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Ramsay C, Pickard R, Robertson C, et al. Systematic Review and Economic Modelling of the Relative Clinical Benefit and Cost-Effectiveness of Laparoscopic Surgery and Robotic Surgery for Removal of the Prostate in Men with Localised Prostate Cancer. Southampton (UK): NIHR Journals Library; 2012 Nov. (Health Technology Assessment, No. 16.41.)

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Systematic Review and Economic Modelling of the Relative Clinical Benefit and Cost-Effectiveness of Laparoscopic Surgery and Robotic Surgery for Removal of the Prostate in Men with Localised Prostate Cancer.

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5Methods for health economic evaluation

Introduction

In this chapter we report the methodology and parameter value selection for a health economic evaluation comparing robotic radical prostatectomy with laparoscopic radical prostatectomy. This economic evaluation was conducted using a discrete-event simulation model described in detail in subsequent sections. This represents a change to the modelling specified in the original protocol. This change was required to account for the degree of complexity encountered while defining the treatment care pathways.

The original study protocol (see Appendix 1) specified the use of a Markov state transition model in order to explore aspects of heterogeneity within cohorts undergoing treatment for localised prostate cancer. Once the treatment care pathways were defined, however, it became clear that the use of a state transition model would be impracticable for several reasons:

  1. The number of potential health states and their transitions was large.
  2. The discrete-event model explicitly included multiple adverse events that may occur during progression along the care pathway trajectory while also accounting for potential feedback to one or more previous states within the care pathway. Inclusion of multiple event states would necessitate very large transition matrices.
  3. The study required a modelling approach that would provide a high degree of flexibility in modelling interconnected care processes while also accounting for heterogeneity in the populations modelled. In addition, the discrete-event simulation adopted allows the incorporation of interdependent and simultaneously occurring health events and internal feedback loops, a characteristic found within the treatment care pathways. These would be difficult to achieve using a Markov-type approach; this is an important limitation of decision tree-based approaches. The approach adopted also provided more detailed reporting of each individual's journey through the disease trajectory.

Before conducting the economic evaluation we attempted to identify and summarise any existing economic evaluations on this topic systematically (see the following section). The economic evaluation itself involved several stages, described later in this chapter.

Systematic review of previous economic evaluations

We searched for economic evaluations comparing both costs and outcomes of the two surgical procedures systematically. To be included studies had to include costs and effects, regardless of the way that each were estimated. We found no economic evaluations that fully met the inclusion criteria (see Appendix 11). Three publications were identified that reported cost comparisons between robotic and open radical prostatectomy,164166 five publications reported cost comparisons between laparoscopic and open radical prostatectomy121,167170 and three publications reported cost comparisons between robotic and laparoscopic surgery.171173 The publications by Bolenz and colleagues171 and Lotan and colleagues172 estimated the procedure costs of robotic and laparoscopic prostatectomy for a USA setting based on a retrospective patient cohort and a hypothetical costing exercise respectively. In both cases, excluding the capital cost of the robotic system, robotic prostatectomy was $500–700 more expensive per case than laparoscopic surgery. Bolenz and colleagues171 reported that the additional purchase and maintenance costs of a single robotic da Vinci system were $340,000 per year, while Lotan and colleagues172 reported that, assuming 300 cases per year, the cost of purchase plus maintenance costs were an additional $857 per case. Following a financial appraisal, again conducted in a USA setting, Steinberg and colleagues173 concluded that robotic prostatectomy was not financially viable in low-volume centres performing fewer than approximately 80 procedures per year under current tariffs. Although the method used to establish procedure costs in these three papers was clear, none considered costs beyond the hospital period and none attempted to compare procedures in terms of both costs and outcomes. Although the paucity of the evidence base was anticipated at the outset of the study, the results of this systematic attempt to identify relevant economic evaluations have highlighted the need for the economic evaluation that is reported in this monograph.

Methods

Model specification: purpose and design

The purpose of this model was to simulate the outcomes and costs during and following a radical prostatectomy procedure using either a robotic or laparoscopic technique performed in an appropriate UK NHS hospital on a man with clinically apparent localised prostate cancer.43 The model was specified to follow the predefined care pathway for individual men for 10 years from the time of surgery, this being the anticipated duration of use of the current robotic technology under study (Intuitive Surgical, June 2010, personal communication). We also included as a sensitivity analysis the ability to specify the model over the lifetime of the individual, consistent with the epidemiological characteristics of localised prostate cancer, which typically has a long natural history with survival benefits for radical treatment needing at least 10–15 years to accrue.44

