Review of economic evidence in the prevention and early detection of colorectal cancer.

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 Studies used up-to-date evidence on the diagnostic test performance combined with outdated information on CRC treatments.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

Economic evaluations of pharmacogenetic and pharmacogenomic screening tests : a systematic review : second update of the literature

Objective : Due to extended application of pharmacogenetic and pharmacogenomic screening (PGx) tests it is important to assess whether they provide good value for money. This review provides an update of the literature. Methods : A literature search was performed in PubMed and papers published between August 2010 and September 2014, investigating the cost-effectiveness of PGx screening tests, were included. Papers from 2000 until July 2010 were included via two previous systematic reviews. Studies' overall quality was assessed with the Quality of Health Economic Studies (QHES) instrument. Results : We found 38 studies, which combined with the previous 42 studies resulted in a total of 80 included studies. An average QHES score of 76 was found. Since 2010, more studies were funded by pharmaceutical companies. Most recent studies performed cost-utility analysis, univariate and probabilistic sensitivity analyses, and discussed limitations of their economic evaluations. Most studies indicated favorable cost-effectiveness. Majority of evaluations did not provide information regarding the intrinsic value of the PGx test. There were considerable differences in the costs for PGx testing. Reporting of the direction and magnitude of bias on the cost-effectiveness estimates as well as motivation for the chosen economic model and perspective were frequently missing. Conclusions : Application of PGx tests was mostly found to be a cost-effective or cost-saving strategy. We found that only the minority of recent pharmacoeconomic evaluations assessed the intrinsic value of the PGx tests. There was an increase in the number of studies and in the reporting of quality associated characteristics. To improve future evaluations, scenario analysis including a broad range of PGx tests costs and equal costs of comparator drugs to assess the intrinsic value of the PGx tests, are recommended. In addition, robust clinical evidence regarding PGx tests' efficacy remains of utmost importance

Cost-effectiveness simulation and analysis of colorectal cancer screening in Hong Kong Chinese population: comparison amongst colonoscopy, guaiac and immunologic fecal occult blood testing

Background: The aim of this study was to evaluate the cost-effectiveness of CRC screening strategies from the healthcare service provider perspective based on Chinese population. Methods: A Markov model was constructed to compare the cost-effectiveness of recommended screening strategies including annual/biennial guaiac fecal occult blood testing (G-FOBT), annual/biennial immunologic FOBT (I-FOBT), and colonoscopy every 10 years in Chinese aged 50 year over a 25-year period. External validity of model was tested against data retrieved from published randomized controlled trials of G-FOBT. Recourse use data collected from Chinese subjects among staging of colorectal neoplasm were combined with published unit cost data ($USD in 2009 price values) to estimate a stage-specific cost per patient. Quality-adjusted life-years (QALYs) were quantified based on the stage duration and SF-6D preference-based value of each stage. The cost-effectiveness outcome was the incremental cost-effectiveness ratio (ICER) represented by costs per life-years (LY) and costs per QALYs gained. Results: In base-case scenario, the non-dominated strategies were annual and biennial I-FOBT. Compared with no screening, the ICER presented$20,542/LYs and $3155/QALYs gained for annual I-FOBT, and$19,838/LYs gained and $2976/QALYs gained for biennial I-FOBT. The optimal screening strategy was annual I-FOBT that attained the highest ICER at the threshold of$50,000 per LYs or QALYs gained. Conclusion: The Markov model informed the health policymakers that I-FOBT every year may be the most effective and cost-effective CRC screening strategy among recommended screening strategies, depending on the willingness-to-pay of mass screening for Chinese population. Trial registration: ClinicalTrials.gov Identifier NCT02038283published_or_final_versio

Cost Effectiveness Analysis Evaluating Real-Time Characterization of Diminutive Colorectal Polyp Histology using Narrow Band Imaging (NBI)

