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Value-of-Information Analysis to Guide Future Research in Colorectal Cancer Screening 1
Abstract
To identify the most useful areas for research in colorectal cancer (CRC) screening by using a value-of-information analysis.
Cost-effectiveness of screening strategies, including colonoscopy, computed tomographic (CT) colonography, flexible sigmoidoscopy, and barium enema examination, were compared by using a Markov model. Monetary net benefit (NB), a measure of cost-effectiveness, was calculated by multiplying effect (life-years gained) by willingness to pay (100,000 dollars per life-year gained) and subtracting cost. A value-of-information analysis was used to estimate the expected benefit of future research that would eliminate the decision uncertainty.
In the reference-case analysis, colonoscopy was the optimal test with the highest NB (1945 dollars per subject invited for screening compared with 1862 dollars, 1717 dollars, and 1653 dollars for CT colonography, flexible sigmoidoscopy, and barium enema examination, respectively). Results of probabilistic sensitivity analysis indicated that colonoscopy was the optimal choice in only 45% of the simulated scenarios, whereas CT colonography, flexible sigmoidoscopy, and barium enema examination were the optimal strategies in 23%, 16%, and 15% of the scenarios, respectively. Only two parameters were responsible for most of this uncertainty about the optimal test for CRC screening: the increase in adherence with less invasive tests and CRC natural history. The expected societal monetary benefit of further research in these areas was estimated to be more than 15 billion dollars.
Results of value-of-information analysis show that future research on the optimal test for CRC screening has a large societal impact. Priority should be given to research on the increase in adherence with screening by using less invasive tests and to better understanding of the natural history of CRC.
... Each data element abstracted from each of the included studies can be found in Tables 1 and 2. 9-26 Table 1 lists the perspective taken, models used, strategies evaluated, and basic results for each study. [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] If a study used more than 1 model, then an additional entry was made in Table 1 for the given study. Table 2 provides further details, particularly on the sensitivity and specificity rates, costs for tests, and the types of sensitivity analyses performed. ...
... Table 2 provides further details, particularly on the sensitivity and specificity rates, costs for tests, and the types of sensitivity analyses performed. [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] This review includes 13 studies not included in the review published in 2011 by Lansdorp-Vogelaar et al. 7 ...
Several screening tests are available to detect colorectal cancer (CRC) and reduce the incidence and mortality of CRC. The purpose of this review was to determine how current CRC screening strategies for CRC compare with no screening and whether agreement exists with regard to the cost effectiveness of different strategies.
Databases were searched for cost-effectiveness analyses focused on CRC screening strategies in the United States and published between May 2007 and February 2014. We analyzed the uses of fecal occult blood, fecal immunochemistry, and stool DNA tests, as well as sigmoidoscopy, colonoscopy, and virtual colonoscopy. A paired comparison of each screening strategy with no screening across each of the studies reviewed was conducted. A series of paired comparisons of the results reported in each of the studies is also included.
When compared with no screening, all CRC screening strategies evaluated in this review were cost effective. There was disagreement as to which screening strategy was the most cost effective. However, sigmoidoscopy combined with fecal blood testing always dominated either strategy alone. Studies comparing colonoscopy with fecal blood testing, sigmoidoscopy, or both had mixed results.
Compared with no screening, all CRC screening strategies are more cost effective. Study results disagree as to which screening strategy should be the preferred method.
... Detected polyps were grouped into a single state or two or three depending on number and size of polyps found at baseline COL [30,42,65,76]. Modelled disease states of CRC were mainly local, regional or distant (disseminated) (CRC or Dukes' stages A to D). ...
... In the absence of sensitivity and specificity data for new technologies test performance similar to existing tests was assumed [49]. Quality of life relating to CRC was repeatedly taken from a single study [76] for over a decade [26,45,65,75]. More recently, EQ-5D values of cancer-free and cancer states have been estimated from a national survey [70]. ...
This paper aims to systematically review the cost-effectiveness evidence, and to provide a critical appraisal of the methods used in the model-based economic evaluation of CRC screening and subsequent surveillance. A search strategy was developed to capture relevant evidence published 1999-November 2012. Databases searched were MEDLINE, EMBASE, National Health Service Economic Evaluation (NHS EED), EconLit, and HTA. Full economic evaluations that considered costs and health outcomes of relevant intervention were included. Sixty-eight studies which used either cohort simulation or individual-level simulation were included. Follow-up strategies were mostly embedded in the screening model. Approximately 195 comparisons were made across different modalities; however, strategies modelled were often simplified due to insufficient evidence and comparators chosen insufficiently reflected current practice/recommendations. Studies used up-to-date evidence on the diagnostic test performance combined with outdated information on CRC treatments. Quality of life relating to follow-up surveillance is rare. Quality of life relating to CRC disease states was largely taken from a single study. Some studies omitted to say how identified adenomas or CRC were managed. Besides deterministic sensitivity analysis, probabilistic sensitivity analysis (PSA) was undertaken in some studies, but the distributions used for PSA were rarely reported or justified. The cost-effectiveness of follow-up strategies among people with confirmed adenomas are warranted in aiding evidence-informed decision making in response to the rapidly evolving technologies and rising expectations.
... We used decision-theoretic methods to design and prioritize future research to efficiently improve decision making and develop best practices with respect to TP53-NBS. These methods have been acknowledged by several authorities (44)(45)(46)(47) and previously used to determine the focus and design of research (36,(48)(49)(50)(51)(52)(53). ...
Background
Identification of children and infants with Li-Fraumeni syndrome (LFS) prompts tumor surveillance and allows potential early cancer detection. We assessed the clinical benefits and cost-effectiveness of population-wide newborn screening for TP53 variants (TP53-NBS).
Methods
We simulated the impact of TP53-NBS using data regarding TP53-associated pediatric cancers and pathogenic or likely pathogenic (P/LP) TP53 variants from SEER, ClinVar and gnomAD and clinical studies. We simulated an annual US birth cohort under usual care and TP53-NBS and estimated clinical benefits, life years and costs associated with usual care and TP53-NBS.
Results
Under usual care, out of 4 million newborns, 608 individuals (Uncertainty Interval [UI] = 581–636) would develop TP53-associated cancers before age 20 years. Under TP53-NBS, 894 individuals would have P/LP TP53 variants detected. These individuals would undergo routine surveillance after detection of P/LP TP53 variants decreasing the number of cancer-related deaths by 7.2% overall (UI = 4.0–12.1%) via early malignancy detection. Compared to usual care, TP53-NBS had an incremental cost-effectiveness ratio of 100,000 per-life-year-gained willingness-to-pay threshold. Using this threshold, a value-of-information analysis found that additional research on the prevalence of TP53 variants among rhabdomyosarcoma cases would resolve most of the decision uncertainty, resulting in an expected benefit of 349 life-years gained (or $36.6 million).
Conclusions
While we found that TP53-NBS could be cost-effective, our findings suggest that further research is needed to reduce the uncertainty in the potential health outcomes and costs associated with TP53-NBS.
... Sensitivity analyses in Knudsen et al 2010 [33] demonstrated that the optimal CRC screening modality can change when adherence is varied. Adherence to less-invasive tests appears to be an important, yet under-appreciated, factor when assessing the relative cost-effectiveness of CRC screening [40]. ...
Background
Real-world adherence to colorectal cancer (CRC) screening strategies is imperfect. The CRC-AIM microsimulation model was used to estimate the impact of imperfect adherence on the relative benefits and burdens of guideline-endorsed, stool-based screening strategies.
Methods
Predicted outcomes of multi-target stool DNA (mt-sDNA), fecal immunochemical tests (FIT), and high-sensitivity guaiac-based fecal occult blood tests (HSgFOBT) were simulated for 40-year-olds free of diagnosed CRC. For robustness, imperfect adherence was incorporated in multiple ways and with extensive sensitivity analysis. Analysis 1 assumed adherence from 0%-100%, in 10% increments. Analysis 2 longitudinally applied real-world first-round differential adherence rates (base-case imperfect rates = 40% annual FIT vs 34% annual HSgFOBT vs 70% triennial mt-sDNA). Analysis 3 randomly assigned individuals to receive 1, 5, or 9 lifetime (9 = 100% adherence) mt-sDNA tests and 1, 5, or 9 to 26 (26 = 100% adherence) FIT tests. Outcomes are reported per 1000 individuals compared with no screening.
Results
Each screening strategy decreased CRC incidence and mortality versus no screening. In individuals screened between ages 50–75 and adherence ranging from 10%a-100%, the life-years gained (LYG) for triennial mt-sDNA ranged from 133.1–300.0, for annual FIT from 96.3–318.1, and for annual HSgFOBT from 99.8–320.6. At base-case imperfect adherence rates, mt-sDNA resulted in 19.1% more LYG versus FIT, 25.4% more LYG versus HSgFOBT, and generally had preferable efficiency ratios while offering the most LYG. Completion of at least 21 FIT tests is needed to reach approximately the same LYG achieved with 9 mt-sDNA tests.
Conclusions
Adherence assumptions affect the conclusions of CRC screening microsimulations that are used to inform CRC screening guidelines. LYG from FIT and HSgFOBT are more sensitive to changes in adherence assumptions than mt-sDNA because they require more tests be completed for equivalent benefit. At imperfect adherence rates, mt-sDNA provides more LYG than FIT or HSgFOBT at an acceptable tradeoff in screening burden.
... Identification of efficient research design, conditional coverage, and early development [12][13][14] Value of individualized care and precision medicine 15,16 Value of regulatory trials from the perspective of the pharmaceutical industry 17 Informing decisions about public and mental health interventions 18,19 Value of a sequence of trial designs, optimizing the order and respective sample sizes 20,21 Value of promoting uptake of an evidence-based technology 22 Value of managed entry agreements 23,24 Value of biomarker collection in clinical practice 25 Value of subgroup information and value of identifying subgroups 15,16,[26][27][28] Outcomes-based contracting for risk-averse manufacturers 29 Portfolio balance-risk over multiple projects 30,31 Prioritizing the update of systematic literature reviews 32 Alternative designs for research studies and program of studies (eg, Bayesian Clinical Trial Simulation of phase II and III programs) 33 Thorn et al 34 reduced uncertainty and the expected value of the decision based on the current evidence. Expected net benefit of sampling (ENBS) quantifies the net payoff for a given research study with a specific sample size and particular design (ie, the difference between the EVSI and the expected total cost of the study). ...
Healthcare resource allocation decisions made under conditions of uncertainty may turn out to be suboptimal. In a resource constrained system in which there is a fixed budget, these suboptimal decisions will result in health loss. Consequently, there may be value in reducing uncertainty, through the collection of new evidence, to make better resource allocation decisions. This value can be quantified using a value of information (VOI) analysis. This report, from the ISPOR VOI Task Force, introduces VOI analysis, defines key concepts and terminology, and outlines the role of VOI for supporting decision making, including the steps involved in undertaking and interpreting VOI analyses. The report is specifically aimed at those tasked with making decisions about the adoption of healthcare or the funding of healthcare research. The report provides a number of recommendations for good practice when planning, undertaking, or reviewing the results of VOI analyses.
... More recently, value of information analyses (VOI) of screening interventions have been undertaken using the currently available evidence, prior to a large trial being undertaken, aiming at determining the value of investing future funds into further research [1]. Indeed, VOI has been used to examine uncertainty surrounding the optimal screening strategy for colorectal cancer and therefore prioritise future research efforts [2]. ...
Background:
Screening for renal cell carcinoma (RCC) has been identified as a key research priority; however, no randomised control trials have been performed. Value of information analysis can determine whether further research on this topic is of value.
Objective:
To determine (1) whether current evidence suggests that screening is potentially cost effective and, if so, (2) in which age/sex groups, (3) identify evidence gaps, and (4) estimate the value of further research to close those gaps.
Design, setting, and participants:
A decision model was developed evaluating screening in asymptomatic individuals in the UK. A National Health Service perspective was adopted.
Intervention:
A single focused renal ultrasound scan compared with standard of care (no screening).
Outcome measurements and statistical analysis:
Expected lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER), discounted at 3.5% per annum.
Results and limitations:
Given a prevalence of RCC of 0.34% (0.18-0.54%), screening 60-yr-old men resulted in an ICER of £18 092/QALY (€22 843/QALY). Given a prevalence of RCC of 0.16% (0.08-0.25%), screening 60-yr-old women resulted in an ICER of £37327/QALY (€47 129/QALY). In the one-way sensitivity analysis, the ICER was <£30000/QALY as long as the prevalence of RCC was ≥0.25% for men and ≥0.2% for women at age 60yr. Given the willingness to pay a threshold of £30000/QALY (€37 878/QALY), the population-expected values of perfect information were £194 million (€244 million) and £97 million (€123 million) for 60-yr-old men and women, respectively. The expected value of perfect parameter information suggests that the prevalence of RCC and stage shift associated with screening are key research priorities.
Conclusions:
Current evidence suggests that one-off screening of 60-yr-old men is potentially cost effective and that further research into this topic would be of value to society.
Patient summary:
Economic modelling suggests that screening 60-yr-old men for kidney cancer using ultrasound may be a good use of resources and that further research on this topic should be performed.
... VOI analysis is a quantitative method that helps decision makers choose between an immediate decision based on the best available evidence and delaying that decision in anticipation of better information, sometime in the future [44][45][46]. VOI methods have been used previously to determine if further research is needed in different health problems [47][48][49], including chemotherapy decisions in early-stage breast cancer [50,51]. In the present analysis, we used VOI methods to quantify the value of three possible research studies to address uncertainties surrounding 21-gene assay-based chemotherapy recommendations. ...
Objectives
The 21-gene assay Oncotype DX (21-GA) shows promise as a guide in deciding when to initiate adjuvant chemotherapy in women with hormone receptor–positive early-stage breast cancer. Nevertheless, its routine use remains controversial, owing to insufficient evidence of its clinical utility and cost-effectiveness. Accordingly, we aim to quantify the value of conducting further research to reduce decision uncertainty in the use of the 21-GA.
Methods
Using value of information methods, we first generated probability distributions of survival and costs for decision making with and without the 21-GA alongside traditional risk prediction. These served as the input to a comparison of 3 alternative study designs: a retrospective observational study to update risk classification from the 21-GA, a prospective observational study to estimate prevalence of chemotherapy use, and a randomized controlled trial (RCT) of the 21-GA predictive value.