We selected an individual-based event model in which surgical procedure, steps in the care pathway, the occurrence of longer-term adverse events and ultimately death are modelled as discrete events for individuals within the model.174 The transition of individual men between events was driven by the previous health states, processes involved in their clinical treatment and subsequent care that arose as a consequence of the surgery, the underlying disease and natural lifespan. These included adverse events associated with the prostatectomy, events during clinical management of individuals who were cured of prostate cancer by the surgery and events driven by disease persistence or recurrence following prostatectomy. The clinical characteristics of individuals entering the simulation could be varied to represent the complete spectrum of patient and disease characteristics among the overall population of men with localised prostate cancer requiring radical prostatectomy. Each event and each subsequent patient management decision at all decision points in the pathway was modelled probabilistically based on available data relevant to patient care in the UK NHS. The hierarchy of data sources used was in the order of the associated systematic review, available relevant literature including web-based sources and consultation with relevant experts. The model was parameterised using data obtained from these sources describing disease progression, survival and the prevalence of adverse events. Data on costs to the UK NHS of laparoscopic and robotic prostatectomy were predominantly obtained directly from the manufacturer of the robotic system, Intuitive Surgical,30 and from national and local NHS sources (see Costs). To enable analysis of cost-effectiveness, utility values for the various health states within the care pathway were obtained from the literature (see Utilities). The model was constructed using the scripting language available for the R statistical package for computing.175

State variables and timescales

State variables

Postoperatively each individual was assigned a combination of eight state variables. The first was age at the time of surgery. This was simulated by drawing a random deviate from a triangular distribution with minimum, peak and maximum shape parameters derived respectively from the 25th percentile, median and 75th percentile of the age distribution of men undergoing radical prostatectomy. The age range for each intervention was identical.

Four variables specified individual disease characteristics following pathological examination of the removed prostate:

  • surgical margin: negative or positive
  • tumour stage: pT0–T2 or pT3–pT4
  • Gleason sum score: ≤ 7 or 8–10
  • lymph node status: unknown, negative or positive.

Three variables indicated adverse events arising from prostatectomy that would not be resolved in the 3-month treatment phase:

  • bladder neck contracture (stenosis): absent or present
  • urinary incontinence (moderate or severe): absent or present
  • erectile dysfunction (bothersome to individual): absent or present.

Time step

The modelled time step (cycle length) was a quarter (3 months). For variables for which only annual data could be obtained the probabilities were converted to a standard time base of a quarter using Equation 1:

P′ = 1 − ((1 − P)¼)
[Equation 1]

where P is the yearly probability of an event occurring and P′ is the probability of an event occurring in a 3-month period.

Time horizons

The base-case time horizon for the model was 10 years, this being consistent with the anticipated duration of use of the current technology under test – the da Vinci surgical robotic system. A longer time horizon (40 years) that would cover the expected lifetime of the men included in the model was also used, consistent with the epidemiology of localised prostate cancer.176

Assumptions within the model

Modelled events at each decision point within the pathway were discrete and independent. For example, surveillance for biochemical recurrence was simulated in the same way irrespective of events previously experienced by the individual. In the absence of suitable data the probability of further biochemical recurrence was independent of previous biochemical recurrences that had been successfully treated. In practice, care options inevitably are affected by previous disease characteristics and other related events, but the multitude of possibilities of care for particular individuals during the course of their cancer care subsequent to radical prostatectomy could not be fully parameterised in the model in the absence of sufficiently detailed individual-level data sets. Proportions of individuals undergoing different procedures within the care pathway were defined by the probability of being assigned to those procedures. This simplification was necessary because of the lack of data on the underlying causal factors leading to events; they were therefore modelled as random processes (see Modelling of discrete events).

The imprecision/uncertainty surrounding parameter estimates used within the model was characterised by assigning statistical distributions to parameters. For parameter estimates provided by the systematic review, the log-normal distribution was used to define the degree of surrounding uncertainty. Other parameters derived from the literature or other sources were considered for accuracy, credibility and plausibility at meetings of the expert panel. Identifying a suitable distribution for estimates and describing the uncertainty around these values was problematic. In such circumstances, uncertainty was calculated as a potential range of plausible values of ±25% of the estimate.

For parameters not defined by the systematic review we assumed that the point estimate was the most likely ‘real’ value and therefore did not consider that a uniform rectangular distribution was appropriate. Furthermore, by defining the extreme limits of the distribution using the triangular method (as described above) we ensured that the upper and lower bounds of variability did not exceed clinical plausibility. And finally, the way in which variability was calculated ensured that the degree of uncertainty applied to each intervention equally.

Modelling the care pathway

Following robotic or laparoscopic prostatectomy each individual was entered into the specific pathway dictated by his clinical and disease state after the operation (Figure 15). This state was characterised in terms of, first, cancer status and, second, the presence of one or more of the three adverse events that were deemed to persist beyond the treatment period: bladder neck contracture, urinary incontinence and erectile dysfunction. The individuals then proceeded through a series of events dependent on where they were in the care pathway and which would result in changes to, or resolutions of, differing health states. This would particularly include remission or relapse following additional treatment for recurrent prostate cancer or resolution of a longer-term adverse event by treatment.

