Clinical Question (in PICO format if possible)Requires analysis?fComment and explanation
1TOPIC A: What is the most effective initial diagnostic intervention(s) in patients with suspected colorectal cancer to establish a diagnosis?4. Medium priority for analysisA cursory search of the economic literature did not identify any existing published economic studies that include all interventions and comparators of interest (flexible sigmoidoscopy + barium enema, CT colonography, flexible sigmoidoscopy + colonoscopy compared to colonoscopy + biopsy). The feasibility of undertaking a cost-effectiveness modelling exercise for this topic would be contingent upon (i) agreeing a model structure that appropriately takes into account downstream events beyond test accuracy (ii) identifying appropriate data sources that can be synthesised to estimate both costs and effects associated with these downstream events. Prior to the 2nd GDG meeting, it was highlighted that results of a prospective trial conducted in the UK (SIGGAR1) are anticipated to report in 2010. This study was designed to compare colonography vs barium enema and CT colonography vs colonoscopy. The protocol for the SIGGAR1 study includes collection of data on subsequent tests and healthcare resource use as well as a planned cost-utility analysis. Given the overlap in timing and objectives of the planned economic analysis that is part of the SIGGAR1 study with any potential modelling efforts for this topic within the guideline, it was felt that resources for economic modelling should be directed towards other higher priority topics (agreed at 3rd GDG meeting).
2TOPIC B: For patients with primary colorectal cancer, what is the most effective technique(s) in order to accurately stage the disease (excluding pathology)?5. Low priority for analysisThe focus of this question is on accuracy of staging and the interventions under consideration include CT, PET-CT, MRI, endoanal ultrasound and digital rectal examination. An economic analysis of this topic should take into account downstream consequences of staging accuracy. An initial review of the clinical evidence identified mostly low quality case studies with a large degree of variation between studies in terms of interventions, outcomes reported and inclusion/exclusion criteria. No studies reported on reclassification. This topic was considered a lower priority for economic modelling partly due to the complexity that would be involved in downstream decisions that could vary according to the different diagnostic interventions of interest (i.e. different interventions may provide different kinds of information to inform treatment decisions) and partly due to the poor quality of available data to inform an economic analysis.
3TOPIC C: For patients diagnosed with stage I colorectal cancer, including/or polyp cancer, what are the prognostic factors for determining the most effective curative treatment?1. Not relevantThe focus of this question is on prognostic factors to determine treatment rather than a comparative analysis of effectiveness, therefore economic modelling is unlikely to help inform this topic.
4TOPIC D: For patients presenting with acute large bowel obstruction as a first presentation of colorectal cancer, what is the optimal course of treatment? a) should all patients presenting with obstruction as a symptom of colorectal cancer have a CT scan to confirm diagnosis to provide evidence of metastases? b) what are the indications for stenting patients and what is the optimal timing for this to occur?5. Low priority for analysisFor part a) high quality data on the many possible downstream outcomes of a CT scan in this setting and patient population is unlikely to be available and/or if available, are likely to extend beyond the issue of primary interest to this PICO (metastases). If appropriate, the budget impact of this could be assessed through a costing exercise based on the recommendation(s) at the end of the guideline process. Part b) focuses on clinical indications and timing of stenting. This does not involve a comparison of costs and consequences and therefore does not lend itself to economic modelling.
5TOPIC E: For patients presenting with a) non-metastatic locally advanced colon cancer, is pre-operative chemotherapy followed by surgery more effective than immediate surgery and for patients presenting with b) locally advanced rectal cancer is pre-operative radiotherapy, pre-operative chemotherapy or pre-operative chemoradiotherapy more effective than immediate surgery?5. Low priority for analysisThe search for clinical evidence will focus on identifying trials that specifically address the issue of sequencing/combinations of treatment modalities. A priori identification of treatment combinations or specific regimens is not planned. It is anticipated that the evidence base may be clinically heterogeneous. This would limit the appropriateness of combining or comparing data across studies using quantitative methods and therefore impact the feasibility of undertaking de novo economic modelling that would help inform this topic in a comprehensive and meaningful manner.
6TOPIC F: In patients with colorectal cancer presenting with overt synchronous metastatic disease, what is the effectiveness of treating metastatic disease before, after or at the same time as treating the primary tumour?5. Low priority for analysisSimilar to Topic E, the search for clinical evidence will focus on identifying trials that specifically address the issue of sequencing of treatment. It is anticipated that the evidence base may be clinically heterogeneous. This would limit the appropriateness of combining or comparing data across studies using quantitative methods and therefore impact the feasibility of undertaking de novo economic modelling that would help inform this topic. In addition, differences in resource implications and expected health gains across different sequences under comparision are expected to be modest.
7TOPIC G: For patients with operable rectal cancer, what is the effectiveness of pre-operative short course radiotherapy or chemoradiotherapy?4. Medium priority for analysisThe addition of radiotherapy or chemoradiotherapy prior to surgery for rectal cancer may reduce occurrence of second malignancies or improve survival, but may be associated with additional morbidity and cost. This is a possible topic for economic analysis, but the size of the population of patients eligible for pre-operative interventions for rectal cancer is small compared to other topics in the guideline and is considered a lower priority for economic modelling.