Results
We found that current evidence strongly supports the use of the 21-GA in intermediate- and high-risk women. Further research should focus on low-risk women, among whom the cost-effectiveness findings remained equivocal. For this population, we identified a high value of reducing uncertainty in the 21-GA use for all proposed research studies. The RCT had the greatest potential to efficiently reduce the likelihood of choosing a suboptimal strategy, providing a value between 1.1 billion at willingness-to-pay thresholds of 200 000/quality-adjusted life years.
Conclusion
Future research to inform 21-GA decision making is of high value. The RCT of the 21-GA predictive value has the greatest potential to efficiently reduce decision uncertainty around 21-GA use in women with low-risk early-stage breast cancer.
... Indeed, VOI has been used to examine uncertainty surrounding the optimal screening strategy for colorectal cancer and therefore prioritize future research efforts. 8 Cost-effectiveness analyses often require information that is either not yet known or not directly measurable through research. There has been a growing body of work regarding expert elicitation to derive information for health economic evaluation. ...
Background:
Population screening for renal cell carcinoma (RCC) using ultrasound has the potential to improve survival outcomes; however, a cost-effectiveness analysis (CEA) has yet to be performed. Owing to the lack of existing evidence, we performed structured expert elicitation to derive unknown quantities to inform the CEA.
Objective:
To elicit the cancer stage distribution (proportion of individuals with each stage of cancer) for different RCC screening scenarios and the annual transition probabilities for undiagnosed disease becoming diagnosed in the National Health Service.
Methods:
The study design and reporting adhered to the Reporting Guidelines for the Use of Expert Judgement in Model-Based Economic Evaluations. The elicitation was conducted face-to-face or via telephone between each individual expert and the facilitator, aided by online material. For multinomial data, Connor-Mosimann and modified Connor-Mosimann distributions were fitted for each expert and for all experts combined using mathematical linear pooling.
Results:
A total of 24 clinical experts were invited, and 71% participated (7 urologists, 6 oncologists, 4 radiologists). The modified Connor-Mosimann distribution provided the best fit for most elicited quantities. Greater uncertainty was noted for the elicited transition probabilities compared with the elicited stage distributions.
Conclusion:
We performed the first expert elicitation of RCC screening parameters, crucial information that will inform the CEA of screening. In addition, the elicited quantities may enable future health economic evaluations assessing the value of diagnostic tools and pathways in RCC.
... Colorectal cancer treatment has recently gained a particular significance due to an increase in the observed number of new cases and deaths related to this disease causing it to rise to fourth place in cancer specific mortality [1][2][3][4][5]. Over 50.000 deaths are expected in the USA in 2014 due to colorectal cancer which is the second prevalent cancer type in women and the third one in men [1,5].The five years survival rate of patients with colorectal cancer, which is generally observed in developed countries and thought to be due to Western dietary habits, is higher in women than men, while the incidence of cancer in women is lower when compared to men [5,6]. ...
Colorectal cancer is one of the most common health problems today, with increasing incidence worldwide; therefore the treatment of colorectal cancer is of great importance. Currently, there are several treatment options such as surgery, chemotherapy and radiotherapy for the patients with colorectal cancer diagnosis; and while making a decision regarding the most appropriate treatment for the patient, different combinations of these options might be selected with regard to the status of that particular patient. In this study, which aims to determine the most appropriate method for the treatment of rectum cancer, sequential decision tree structure was used for determining treatment method taking different criteria into consideration. Therefore, we selected Analytic Hierarchy Process (AHP) method for determining the priorities of the criteria, while constructing the sequential decision tree which, used for the decision process regarding the treatment of colorectal cancer. Criteria used in two decision steps in the decision making process were determined and their priorities over each other were achieved by expert-decision via consulting to general surgeons. Data were analyzed with “Expert Choice” Software, developed specially for AHP; and inconsistency ratios were calculated for each set of judgments, respectively for the first decision step 0.08 and for the second, 0.06. For the first decision step, 0.310 was the highest priority for presence of perforation criteria; for the second step, 0.149 was the highest priority for stage of the disease criteria. The decision tree was constructed with these priorities at hand. For future studies, the decision algorithm developed in this study is planned to be supported by software, thus a clinical decision support system for treatment of rectum cancer patients would be created. If a comprehensive database be gathered in the future, both probabilistic results would be examined, and interpretations could be made for the corresponding patient.
... Al contrario, l'impiego della CV per la prevenzione del cancro del colon-retto nel soggetto asintomatico ed a rischio mediobasso (età > a 50 anni) è ancora dibattuto anche se da più colleghi è ormai usuale l'alternanza delle due metodiche CO/CV [44][45][46][47][48][49] . ...
Colorectal carcinoma is among the most common cancer in developed countries. Until the early 2000s double contrast barium enema was the only available tool for imaging of the colon. Recently the cutting edge of technology has developed an highly advanced diagnostic tool: CT virtual colonoscopy. A soft Bowel preparation is required before VC: a mild laxative for 3 days, oral good hydratation, light dietary restrictions the day before the examination, and administration of a small dose of oral contrast agent (50 ml) the day of the procedure. The procedure is performed with low-dose radiation technique. VC and Optical Colonoscopy (OC) are complementary not competing procedures.
... This method has been applied to health and economic problems (Yokota & Thompson 2004;Bratvold, Bickel & Lohne 2007). A typical example is the decision of whether to adopt widespread screening for certain types of cancer, trading off the benefits of increased screening levels and their economic costs and discomfort for patients (Hassan et al. 2009). The environmental management literature is increasingly exploring the concept of VoI (McDonald & Smith 1997;Mäntyniemi et al. 2009;Runge, Converse & Lyons 2011;Williams & Johnson 2014). ...
1.Applied ecologists continually advocate further research, under the assumption that obtaining more information will lead to better decisions. Value of information (VoI) analysis can be used to quantify how additional information may improve management outcomes: despite its potential, this method is still underused in environmental decision-making. We provide a primer on how to calculate the VoI and assess whether reducing uncertainty will change a decision. Our aim is to facilitate the application of VoI by managers who are not familiar with decision-analytic principles and notation, by increasing the technical accessibility of the tool.
2.Calculating the VoI requires explicit formulation of management objectives and actions. Uncertainty must be clearly structured and its effects on management outcomes evaluated. We present two measures of the VoI. The expected value of perfect information is a calculation of the expected improvement in management outcomes that would result from access to perfect knowledge. The expected value of sample information calculates the improvement in outcomes expected by collecting a given sample of new data.
3.We guide readers through the calculation of VoI using two case studies: (i) testing for disease when managing a frog species and (ii) learning about demographic rates for the reintroduction of an endangered turtle. We illustrate the use of Bayesian updating to incorporate new information.
4.The VoI depends on our current knowledge, the quality of the information collected, and the expected outcomes of the available management actions. Collecting information can require significant investments of resources: VoI analysis assists managers in deciding whether these investments are justified.
... The preponderance of studies originating from the UK is likely to have arisen as a result of national guidelines, with NICE having formally advocated the use of VoI methods in England and Wales in 2004. [33] As Eckermann et al [34] point out, in determining a threshold value of EVPI one needs to consider the costs of undertaking research, which, in turn, depends on the type and size of the proposed research programme. The costs of further research can vary significantly. ...
Expected value of perfect information (EVPI) calculations are increasingly performed to guide and underpin research recommendations. An EVPI value that exceeds the estimated cost of research forms a necessary (although not sufficient) condition for further research to be considered worthwhile. However, it is unclear what factors affect researchers' recommendations and whether there is a notional threshold of positive returns below which research is not recommended. The objectives of this study were to explore whether EVPI and other factors have a bearing on research recommendations and to assess whether there exists a threshold EVPI below which research is typically not recommended.
A systematic literature review was undertaken to identify applied EVPI calculations in the health care field. Study characteristics were extracted, including funder, location, disease group, publication year, primary language, and outcome measure. Population EVPI values and willingness-to-pay thresholds were also extracted alongside verbatim text excerpts describing the authors' research recommendations. Recommendations were classified according to whether further research was recommended (a positive recommendation) or not (negative). Factors affecting the likelihood of a positive recommendation were examined statistically using logistic regression and visually by plotting the results in graphs.
Eighty-six articles were included, of which 13 suggested no further research, 66 recommended further research, and 7 gave no recommendation. EVPI appears to be a key driver of researchers' recommendations for further research. Disease area, funder, study location, publication year, and outcome may have a bearing on recommendations, although none of these factors reached statistical significance. A threshold EVPI value below which research is typically not recommended was found at around £1.48 million.
© The Author(s) 2015.
... Colorectal cancer treatment has recently gained a particular significance due to an increase in the observed number of new cases and deaths related to this disease causing it to rise to fourth place in cancer specific mortality [1][2][3][4][5]. Over 50.000 deaths are expected in the USA in 2014 due to colorectal cancer which is the second prevalent cancer type in women and the third one in men [1,5].The five years survival rate of patients with colorectal cancer, which is generally observed in developed countries and thought to be due to Western dietary habits, is higher in women than men, while the incidence of cancer in women is lower when compared to men [5,6]. ...
Summary
Background: The selection of appropriate rectal cancer treatment is a complex multi-criteria decision making process, in which clinical decision support systems might be used to assist and enrich physicians’ decision making.
Objective: The objective of the study was to develop a web-based clinical decision support tool for physicians in the selection of potentially beneficial treatment options for patients with rectal cancer.
Methods: The updated decision model contained 8 and 10 criteria in the first and second steps respectively. The decision support model, developed in our previous study by combining the Analytic Hierarchy Process (AHP) method which determines the priority of criteria and decision tree that formed using these priorities, was updated and applied to 388 patients data collected retrospectively. Later, a web-based decision support tool named corRECTreatment was developed. The compatibility of the treatment recommendations by the expert opinion and the decision support tool was examined for its consistency. Two surgeons were requested to recommend a treatment and an overall survival value for the treatment among 20 different cases that we selected and turned into a scenario among the most common and rare treatment options in the patient data set.
Results: In the AHP analyses of the criteria, it was found that the matrices, generated for both decision steps, were consistent (consistency ratio<0.1). Depending on the decisions of experts, the consistency value for the most frequent cases was found to be 80% for the first decision step and 100% for the second decision step. Similarly, for rare cases consistency was 50% for the first decision step and 80% for the second decision step.
Conclusions: The decision model and corRECTreatment, developed by applying these on real patient data, are expected to provide potential users with decision support in rectal cancer treatment processes and facilitate them in making projections about treatment options.
... The majority of the applied papers (91 %; n = 54) proclaimed to be real-life applications of VOI. The application areas of these papers varied widely, though assessment of cardiac interventions (n = 9)[78, 81, 90–92, 107, 108, 110, 118]and cancer screening or treatment (n = 14)[77,79,81,82,85,88,104,106,107,114,116,121,122,125]were relatively prevalent among the included papers. ...
Objective:
This article provides a systematic and critical review of the evolving methods and applications of value of information (VOI) in academia and practice and discusses where future research needs to be directed.
Methods:
Published VOI studies were identified by conducting a computerized search on Scopus and ISI Web of Science from 1980 until December 2011 using pre-specified search terms. Only full-text papers that outlined and discussed VOI methods for medical decision making, and studies that applied VOI and explicitly discussed the results with a view to informing healthcare decision makers, were included. The included papers were divided into methodological and applied papers, based on the aim of the study.
Results:
A total of 118 papers were included of which 50 % (n = 59) are methodological. A rapidly accumulating literature base on VOI from 1999 onwards for methodological papers and from 2005 onwards for applied papers is observed. Expected value of sample information (EVSI) is the preferred method of VOI to inform decision making regarding specific future studies, but real-life applications of EVSI remain scarce. Methodological challenges to VOI are numerous and include the high computational demands, dealing with non-linear models and interdependency between parameters, estimations of effective time horizons and patient populations, and structural uncertainties.
Conclusion:
VOI analysis receives increasing attention in both the methodological and the applied literature bases, but challenges to applying VOI in real-life decision making remain. For many technical and methodological challenges to VOI analytic solutions have been proposed in the literature, including leaner methods for VOI. Further research should also focus on the needs of decision makers regarding VOI.
... This assumption, however, may not hold if diagnostics reimbursement is cost-based and not value-based, or if medicine prices and reimbursement are not closely linked to value delivered [48]. HEOR researchers are increasingly using VOI analyses to study the value of research to reduce uncertainties surrounding the benefits, harms, and costs of a health care intervention [53][54][55][56]. These y Is a biomarker required for success of the new pharmaceutical in development? ...
Personalized medicine technologies can improve individual health by delivering the right dose of the right drug to the right patient at the right time but create challenges in deciding which technologies offer sufficient value to justify widespread diffusion. Personalized medicine technologies, however, do not neatly fit into existing health technology assessment and reimbursement processes.
In this article, the Personalized Medicine Special Interest Group of the International Society for Pharmacoeconomics and Outcomes Research evaluated key development and reimbursement considerations from the payer and manufacturer perspectives.
Five key areas in which health economics and outcomes research best practices could be developed to improve value assessment, reimbursement, and patient access decisions for personalized medicine have been identified.
These areas are as follows: 1 research prioritization and early value assessment, 2 best practices for clinical evidence development, 3 best practices for health economic assessment, 4 addressing health technology assessment challenges, and 5 new incentive and reimbursement approaches for personalized medicine.
Key gaps in health economics and outcomes research best practices, decision standards, and value assessment processes are also discussed, along with next steps for evolving health economics and outcomes research practices in personalized medicine.
... Colorectal cancer ranks among the most common health conditions encountered today. In view of its increasing incidence throughout the world, the treatment of colorectal cancer is of great importance [1][2][3]. The frequency of this malignancy has been further aggravated by the rapid Westernization of diets throughout the world [4,5]. ...
The aim of the study is to determine the most appropriate method for construction of a sequential decision tree in the management of rectal cancer, using various patient-specific criteria and treatments such as surgery, chemotherapy, and radiotherapy.
