Papers

# Cost effectiveness analysis of intensive versus conventional follow up after curative resection for colorectal cancer

BMJ 2004; 328 (Published 09 January 2004) Cite this as: BMJ 2004;328:81
1. Andrew G Renehan, senior research fellow (arenehan{at}picr.man.ac.uk)1,
2. Sarah T Dwyer O', director1,
3. David K Whynes, professor2
1. 1Department of Surgery, Christie Hospital NHS Trust, Withington, Manchester M20 4BX
2. 2Department of Economics, University of Nottingham, Nottingham NG7 2RD
1. Correspondence to: A G Renehan
• Accepted 16 November 2003

## Abstract

Objective To determine the cost effectiveness of intensive follow up compared with conventional follow up in patients with colorectal cancer.

Design Incremental cost effectiveness analysis recognising differences in follow up strategies, based on effectiveness data from a meta-analysis of five randomised trials.

Setting United Kingdom.

Main outcome measures Taking a health service perspective, estimated incremental costs effectiveness ratios for each life year gained for five trials and four trials designed for early detection of extramural recurrences (targeted surveillance).

### Censoring and discounting

In the absence of individual patient data, we modelled the distribution of censored events (deaths) by constant numbers for each three month period. In practice, surveillance would generally be discontinued (censored) after recurrence, such that this model tends to overestimate surveillance costs. In the base case analysis, we discounted benefit effects at 1.5% and costs at 6.0%.27

### Sensitivity analyses

We undertook several sensitivity analyses to illustrate the impact of the principal aspects of uncertainty on the estimate of cost effectiveness. These included, separately and together, changes to discount rates as proposed by the US Panel on Cost Effectiveness in Health and Medicine,24 distributions of deaths (constant number, constant rate, and all deaths at end of five years), false positive test rates, and maximum surveillance and treatment costs.

Using the NHS cost acceptability of £30 000 as reference, we calculated the incremental increase in costs required to increase the incremental cost effectiveness ratio to the limit of NHS cost acceptability (incremental cost threshold) by simultaneous incremental increases in surveillance and treatment costs for both intensive and conventional follow up. We calculated the lowest level of effectiveness—absolute reduction in mortality—required to increase the incremental cost effectiveness ratio to the limit of NHS cost acceptability (threshold of effectiveness). The threshold of effectiveness was calculated by altering differences in benefit between follow up strategies by amounts equivalent to 1% change in mortality (see bmj.com).

## Results

### Cost effectiveness

The figure shows the Forest plot for all cause mortality with absolute reductions in mortality, together with the calculated life years lost and gained for each patient for each study and associated incremental cost effectiveness ratios. For the five trial model, the lost and gained calculations favoured intensive follow up by 0.73 life years gained for each patient, increasing to 0.82 life years gained for each patient for the four trial model, consistent with the observations from our previous meta-analysis.5 In the five trial model, the adjusted net (extra) cost for each patient was £2479 and for each life year gained was £3402, substantially lower than the current NHS threshold of cost acceptability. The corresponding values for the four trial model were £2529 and £3077, suggesting that targeted surveillance is more cost effective.

Forest plot of randomised trials. Pooled analysis with summary estimates (Mantel-Haenszel fixed effects method) are for all cause mortality (adapted from Renehan et al 20025). Data are categorised into extramural and intramural detection groups. Positive difference indicates time gained (improved survival). See bmj.com for calculation of estimates. Incremental cost effectiveness ratio=[costs for each patient for intensive follow up minus control follow up]/[discounted life years either gained or lost]

Changes in benefit and discount rates and in false positive test rates made little impact on the incremental cost effectiveness ratios in both models (data for four trial model not shown; table 2). Changing the distributions of deaths yielded similar incremental cost effectiveness ratios, suggesting that the assumptions within the primary models were robust. Worst case scenario analyses showed that substituting with maximum surveillance costs produced greater increases in incremental cost effectiveness ratios compared with substituting with maximum treatment costs, indicating that surveillance cost is the most important determinant of cost effectiveness. All incremental cost effectiveness ratios for maximum cost estimates fell within the NHS cost acceptability threshold. The incremental cost threshold was near ninefold for both the five trial (£30 620) and four trial (£27 695) models. For both models the threshold of cost effectiveness was an absolute reduction in mortality of 3%.

Table 2

Sensitivity analyses

View this table:

## Discussion

Intensive follow up after curative resection for colorectal cancer improves all cause mortality at five years and has a cost effectiveness ratio well within the NHS acceptability of willingness to pay for each life year gained. This economic analysis, based on effectiveness data from a previous meta-analysis, provides firm estimates of the cost of intensive follow up. The data also show that targeted follow up improves cost effectiveness.