Background: Endoscopists and new computer-aided programs can achieve performance benchmarks for real-time diagnosis of colorectal polyps using Narrow-Band Imaging (NBI), though do not perform as well as endoscopists with expertise in advanced imaging. Previous cost-effectiveness studies on optical diagnosis have focused on expert performance, potentially over-estimating its benefits. Aim: Determine cost-effectiveness of an NBI ‘characterize, resect and discard (CRD)’ strategy using updated assumptions based on non-expert performance. Methods: Markov model was constructed to compare cost-effectiveness of the CRD strategy, where diminutive polyps characterized as non-adenomas with high confidence are not resected and adenomas are resected and discarded, versus standard of care (SOC) in which all polyps are resected with histologic analysis. Rates related to NBI performance, missed polyps, polyp progression, malignancy, and complications, as well as quality-adjusted life years (QALYs) were derived from the literature. Costs were age and insurer-specific. Mean QALYs and costs were calculated using first order Monte Carlo simulation. Deterministic and probabilistic sensitivity analyses were conducted. Results: The mean QALY estimates were similar for the CRD (8.563, 95% CI: 8.557-8.571) and SOC strategy (8.563, 8.557-8.571), but costs were reduced ($2,693.06 vs.$2,800.27, mean incremental cost savings: $107.21/person). Accounting for colonoscopy rates, the CRD strategy would save$708 million to $1.06 billion annually. The model was sensitive to the incidence of tubular adenomas; the results were otherwise robust in all other one-way and probabilistic analyses. Conclusions: An NBI CRD strategy is cost-effective when compared to the SOC, even when employed by non-experts. The appreciated benefit is primarily due to cost savings of the CRD strategy

The clinical effectiveness and cost-effectiveness of ablative therapies in the management of liver metastases: systematic review and economic evaluation

Background: Many deaths from cancer are caused by metastatic burden. Prognosis and survival rates vary, but survival beyond 5 years of patients with untreated metastatic disease in the liver is rare. Treatment for liver metastases has largely been surgical resection, but this is feasible in only approximately 20–30% of people. Non-surgical alternatives to treat some liver metastases can include various forms of ablative therapies and other targeted treatments.Objectives: To evaluate the clinical effectiveness and cost-effectiveness of the different ablative and minimally invasive therapies for treating liver metastases.Data sources: Electronic databases including MEDLINE, EMBASE and The Cochrane Library were searched from 1990 to September 2011. Experts were consulted and bibliographies checked.Review methods: Systematic reviews of the literature were undertaken to appraise the clinical effectiveness and cost-effectiveness of ablative therapies and minimally invasive therapies used for people with liver metastases. Studies were any prospective study with sample size greater than 100 participants. A probabilistic model was developed for the economic evaluation of the technologies where data permitted.Results: The evidence assessing the clinical effectiveness and cost-effectiveness of ablative and other minimally invasive therapies was limited. Nine studies of ablative therapies were included in the review; each had methodological shortcomings and few had a comparator group. One randomised controlled trial (RCT) of microwave ablation versus surgical resection was identified and showed no improvement in outcomes compared with resection. In two prospective case series studies that investigated the use of laser ablation, mean survival ranged from 41 to 58 months. One cohort study compared radiofrequency ablation with surgical resection and five case series studies also investigated the use of radiofrequency ablation. Across these studies the median survival ranged from 44 to 52 months. Seven studies of minimally invasive therapies were included in the review. Two RCTs compared chemoembolisation with chemotherapy only. Overall survival was not compared between groups and methodological shortcomings mean that conclusions are difficult to make. Two case series studies of laser ablation following chemoembolisation were also included; however, these provide little evidence of the use of these technologies in combination. Three RCTs of radioembolisation were included. Significant improvements in tumour response and time to disease progression were demonstrated; however, benefits in terms of survival were equivocal. An exploratory survival model was developed using data from the review of clinical effectiveness. The model includes separate analyses of microwave ablation compared with surgery and radiofrequency ablation compared with surgery and one of radioembolisation in conjunction with hepatic artery chemotherapy compared with hepatic artery chemotherapy alone. Microwave ablation was associated with an incremental cost-effectiveness ratio (ICER) of £3664 per quality-adjusted life-year (QALY) gained, with microwave ablation being associated with reduced cost but also with poorer outcome than surgery. Radiofrequency ablation compared with surgical resection for solitary metastases < 3 cm was associated with an ICER of –£266,767 per QALY gained, indicating that radiofrequency ablation dominates surgical resection. Radiofrequency ablation compared with surgical resection for solitary metastases ? 3 cm resulted in poorer outcomes at lower costs and a resultant ICER of £2538 per QALY gained. Radioembolisation plus hepatic artery chemotherapy compared with hepatic artery chemotherapy was associated with an ICER of £37,303 per QALY gained.Conclusions: There is currently limited high-quality research evidence upon which to base any firm decisions regarding ablative therapies for liver metastases. Further trials should compare ablative therapies with surgery, in particular. A RCT would provide the most appropriate design for undertaking any further evaluation and should include a full economic evaluation, but the group to be randomised needs careful selection.Source of funding: Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research