An analytic hierarchy process (AHP) was used to determine the priorities of variables. Relevant criteria used in two decision steps and their relative priorities were established by a panel of five general surgeons. Data were collected via a web-based application and analyzed using the "Expert Choice" software specifically developed for the AHP. Consistency ratios in the AHP method were calculated for each set of judgments, and the priorities of sub-criteria were determined. A sequential decision tree was constructed for the best treatment decision process, using priorities determined by the AHP method.
Consistency ratios in the AHP method were calculated for each decision step, and the judgments were considered consistent. The tumor-related criterion "presence of perforation" (0.331) and the patient-surgeon-related criterion "surgeon's experience" (0.630) had the highest priority in the first decision step. In the second decision step, the tumor-related criterion "the stage of the disease" (0.230) and the patient-surgeon-related criterion "surgeon's experience" (0.281) were the paramount criteria. The results showed some variation in the ranking of criteria between the decision steps. In the second decision step, for instance, the tumor-related criterion "presence of perforation" was just the fifth.
The consistency of decision support systems largely depends on the quality of the underlying decision tree. When several choices and variables have to be considered in a decision, it is very important to determine priorities. The AHP method seems to be effective for this purpose. The decision algorithm developed by this method is more realistic and will improve the quality of the decision tree.
Objective:
Several European countries are implementing organized colorectal cancer (CRC) screening programmes using faecal immunochemical test (FIT) and/or flexible sigmoidoscopy (FS), but the cost-effectiveness of these programmes is not yet available. We aimed to assess cost-effectiveness, based on data from the established Piedmont screening programme.
Methods:
Using the Piedmont programme data, a Markov model was constructed comparing three strategies in a simulated cohort of 100,000 subjects: single FS, biennial FIT, or sequential strategy (FS + FIT offered to FS non-responders). Estimates for CRC incidence and mortality prevention were derived from studies of organized screening. Cost analysis for FS and FIT was based on data from organized programmes. Incremental cost-effectiveness ratios (ICER) between the different strategies were calculated. Sensitivity and probabilistic analyses were performed.
Results:
Direct costs for FS, and for FIT at first and subsequent rounds, were estimated as €160, €33, and €21, respectively. All the simulated strategies were effective (10-17% CRC incidence reduction) and cost-effective vs. no screening (ICER <€1000 per life-year saved). FS and FS + FIT were the only cost-saving strategies, with FS least expensive (€15 saving per person invited). FS + FIT and FS were the only non-dominated strategies. FS + FIT were more effective and cost-effective than FS (ICER €1217 per life-year saved). The residual marginal uncertainty was mainly related to parameters inherent to FIT effectiveness and adherence.
Conclusions:
Organized CRC screening programmes are highly cost-effective, irrespective of the test selected. A sequential approach with FS and FIT appears the most cost-effective option. A single FS is the least expensive, but convenient, approach.
Health research priority-setting exercises aim to maximize the impact of investments in health research. An increasing number of priority-setting exercises for health research have taken place in the past two decades. These exercises have been conducted for various areas of health research and at various levels (global, regional, national, local and institutional). In this chapter, we discuss the similarities and differences between health research priority setting and health intervention priority setting, and we describe the current methodologies used in health research priority setting and the role of multi-criteria decision analysis (MCDA) therein. We provide three concrete suggestions for future methodological development in the field of health research priority setting: (1) recognize that many of the methodologies used to set health research priorities apply MCDA, (2) make use of well-established approaches or best practices for health research priority setting and (3) study in more detail the differences between health intervention and health research priority setting.
Data mining techniques and multi criteria decision making techniques have been used widely in many areas, such as customer relationship management, medicine, engineering, education, geographic information systems, and recommendation systems. The present study aims to design a hybrid approach based on Deep Neural Networks (DNNs) and multi criteria decision making. DNNs and multi criteria decision making techniques are integrated with Analytical Hierarchy Process (AHP) to improve classification accuracy and deal with large datasets. Three different breast cancer datasets are used for evaluating the performance of the proposed hybrid approach. In most cases, the hybrid approach of applying DNN Backpropagation with three hidden layers and AHP gives better accuracy rate 84.33%, precision 95.9%, recall 86.6%, and F-measure of 90.2% than using one hidden layer or applying DNN Backpropagation with three hidden layers without AHP. In addition, classical classification algorithm are also compared: J48, naive bayes, and random tree, where they give less results than proposed approach.
Background:
After lung and prostate cancers, colorectal cancer (CRC) is the third most common cancer in men and the second most common cancer in women after breast cancer worldwide. Every year, more than one million people are diagnosed with colorectal cancer worldwide and half of these patients die from this disease, making it the fourth leading cause of death in the world. This systematic review aimed to assess the effectiveness of the two colorectal diagnostic tests of FOBT (fecal occult blood test) and FIT (fecal immunochemical test)) in terms of technical performance.
Methods:
To retrieve the relevant evidence, appropriate medical databases such as Cochrane library, NHSEED, Scopus and Google scholar were searched from February 2013 to July 2014, using free-texts and Mesh. In this study, inclusion/exclusion criteria of the papers, randomized controlled trials, economic evaluations, systematic reviews, meta-analyses and meta-syntheses of the effectiveness of FIT versus FOBT tests in moderate-risk populations (age: 50 to 70 years), which had reported the least of such outcomes as sensitivity, specificity and clinical outcomes were reviewed. The analyses of the effectiveness outcomes were performed in the form of meta-analysis.
Results:
Five papers were eligible to be included in the final phase of the study for synthesis. FIT showed a better performance in participation and positivity rate. Moreover, in terms of false positive and negative rate, FIT showed fewer rates compared to FOBT (RR:-4.06; 95% CI (-7.89-0.24), and NN-scope (Number need to scope) (2.2% vs. 1.6%), and NN-screen (Number need to screen) (84% vs. 31-49% in different cut off levels) showed significant differences in FOBT vs. FIT, respectively.
Conclusion:
In the five included studies (3, 11-14), the acceptability of FIT was more than FOBT. However, in our meta-analysis, no difference was found between the two tests. FIT was significant in positivity rate and had a better performance in participation rate, and a fewer false negative numbers compared to FOBT.
Health outcomes research is essential to align radiology with current standards of high-value patient care, through the assessment of end results of diagnostic tests, interventions, or policy on patient health. To bridge studies of diagnostic test accuracy and health outcomes research, key considerations include: (1) how to determine when a diagnostic test merits evaluation of impact on outcomes, (2) when study of intermediate/surrogate outcomes can be useful, (3) how to consider the possible harms as well as potential benefits of a test, and (4) how to integrate evidence of an imaging test's efficacy/effectiveness with clinical data to assess outcomes. Due to challenges in conducting studies of long-term outcomes consequent to imaging use, intermediate health outcomes may capture a test's impact on successful diagnosis and therapy, and can provide readily measurable, incremental insights into the role of imaging in health-care delivery and efficiency. In an era marked by recognition of quality and value of care, outcomes research will provide essential evidence to inform radiologists' guidance of imaging use toward improved patient care, creation of clinical guidelines, and policy decisions.
Objectives:
To establish whether evidence about the effectiveness of a healthcare intervention is sufficient to justify use of the intervention in practice and show how value of information (VOI) analysis can be used to place a value on the need for additional evidence and inform research prioritisation decisions.
Study design and setting:
Meta-analysis provides an estimate of the effect of an intervention with some level of uncertainty. VOI analysis determines the adverse health consequences of not resolving this uncertainty. A case study examining the evidence before the high profile trial of Corticosteroid Randomisation After Significant Head injury (CRASH) shows the consequences on patient outcomes if this trial had not been successfully funded.
Results:
The consequences of uncertainty before CRASH were high at 40 deaths and 1,067 years of full health per annum. VOI analysis indicates that CRASH was worthwhile and the UK National Health Service would have had to spend an additional £205 million elsewhere to generate health benefits similar to CRASH.
Conclusions:
VOI analysis can be integrated with the results of meta-analysis to help inform whether a particular research proposal is potentially worthwhile and whether it should be prioritised over other research topics that could be commissioned with the same resources.
Computed tomographic colonography (CTC) is a relatively new diagnostic test that may be superior to existing alternatives to investigate the large bowel.
To compare the diagnostic efficacy, acceptability, safety and cost-effectiveness of CTC with barium enema (BE) or colonoscopy.
Parallel randomised trials: BE compared with CTC and colonoscopy compared with CTC (randomisation 2 : 1, respectively).
A total of 21 NHS hospitals.
Patients aged ≥ 55 years with symptoms suggestive of colorectal cancer (CRC).
CTC, BE and colonoscopy.
For the trial of CTC compared with BE, the primary outcome was the detection rate of CRC and large polyps (≥ 10 mm), with the proportion of patients referred for additional colonic investigation as a secondary outcome. For the trial of CTC compared with colonoscopy, the primary outcome was the proportion of patients referred for additional colonic investigation, with the detection rate of CRC and large polyps as a secondary outcome. Secondary outcomes for both trials were miss rates for cancer (via registry data), all-cause mortality, serious adverse events, patient acceptability, extracolonic pathology and cost-effectiveness.
A total of 8484 patients were registered and 5384 were randomised and analysed (BE trial: 2527 BE, 1277 CTC; colonoscopy trial: 1047 colonoscopy, 533 CTC). Detection rates in the BE trial were 7.3% (93/1277) for CTC, compared with 5.6% (141/2527) for BE (p = 0.0390). The difference was due to better detection of large polyps by CTC (3.6% vs. 2.2%; p = 0.0098), with no significant difference for cancer (3.7% vs. 3.4%; p = 0.66). Significantly more patients having CTC underwent additional investigation (23.5% vs. 18.3%; p = 0.0003). At the 3-year follow-up, the miss rate for CRC was 6.7% for CTC (three missed cancers) and 14.1% for BE (12 missed cancers). Significantly more patients randomised to CTC than to colonoscopy underwent additional investigation (30% vs. 8.2%; p < 0.0001). There was no significant difference in detection rates for cancer or large polyps (10.7% for CTC vs. 11.4% for colonoscopy; p = 0.69), with no difference when cancers (p = 0.94) and large polyps (p = 0.53) were analysed separately. At the 3-year follow-up, the miss rate for cancer was nil for colonoscopy and 3.4% for CTC (one missed cancer). Adverse events were uncommon for all procedures. In 1042 of 1748 (59.6%) CTC examinations, at least one extracolonic finding was reported, and this proportion increased with age (p < 0.0001). A total of 149 patients (8.5%) were subsequently investigated, and extracolonic neoplasia was diagnosed in 79 patients (4.5%) and malignancy in 29 (1.7%). In the short term, CTC was significantly more acceptable to patients than BE or colonoscopy. Total costs for CTC and colonoscopy were finely balanced, but CTC was associated with higher health-care costs than BE. The cost per large polyp or cancer detected was £4235 (95% confidence interval £395 to £9656).
CTC is superior to BE for detection of cancers and large polyps in symptomatic patients. CTC and colonoscopy detect a similar proportion of large polyps and cancers and their costs are also similar. CTC precipitates significantly more additional investigations than either BE or colonoscopy, and evidence-based referral criteria are needed. Further work is recommended to clarify the extent to which patients initially referred for colonoscopy or BE undergo subsequent abdominopelvic imaging, for example by computed tomography, which will have a significant impact on health economic estimates.
Current Controlled Trials ISRCTN95152621.
This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 54. See the NIHR Journals Library website for further project information. Funding was also provided by the UK Department of Health, which stipulated a randomised controlled design but had no involvement in the collection, analysis or interpretation of data, in writing the report, or in the decision to submit for publication. This was also the case for manufacturers who donated equipment for the study (Bracco UK Ltd, High Wycombe, UK; Viatronix Inc., Stony Brook, NY, USA; Medicsight plc, London, UK; Barco Ltd, Bracknell, UK).
Objectives:
To determine the cost-effectiveness of tyrosine kinase inhibitors erlotinib or afatinib, or chemotherapy cisplatin-pemetrexed, for first-line treatment of advanced epithelial growth factor receptor mutation-positive non-small-cell lung cancer in the United States. We also assessed the expected benefit of further research to reduce uncertainty regarding which treatment is optimal.
Methods:
We developed a Markov model to compare the cost-effectiveness of erlotinib, afatinib, and cisplatin-pemetrexed. Model transition and adverse-effect probabilities were from two published phase III trials: EURTAC (Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer) and LUX-Lung (Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma) 3. EURTAC survival estimates were corrected for patients entering the trial with more severe disease, compared with LUX-Lung 3. Health utilities and costs were from national estimates or the published literature. Inputs were modeled as distributions for probabilistic sensitivity analysis and expected value of perfect information (EVPI) analysis to estimate the expected benefit of reducing uncertainty regarding the decision of optimal treatment.
Results:
In the base case, both tyrosine kinase inhibitors were more cost-effective than cisplatin-pemetrexed. Erlotinib had an incremental cost-effectiveness ratio of 100,000/QALY (10-year population EVPI = 50,000/QALY to 211.5 million-$261.8 million), however, there was considerable uncertainty whether erlotinib or afatinib was the optimal treatment.
Conclusions:
Our analysis suggests that erlotinib is the preferred first-line treatment for advanced epithelial growth factor receptor mutation-positive non-small-cell lung cancer. Further research comparing erlotinib and afatinib is potentially justified, although accurate data are needed on the required cost and sample size of the trial.
Although colorectal cancer (CRC) is a common cause of cancer-related death, it is fortunately amenable to screening with faecal tests for occult blood and endoscopic tests. Despite the evidence for the efficacy of guaiac-based faecal occult blood tests (gFOBT), they have not been popular with primary care providers in many jurisdictions, in part because of poor sensitivity for advanced colorectal neoplasms (advanced adenomas and CRC). In order to address this issue, high sensitivity gFOBT have been recommended, however, these tests are limited by a reduction in specificity compared with the traditional gFOBT. Where colonoscopy is available, some providers have opted to recommend screening colonoscopy to their patients instead of faecal testing, as they believe it to be a better test. Newer methods for detecting occult human blood in faeces have been developed. These tests, called faecal immunochemical tests (FIT), are immunoassays specific for human haemoglobin. FIT hold considerable promise over the traditional guaiac methods including improved analytical and clinical sensitivity for CRC, better detection of advanced adenomas, and greater screenee participation. In addition, the quantitative FIT are more flexible than gFOBT as a numerical result is reported, allowing customisation of the positivity threshold. When compared with endoscopy, FIT are less sensitive for the detection of advanced colorectal neoplasms when only one time testing is applied to a screening population; however, this is offset by improved participation in a programme of annual or biennial screens and a better safety profile. This review will describe how gFOBT and FIT work and will present the evidence that supports the use of FIT over gFOBT, including the cost-effectiveness of FIT relative to gFOBT. Finally, specific issues related to FIT implementation will be discussed, particularly with respect to organised CRC screening programmes.