FIGURE 15. Schematic showing care pathway for the perioperative state during and immediately after radical prostatectomy.

FIGURE 15

Schematic showing care pathway for the perioperative state during and immediately after radical prostatectomy. A0, perioperative health state; A1, postoperative health state; B2, surgeon learning effect; B3, perioperative complication classified using (more...)

Events were modelled probabilistically using data derived from the hierarchy of sources defined previously in Model specification: purpose and design. Where possible the data used were relevant to both the clinical context of radical prostatectomy and current practice in the UK NHS.43 Parameters, their values, their distributions and their sources are listed in abbreviated form in the relevant sections. Events experienced by individuals were scheduled in interacting ‘streams’. Surveillance, cancer treatment and mortality were first simulated either until the end of the time horizon if the individual survived or until a process within the care pathway led to death either from prostate cancer or from any other cause (see Figure 15). This provided the framework for each individual's trajectory through the cancer care pathway. The second set of events simulated the management of the three postoperative dysfunctions: bladder neck contracture, urinary incontinence and erectile dysfunction. If a process led to an intervention event, such as surgery for urinary incontinence, this was scheduled only after at least 12 months of surveillance without a cancer-related event.

Modelling of discrete events

All events were assumed to be binomial in the sense that an event either occurred, 1, or did not occur, 0. Simulation of the occurrence of an event for an individual was undertaken by drawing random uniform deviates and comparing the observed deviate with the known probability of that event occurring given the relevant conditions. Thus, if x represents the proportion of men who experienced bothersome erectile dysfunction after laparoscopic prostatectomy, any random deviate drawn for an individual that was less than x would lead to that individual suffering the dysfunction and progressing down the appropriate pathway of care, whereas any deviate greater than x corresponded to no dysfunction. The proportion of men experiencing each event in each pathway was derived where possible from the systematic review reported in detail in Chapter 4. Other relevant literature or expert opinion were used where necessary.

Model health states and associated parameter values

Perioperative state

In line with the objective of this HTA all patients were assumed to have undergone radical prostatectomy by either laparoscopic or robotic means (see Figure 15). In addition, those individuals deemed to be at intermediate or high risk of early biochemical recurrence according to preoperative disease characteristics (Table 22) were allocated to undergo a concurrent pelvic lymph node dissection; the probability of this was defined from an appropriate additional literature source177 as the information was not available from the systematic review. Adverse events during surgery could initiate two further model events. First, the probability of suffering perioperative adverse events, categorised using systematic review data according to the Clavien–Dindo system into one of six levels, was defined as the proportion of patients who suffered that event68,69 (Figure 16). Second, and independently of adverse events categorised by the Clavien–Dindo system, a proportion of men undergoing laparoscopic or robotic prostatectomy were deemed to require conversion to an open procedure because of intraoperative difficulties. The rate for each of the procedures was determined from the systematic review and the consequence in terms of costs was defined as an extra 3-day hospital stay, decided by expert opinion (see Table 22).

TABLE 22. Parameter values with distributions and sources for the perioperative state for individuals undergoing robotic or laparoscopic prostatectomy.

TABLE 22

Parameter values with distributions and sources for the perioperative state for individuals undergoing robotic or laparoscopic prostatectomy.

FIGURE 16. Flow chart illustrating the classification of various intraoperative adverse events using the Clavien–Dindo system for the grading of operative complications and their input into the perioperative care pathway.

FIGURE 16

Flow chart illustrating the classification of various intraoperative adverse events using the Clavien–Dindo system for the grading of operative complications and their input into the perioperative care pathway. A0, perioperative health state; (more...)

For each specific Clavien–Dindo level or adverse event the associated financial cost was modelled solely through the extra duration of hospitalisation measured in days that a patient would require according to expert opinion (Table 23). These events were assumed to have resolved during the 3-month perioperative state.

TABLE 23. Care consequences in terms of increased length of stay according to level of perioperative complication.

TABLE 23

Care consequences in terms of increased length of stay according to level of perioperative complication.

Postoperative state

Immediate further cancer treatment

A proportion of men were assigned to require and undergo immediate further cancer treatment; the probability of this occurring was defined according to the findings of the systematic review, other literature sources and consensus of expert opinion (Table 24). First, men who had undergone pelvic lymphadenectomy as part of their radical prostatectomy and were found to have lymph node metastases on pathological examination of the removed lymph nodes were automatically selected for immediate further treatment.178 The proportion of men who underwent lymphadenectomy and the proportion of those who were positive were assigned independently from other variables according to the observed rates following either type of surgery from literature sources validated by our expert panel.177,179 Expert opinion deemed that all men with positive lymph nodes were assigned to further cancer treatment without the opportunity for a period of surveillance.