### Strengths compared with other studies

Previous studies have examined economic issues related to follow up after treatment for colorectal cancer,2833 but predated the effectiveness data provided by the two recently published meta-analyses.5 6 The present analysis is strengthened by the inclusion of a comprehensive search to include many aspects of cost estimates (a “bottom-up” approach) and sensitivity analyses at several levels. Further strengths were the robustness of the results: adjustments to maximise costs yielded incremental cost effectiveness ratios well within the threshold for NHS cost acceptability, the incremental cost threshold was high (ninefold increases), and the thresholds of effectiveness were 3% for both models.

Our study emphasises a further aspect, that around equal proportions (one third) of patients with colorectal cancer develop recurrences, irrespective of follow up strategy. After detection of recurrence, palliative therapy (more common in control patients) is not without expense and partially offsets the costs of salvage therapy (more common in patients intensively followed).

### Study limitations

The first limitation of our study was the clinical heterogeneity of follow up regimens among the five trials.5 No study directly compared specific tests, and therefore it was not possible to evaluate the cost effectiveness of specific surveillance tools. A second limitation was the lack of quality of life data for follow up of patients with colorectal cancer, although one study has assigned a quality adjusted life year of 0.83 based on data from a chemotherapy trial.29 As intensive follow up does not significantly raise patient anxieties, this may prove a reasonable estimate, but further studies are required before these values can be incorporated into health economic calculations.34 The third limitation was the absence of individual patient data, such that we had to make assumptions about survival and recurrence patterns. These assumptions, however, held firm, as shown by the sensitivity analysis. The fourth limitation was that the included trials were conducted over a decade ago, and thus did not include aspects of contemporary practice (for example, multidisciplinary management) that could impact on costs or effectiveness. The final limitation is that we were unable to compare intensive follow up with absolute no follow up (zero surveillance costs), although in modern practice the acceptability of a no follow up strategy is questionable.35

### Implications for health policy

The strategy of intensive follow up after curative resection for colorectal cancer is economically justified and should be normal practice. As a screening type health strategy, intensive follow up of patients with colorectal cancer compares favourably with screening for breast and colorectal cancers and for abdominal aortic aneurysms.18 36 37 Moreover, compared with population screening, these patients are self defined, well motivated, and compliant.38

### Factors that could affect future results

Large randomised trials are needed to evaluate the efficacy of specific surveillance tools.5 35 These studies must include cost effectiveness analyses and quality of life assessments, in addition to other issues that were beyond the scope of our analysis. Firstly, costs beyond five years after initial treatment need to be considered as a proportion of patients with recurrences undergoing salvage therapy will have delayed second recurrences. Secondly, the included trials predated the widespread use of chemotherapy for advanced colorectal cancer or as an adjunct to salvage reoperation, approaches that may improve survival.39 This potential improvement in effectiveness will be coupled with increased costs. However, as maximising treatments costs (without changes in surveillance costs) had only minor effects on incremental cost effectiveness ratios, it is tempting to speculate that chemotherapy, expensive when considered in selected groups, may be cost effective in the wider context.39 Thirdly, our analysis treated local, hepatic, and other site recurrences as mutually exclusive events. In practice there is overlap, which will tend to attenuate costs. Fourthly, we did not address societal perspectives, such as travel and time off work, which are important determinants of compliance in screening for colorectal cancer and may thus be relevant in cancer surveillance.40 Fifthly, it was not possible to estimate capital costs for additional laboratory and clinical capacity. Finally, we did not consider the benefits of intensive follow up from factors other than salvage for recurrent disease—for example, psychosocial or improved treatment of coincidental disease. Evidence from our meta-analysis shows that some reductions in all cause mortality associated with intensive follow up are attributable to factors other than salvage therapy (unpublished data).5

#### What is already known on this topic

Intensive follow up after curative resection for colorectal cancer improves survival (absolute effects 7-9%)

The cost effectiveness of intensive surveillance is uncertain

The number of years gained through intensive surveillance over five years is 0.73 to 0.82 for each patient

The adjusted net cost for each patient was £2479 and for each life year gained was £3402, substantially lower than the NHS threshold of cost acceptability (£30 000)

Corresponding values for four trials using targeted surveillance were £2529 and £3077, suggesting that this approach may be more expensive but improves cost effectiveness

## Acknowledgments

Additional information and a file for calculation of estimates are on bmj.com

## Footnotes

• Contributors AGR and STO'D initiated the design of the study. AGR and DKW undertook the economic analyses. All authors contributed to the writing of the final draft of the manuscript. STO'D will act as guarantor for the paper.

• Funding None.

• Competing interests None declared.

• Ethical approval Not required.

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