Value of information (VOI) analysis is a novel systematic approach for assessing whether there is sufficient evidence to support regulatory approval of new technologies, estimating the value of additional research, informing trial design, and setting research priorities. This article reviews the use of VOI methods in oncology and identifies the potential applications of VOI in this field.
A systematic literature search was undertaken to identify studies explicitly reporting VOI analyses for interventions directed at cancer management. Articles published from 2000 onward addressing prevention, screening, diagnosis, treatment, or symptom management in oncology were selected.
A total of 35 articles were included in the review; most were published after 2006. The main cancers addressed were breast (n = 10; 29%), prostate (n = 5; 14%), lung (n = 5; 14%), and colorectal (n = 3; 9%). The VOI analyses were of an applied nature in 31 studies (89%). In the applied studies, VOI was used to characterize decision uncertainty in all studies and to inform future research focus in 16 (52%). Additionally, one article (3%) addressed the value of optimal trial design, and one article (3%) reported the use of VOI methods to prioritize research.
The application of VOI analysis in oncology is growing but remains limited. Benefits in oncology research and practice will potentially be optimized with an increase in the application of VOI methods to inform decision making, optimal trial design, and research prioritization in this field.
The value of information (VoI) is a decision analytic method for quantifying the potential benefit of additional information in the face of uncertainty. This paper reviews the prevalence of VoI applications reported in the peer-reviewed literature from the years 1990–2011. We categorize papers’ applications across the types of uncertainties considered, modeling choices, and contexts of social importance (such as health care and environmental science). We obtain and analyze statistics on the range of applications and identify trends and patterns in them, and conclude with an interpretation of what these mean for researchers and practitioners as they pursue new efforts. Key results include a substantial increase over the last 20 years in published papers utilizing VoI, particularly in the medical field. Nineteen trends in VoI applications from the period of 1990–2000 to 2001–2011 were found to be at least weakly significant. Beyond simple trends, some characteristics of VoI usage depend on the area of application, and in some cases, certain sets of characteristics tend to be found together.
Economic models are developed to provide decision makers with information related to the real-world effectiveness of therapeutics, screening and diagnostic regimens. Although compliance with these regimens often has a significant impact on real-world clinical outcomes and costs, compliance and persistence have historically been addressed in a relatively superficial fashion in economic models. In this review, we present a discussion of the current state of economic modelling as it relates to the consideration of compliance and persistence. We discuss the challenges associated with the inclusion of compliance and persistence in economic models and provide an in-depth review of recent modelling literature that considers compliance or persistence, including a brief summary of previous reviews on this topic and a survey of published models from 2005 to 2012. We review the recent literature in detail, providing a therapeutic-area-specific discussion of the approaches and conclusions drawn from the inclusion of compliance or persistence in economic models. In virtually all publications, variation of model parameters related to compliance and persistence was shown to have a significant impact on predictions of economic outcomes. Growing recognition of the importance of compliance and persistence in the context of economic evaluations has led to an increasing number of economic models that consider these factors, as well as the use of more sophisticated modelling techniques such as individual simulations that provide an avenue for more rigorous consideration of compliance and persistence than is possible with more traditional methods. However, we note areas of continuing concern cited by previous reviews, including inconsistent definitions, documentation and tenuous assumptions required to estimate the effect of compliance and persistence. Finally, we discuss potential means to surmount these challenges via more focused efforts to collect compliance and persistence data.
The majority of recent cost-effectiveness reviews concluded that computerised tomographic colonography (CTC) is not a cost-effective colorectal cancer (CRC) screening strategy yet. The objective of this review is to examine cost-effectiveness of CTC versus optical colonoscopy (COL) for CRC screening and identify the main drivers influencing cost-effectiveness due to the emergence of new research.
A systematic review was conducted for cost-effectiveness studies comparing CTC and COL as a screening tool and providing outcomes in life-years saved, published between January 2006 and November 2012.
Nine studies were included in the review. There was considerable heterogeneity in modelling complexity and methodology. Different model assumptions and inputs had large effects on resulting cost-effectiveness of CTC and COL. CTC was found to be dominant or cost-effective in three studies, assuming the most favourable scenario. COL was found to be not cost effective in one study.
CTC has the potential to be a cost-effective CRC screening strategy when compared to COL. The most important assumptions that influenced the cost-effectiveness of CTC and COL were related to CTC threshold-based reporting of polyps, CTC cost, CTC sensitivity for large polyps, natural history of adenoma transition to cancer, AAA parameters and importantly, adherence. There is a strong need for a differential consideration of patient adherence and compliance to CTC and COL. Recent research shows that laxative-free CTC screening has the potential to become a good alternative screening method for CRC as it can improve patient uptake of screening.
Colorectal cancer kills 210,000 persons every year in Europe, its average incidence is 50 in 100,000 people/year, and the average lifetime risk of developing colorectal cancer is 5%. Treatment of colorectal cancer imposes a huge economical burden. The individual direct cost for treating colon cancer early is approximately €20,000. One course of chemotherapy using new combination regimens costs approximately €23,000, and caring for one patient with late-stage colorectal cancer costs approximately €80,000. Prevention of colorectal cancer is possible, and widespread implementation of CT colonography can reduce colorectal cancer incidence and mortality by up to 90%. Advances in technology have provided us with CT colonography, an effective test for imaging the colon, that may represent a formidable prevention tool, and be well accepted owing to its minimal invasiveness. This article gives an outline of the epidemiology and the available prevention strategies for colorectal cancer, illustrates the progress in CT colonography development, and discusses future perspectives.
To assess the value of a randomized controlled trial (RCT) of lymph node dissection (LND) at the time of hysterectomy for high-risk subsets of women with endometrial cancer.
A modified Markov decision model compared routine LND to no LND for women with grade 3 or grade 2-3 endometrial cancer. Inputs were modeled as distributions for Monte Carlo probabilistic sensitivity and value of information (VOI) analyses. Survival without LND was modeled from Surveillance, Epidemiology and End Results program data. A hazard ratio (HR) describing survival in the high-risk group undergoing LND (estimate 0.9, 95% CI 0.6-1.1), adverse event rates, probability and type of adjuvant therapy were modeled from published RCTs. Costs were obtained from national reimbursement data. VOI estimated the value of reducing uncertainty regarding the survival benefit of LND.
For grade 3, LND had an incremental cost-effectiveness ratio of 4,195 per patient at societal willingness to pay of 3,702 per patient. Assuming 8,000 individuals annually with grade 3 endometrial cancer in the US, the upper limit of VOI for the HR was $29.6 million annually. For grade 2 and 3 combined, analysis revealed a much lower likelihood of finding LND cost-effective.
A clinical trial defining the survival effect of LND in women with grade 3 endometrial cancer is a worthwhile use of resources.
Objectives: The European Code Against Cancer recommends individuals aged ≥50 should participate in colorectal cancer screening. CT-colonography (CTC) is one of several screening tests available. We systematically reviewed evidence on, and identified key factors influencing, cost-effectiveness of CTC screening.
Methods: PubMed, Medline, and the Cochrane library were searched for cost-effectiveness or cost-utility analyses of CTC-based screening, published in English, January 1999 to July 2010. Data was abstracted on setting, model type and horizon, screening scenario(s), comparator(s), participants, uptake, CTC performance and cost, effectiveness, ICERs, and whether extra-colonic findings and medical complications were considered.
Results: Sixteen studies were identified from the United States (n = 11), Canada (n = 2), and France, Italy, and the United Kingdom (1 each). Markov state-transition (n = 14) or microsimulation (n = 2) models were used. Eleven considered direct medical costs only; five included indirect costs. Fourteen compared CTC with no screening; fourteen compared CTC with colonoscopy-based screening; fewer compared CTC with sigmoidoscopy (8) or fecal tests (4). Outcomes assessed were life-years gained/saved (13), QALYs (2), or both (1). Three considered extra-colonic findings; seven considered complications. CTC appeared cost-effective versus no screening and, in general, flexible sigmoidoscopy and fecal occult blood testing. Results were mixed comparing CTC to colonoscopy. Parameters most influencing cost-effectiveness included: CTC costs, screening uptake, threshold for polyp referral, and extra-colonic findings.
Conclusion: Evidence on cost-effectiveness of CTC screening is heterogeneous, due largely to between-study differences in comparators and parameter values. Future studies should: compare CTC with currently favored tests, especially fecal immunochemical tests; consider extra-colonic findings; and conduct comprehensive sensitivity analyses.
Simulation modeling is extensively applied to CT colonography (CTC) to define its long-term efficacy and cost-effectiveness for colorectal cancer (CRC) screening. CTC is effective in reducing CRC incidence and mortality (40%-77% and 58%-84%, respectively). Several factors may explain this variability. CTC is cost-effective compared with no screening, indicating that it represents an attractive test noncompliance with the available options. CTC needs to achieve a higher attendance rate or cost less than colonoscopy to be cost-effective relative to colonoscopy. Fortunately, both conditions appear to be achievable if CTC becomes a widely utilized and reimbursed screening tool.
A variety of tests have been proposed for colorectal cancer (CRC), giving rise to uncertainty regarding the optimal approach. The efficacy and effectiveness of different tests are related to both screenee participation and the detection rate.
To perform a meta-analysis on adherence and detection rates of CRC screening tests.
Relevant publications were identified by MEDLINE/EMBASE and other databases for the period 1999-2012. A previous systematic review was used for the period before 1966-1999. RCTs and controlled studies including a direct comparison of the uptake rates among different options for CRC screening were included. Adherence and detection rates for advanced neoplasia and cancer were extracted. Risk for bias was ascertained according to CONSORT guidelines. Forrest plots were produced based on random-effect models.
Fourteen studies provided data on 197 910 subjects. Endoscopic strategies were associated with a lower participation (RR: 0.67, 95% CI: 0.56, 0.80) rate, but a higher detection rate of advanced neoplasia (RR: 3.21, 95% CI: 2.38, 4.32) compared with faecal tests. FIT was superior to g-FOBT with regard to both adherence (RR: 1.16, 95% CI 1.03, 1.30) and detection of advanced neoplasia (RR: 2.28, 95% CI 1.68, 3.10) and cancer (RR: 1.96, 95% CI: 1.2, 3.2).
The superior accuracy of endoscopy compared with faecal tests minimised any impact of the participation rate in determining the detection rate of advanced neoplasia in a screening setting.
Economic models are developed to provide decision makers with information related to the real-world effectiveness of therapeutics, screening and diagnostic regimens. Although compliance with these regimens often has a significant impact on real-world clinical outcomes and costs, compliance and persistence have historically been addressed in a relatively superficial fashion in economic models. In this review, we present a discussion of the current state of economic modelling as it relates to the consideration of compliance and persistence. We discuss the challenges associated with the inclusion of compliance and persistence in economic models and provide an in-depth review of recent modelling literature that considers compliance or persistence, including a brief summary of previous reviews on this topic and a survey of published models from 2005 to 2012. We review the recent literature in detail, providing a therapeutic-area-specific discussion of the approaches and conclusions drawn from the inclusion of compliance or persistence in economic models. In virtually all publications, variation of model parameters related to compliance and persistence was shown to have a significant impact on predictions of economic outcomes. Growing recognition of the importance of compliance and persistence in the context of economic evaluations has led to an increasing number of economic models that consider these factors, as well as the use of more sophisticated modelling techniques such as individual simulations that provide an avenue for more rigorous consideration of compliance and persistence than is possible with more traditional methods. However, we note areas of continuing concern cited by previous reviews, including inconsistent definitions, documentation and tenuous assumptions required to estimate the effect of compliance and persistence. Finally, we discuss potential means to surmount these challenges via more focused efforts to collect compliance and persistence data.
Propofol for colonoscopy is largely administered by anesthesiologists or anesthesiology nurses in the United States (US) and Europe. Endoscopist-directed administration of propofol (EDP) by nonanesthesiologists has recently been proposed, with potential savings of anesthetist reimbursement costs. We aimed to assess potential EDP-related benefit in a screening setting.
In a Markov model the total number of screening and follow-up colonoscopies in a cohort of 100 000 US subjects were estimated. Anesthetist-assisted colonoscopy was compared with an EDP strategy. Model outputs were projected onto the 50 - 80-year-old US population, assuming 27 % as the current uptake for colonoscopy screening. Anesthetist costs were estimated using the mean reimbursement for the corresponding Medicare code (≥ 65-year-olds) and from commercial insurance information (50 - 64-year-olds). The proportion of colonoscopies with anesthesiologist assistance was estimated from the Medicare database. Mean nurse salary was used to estimate the cost of a 2-week EDP training. The absolute number of US endoscopists was estimated by inflating by 33 % the number of board-certified gastroenterologists. No EDP mortality was assumed in the reference scenario, and 0.0008 % mortality in the sensitivity analysis. US census data were adopted. Analogous inputs were used for France to assess EDP-related benefit in a European country.
EDP training for 17 166 nurses (one for each US endoscopist) showed a cost of 95 (Medicare) and 3.2 billion (Monte Carlo analysis 5 - 95 % percentiles 11.9 billion). In the sensitivity analysis, assuming 50 % of colonoscopies were anesthetist-assisted showed an EDP benefit of 1.5 million per life-year gained, supporting EDP as the optimal choice. A 31-fold increase of EDP-related mortality or a 17-fold cost reduction for anesthetist-assisted colonoscopy was required for EDP to become not cost-effective in this scenario. Implementation of an EDP policy in France, within a guaiac-fecal occult blood test (g-FOBT) screening program, was estimated to save € 0.8 billion in 10 years.
The absolute economic benefit of EDP implementation in a screening setting is probably substantial with 10-year savings of $3.2 billion in the US and €0.8 billion in France. The impact of an eventual EDP-related mortality on EDP cost - effectiveness seems marginal. The huge economic and medical resources entailed by anesthetist-assisted colonoscopy could be more efficiently invested in other clinical fields.