TABLE 24. Parameter values (base case) with distributions and sources for lymph node metastases (for men undergoing pelvic lymphadenectomy) and positive margin status (all men).

TABLE 24

Parameter values (base case) with distributions and sources for lymph node metastases (for men undergoing pelvic lymphadenectomy) and positive margin status (all men).

Second, men who had two or more of the following features found on pathological examination of the removed prostate were considered for immediate further treatment:

  • positive surgical margin
  • Gleason score 8–10
  • tumour stage pT3–pT4.

If only one of these pathological disease characteristics was present the individual entered the surveillance pathway (Figure 17).

FIGURE 17. Schematic representation of postoperative care pathway for men being considered for immediate further cancer treatment.

FIGURE 17

Schematic representation of postoperative care pathway for men being considered for immediate further cancer treatment. A1, postoperative health state; A2, further cancer treatment state; A3, long-term adverse event dysfunction state; A4, surveillance (more...)

Parameterisation of this decision-based approach required linked data for individuals concerning the three features and this was not available from the systematic review. We therefore decided on the following approach. Linked values of postoperative Gleason sum score and postoperative tumour stage for 4669 individuals were kindly provided from a large single institutional database of men undergoing radical prostatectomy maintained at the Vanderbilt-Ingram Cancer Center, TN, USA (D Barocas, February 2011, personal communication). The numbers of men from this data set with each combination of Gleason sum score and tumour stage were then multiplied by the probability of men having a negative or positive surgical margin following robotic or laparoscopic prostatectomy defined by the systematic review and meta-analysis (see Table 24).

The calculated patient numbers were then converted to percentages of the sample population, which defined the probability of each combination of the three variables (margin, Gleason sum score and tumour stage) for each procedure. These probabilities were then mapped to the decision matrix. The decision matrix, which directed the subsequent care pathway for individual men in the model, was formulated by rounds of consensus building with relevant members of the expert panel. The decision to be made was whether men would enter the surveillance state or proceed to further cancer treatment (Tables 25 and 26). The decision matrix gave total probabilities of 0.098 following robotic prostatectomy and 0.113 following laparoscopic prostatectomy for individual men requiring consideration for immediate further treatment.

TABLE 25. Immediate further cancer treatment matrix for individuals following robotic prostatectomy according to findings on pathological examination of the removed prostate.

TABLE 25

Immediate further cancer treatment matrix for individuals following robotic prostatectomy according to findings on pathological examination of the removed prostate.

TABLE 26. Immediate further cancer treatment matrix for individuals following laparoscopic prostatectomy according to findings on pathological examination of removed prostate.

TABLE 26

Immediate further cancer treatment matrix for individuals following laparoscopic prostatectomy according to findings on pathological examination of removed prostate.

Death due to causes other than prostate cancer

The age-related quarterly probability of non-prostate cancer-related mortality was obtained from actuarial tables published by the UK Office for National Statistics180 and was treated as a separate event from prostate cancer-related mortality.

Biochemical recurrence

The probability of biochemical recurrence was calculated for each 3-month time step according to the time since either prostatectomy or the most recent localised cancer event for men successfully treated for recurrent localised cancer by radical radiotherapy. The 12-month probability of biochemical recurrence was derived from the systematic review and then was assumed to decline exponentially according to published longer-term data (Table 27).181 As described later, the use of selected alternative values for biochemical recurrence was explored in a sensitivity analysis.

TABLE 27. Parameter values with distributions and sources for the further cancer treatment state for all individuals in the model.

TABLE 27

Parameter values with distributions and sources for the further cancer treatment state for all individuals in the model.

At each decision point the individual would continue surveillance without recurrence or experience a biochemical recurrence leading to further treatment or die from causes other than prostate cancer. In base-case simulations with a 10-year time horizon an individual could remain in the surveillance state or else be in a recurrence state at the end of the simulation and would be recorded as surviving without or with recurrent cancer respectively. If biochemical recurrence occurred, this was recorded before initiating the further cancer treatment process. Each time step that an individual spent under surveillance incurred a utility and a cost (described in Costs and Utilities).

Cancer treatment allocation

Men with pathologically involved lymph nodes or with two or more adverse pathological characteristics listed earlier were immediately assigned to the cancer treatment process following prostatectomy (Figure 18). The extent of the likely residual disease was defined as localised or systemic (metastatic) and this was randomly determined according to known probabilities using the same method described in Modelling of discrete events; this was independent of the precise cancer state variables (see Table 27). A similar process was used for men who underwent an initial period of surveillance and then suffered biochemical recurrence.

FIGURE 18. Schematic diagram for the further cancer treatment care pathway.

FIGURE 18

Schematic diagram for the further cancer treatment care pathway. A2, cancer treatment health state; A3, long-term adverse event dysfunction health state; A4, surveillance health state.