8TOPIC H: In patients with clinical or pathological stage II and III rectal cancer, what is the effectiveness of adjuvant chemotherapy following surgery?4. Medium priority for analysisThe patient population for this topic has been divided into three subgroups (i) those who have had primary surgery (ii) those who have had short-course radiotherapy prior to surgery and (iii) those who have had chemoradiotherapy prior to surgery. The feasibility of conducting an economic analysis depends on the availability of clinical data relevant to each of the subgroups. However, this topic is considered lower priority than other topics (e.g. Topic I) because the estimated impact in terms of the size of the target patient population and the level of uncertainty/controversy regarding current practice are considered to be lower.
9TOPIC I: In patients with high-risk stage II colon cancer, what is the effectiveness of adjuvant chemotherapy after surgery?3. High priority for analysisThe clinical and cost effectiveness of adjvuant chemotherapy in Stage III colon cancer has been previously demonstrated, however controversy remains about the benefit of adjuvant chemotherapy in high-risk Stage II patients. This topic was therefore considered a high priority for cost-effectiveness modelling. However, the initial search of the clinical literature revealed that there is a paucity of effectiveness data on adjuvant chemotherapy in the patient population of interest. There is no consistent definition of high-risk patients in the literature and outcomes are generally not reported separately for this specific patient population. In the absence of reliable data to inform the effectiveness parameters in the cost effectiveness model, a decision was reached at the 4th GDG meeting to stop further development of the economic analysis for this topic.
10TOPIC J: What is the most effective additional treatment to systemic chemotherapy to achieve cure or long term survival in patients with apparently unresectable metastatic disease?4. Medium priority for analysisThe interventions/comparators that have been identified for this topic include treatment modalities (ablation, surgery, regional therapy, systemic therapy, best supportive care) or combinations of treatment modalities rather than specific interventions. If sufficient high quality data comparing specific treatments or treatment sequences is available, economic modelling could be considered, but it was considered unlikely that direct evidence will exist to inform all comparators of interest.
11TOPIC K: In a patient with colorectal cancer metastasised to the liver, which imaging modality(s) most accurately determines the number and extent of metastases pre-operatively?3. High priority for analysisThe focus of this question is on the use of imaging modalities (CT, PET-CT, MRI or ultrasound) for the detection of liver metastases to inform a decision about resectability. An economic analysis of this topic should take into account not only accuracy of the imaging modality in detecting metastases, but also downstream consequences on treatment decisions and patient outcomes. An initial search of the clinical literature revealed that most of the relevant studies identified do not report information on resectability or change in patient management in relation to the information obtained by the imaging test. As the decision to resect is based on a number of different considerations, there is insufficient information to model the link between the imaging results and the treatment decision Therefore the feasibility of conducting a comprehensive cost-effectiveness analysis based on currently available data is limited. These limitations were discussed with the GDG and at the 7th GDG meeting, agreement was reached not to continue development of the economic model for this topic.
12TOPIC L: In a patient with colorectal cancer and extrahepatic metastases (e.g. lung, brain, peritoneum), which imaging modality most accurately determines the extent of metastases?5. Low priority for analysisThe focus of this question is on the use of imaging modalities for the detection of extrahepatic metastases. An economic analysis of this topic should take into account not only accuracy of the imaging modality in detecting metastases, but any downstream consequences on treatment decisions and patient outcomes. The delineation of patient pathways in this context is complicated by the fact that different imaging modalities may provide different types of information beyond just presence or absence of metastases (including location, size etc) and that patients may also have multiple sites of metastases that will impact treatment options and may require consideration of treatment decisions that fall outside the scope and focus of the current guideline (e.g.specific issues related to management of brain metastases). The feasibility of modelling this topic within the time and resources available is limited, therefore this topic is considered a low priority.
13TOPIC M: What is the effectiveness of chemotherapy for patients with advanced and metastatic colorectal cancer?3. High priority for analysisUpdate of TA93 (irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer). Further details provided in Section 3.2.
14TOPIC N: In asymptomatic patients who have undergone treatment with curative intent for colorectal cancer, what is the optimal method(s), frequency and duration of follow-up?2. In literatureA cursory search of the literature suggests there are a number of published economic studies that may address this topic. De novo economic modelling is unlikely to add to existing evidence if high quality data on costs and effectiveness of alternate follow-up strategies is not readily available. Therefore a systematic review of the economic literature will be undertaken to inform for this topic.
15TOPIC O: What colorectal specific support should be offered to patients diagnosed with colorectal cancer?1. Not relevantThis topic is unlikely to lend itself to economic evalaution (not comparative analysis of cost and outcomes).
f

  1. Not relevant’: questions where economic analysis is not appropriate (e.g. about definitions, prognosis or information needs for patient);
  2. In literature’: questions where high-quality, recent and relevant economic evaluations are already available;
  3. High priority for analysis’: questions where an economic analysis is planned (important implications and analysis is thought to be feasible);
  4. Medium priority for analysis’ questions where an economic analysis may be done (less important implications or questions over feasibility);
  5. Low priority for analysis’: questions where economic analysis could be done, but the expected impact on outcomes and NHS resources is low.

From: Appendix 2, Economic Plan

Cover of Colorectal Cancer
Colorectal Cancer: The Diagnosis and Management of Colorectal Cancer.
NICE Clinical Guidelines, No. 131.
National Collaborating Centre for Cancer (UK).
Copyright © 2011, National Collaborating Centre for Cancer.

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