1 and 5.2. The price of one consultation at the GP is calculated by multiplying the consultation fee with two, giving a price of DKK [41]. By utilizing this method, GP income from capitation fees is included in the price as roughly 50 % of Danish GP income comes from capitation fees [13]. Patients personal expenses to medicine and transport are not included. The calculations can be seen in appendix A; A.10 and A Early Readmissions to Hospital A case-control study by Bilal et al. [42] from 2010 showed no difference in readmission rates, which is contradicted by Cheng et al. [12] in a meta-analysis from 2005, showing a significant difference in readmission rates between the two surgery methods. In the meta-analysis, almost twice as many in the OVH group were readmitted due to wound complications in comparison with the EVH group; 1.5 % and 0.8 %, respectively [12]. Due to the evidence hierarchical superiority of the meta-analysis, the numbers given by Cheng et al. [12] will be used for further investigations in this report. A diagnose related group (DRG) charge of DKK is used regarding costs linked to readmission for post-operative and post-traumatic infections, assuming a mean readmission time of six days [43], see table 5.1 and 5.2. Calculations can be seen in appendix A; A.5 and A.6.

25 5.3. COSTS Late Readmissions to Hospital Lopes et al. [10] in 2009 found that EVH was associated with a significant higher rate of graft failure and occlusion 3 year after CABG, compared to patients who underwent OVH. [10] In contrary, in a randomized prospective trial from 2003, 112 patients were followed for five years after CABG surgery [44]. The study found no differences in the the rate of MI, recurrent ischemia, and death between EVH and OVH during follow-up. The same results are seen in a more recent study involving 8542 patients, who underwent CABG between 2001 and 2004 [45]. At a four year follow-up, EVH was associated with a reduced mortality risk, and no difference in rate of revascularization was found [45]. Additionally, a study from 2010 including 5825 patients concludes that there is no difference between EVH and OVH groups in readmission to hospital for revascularization, heart failure, or acute coronary syndromes. [20] Furthermore, based on a recent, retrospective study from 2011, Grant et al. [11] state that there is no difference between EVH and OVH in mortality, death, repeated vascularization, and MI at a 22 months follow-up. Since the most recent studies show no differences in late term complications causing readmission, this variable will not be included in further cost calculations Learning Curve of Endoscopic Vein Harvesting Several studies confirm the existence of a learning curve for EVH [11, 29]. As can be seen in figure 5.1 on the next page, Bonde et al. [3] suggests a learning curve requiring approximately 20 operations before a surgeon masters the EVH technique, timewise. It is assumed that surgeons performing EVH excisions are specialized surgeons, and thus are experienced in the art of surgery, if not endoscopic surgery, yet. Based on the graph it is estimated, that the initial excision time for the surgeon in Bonde et al. s study was 125 min. In contrast, an average harvest time of 56.5 min is assumed to be the time a trained surgeon usually needs to harvest the vein endoscopically. [3] Although the initial excision time is assumed to be 125 min for an untrained surgeon, it is contrary to what Chiu et al. [27] have reported; in the study by Chiu et al. [27] the mean harvest time from 1348 cases was reported to be 45 min, with a mean harvest time of 68 min reported for the first 50 cases, but only 23 min for the last 200 cases. This indicates a learning curve of a different nature than reported by Bonde et al. [3]. Many studies report mean harvesting times more similar to the one reported by Bonde et al. [3, 18, 46]. As a result it seems reasonable to suspect that the learning curve reported by Bonde et al. [3] represents the general learning curve of EVH better than the one presented by Chui et al. [27]. For this reason it is assumed that the learning curve in figure 5.1 depicts the expected normal learning curve of EVH fairly. Calculated from the learning curve, it is found that an extra surgeon participating in the vein harvesting procedure 20 times, will account for a total of min. A recently qualified specialist is payed DKK per month at Aalborg Hospital [47] and assuming they work 37 hours per week, the time rate is DKK 340 [48]. Since the extra surgeon is participating in an operation with standard personnel and facilities it is necessary to include the extra costs

26 20 CHAPTER 5. METHODS Figure 5.1: Learning curve of endoscopic vein harvesting: The total procedure time in minutes to harvest the vein versus the number of cases performed. Bonde et al. [3] by this graph propose a declining need of time as technicians become more experienced. EVH: Endoscopic Vein Harvesting. Graph from [3]. for the time consumed. Since at Aalborg Hospital three surgeons are employed with education in the endoscopic system, the cost for the EVH training is multiplied by three. These estimations result in a cost of DKK for EVH training of three surgeons, personnel salary, and theater rental, which is discounted as it is considered an investment for the next 25 years for these particular surgeons. This cost is allocated on the number of EVH patient per year giving a final sum of DKK per EVH patient, see table 5.2. The calculations can be seen in appendix A; A.12 - A.20. It is assumed that the cost of education of nurses assisting in endoscopic surgery only represents a small part of the total costs connected to training in the endoscopic system, why it is excluded from the calculations. As seen in table 5.2, the total incremental cost between EVH and OVH is estimated to be DKK per case, taking the resources in which a difference was observed into account. 5.4 Utilities When performing the CUA in this report, post-operative HRQoL within the EVH and OVH group has been estimated, utilizing existing literature. Therefore, it was chosen to map mobility and pain, attributed to the excision wound, into EQ-5D options to produce QALY measures on HRQoL. That is, only impact on HRQoL directly attributable to the excision methods is included; thus it is of no concern in this analysis if patients achieve lower scores due to e.g. diabetes, etc.. Though there may be some impact on the other dimensions measured by EQ-5D, they are assumed not to be particularly altered from the vein harvesting wound for which reason, they will not be valuated in this estimation of QALY. Thus, the topics self-care, usual activities, and anxiety/depression are all set to no problems, equal to EQ-5D option 1 for both the EVH and

27 5.4. UTILITIES 21 Consumption of Resources Resource EVH OVH Unit Price Extra hospitalization (day base) Early readmission to hospital District nurse visits GP consultation EVH induction training Disposable EVH equipment Vesselloops Insufflation tube for CO Pincer Hylocain spray Spray tube Anti-mist Camera covering Label pen Curapor R plaster Plastic bags for x-ray pictures Covering sheet Syringe CO Non-disposable EVH equipment Rack w. monitor etc. used not used Optics used not used Diathermy cable used not used Optical fiber cable used not used Non-disposable EVH equipment, total discounted, price per year Table 5.1: Consumption of resources is given as the average consumption per EVH and OVH patient. Unit prices are stated in DKK and converted to newest price available, when necessary. EVH: Endoscopic vein harvesting, OVH: Open vein harvesting, GP: General practitioner. Costs of Resources Resource, DKK per operation EVH OVH Incremental Costs Extra hospitalization (day base) Early readmission to hospital District nurse visits GP consultation EVH induction training Disposable EVH equipment Non-disposable EVH equipment Total costs Table 5.2: Costs are stated in DKK and converted to newest price available, when necessary. For details on disposable and non-disposable EVH equipment, see table 5.1. EVH: Endoscopic vein harvesting, OVH: Open vein harvesting, GP: General Practitioner.