Colorectal cancer (CRC) is a major cause of morbidity and mortality in France. Only scanty data on cost-effectiveness of CRC screening in Europe are available, generating uncertainty over its efficiency. Although immunochemical fecal tests (FIT) and guaiac-based fecal occult blood tests (g-FOBT) have been shown to be cost-effective in France, cost-effectiveness of endoscopic screening has not yet been addressed.
Cost-effectiveness of screening strategies using colonoscopy, flexible sigmoidoscopy, second-generation colon capsule endoscopy (CCE), FIT and g-FOBT were compared using a Markov model. A 40 % adherence rate was assumed for all strategies. Colonoscopy costs included anesthesiologist assistance. Incremental cost-effectiveness ratios (ICERs) were calculated. Probabilistic and value-of-information analyses were used to estimate the expected benefit of future research. A third-payer perspective was adopted.
In the reference case analysis, FIT repeated every year was the most cost-effective strategy, with an ICER of €48165 per life-year gained vs. FIT every 2 years, which was the next most cost-effective strategy. Although CCE every 5 years was as effective as FIT 1-year, it was not a cost-effective alternative. Colonoscopy repeated every 10 years was substantially more costly, and slightly less effective than FIT 1-year. When projecting the model outputs onto the French population, the least (g-FOBT 2-years) and most (FIT 1-year) effective strategies reduced the absolute number of annual CRC deaths from 16037 to 12916 and 11217, respectively, resulting in an annual additional cost of €26 million and €347 million, respectively. Probabilistic sensitivity analysis demonstrated that FIT 1-year was the optimal choice in 20% of the simulated scenarios, whereas sigmoidoscopy 5-years, colonoscopy, and FIT 2-years were the optimal choices in 40%, 26%, and 14%, respectively.
A screening program based on FIT 1-year appeared to be the most cost-effective approach for CRC screening in France. However, a substantial uncertainty over this choice is still present.
Tailoring colorectal cancer screening interventions to address the needs of individuals for whom screening is recommended requires accurate identification of the barriers experienced by each targeted group. The primary purpose of this survey study was to test differences in the barriers to undergoing screening colonoscopy reported by men and women. In addition, we were interested in differences in barriers reported by 1) 50-year-olds versus those age 51 to 80 years, 2) persons reporting readiness for colonoscopy versus those not reporting readiness, and 3) persons who had had a primary care encounter in the preceding 12 months versus those who had not. Four thousand members of a health maintenance organization (Scott & White Health Plan) were surveyed. Response rate overall was 30.85%. No differences in barriers to screening colonoscopy were identified for men versus women. We did identify differences in barriers reported by persons reporting readiness versus those not reporting readiness. Findings suggest that interventions to increase rates of screening colonoscopy require addressing different sets of barriers depending on whether persons report readiness to have a colonoscopy within 6 months.
Computer disease simulation models are increasingly being used to evaluate and inform health care decisions across medical disciplines. The aim of researchers who develop these models is to integrate and synthesize short-term outcomes and results from multiple sources to predict the long-term clinical outcomes and costs of different health care strategies. Policy makers, in turn, can use the predictions generated by disease models together with other evidence to make decisions related to health care practices and resource utilization. Models are particularly useful when the existing evidence does not yield obvious answers or does not provide answers to the questions of greatest interest, such as questions about the relative cost-effectiveness of different practices. This review focuses on models used to inform decisions about imaging technology, discussing the role of disease models for health policy development and providing a foundation for understanding the basic principles of disease modeling. This manuscript draws from the collective computed tomographic colonography modeling experience, reviewing 10 published investigations of the clinical effectiveness and cost-effectiveness of computed tomographic colonography relative to colonoscopy. The discussion focuses on implications of different modeling assumptions and difficulties that may be encountered when evaluating the quality of models. This underscores the importance of forging stronger collaborations between researchers who develop disease models and radiologists, to ensure that policy-level models accurately represent the experience of everyday clinical practices.
Methods:
to estimate the cost-effectiveness of technologies are well developed with increasing experience of their application to inform adoption decisions in a timely way. However, the experience of using similarly explicit methods to inform the associated research decisions is less well developed despite appropriate methods being available with an increasing number of applications in health. The authors demonstrate that evaluation of both adoption and research decisions is feasible within typical time and resource constraints relevant to policy decisions, even in situations in which data are sparse and formal elicitation is required. In addition to demonstrating the application of expected value of sample information (EVSI) in these circumstances, the authors examine and carefully distinguish the impact that the research decision is expected to have on patients while enrolled in the trial, those not enrolled, and once the trial reports. In doing so, the authors are able to account for the range of opportunity cost associated with research and evaluate a number of
Research design:
s including length of follow-up and sample size. The authors also explore the implications for research design of conducting research while the technology is approved for widespread use and whether approval should be withheld until research reports. In doing so, the authors highlight the impact of irrecoverable opportunity costs when the initial costs of a technology are compensated only by later gains in health outcome.
A "resect and discard" policy has been proposed for diminutive polyps detected by screening colonoscopy, because hyperplastic and adenomatous polyps can be distinguished, in vivo, by using narrow-band imaging (NBI). We modeled the cost-effectiveness of this policy.
Markov modeling was used to compare the cost-effectiveness of universal pathology evaluations with a resect and discard policy for colonoscopy screening. In a resect and discard approach, diminutive lesions (≤5 mm), classified by endoscopy with high confidence, were not analyzed by a pathologist. Base case assumptions of an 84% rate of high-confidence classification, with a sensitivity and specificity for adenomas of 94% and 89%, respectively, were used. Census data were used to project outputs of the model onto the US population, assuming 23% as the current rate of adherence to a colonoscopy screening.
With universal referral of resected polyps to pathology, colonoscopy screening costs an estimated 179/person, of which 25/person, without any meaningful effect on screening efficacy. Projected onto the US population, this approach would result in an undiscounted annual savings of $33 million. In the sensitivity analysis, the rate of high-confidence diagnosis and the accuracy for endoscopic polyp determination were the most meaningful variables.
In a simulation model, a resect and discard strategy for diminutive polyps detected by screening colonoscopy resulted in a substantial economic benefit without an impact on efficacy.
To analyze the cost-effectiveness of adding computer-aided detection (CAD) to a computed tomographic (CT) colonography screening program and to compare it with other options of colorectal cancer (CRC) prevention.
The cost-effectiveness of screening strategies by using CT colonography with and without CAD, flexible sigmoidoscopy (FS), and optical colonoscopy were compared by using a Markov-based computer model. In the model, a hypothetical population of 100,000 persons aged 50 years underwent colorectal screening every 10 years. Baseline sensitivities for both experienced and inexperienced readers and the incremental accuracy when adding CAD were estimated from a systematic review of the literature.
At baseline, the addition of CAD resulted in 9% and 2% increases in CRC prevention rates for inexperienced and experienced readers, respectively, when compared with CT colonography without CAD. Assuming a CAD cost of 8661 and 498,668 per life-year gained. CT colonography with CAD for inexperienced readers was more clinically effective and cost-effective than FS. At analysis, sensitivity of CT colonography with CAD for polyps 6 mm or larger was the most meaningful variable.
The addition of CAD to CT colonography screening improves the CRC prevention rate, resulting in advantageous cost-effectiveness for screening. Supplemental material: http://radiology.rsnajnls.org/cgi/content/full/250/2/488/DC1.
The disease natural history of colorectal neoplasm regarding two opposing theories, adenoma-carcinoma sequence and de novo carcinoma theory, is controversial and rarely quantified. The aims of this study are therefore to estimate the dwelling times of adenoma-carcinoma sequence by adenoma size and histological type, taking de novo carcinoma into account. The efficacy of polypectomy was therefore estimated making allowance for two pathways. A case-cohort design, underpinning a cohort with 13 908 subjects (including 10 496 normal subjects, 2652 polyps, 760 colorectal cancers) who underwent the first examination of colonoscopy between 1979 and 1998, was devised to estimate parameters associated with two opposing theories by randomly selecting 305 normal subjects, 300 patients with polyps, and 116 colorectal cancers from the cohort. All the 2652 polyps were linked to national cancer registry to ascertain 25 invasive carcinomas after polypectomy. For the five-state model associated with adenoma size, dwelling times of small (0.6-1 cm) and large adenoma (>1 cm) are 7.75 and 5.27 years for the model without considering de novo, and 17.48 and 15.90 years for the model taking de novo carcinoma into account. Similar findings are observed for the model associated with histological type. The estimated proportions of de novo carcinoma are 31.87% from the model by adenoma size and 27.81% from the model by histological type. Compared to size less than 5 mm, patients with adenoma size between 6 and 10 mm and patients with adenoma size larger than 1 cm have 2.17-fold (0.67-10.74) and 4.25-fold (1.23-14.70), respectively, for the risk of malignant transformation. There are similar findings for the model by histological type. The estimates of overall efficacy of colonoscopy in reducing CRC is 73% for the model allowing for de novo carcinoma and 88% for the model without considering de novo carcinoma theory. The efficacy of diminutive adenoma and small adenoma increases with follow-up years, whereas the efficacy of large adenoma decreases with follow-up years. In conclusion, about 30% of cancers arising from de novo sequence are demonstrated. This finding, together with the adenoma-carcinoma sequence associated with adenoma size and histological type, is important for the estimation of dwelling times, the efficacy of colonoscopy, and the surveillance of polyp after polypectomy.
We evaluated the performance characteristics of computed tomographic (CT) virtual colonoscopy for the detection of colorectal neoplasia in an average-risk screening population.
A total of 1233 asymptomatic adults (mean age, 57.8 years) underwent same-day virtual and optical colonoscopy. Radiologists used the three-dimensional endoluminal display for the initial detection of polyps on CT virtual colonoscopy. For the initial examination of each colonic segment, the colonoscopists were unaware of the findings on virtual colonoscopy, which were revealed to them before any subsequent reexamination. The sensitivity and specificity of virtual colonoscopy and the sensitivity of optical colonoscopy were calculated with the use of the findings of the final, unblinded optical colonoscopy as the reference standard.
The sensitivity of virtual colonoscopy for adenomatous polyps was 93.8 percent for polyps at least 10 mm in diameter, 93.9 percent for polyps at least 8 mm in diameter, and 88.7 percent for polyps at least 6 mm in diameter. The sensitivity of optical colonoscopy for adenomatous polyps was 87.5 percent, 91.5 percent, and 92.3 percent for the three sizes of polyps, respectively. The specificity of virtual colonoscopy for adenomatous polyps was 96.0 percent for polyps at least 10 mm in diameter, 92.2 percent for polyps at least 8 mm in diameter, and 79.6 percent for polyps at least 6 mm in diameter. Two polyps were malignant; both were detected on virtual colonoscopy, and one of them was missed on optical colonoscopy before the results on virtual colonoscopy were revealed.
CT virtual colonoscopy with the use of a three-dimensional approach is an accurate screening method for the detection of colorectal neoplasia in asymptomatic average-risk adults and compares favorably with optical colonoscopy in terms of the detection of clinically relevant lesions.
The purpose of this review is to illustrate how tools and concepts from decision and cost-effectiveness analyses can be used to help make decisions in the face of uncertainty and resource constraints, select appropriate subjects for imaging, choose between competing imaging modalities, and prioritize future research. Examples from trauma imaging illustrate the use of the presented tools. The author advocates the PROACTIVE approach in deciding which imaging strategies are cost-effective (PRO for defining the problem, reframing the problem from multiple perspectives, and focusing on the objective; ACT for expanding the alternatives, considering the consequences and associated chances of each alternative, and identifying the trade-offs involved; IVE for integrating the evidence and values, optimizing the value of interest, and exploring uncertainty). Simulation models play an important role in the assessment of imaging strategies by helping to identify alternative strategies and to integrate the best-available evidence related to risks, benefits, patient values, and costs. Exploring the uncertainty in the evidence and assessing the value of obtaining more information can help prioritize future research and guide study design.
To compare the accuracy of polyp measurement at computed tomographic (CT) colonography by using two-dimensional (2D) multiplanar reformation (MPR) and three-dimensional (3D) endoluminal displays obtained both in a colon phantom and at clinical examinations.
This HIPAA-compliant study had institutional review board approval, and all patients provided signed informed consent, both of which allowed for additional retrospective evaluation. Two-dimensional and 3D CT colonography displays were generated from data obtained in an in vitro colon phantom that contained 10 6-13-mm synthetic polyps and from data obtained at in vivo clinical CT colonography examinations performed in 10 patients (five men, five women; mean age, 56.3 years) with proved polyps (size range, 7-25 mm). The reference standard for in vivo polyp size was optical colonoscopic measurement with a calibrated linear probe. Polyps were measured at CT colonography with 2D MPR and 3D endoluminal displays and electronic calipers by four radiologists who were unaware of the reference size measurements. The largest of the three 2D MPR measurements was considered the "optimized" 2D projection. Statistical analysis was performed with Wilcoxon signed rank, repeated-measures analysis of variance, and paired t testing.
For the phantom, the mean errors (differences between actual polyp size and that measured at CT colonography) for 2D transverse, 2D coronal, and 3D endoluminal displays were 1.6 mm +/- 0.8 (standard deviation), 1.4 mm +/- 0.7, and 0.8 mm +/- 0.5, respectively. For in vivo polyp measurements, the mean errors for 2D transverse, 2D coronal, 2D sagittal, and 3D displays were 4.4 mm +/- 3.5, 3.8 mm +/- 3.3, 4.6 mm +/- 3.0, and 1.9 mm +/- 1.6, respectively. The 2D measurements underestimated actual polyp sizes in all cases. The differences in mean errors between 2D MPR and 3D endoluminal measurements were significant (P < .05). When the optimized 2D view was considered for in vivo measurement, the mean error decreased to 3.0 mm +/- 2.6 (P = .2).
Linear polyp measurement on 3D endoluminal views was significantly more accurate than measurement on 2D transverse, coronal, or sagittal views, both in vitro and in vivo, for the CT colonography system evaluated. Use of the optimized 2D view substantially reduced 2D measurement error and may be valuable when used in conjunction with 3D measurement.
Computerized tomographic (CT) colonography is a potential alternative to colonoscopy for colorectal cancer screening. Its main advantage, a better safety profile, may be offset by its limitations: lower sensitivity, need for colonoscopy in cases where results are positive, and expense.