Localised cancer treatment

Diagnosis of persistent or recurrent cancer localised to the prostatic bed was an event with three outcomes. First, further cancer treatment in the form of radical radiotherapy with or without a 6-month course of androgen deprivation therapy could be successful, resulting in the remission event; these men then returned to the surveillance process. Second, further cancer treatment could be unsuccessful, leading to metastases, further treatment for systemic cancer by lifelong androgen deprivation therapy and cancer-related death. The probability of either of these two events was determined by survival rates from the literature concerning radical radiotherapy used to treat localised recurrence after prostatectomy (see Table 27). Finally, the individual could suffer non-prostate cancer-related mortality before completing treatment. For the base-case simulation individuals could be in the further cancer treatment state at the end of the 10-year period and were considered to be survivors with prostate cancer recurrence. The time from further cancer treatment and remission or cancer-related death was randomly determined according to rates of survival obtained from the literature.

Systemic (metastatic) cancer treatment

Diagnosis of systemic cancer was an event occurring because of unfavourable disease characteristics such as positive lymph nodes in the immediate postoperative period or because of failure of radical radiotherapy for localised recurrence or following the process of biochemical recurrence. Such men were treated with androgen deprivation therapy (medical castration) until cancer-related death, the only outcome possible. In the base-case simulation with a 10-year time horizon it was possible for men to survive if they remained in the systemic cancer treatment state at the end of the 10 years; the duration of survival while on treatment for systematic cancer was randomly determined according to known metastatic prostate cancer mortality rates (see Table 27).

Persistent adverse event states

Introduction

The incidence of the considered postoperative adverse events or dysfunctions – bladder neck contracture, urinary incontinence and erectile dysfunction – was defined according to the standard parameterisation hierarchy described above. Management of these postoperative dysfunctions was modelled by treating them as independent processes. If dysfunctions were found to be present, self-management and/or treatment began immediately according to current clinical practice (Figures 19 and 20). Each of the three dysfunction-related state variables was recorded as a categorical variable encoding the presence or absence of the pathological condition. These three variables were randomly determined to be present according to the observed rates following either type of surgery defined by the systematic review, other literature source or expert opinion (Table 28). We assumed that there was no systematic co-occurrence of dysfunctions, so they were assigned independently. In this way it was possible for an individual to experience each dysfunction simultaneously.

FIGURE 19. Schematic showing care pathway for individuals in long-term adverse event state with bladder neck contracture, urinary incontinence and erectile dysfunction.

FIGURE 19

Schematic showing care pathway for individuals in long-term adverse event state with bladder neck contracture, urinary incontinence and erectile dysfunction. A3, adverse event state; B1, treatment of adverse event.

FIGURE 20. Expanded care pathway for the management and treatment of individuals incurring long-term postoperative adverse events.

FIGURE 20

Expanded care pathway for the management and treatment of individuals incurring long-term postoperative adverse events. A4, surveillance health state; B1, treatment of long-term adverse events.

TABLE 28. Parameter values with distributions and sources for longer-term adverse events for individuals undergoing robotic or laparoscopic prostatectomy.

TABLE 28

Parameter values with distributions and sources for longer-term adverse events for individuals undergoing robotic or laparoscopic prostatectomy.

Bladder neck contracture

All men who suffered bladder neck contracture (stenosis) were assumed to require treatment during the first quarter time step following radical prostatectomy. The intervention required was taken to be endoscopic bladder neck incision. This event incurred a one-off cost that was included in the first-year costs for that individual, and an appropriate utility value was assigned to the quarter during which the individual suffered the condition (see Costs and Utilities). Discussion within our expert group suggested that recovery was likely to occur in most cases following a single treatment and this was supported by the available literature.70 For the purposes of the model we therefore chose to assume that recovery occurred after a single incision in all cases with no continuing costs and utility returned to that of the surveillance state. We acknowledge, however, that this is likely to be a simplification of day-to-day patient care.

Urinary incontinence

In the second quarter immediately following their prostatectomy, men with moderate or severe urinary incontinence commenced self-management using containment pads, which incurred a cost and was associated with a specific utility value every quarter. There were three outcomes allowed for this self-management: spontaneous recovery, further surgery consisting of insertion of an AUS, or a persistent state that remained until the end of the studied time horizon or the man's death and continued to accrue costs and associated disutility. The probability of the first two outcomes was assessed at each time step; if neither event occurred then the patient remained in a state of persistent incontinence. Men who recovered ceased to incur a cost and their utility was returned to that of the surveillance state. Men with persistent incontinence were eligible for insertion of an artificial sphincter as long as they had spent at least 12 months in the surveillance state since prostatectomy without biochemical recurrence, were not currently undergoing cancer treatment and had not previously undergone unsuccessful sphincter insertion. Surgical insertion of an artificial sphincter resulted in either recovery (success) or persistence (failure) of urinary incontinence according to published success rates of this surgery. The surgery incurred a one-off cost that was assigned to that year's total cost for the individual. We chose to assume that implantation of an artificial sphincter would continue to successfully resolve symptoms throughout the studied time horizon without the need for any further treatment of incontinence. The proportion of men suffering recurrent incontinence after initial successful implantation is approximately 25% at 5 years but given the low overall probability of need for this device and the lack of difference in incontinence rates between the procedures under study we elected not to build this failure rate into our model.184