We performed an economic evaluation, using decision analysis, to compare CT colonography with colonoscopy for colorectal cancer screening in patients over 50 years of age. Three-year outcomes included number of colonoscopies, perforations and adenomas removed; deaths from perforation and from colorectal cancer from missed adenomas; and direct health care costs. The expected prevalence of adenomas, test performance characteristics of CT colonography and colonoscopy, and probability of colonoscopy complications and cancer from missed adenomas were derived from the literature. Costs were determined in detail locally.
Using the base-case assumptions, a strategy of CT colonography for colorectal cancer screening would cost 2.27 million dollars extra per 100,000 patients screened; 3.78 perforation-related deaths would be avoided, but 4.11 extra deaths would occur from missed adenomas. Because screening with CT colonography would cost more and result in more deaths overall compared with colonoscopy, the latter remained the dominant strategy. Our results were sensitive to CT colonography's test performance characteristics, the malignant risk of missed adenomas, the risk of perforation and related death, the procedural costs and differences in screening adherence.
At present, CT colonography cannot be recommended as a primary means of population-based colorectal cancer screening in Canada.
To conduct a population-based study on the provision of large bowel endoscopic services in Ontario.
Data from the following databases were analyzed: the Ontario Health Insurance Plan, the Institute for Clinical Evaluative Sciences Physicians Database and Statistics Canada. The flexible sigmoidoscopy and colonoscopy rates per 10,000 persons (50 to 74 years of age) by region between April 1, 2001, and March 31, 2002, were calculated, as well as the numbers and types of physicians who performed each procedure.
In 2001/2002, a total of 172,108 colonoscopies and 43,400 flexible sigmoidoscopies were performed in Ontario for all age groups. The colonoscopy rate was approximately five times that of flexible sigmoidoscopy; rates varied from 463.1 colonoscopies per 10,000 people in the north to 286.8 colonoscopies per 10,000 people in the east. Gastroenterologists in all regions tended to perform more procedures per physician, but because of the large number of general surgeons, the total number of procedures performed by each group was almost the same.
Population-based rates of colonoscopies and flexible sigmoidoscopies are low in Ontario, as are the procedure volumes of approximately one-quarter of physicians.
Advanced neoplasia represents the primary target for colorectal-cancer screening and prevention. We compared the diagnostic yield from parallel computed tomographic colonography (CTC) and optical colonoscopy (OC) screening programs.
We compared primary CTC screening in 3120 consecutive adults (mean [+/-SD] age, 57.0+/-7.2 years) with primary OC screening in 3163 consecutive adults (mean age, 58.1+/-7.8 years). The main outcome measures included the detection of advanced neoplasia (advanced adenomas and carcinomas) and the total number of harvested polyps. Referral for polypectomy during OC was offered for all CTC-detected polyps of at least 6 mm in size. Patients with one or two small polyps (6 to 9 mm) also were offered the option of CTC surveillance. During primary OC, nearly all detected polyps were removed, regardless of size, according to established practice guidelines.
During CTC and OC screening, 123 and 121 advanced neoplasms were found, including 14 and 4 invasive cancers, respectively. The referral rate for OC in the primary CTC screening group was 7.9% (246 of 3120 patients). Advanced neoplasia was confirmed in 100 of the 3120 patients in the CTC group (3.2%) and in 107 of the 3163 patients in the OC group (3.4%), not including 158 patients with 193 unresected CTC-detected polyps of 6 to 9 mm who were undergoing surveillance. The total numbers of polyps removed in the CTC and OC groups were 561 and 2434, respectively. There were seven colonic perforations in the OC group and none in the CTC group.
Primary CTC and OC screening strategies resulted in similar detection rates for advanced neoplasia, although the numbers of polypectomies and complications were considerably smaller in the CTC group. These findings support the use of CTC as a primary screening test before therapeutic OC.
Purpose: To perform a systematic review of the cost-effectiveness of colorectal cancer screening for the U.S. Preventive Services Task Force. Data Sources: MEDLINE and the British National Health Service Economic Evaluation Database, January 1993 through September 2001. Study Selection: Original economic evaluations of colorectal cancer screening in average-risk patients were reviewed. The authors sought studies addressing the incremental cost-effectiveness of different screening strategies compared with no screening, of different screening strategies compared with one another, and of different ages of screening initiation and cessation. Two investigators independently reviewed each abstract, and potentially eligible articles were retrieved. A four-member working group reached consensus regarding final inclusion or exclusion of articles. Data Extraction: One reviewer extracted data into evidence tables. The results were checked by other members and discrepancies resolved by consensus. Data Synthesis: Among 180 potential articles identified, 7 were retained in the final analysis. Compared with no screening, cost-effectiveness ratios for screening with any of the commonly considered methods were generally between 25000 per life-year saved. No one strategy was consistently found to be the most effective or to have the best incremental cost-effectiveness ratio. Currently available models provided insufficient evidence to determine optimal starting and stopping ages for screening. Conclusions: Screening for colorectal cancer appears cost-effective compared with no screening, but a single optimal strategy cannot be determined from the currently available data. Additional data regarding adherence with screening over time, complication rates in real-world settings, and colorectal cancer biology are needed. Additional analyses are necessary to determine optimal ages of initiation and cessation.
Objective : To determine whether patients with colorectal cancer are less likely than unaffected controls to have had one or more endoscopic procedures (flexible sigmoidoscopy, colonoscopy, or polypectomy) before being diagnosed with cancer. Design : Case-control study. Setting : Hospitals of the Department of Veterans Affairs. Patients : 8722 and 7629 case-patients with colon and rectal cancer, respectively, and age-, sex-, race-matched controls who were discharged at the same time as the corresponding case-patients. Measurements : Number and type of endoscopic procedures of the large bowel done from 1981 until the development of colorectal cancer in each case-patient. The influence of endoscopic procedures on the development of colorectal cancer was tested by conditional multiple logistic regression analysis. Results : Compared with controls, patients with colorectal cancer were less likely to have had an endoscopic procedure of the large bowel before being diagnosed with cancer (odds ratio for colon cancer, 0.51 [95% Cl, 0.44 to 0.58] ; odds ratio for rectal cancer, 0.55 [Cl, 0.47 to 0.64]). In patients who had flexible sigmoidoscopy, colonoscopy, and polypectomy, the odds ratios were even smaller. When analyzed by separate 1-year intervals, patients with cancer had significantly fewer procedures during periods of up to 6 years before the onset of their cancer. Similarly, fewer inpatient and outpatient procedures were done in patients than in controls. Conclusions : Endoscopic procedures of the large bowel reduce the risk for developing colon and rectal cancer by 50%, their protective influence lasting 6 years.
Decision making in health care means navigating through a complex and
tangled web of diagnostic and therapeutic uncertainties, patient
preferences and values, and costs. In addition, medical therapies may
include side effects, surgery may lead to undesirable complications, and
diagnostic technologies may produce inconclusive results. In many
clinical and health policy decisions it is necessary to counterbalance
benefits and risks, and to trade off competing objectives such as
maximizing life expectancy vs optimizing quality of life vs minimizing
the required resources. This textbook plots a clear course through these
complex and conflicting variables. It clearly explains and illustrates
tools for integrating quantitative evidence-based data and subjective
outcome values in making clinical and health policy decisions. An
accompanying CD-ROM features solutions to the exercises, PowerPoint®
presentations of the illustrations, and sample models and tables.
The current practice of removing adenomatous polyps of the colon and rectum is based on the belief that this will prevent colorectal cancer. To address the hypothesis that colonoscopic polypectomy reduces the incidence of colorectal cancer, we analyzed the results of the National Polyp Study with reference to other published results.
The study cohort consisted of 1418 patients who had a complete colonoscopy during which one or more adenomas of the colon or rectum were removed. The patients subsequently underwent periodic colonoscopy during an average follow-up of 5.9 years, and the incidence of colorectal cancer was ascertained. The incidence rate of colorectal cancer was compared with that in three reference groups, including two cohorts in which colonic polyps were not removed and one general-population registry, after adjustment for sex, age, and polyp size.
Ninety-seven percent of the patients were followed clinically for a total of 8401 person-years, and 80 percent returned for one or more of their scheduled colonoscopies. Five asymptomatic early-stage colorectal cancers (malignant polyps) were detected by colonoscopy (three at three years, one at six years, and one at seven years). No symptomatic cancers were detected. The numbers of colorectal cancers expected on the basis of the rates in the three reference groups were 48.3, 43.4, and 20.7, for reductions in the incidence of colorectal cancer of 90, 88, and 76 percent, respectively (P < 0.001).
Colonoscopic polypectomy resulted in a lower-than-expected incidence of colorectal cancer. These results support the view that colorectal adenomas progress to adenocarcinomas, as well as the current practice of searching for and removing adenomatous polyps to prevent colorectal cancer.
Screening is effective in reducing colorectal cancer mortality. Recommended colorectal cancer screening options include a home fecal occult blood test (FOBT) or colorectal endoscopy (sigmoidoscopy or colonoscopy). Past surveys have indicated that colorectal cancer screening prevalence in the United States is low. The purpose of this analysis was to determine the prevalence of colorectal cancer test use in the United States by various factors and to examine reasons for not having a colorectal cancer test.
Data on respondents ages > or =50 years from the 2005 National Health Interview Survey (n = 13,269) were analyzed. The proportion of the U.S. population that had home FOBT within the past year or endoscopy within the past 10 years was examined by sociodemographic, health-care access, and other health-related factors. Reported reasons for not having FOBT or endoscopy were also analyzed.
The age-standardized proportion of respondents who reported FOBT within the past year and/or endoscopy within the past 10 years was 50.0% [95% confidence interval (95% CI), 48.8-51.2]. Colorectal cancer testing rates were particularly low among people without health-care coverage (24.1%; 95% CI, 19.2-29.7) or without a usual source of health care (24.7%; 95% CI, 20.8-29.0). The most commonly reported reason for not having a colorectal cancer test was "never thought about it."
In 2005, about half of Americans ages > or =50 years did not have appropriate colorectal cancer testing. Increased efforts to expand health-care coverage or to provide colorectal cancer tests to people without health-care coverage are needed to increase colorectal cancer screening.
Incorporating patients' preferences into colorectal cancer (CRC) screening recommendations has been identified as a potential mechanism for increasing adherence. This study used conjoint analysis to describe variation in CRC screening preferences among racially/ethnically diverse primary care patients.
We recruited patients ages 50-80 of a large practice-based research network stratified by white, African American, or Hispanic race/ethnicity to complete a preference assessment instrument. Participants were asked to rate 8 hypothetical CRC screening test scenarios comprised of different combinations of 5 attributes and 6 scenarios designed to depict guideline-recommended CRC screening tests (eg, fecal occult blood test, flexible sigmoidoscopy, colonoscopy, and double contrast barium enema) including new technology (eg, virtual colonoscopy, fecal immunochemical test). Responses were used to calculate the overall importance of test attributes, the relative importance of attribute levels, and to identify factors associated with preferences.
Two hundred twelve primary care patients were recruited to the study (74 white, 60 African American, 78 Hispanic). Of the guideline-recommended tests, 37% preferred COL, 31% FOBT, 15% BE, and 9% SIG. Ratings of new technology tests were significantly (P < 0.05) higher than ratings of guideline-recommended tests. The order of the importance of attributes was: what the test involved (37%), accuracy (19%), frequency (17%), discomfort (15%), and preparation (13%). Part-worth utilities for 1 attribute showed that collecting a stool sample was most preferable and endoscopy without sedation least preferable. Multivariate regression found that race/ethnicity and specific test attributes were independently associated (P < 0.05) with test preferences.
Primary care patients have distinct preferences for CRC screening tests that can be linked to test attributes. Racial/ethnic variations in test preferences persist when controlling for attributes. Tailoring screening recommendations to patients' preferences may increase screening adherence.
Surveillance by repeated colonoscopy is currently recommended for patients with colorectal adenomas. We assessed the long-term risk of colorectal cancer after rigid-instrument sigmoidoscopy and polypectomy in 1618 patients with rectosigmoid adenomas (tumor of the rectum or distal sigmoid colon) who did not undergo surveillance. A total of 22,462 person-years of observation were accrued (mean, 14 years per patient).
The incidence of subsequent rectal cancer in these patients was similar to that in the general population (standardized incidence ratio, 1.2; 95 percent confidence interval, 0.7 to 2.1). Most rectal cancers developed in patients whose adenomas had been inadequately removed; the risk was very low after complete removal. The risk of subsequent colon cancer depended on the histologic type, size, and number of adenomas in the rectosigmoid. Among 842 patients with a rectosigmoid adenoma that was tubulovillous, villous, or large (greater than or equal to 1 cm), colon cancer developed in 31 patients. The standardized incidence ratio was 3.6 (95 percent confidence interval, 2.4 to 5.0) overall and 6.6 (95 percent confidence interval, 3.3 to 11.8) if there were multiple rectosigmoid adenomas. Among the remaining 776 patients with only small, tubular adenomas (whether single or multiple), colon cancer developed in only 4 patients. The standardized incidence ratio in this group was 0.5 (95 percent confidence interval, 0.1 to 1.3).
Follow-up colonoscopic examinations may be warranted in patients with tubulovillous, villous, or large adenomas in the rectosigmoid, particularly if the adenomas are also multiple. In patients with only a single, small tubular adenoma that is only mildly or moderately dysplastic (43 percent of our series), however, surveillance may not be of value because the risk of cancer is so low.
Computed tomography (CT) or magnetic resonance (MR) colonography is a new technique that uses data generated from CT or MR imaging to create two- and three-dimensional scans of the colon. It has been advocated to become the new primary technique of screening for colorectal cancer. The economic feasibility of such recommendation, however, has not yet been evaluated.
The cost-effectiveness of two screening strategies using CT colonography or conventional colonoscopy was compared by computer models based on a Markov process. We supposed that a hypothetical population of 100,000 subjects aged 50 yr undergoes a screening procedure every 10 yr. Suspicious findings of CT colonography are worked-up by colonoscopy. After polypectomy, colonoscopy is repeated every 3 yr until no adenomatous polyps are found.
Under baseline conditions, screening by CT colonography costs 20,930 spent on colonoscopy screening. The incremental cost-effectiveness ratios comparing CT colonography to no screening and colonoscopy to CT colonography were 10,408, respectively. Screening by colonoscopy remains more cost-effective even if the sensitivity and specificity of CT colonography both rise to 100%. For the two screening procedures to become similarly cost-effective, CT colonoscopy needs to be associated with an initial compliance rate 15-20% better or procedural costs 54% less than colonoscopy.
To become cost-effective and be able to compete with colonoscopy in screening for colorectal cancer, CT or MR colonography would need be offered at a very low price or result in compliance rates much better than those associated with colonoscopy.
The literature which considers the statistical properties of cost-effectiveness analysis has focused on estimating the sampling distribution of either an incremental cost-effectiveness ratio or incremental net benefit for classical inference. However, it is argued here that rules of inference are arbitrary and entirely irrelevant to the decisions which clinical and economic evaluations claim to inform. Decisions should be based only on the mean net benefits irrespective of whether differences are statistically significant or fall outside a Bayesian range of equivalence. Failure to make decisions in this way by accepting the arbitrary rules of inference will impose costs which can be measured in terms of resources or health benefits forgone. The distribution of net benefit is only relevant to deciding whether more information is required. A framework for decision making and establishing the value of additional information is presented which is consistent with the decision rules in CEA. This framework can distinguish the simultaneous but conceptually separate steps of deciding which alternatives should be chosen, given existing information, from the question of whether more information should be acquired. It also ensures that the type of information acquired is driven by the objectives of the health care system, is consistent with the budget constraint on service provision and that research is designed efficiently.
Analysts performing cost-effectiveness analyses often do not have the resources to gather original quality-of-life (QOL) weights. Furthermore, variability in QOL for the same health state hampers the comparability of cost-effectiveness analyses. For these reasons, opinion leaders such as the Panel on Cost-Effectiveness in Health and Medicine have called for a national repository of QOL weights. Some authors have responded to the call by performing large primary studies of QOL. We take a different approach, amassing existing data with the hope that it will be combined responsibly in meta-analytic fashion. Toward the goal of developing a national repository of QOL weights to aid cost-effectiveness analysts, 1,000 health-related QOL estimates were gathered from publicly available source documents.
To identify documents, we searched databases and reviewed the bibliographies of articles, books, and government reports. From each document, we extracted information on the health state, QOL weight, assessment method, respondents, and upper and lower bounds of the QOL scale. Detailed guidelines were followed to ensure consistency in data extraction.
We identified 154 documents yielding 1,000 original QOL weights. There was considerable variation in the weights assessed by different authors for the same health state. Methods also varied: 51% of authors used direct elicitation (standard gamble, time tradeoff, or rating scale), 32% estimated QOL based on their own expertise or that of others, and 17% used health status instruments.
This comprehensive review of QOL data should lead to more consistent use of QOL weights and thus more comparable cost-effectiveness analyses.
The clinical significance of a distal colorectal polyp is uncertain. We determined the risk of advanced proximal neoplasia, defined as a polyp with villous features, a polyp with high-grade dysplasia, or cancer, among persons with distal hyperplastic or neoplastic polyps as compared with the risk among persons with no distal polyps. We analyzed data from 1994 consecutive asymptomatic adults (age, 50 years or older) who underwent colonoscopic screening for the first time between September 1995 and December 1998 as part of a program sponsored by an employer. The location and histologic features of all polyps were recorded. Colonoscopy to the level of the cecum was completed in 97.0 percent of the patients.
Sixty-one patients (3.1 percent) had advanced lesions in the distal colon, including 5 with cancer, and 50 (2.5 percent) had advanced proximal lesions, including 7 with cancer. Twenty-three patients with advanced proximal neoplasms (46 percent) had no distal polyps. The prevalence of advanced proximal neoplasia among patients with no distal polyps was 1.5 percent (23 cases among 1564 persons; 95 percent confidence interval, 0.9 to 2.1 percent). Among patients with distal hyperplastic polyps, those with distal tubular adenomas, and those with advanced distal polyps, the prevalence of advanced proximal neoplasia was 4.0 percent (8 cases among 201 patients), 7.1 percent (12 cases among 168 patients), and 11.5 percent (7 cases among 61 patients), respectively. The relative risk of advanced proximal neoplasia, adjusted for age and sex, was 2.6 for patients with distal hyperplastic polyps, 4.0 for those with distal tubular adenomas, and 6.7 for those with advanced distal polyps, as compared with patients who had no distal polyps. Older age and male sex were associated with an increased risk of advanced proximal neoplasia (relative risk, 1.3 for every five years of age and 3.3 for male sex).
Asymptomatic persons 50 years of age or older who have polyps in the distal colon are more likely to have advanced proximal neoplasia than are persons without distal polyps. However, if colonoscopic screening is performed only in persons with distal polyps, about half the cases of advanced proximal neoplasia will not be detected.
Colorectal cancer is one of the leading causes of death from cancer in Western countries. Removal of adenomas is based on the assumption that it could lead to a reduction in the incidence of colorectal cancer, as demonstrated by the National Polyp Study in the USA. A critical issue is whether the benefit observed in clinical trials can also be observed in standard clinical practice. To address the issue, a multicentre Italian collaborative study was organised.
The study cohort comprised 1693 subjects of both sexes, aged 40-69 years, enrolled between 1980 and 1987 following a total colon examination (TCE) (that is, total colonoscopy or colonoscopy and double contrast barium enema), with removal of at least one adenoma larger than 5 mm in diameter. Exclusion criteria were genetic syndromes, previous adenomas or colorectal cancer, previous colonic resection, inflammatory bowel disease, or sessile adenomas more than 3 cm in diameter. Follow up ended in December 1996 by TCE or telephone interview, and review of the medical records, clinical files, or death certificates. Incidence ratios for colorectal cancer were compared with expected age and sex specific incidences in the Italian general population.
Follow up data were obtained for 97.3% of cases for a total of 14 211 person/years. Mean follow up was 10.5 years. Six colorectal cancer cases (four in males, two in females) at various stages were ascertained (one at 29 months, two at five years, one at seven years, one at eight years, and one at 10 years from the index examination). The number of cancers expected in the reference population was 17.7 for an incidence ratio of 0.34 (confidence interval 0.23-0.63; p<0.01).
Colonoscopic polypectomy substantially reduced the incidence of colorectal cancer in the cohort compared with that expected in the general population. These results are of particular relevance considering that those with adenomas are at increased risk of colorectal cancer and that this retrospective study was performed on data obtained in standard clinical practice. This observation strengthens the concept of effective population screening in view of the fact that adenomatous polyps are the most frequent neoplastic outcome of screening and their removal is associated with a decrease in the incidence of colorectal cancer.
Most colorectal carcinomas develop from preformed adenomas, but only a minority of adenomas undergo malignant transformation. The clinical significance of polyps of size < 0.5 cm is controversial. The primary goal of this study was to assess the independent risk factors of adenoma and patient characteristics associated with advanced pathological features (APF; i.e. high-grade dysplasia or invasive carcinoma) in colorectal adenomas. A secondary goal was to assess the malignant potential of adenomas with a diameter of < 0.5 cm.
Patients who underwent total colonoscopy at our Medical Department between 1978 and 1996 and had at least one colorectal adenoma were considered for this study. Patients with a history of colorectal cancer, prior polypectomy or colorectal surgery were excluded. A total of 7590 adenomas removed from 4216 patients were included in this analysis. Logistic regression analysis was used to study the impact of different adenoma and patient characteristics on the risk of APF.
Size proved to be the most important risk factor for APF. The percentage of adenomas with APF was 3.4%, 13.5% and 38.5% for adenomas of diameter < 0.5 cm, 0.5-1 cm and > 1 cm, respectively. Villous or tubulovillous histology, left-sided location and age >or= 60 years were also associated with APF, whereas sex and number of adenomas had no significant impact. Logistic regression analysis revealed that the risk of an adenoma containing APF was best described by a model incorporating the factors size, location, age, and the age by histology interaction. In the class of adenomas with diameter < 0.5 cm, no invasive carcinoma was found, but 3.4% of adenomas had high-grade dysplasia.
The risk of a colorectal adenoma containing APF can be estimated only by a complex model taking into account several adenoma and patient characteristics. Size, histological type, location and age are independent risk factors for APF in colorectal adenomas. As a considerable percentage of adenomas with diameter < 0.5 cm contain high-grade dysplasia, the clinical conclusion from our study is that all adenomas, including those with diameter < 0.5 cm, should be removed whenever possible.
There has been much speculation about the potential impact on the use of conventional colonoscopy if "virtual" computed tomographic colonography (CTC) became a widely accepted modality for colorectal cancer (CRC) screening. However, no formal analysis of the impact of CTC on colonoscopy demand has been reported.
A mathematical model to predict colonoscopy demand based on several relevant input parameters was constructed. Current national colonoscopy practice, estimated using various published reports, was used as the foundation to project colonoscopy demand if CTC were implemented as the primary CRC screening modality.
In the base-case analysis, if CTC were used as the primary modality for CRC screening, 1.78 million colonoscopies could be eliminated from the total 6.47 million in 2003. Depending on the polyp size threshold used to define a CTC study as positive (6 or 10 mm), this loss would be partially offset by 1.21 million (6 mm) or .34 million (10 mm) follow-up colonoscopies for CTC examinations with positive findings, resulting in a net loss of .57 million (8.8% decrease) (6 mm) or 1.44 million (22.3% decrease) (10 mm). Extensive sensitivity analyses showed that the findings of this model were robust and insensitive to most parameters tested but were sensitive to a few parameters, including the percentage of CTC examinations with positive findings.
Wide-scale implementation of CTC for CRC screening would likely lead to a decrease in use of conventional colonoscopy. The percentage of CTC studies with positive findings seemed to be a pivotal variable, which would be determined in large part by the polyp size ultimately established to define a positive finding.
Decisions in health care must be made, despite uncertainty about benefits, risks, and costs. Value of information analysis is a theoretically sound method to estimate the expected value of future quantitative research pertaining to an uncertain decision. If the expected value of future research does not exceed the cost of research, additional research is not justified, and decisions should be based on current evidence, despite the uncertainty. To assess the importance of individual parameters relevant to a decision, different value of information methods have been suggested. The generally recommended method assumes that the expected value of perfect knowledge concerning a parameter is estimated as the reduction in expected opportunity loss. This method, however, results in biased expected values and incorrect importance ranking of parameters. The objective of this paper is to set out the correct methods to estimate the partial expected value of perfect information and to demonstrate why the generally recommended method is incorrect conceptually and mathematically.
The purpose of this study was to determine the rate of cancer in a modern series of colorectal polyps. All pathology reports from colon and rectal polyps from 1999 to 2002 were reviewed. Reports of bowel resections, cancer-free polyps, and polyp-free mucosal biopsies were excluded. Polyps were grouped by size, and the rate of adenocarcinoma was determined. x2 was used for analysis. A total of 4,443 polyps were found, of which 3,225 were adenomatous [2,883 (89.4%) tubular adenomas, 399 (9.3%) tubulo-villous adenomas, 32 (1.0%) villous adenomas, and 11 (0.3%) carcinomas]. The rate of adenocarcinoma by size was 0.07 per cent for polyps <1 cm, 2.41 per cent for polyps 1-2 cm, and 19.35 per cent for polyps >2 cm, representing significantly fewer cancers for each category of polyp size than the accepted standard. The rate of carcinoma in colon polyps is much lower than previously thought and currently stated in many texts. These data do not alter the recommendations for polyp removal, however, failure to retrieve a specimen in a polyp <1 cm in size is unlikely to have an adverse outcome because the chances of malignancy are very low.
The prevalence of advanced histology in small polyps has become a crucial issue in optimizing colorectal cancer screening strategies, especially in view of the advent of computed tomography colonography. We evaluated the prevalence of advanced histology in small and diminutive adenomas to clarify their clinical importance in terms of malignant potential.
Data were reviewed retrospectively from 3291 colonoscopies performed on asymptomatic patients found to have an adenoma on screening with flexible sigmoidoscopy a few weeks before the colonoscopy or who had a family history of colorectal cancer. All polyps were excised endoscopically and sent for pathology testing. Specimens with advanced histology were confirmed by a second reading.
Of the 3291 colonoscopies performed, 1235 colonoscopies yielded a total of 1933 small or diminutive adenomatous polyps. Advanced histology including carcinoma was found in 10.1% of small (5-10 mm) adenomas and in 1.7% of diminutive adenomas (< or = 4 mm). Carcinoma was found in .9% of small adenomas, and 0% of diminutive adenomas. Of the 107 patients found to have polyps 2-10 mm with advanced histology, 100 (93%) were referred for colonoscopy because of an adenoma found on a recent screening with flexible sigmoidoscopy. Seven patients underwent colonoscopy for a positive family history of colon cancer; all 7 had a single affected first-degree relative older than age 50.
Adenomas 5-10 mm in size harbor pathologically significant histology, and the need for removal of these lesions must be addressed to optimize colorectal cancer prevention.
Purpose:
Since the concept of "advanced" or "dangerous" adenomas was introduced in 1992, less concern has been directed to diminutive colorectal adenomas. They apparently confer no increased risk of metachronous colorectal cancer and some investigators have suggested that they need neither follow-up nor treatment. This study is intended to discover how often small colorectal adenomas have unfavorable histologic features.
Methods:
Since 1995 the details of all colorectal polyps have been entered into a database, along with data concerning patients, symptoms, treatment, and outcome. Using this database all adenomas were categorized into three groups: Group I, <6 mm diameter, Group II, 6 to 10 mm diameter, and Group III, >10 mm diameter. "High risk" adenomas were defined as those containing >25 percent villous architecture, those with severe dysplasia, and those over 10 mm in size. Thus all Group III adenomas are high-risk by definition. The effects of family history, patient age, and polyp location on the proportions of Group I and Group II adenomas that were histologically high risk were examined.
Results:
There were 5,722 polyps of which 4,381 (76.6 percent) were Group I, 666 (11.6 percent) were Group II, and 675 (11.8 percent) were Group III. These included 24 invasive cancers (2 in Group I, 1 in Group II, and 21 in Group III. Of the Group I adenomas, 91/2,064 (4.4 percent) were high risk compared to 65/417 (15.6 percent) in Group II. Of the 564 Group III adenomas, 326 (57.8 percent) had unfavorable histology. There was no effect of age, family history, or site of the polyp on the proportion of polyps that were high risk.