Erectile dysfunction

Immediately following prostatectomy men who suffered bothersome erectile dysfunction were assigned to either self-management or drug therapy, incurring extra costs if relevant and associated with a defined utility value every quarter. Costs for drug treatments were obtained from the British National Formulary185 whereas cost information relating to surgical intervention was obtained from the Department of Health's reference costs 2008–9.186 Self-management was defined as no active treatment. Men undergoing drug therapy were assumed to be taking either oral medication, with sildenafil (Viagra®, Pfizer Inc., USA) being the index drug, or intrapenile medication, with intracavernosal injection of alprostadil (Caverject®, Pfizer Inc., USA) being the index treatment. The rates of use of these options were obtained from relevant literature. There were three outcomes of both self-management and drug therapy: the man could recover, undergo surgical implantation of a penile prosthesis to cure erectile dysfunction or enter a persistent state of continued self-management or drug use that remained until the end of the time horizon or the man's death. The probability of the first two outcomes was assessed at each time step; if neither event occurred then the patient remained in a state of persistent erectile dysfunction. Men who recovered ceased to incur a cost and their utility returned to that of the cancer surveillance state. Individuals were eligible for penile prosthesis implantation if after at least 12 months of surveillance they did not have a biochemical recurrence, were not currently undergoing cancer treatment and had not already had a penile prosthesis implanted. Implantation of a penile prosthesis resulted in either recovery of erectile function or a persistent state, which was determined according to the success rates of this surgery published in the literature. The surgery incurred a one-off cost assigned to that year's total cost for the specific individual.

Costs

Perioperative costs

General

A general cost for the standard length of hospital stay was derived from the relevant excess NHS bed-day cost tariff for the procedure (LB22Z) of £255186 multiplied by the average hospital stay for robotic/laparoscopic prostatectomy within the NHS of 3.48 days obtained from hospital episode statistics for 2008–9.48 Hospital stay estimates from the systematic review were not used because they derived from a number of different heath-care systems. A cost per hour of NHS operating theatre time was derived from the baseline information calculated from General Hospital (Acute) obtained from ISD (Information Services Division) Scotland Theatre Services R140193 (Table 29). This was then multiplied by the duration of laparoscopic and robotic prostatectomy derived from the systematic review (see Table 22). The cost of pathological examination of the removed prostate and lymph nodes of £329.82 was obtained from the Newcastle upon Tyne Hospitals NHS Foundation Trust (D Evans, May 2010, personal communication).

TABLE 29. Standard operating theatre costs per hour derived from ISD Scotland cost data.

TABLE 29

Standard operating theatre costs per hour derived from ISD Scotland cost data.

Equipment costs

The cost of undertaking one procedure using either intervention was obtained by adding together the basic unit cost of each surgical system, the cost of any specialised surgical equipment and the cost of any consumables. These costs were then adjusted for the lifetime of the equipment and by the number of cases performed per year to obtain a cost for each procedure. This cost did vary with the number of procedures performed in each centre per year, principally because the contribution of capital equipment costs was different.

The specific costs to the NHS in terms of specialised equipment were obtained from individual NHS units carrying out the procedures, including hospitals in Aberdeen, Cambridge and Newcastle upon Tyne, UK. The list of reusable equipment and consumables used during a laparoscopic radical prostatectomy came from the Newcastle upon Tyne Hospitals NHS Foundation Trust (Maggie Birkbeck, Urology Theatre Manager, personal communication, June 2010). UK costs for the robotic system and ancillary devices or instruments were obtained from the manufacturer of the da Vinci system, Intuitive Surgical.30 For the robotic system we chose to use for the base-case analysis the capital and maintenance costs of the most expensive system available (a four-arm manipulator and two consoles) but also performed sensitivity analyses using the least costly system available. For both procedures the process of calculating costs involved summing the following costs per procedure: unit cost + service contract cost (for robotic procedure only) + specialised equipment cost + consumables cost.

For the robotic system, as an alternative to outright purchase, various permutations of payment and leasing plans were considered, such as payments spread over differing number of years, paid either in advance or in arrears. The cost per procedure varied markedly between these payment options; it also varied by the anticipated throughput of patients per annum. The cost per procedure according to number of procedures performed per year using the equipment purchase plan defined for the base-case analysis is shown in Table 30. These costs are based on the use of the most expensive system option consisting of a four-arm manipulator and two consoles and are calculated on the basis of different throughputs, with 200 cases per year representing a maximum number and 50 cases per year representing the throughput of one of the smaller UK centres. These costs represent the higher range of expected costs of equipment and in sensitivity analysis we explore the impact of using less expensive system options. The costs of laparoscopic equipment were similarly estimated. For laparoscopic equipment we have assumed that reusable equipment was reused 200 times per year. The cost per procedure of laparoscopic equipment was £94.48. Appendices 12 and 13 describe the equipment costs in detail for both robotic and laparoscopic surgery.