Conclusions:
Four percent of adenomas less than 6 mm diameter and 16 percent of those between 6 and 10 mm have unfavorable histology. Small adenomas can still be clinically significant and should not be ignored. Since the concept of "advanced" or "dangerous" adenomas was introduced in 1992, less concern has been directed to diminutive colorectal adenomas. They apparently confer no increased risk of metachronous colorectal cancer and some investigators have suggested that they need neither follow-up nor treatment. This study is intended to discover how often small colorectal adenomas have unfavorable histologic features.
The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastroenterological disorders seen most often in patients. Published with practicing clinicians in mind, the journal aims to be easily accessible, organizing its content by topic, both online and in print. www.amjgastro.com, *2007 Journal Citation Report (Thomson Reuters, 2008)
Colorectal cancer is a major cause of cancer death in European countries and differences in screening implementation may in part explain USA vs European survival differences. Despite the evidence, no study has evaluated the population colorectal cancer screening (CCS) coverage in any European country. We aimed to index the current CCS practices among a large sample of Greek healthy adults.
The study was designed as a cross-sectional survey. Screening practice habits of 5,259 healthy adults, aged 50-80, were surveyed. Both overall and screening practices of stool occult blood test (SOBT), digital rectal examination (DRE), and colonoscopy or sigmoidoscopy (COL/SIG) were analyzed.
Of the population analyzed, 90.1% declared that they were interested in cancer prevention activities. Overall SOBT practice rate within the last 2 years was 4.77%. When only screening procedures were analyzed, this percentage shrank to 1.73%. Overall and screening COL/SIG rates within the last 10 years were 8.76 and 1.74%, respectively. The respective proportions of individuals who underwent DRE were 14.54 and 5.2%. Evidence-based screening practices were influenced by age, family history of colorectal cancer, profession, and educational level; however, SOBT and colonoscopy/sigmoidoscopy did not overcome 4.1 and 4.6% in any subpopulation analyzed.
The level of CCS coverage among the examined sample of Greek adults was discouraging. Surveys among other European countries are encouraged.
Decisions to adopt, reimburse or issue guidance on the use of health technologies are increasingly being informed by explicit cost-effectiveness analyses of the alternative interventions. Healthcare systems also invest heavily in research and development to support these decisions. However, the increasing transparency of adoption and reimbursement decisions, based on formal analysis, contrasts sharply with research prioritisation and commissioning. This is despite the fact that formal measures of the value of evidence generated by research are readily available.
The results of two recent opportunities to apply value of information analysis to directly inform policy decisions about research priorities in the UK are presented. These include a pilot study for the UK National Co-ordinating Centre for Health Technology Assessment (NCCHTA) and a pilot study for the National Institute for Health and Clinical Excellence (NICE). We demonstrate how these results can be used to address a series of policy questions, including: is further research required to support the use of a technology and, if so, what type of research would be most valuable? We also show how the results can be used to address other questions such as, which patient subgroups should be included in subsequent research, which comparators and endpoints should be included, and what length of follow up would be most valuable.
We examined the cost-effectiveness of 2- and 3-dimensional computerized tomography (CT) colonography as a screening test for colorectal neoplasia.
We created a Markov model of the natural history of colorectal cancer. Effectiveness of screening was based upon the diagnostic accuracy of tests in detecting polyps and cancer.
CT colonography every 5 or 10 yr was effective and cost-effective relative to no screening. Optical colonoscopy dominates 2-dimensional CT colonography done every 5 or 10 yr. Optical colonoscopy is weakly dominant over 3-dimensional CT colonography done every 10 yr. 3-D CT colonography done every 5 yr is more effective than optical colonoscopy every 10 yr, but costs an incremental 156,000 dollars per life-year gained. Sensitivity analyses show that test costs, accuracy, and adherence are critical determinants of incremental cost-effectiveness. 3-D CT colonography every 5 yr is a dominant strategy if optical colonoscopy costs 1.6 times more than CT colonography. However, optical colonoscopy is a dominant strategy if the sensitivity of CT colonography for 1 cm adenomas is 83% or lower.
CT colonography is an effective screening test for colorectal neoplasia. However, it is more expensive and generally less effective than optical colonoscopy. CT colonography can be reasonably cost-effective when the diagnostic accuracy of CT colonography is high, as with primary 3-dimensional technology, and if costs are about 60% of those of optical colonoscopy. Overall, CT colonography technology will need to improve its accuracy and reliability to be a cost-effective screening option.
National guidelines recommending colorectal cancer (CRC) screening for average risk Canadians were released in 2001. The current study determined rates of CRC screening and predictors of screening 3 yr after the guidelines were released.
A population-based random digit dial telephone survey of 1,808 Alberta men and women aged 50-74 yr assessed awareness about, and self-reported rates of, screening.
More average risk women than men reported a recent screening with a home fecal occult blood test (FOBT) (14.0%vs 9.8%, P= 0.013) but men had slightly higher rates of screening endoscopy in the past 5 yr (4.3%vs 1.6%, P= 0.003). Overall, only 14.3% of average risk adults (N = 1,476) were up-to-date on CRC screening. Multivariable predictors of being up-to-date on CRC screening differed for men and women although a doctor's recommendation for screening was a strong predictor for both genders (men OR 5.0, 2.9-8.3, women OR 3.8, 2.3-6.5). Screening for other cancers was also an important predictor in both men and women.
Three years after the release of national guidelines, rates of screening among average risk adults aged 50-74 yr were very low. Public education programs and primary care interventions to specifically invite average risk adults for screening may be required to increase CRC screening rates.
Prior cost-effectiveness models analyzing computed tomography colonography (CTC) screening have assumed that patients with diminutive lesions (<or=5 mm) will be referred to optical colonoscopy (OC) for polypectomy. However, consensus guidelines for CTC recommend reporting only polyps measuring >or=6 mm. The purpose of the current study was to assess the potential harms, benefits, and cost-effectiveness of CTC screening without the reporting of diminutive lesions compared with other screening strategies.
The cost-effectiveness of screening with CTC (with and without a 6-mm reporting threshold), OC, and flexible sigmoidoscopy (FS) were evaluated using a Markov model applied to a hypothetical cohort of 100,000 persons age 50 years.
The model predicted an overall cost per life-year gained relative to no screening of 4361, 7138, 9180, respectively, for CTC with a 6-mm reporting threshold, CTC with no threshold, FS, and OC. The incremental costs associated with reporting diminutive lesions at the time of CTC amounted to $118,440 per additional life-year gained, whereas the incidence of colorectal cancer was reduced by only 1.3% (from 36.5% to 37.8%). Compared with primary OC screening, CTC with a 6-mm threshold resulted in a 77.6% reduction in invasive endoscopic procedures (39,374 compared with 175,911) and 1112 fewer reported OC-related complications from perforation or bleeding.
CTC with nonreporting of diminutive lesions was found to be the most cost-effective and safest screening option evaluated, thereby providing further support for this approach. Overall, the removal of diminutive lesions appears to carry an unjustified burden of costs and complications relative to the minimal gain in clinical efficacy.
We conducted a study to estimate population coverage and detection rate (DR) achievable through different strategies of colorectal cancer (CRC) screening.
A population-based multicenter randomized trial comparing 3 strategies was used: (1) biennial immunologic fecal occult blood test (FIT), (2) "once only" sigmoidoscopy (FS), and (3) "once only" colonoscopy (TC). A random sample of men and women, aged 55 to 64 years, was drawn from general practitioners' (GP) rosters. Eligible subjects, randomized within GP, were mailed a personal invitation. Nonresponders in groups 2 and 3 were invited again at 12 and 24 months. Screenees with "high-risk" distal polyps (villous component >20%, high-grade dysplasia, CRC, size >or=10 mm, >2 adenomas) at FS, or with positive FIT, were referred for TC.
The attendance rate was 32.3% (1965/6075) for FIT, 32.3% (1944/6018) for FS, 26.5% (1597/6021) for TC. FIT detected 2 patients with CRC (0.1%) and 21 with an advanced adenoma (1.1%). The corresponding figures were as follows: 12 (0.6%) and 86 (4.5%) patients, respectively, for FS; 13 (0.8%) and 100 (6.3%) patients, respectively, for TC. To detect 1 advanced neoplasm, it would be necessary to invite 264 people with FIT, 60 with FS, 53 with TC. FS would have detected 27.3% of the proximal advanced neoplasms detected at TC. Assuming the same participation rate at TC as at FS, 48 TCs would be necessary to detect 1 additional advanced neoplasm missed by FS.
When participants are offered 1 screening test, participation is lower in a TC than in an FS program. However, DR of advanced neoplasia is higher with TC.
Losses to follow-up and administrative censoring can cloud the interpretation of trial-based economic evaluations. A number of investigators have examined the impact of different levels of adjustment for censoring, including nonadjustment, adjustment of effects only, and adjustment for both costs and effects. Nevertheless, there is a lack of research on the impact of censoring on decision-making. The objective of this study was to estimate the impact of adjustment for censoring on the interpretation of cost-effectiveness results and expected value of perfect information (EVPI), using a trial-based analysis that compared rate- and rhythm-control treatments for persons with atrial fibrillation.
Three different levels of adjustment for censoring were examined: no censoring of cost and effects, censoring of effects only, and censoring of both costs and effects. In each case, bootstrapping was used to estimate the uncertainty incosts and effects, and the EVPI was calculated to determine the potential worth of further research.
Censoring did not impact the adoption decision. Nevertheless, this was not the case for the decision uncertainty or the EVPI. For a threshold of 626,000 (partial censoring) to $117 million (full censoring) for the eligible US population.
The level of adjustment for censoring in trial-based cost-effectiveness analyses can impact on the decisions to fund a new technology and to devote resources for further research. Only when censoring is taken into account for both costs and effects are these decisions appropriately addressed.
Colorectal cancer (CRC) screening uptake remains poor. Until we understand patient motivation and preferences for undertaking screening, it is unlikely the uptake will be optimal. Our objective is to examine patient preferences for CRC screening modalities and uptake rates using utility-based methods.
The preference survey was mailed to a random sample of Canadian subjects aged 40 to 60 years from a primary care network. A fractional factorial experimental design maximized D-efficiency and included four blocks with 12 choice tasks in a conditional two-step design, two-alternative discrete choice format with five screening attributes (process, pain, preparation, sensitivity, and specificity). Bivariate probit regression analysis was used to estimate patient preferences for attributes, choice probabilities for alternative modalities and expected rates of uptake.
Five hundred forty-seven of 1047 surveys were returned. Almost 30% of respondents preferred no screening. The most preferred test attribute levels were noninvasive process (e.g., CT), no preparation, no pain, 100% specificity, and 90% sensitivity. Accuracy-related attributes were more important than test process-related attributes. Virtual colonoscopy was the most preferred, followed by colonoscopy, barium enema, sigmoidoscopy, and fecal DNA testing, based on simulated choice probability estimates. Fecal occult blood testing (FOBT) was least preferred. Adjusted screening uptake rate estimates showed the greatest impact (42% increase) would be achieved if all CRC screening modalities were available rather than FOBT alone.
Our findings emphasize the important role of patient preferences for no screening and in selecting alternative CRC screening modalities. CRC screening implementation in Canada should consider patient preferences to optimize uptake.
The objective of this study was to assess the clinical and economic impact of colonoscopic referral for small and diminutive polyps detected at CT colonography (CTC) screening.
A decision analysis model was constructed incorporating the expected polyp distribution, advanced adenoma prevalence, colorectal cancer (CRC) risk, CTC performance, and costs related to CRC screening and treatment. The model conservatively assumed that CRC risk was independent of advanced adenoma size. The number of diminutive (< or = 5 mm), small (6-9 mm), and large (> or = 10 mm) CTC-detected polyps needed to be removed to detect one advanced adenoma or prevent one CRC over a 10-year time horizon was calculated. The cost-effectiveness of polypectomy was also assessed.
The estimated 10-year CRC risk for unresected diminutive, small, and large polyps was 0.08%, 0.7%, and 15.7%, respectively. The number of diminutive, small, and large polyps needed to be removed to avoid leaving behind one advanced adenoma was 562, 71, and 2.5, respectively; similarly, 2,352, 297, and 10.7 polypectomies would be needed, respectively, to prevent one CRC over 10 years. The incremental cost-effectiveness ratio of removing all diminutive and small CTC-detected polyps was 59,015 per life-year gained, respectively. Polypectomy for large CTC-detected polyps yielded a cost-saving of $151 per person screened.
For diminutive polyps detected at CTC screening, the very low likelihood of advanced neoplasia and the high costs associated with polypectomy argue against colonoscopic referral, whereas removal of large CTC-detected polyps is highly effective. The yield of colonoscopic referral for small polyps is relatively low, suggesting that CTC surveillance may be a reasonable management option.
To help guide future outcomes research regarding the use of magnetic resonance (MR) imaging in patients with acute knee trauma in an emergency department setting, with use of prospective data from a randomized clinical trial and value of information analysis.
A total of 189 patients (123 male, 66 female; mean age, 33.4 years) were randomly assigned to undergo radiography alone (n = 93) or radiography and MR imaging (n = 96). Institutional review board approval and informed consent (parental consent for minors) were obtained. During 6 months of follow-up, data on quality of life and 39 cost parameters were collected. Value-of-information analysis was used to estimate the expected benefit of future research to eliminate the decision uncertainty that remained after trial completion. In addition, the parameters that were responsible for most of the decision uncertainty were identified, the expected benefits of various study designs were evaluated, and the optimal sample size was estimated.
Only three parameters were responsible for most of the decision uncertainty: number of quality-adjusted life-years, cost of an overnight hospital stay, and friction costs. A study in which data on these three parameters are gathered would have an optimal sample size of 3500 patients per arm and would be expected to result in a societal benefit of euro 5.6 million or 70 quality-adjusted life-years.
The optimal study design for use of MR imaging to evaluate acute knee trauma involves a trial in which there are 3500 patients per trial arm, and data on the number of quality-adjusted life-years, cost of an overnight hospital stay, and friction costs are collected.