TABLE 30. Cost per procedure of equipment used for robotic prostatectomy: procurement cost based on purchase plan 1 (base case).

TABLE 30

Cost per procedure of equipment used for robotic prostatectomy: procurement cost based on purchase plan 1 (base case).

Costs associated with perioperative adverse events

As described in Model health states and associated parameter values, Perioperative state, perioperative adverse events were categorised using the Clavien–Dindo classification. For each Clavien level a judgement was made by the project team and expert panel about the implications for further care of a particular adverse event occurring (Table 31). This extra care was categorised in terms of the extra length of stay that an individual would undergo, which was combined with information on the cost of an additional day in hospital186 to obtain a cost of each adverse event. A similar process was followed for the cost of conversion to open surgery.

TABLE 31. Additional costs for individuals who suffered perioperative adverse events, including conversion to open surgery.

TABLE 31

Additional costs for individuals who suffered perioperative adverse events, including conversion to open surgery.

Costs associated with postoperative care

Surveillance

The cost of a single PSA test at £5.91 was obtained from the Newcastle upon Tyne Hospitals NHS Foundation Trust laboratory services directorate and applied throughout the period of surveillance according to the defined follow-up schedule (Table 32).

TABLE 32. Cost of PSA testing during surveillance schedule for individuals in the model.

TABLE 32

Cost of PSA testing during surveillance schedule for individuals in the model.

The costs of further cancer treatment were derived from the tariff applied to the relevant HRG code186 in the case of radiotherapy and from the British National Formulary185 in the case of drug treatments. The one-off cost used for radiotherapy was calculated on the basis of 33 treatments at £135 = £4455. The cost of androgen deprivation therapy was based on an initial 14-day course of cyproterone acetate at £63.08 followed by a monthly cost for the LHRH agonist goserelin acetate (Zoladex®, Astra Zeneca) of £403.80, which was continued for the specified duration of treatment (6 months for localised recurrent cancer and lifelong for systemic recurrent cancer) (Table 33).

TABLE 33. Cost of cancer treatment.

TABLE 33

Cost of cancer treatment.

The costs of treatment of adverse events beyond the perioperative period were again derived from the relevant NHS tariff through the HRG code186 or from the British National Formulary185 or from a recent HTA-funded trial of conservative treatment for urinary incontinence after prostatectomy (men after prostate surgery trial, MAPS; C Glazener, Aberdeen University 2011, personal communication; Table 34).77 We did not apply costs related to outpatient visits for follow-up or GP visits for associated care. Patient costs and societal costs were also not included.

TABLE 34. Costs associated with longer-term postoperative adverse events following laparoscopic and robotic prostatectomy.

TABLE 34

Costs associated with longer-term postoperative adverse events following laparoscopic and robotic prostatectomy.

Utilities

A utility value was assigned to each individual in each 3-month time step over the 10-year or lifetime horizon. The utility value encompassed the cancer management state (surveillance, biochemical recurrence, localised cancer, systemic cancer) and the longer-term adverse event state (bladder neck contracture, urinary incontinence and erectile dysfunction) (Table 35). Individuals present in more than one state during any 3-month step – localised recurrence and urinary incontinence, for example – were assigned a utility value equal to the product of the utility values applying to each of the states.

TABLE 35. Utility values and their distributions used in the model.

TABLE 35

Utility values and their distributions used in the model.

Data analysis

The model compared effectiveness and cost-effectiveness [defined as incremental cost per quality-adjusted life-year (QALY)] for robotic compared with laparoscopic radical prostatectomy. The timing and nature of each event was recorded, allowing the construction of individual trajectories through the care pathways. When processes incurred costs, these were added to the total costs accrued for that patient in that year. When processes led to a change in utility then the value of that new utility was multiplied by the current QALYs for that patient in that year. Estimates of the mean costs, QALYs and incremental cost per QALY were obtained by simulating the outcomes for a group of 5000 men for each treatment. In the base-case analysis the time horizon has been taken to be 10 years. Both costs and QALYs are discounted at 3.5%.197

Variations around the estimates of mean costs and QALYs were obtained by producing 1000 bootstrap estimates for mean costs and QALYs for each treatment. These data were then used to produce cost-effectiveness acceptability curves (CEACs). In the base-case analysis CEACs have been used to illustrate the imprecision surrounding the results caused by the variation in care and events experienced by the men modelled. These curves illustrate the likelihood that a strategy is cost-effective at various threshold values for society's willingness to pay for an additional QALY. The CEACs are the product of a probabilistic analysis. In this analysis we have assumed that each of the parameters is associated with a degree of imprecision, as described in each of the data input tables, characterised by a triangular distribution. This distribution was chosen as the data available to inform an alternative distributional form were sparse.

Sensitivity analyses

Extension of the time horizon to 40 years

In this sensitivity analysis we explored the impact of extending the time horizon. Conceptually this should allow more time for any benefits of robotic surgery to offset the increased procedure costs.

Changes in the costs of robotic equipment

Robotic equipment comes in several different variants and can be obtained from the manufacturers using several different payment plans. The precise cost of each of these variants may vary between provider and Appendix 12 provides illustrative examples of the cost variants. These costs have been converted into an annual cost, assuming the manufacturers' recommended lifespan of the equipment of 7 years, and a cost per procedure estimated. In this analysis we explore what the impact on the incremental cost per QALY is of using a lower cost for the robotic system. This analysis has been repeated for the different numbers of annual cases performed (from 50 per year to 200 per year). From these results it was possible to determine the effect on estimates of cost-effectiveness of varying the cost per procedure of robotic prostatectomy consequent to any particular payment plan or throughput.

Changes in the risk of having a positive margin

The estimates of positive margin rates following robotic and laparoscopic surgery were based on the point estimates derived from the systematic review. In this sensitivity analysis we explored the impact of using both the lower and the upper 95% CrI limits of the OR of the difference in positive margin rates between robotic and laparoscopic surgery (base-case OR 0.69; 95% CrI 0.506 to 0.955). The further cancer treatment matrices defined by using the lower and higher risks of having a positive margin following robotic surgery are shown in Tables 36 and 37, respectively. The probabilities for laparoscopic surgery remained the same as in the base case.

TABLE 36. Immediate further cancer treatment matrix for individuals following robotic prostatectomy according to findings on pathological examination of the removed prostate: lower limit of CrI for positive margin (OR = 0.506).

TABLE 36

Immediate further cancer treatment matrix for individuals following robotic prostatectomy according to findings on pathological examination of the removed prostate: lower limit of CrI for positive margin (OR = 0.506).

TABLE 37. Immediate further cancer treatment matrix for individuals following robotic prostatectomy according to findings on pathological examination of the removed prostate: higher limit of CrI for positive margin (OR =0.955).

TABLE 37

Immediate further cancer treatment matrix for individuals following robotic prostatectomy according to findings on pathological examination of the removed prostate: higher limit of CrI for positive margin (OR =0.955).

Combining change in costs per procedure and positive margin rates

In this analysis we explored the impact on the incremental cost per QALY of changes in both the cost per procedure and the risk of a positive margin. These data have been presented as plots of the incremental cost per QALY against the positive margin rate, defined in terms of an OR, for different numbers of procedures performed per year.

Changes in the risk of biochemical recurrence

In the base-case analysis it was assumed that the risk of biochemical recurrence was the same regardless of which procedure a man received. The rationale behind this assumption was that the meta-analysis reported in Chapter 4 provided no evidence of any difference; the CI surrounding the OR was wide and included 1. In the first sensitivity analysis concerning biochemical recurrence rates we assumed that on average robotic surgery was associated with a lower rate of biochemical recurrence. This lower rate was estimated by combining the long-term rates from Menon and colleagues181 with the point estimate of the OR for risk of biochemical recurrence at 12 months obtained from the systematic review (0.89). The CIs around the OR were not clinically plausible and therefore we assumed a triangular distribution with upper and lower limits for the 12-month risk of biochemical recurrence for robotic surgery set at ±2% (based on the finding of Menon and colleagues181; Table 38).

TABLE 38. Biochemical recurrence estimated using the OR from the systematic review multiplied by the rates found by Menon and colleagues to obtain a plausible difference between therapies.

TABLE 38

Biochemical recurrence estimated using the OR from the systematic review multiplied by the rates found by Menon and colleagues to obtain a plausible difference between therapies.

In a second sensitivity analysis around the risk of biochemical recurrence we explored the impact of there being a higher rate of biochemical recurrence. The rationale behind this analysis was that the rates reported by Menon and colleagues181 were approximately 50% of those predicted in the meta-analysis. Therefore, in this sensitivity analysis we have simply doubled the rates observed by Menon and colleagues181 (Table 39).

TABLE 39. Biochemical recurrence estimated by doubling the rates from Menon and colleagues and using an OR = 0.89 favouring robotic prostatectomy.

TABLE 39

Biochemical recurrence estimated by doubling the rates from Menon and colleagues and using an OR = 0.89 favouring robotic prostatectomy.

© 2012, Crown Copyright.

Included under terms of UK Non-commercial Government License.

Bookshelf ID: NBK115688

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