Cost effectiveness of strategies to combat breast, cervical, and colorectal cancer in sub-Saharan Africa and South East Asia: mathematical modelling study

Objective To determine the costs and health effects of interventions to combat breast, cervical, and colorectal cancers in order to guide resource allocation decisions in developing countries

Palliative care for cancer patients in resource-limited settings of Kazakhstan: implications for cost-effectiveness and health policy

ABSTRACT Introduction: About 60 million people need palliative care worldwide, and nearly 80% of them live in low-to middle- income countries (LMICs) where only 12% of patients who require palliative services have access to them. As a Central Asian LMIC with a transitional economy and a reforming healthcare system, Kazakhstan has recently taken on the task of integrating palliative care into the general healthcare system to meet its national needs and international standards. Although palliative care services in Kazakhstan have significantly improved care for persons nearing the end of life, patients needing these services still suffer from pain, lack of access, and high out-of-pocket expenditures. Palliative care in Kazakhstan is provided by hospices, cancer centers, general hospitals, and mobile teams. More than 100,000 people need palliative care in Kazakhstan; however, as one or more family members are usually involved in the care of a terminal patient, more than 200,000 people would benefit from high-quality palliative care services in this country. Considering that cancer is a primary illness necessitating palliative care, there is a need for a comprehensive understanding of how strategies aimed at preventing cancer could reshape the demand and delivery of the spectrum of cancer care services, including palliative care. Objectives of this study include: • Present a detailed analysis of palliative care in Kazakhstan, including funding, policy, workforce, education, infrastructure, etc., providing an evidence base for future assessments and research of palliative care in Kazakhstan and in other LMICs. • Assess the cost-effectiveness of hospice-based palliative care for cancer patients compared to the current standard of care provided in cancer centers across the country. • Explore the challenges faced by palliative care stakeholders in resource-limited settings, and to offer evidence-based recommendations for policymakers to facilitate the advancement of palliative care in Kazakhstan and other LMICs. • Asses the cost-effectiveness of genetic testing for Lynch syndrome provided to patients newly diagnosed with colorectal cancer, followed by cascade genetic screening of biological relatives from the perspective of the Swiss healthcare system. Methods: The authors assessed the nation's palliative care landscape using data from the Ministry of Health, regional healthcare centers, and NGOs (Study 1). This comprehensive evaluation involved soliciting information through official correspondence and engaging with key stakeholders. 6 For the cost-effectiveness analysis, a total of 182 family caregivers were recruited, 104 from three hospices and 78 from three palliative care units of cancer centers (Study 2). Patients’ state of health and family caregivers’ burden were assessed with the Palliative Outcome Scale (POS) and the Zarit Burden Inventory (ZBI). Direct medical and non-medical costs, and family caregivers’ out-of-pocket expenses associated with palliative care were collected. One-way and probabilistic sensitivity analysis was conducted by generating 1,000 resamples using bootstrapping with Monte-Carlo simulation. To assess challenges of palliative care stakeholders, we conducted 29 semi-structured interviews with palliative stakeholders (family caregivers n=12, healthcare professionals =12, administrators n= 5) across five regions (Study 3). Verbatim transcripts were analyzed using content analysis to identify challenges of palliative stakeholders in resource-limited settings. Recognizing that these findings mirror the well-documented challenges faced by palliative care stakeholders, we converted these insights into evidence-based recommendations, specifically designed for the resource-constrained contexts of LMICs, and in congruence with the latest body of literature on palliative care and family caregiving. Additionally, we used decision trees with Markov models to conduct a cost-effectiveness analysis of universal genetic testing for Lynch syndrome of all patients newly diagnosed with colorectal cancer, and compared it with the current tumour-based testing with immunohistochemistry techniques followed by DNA sequencing that examines for germline pathogenic variants associated with Lynch syndrome. Results: The authors obtained the necessary data through official responses from the Ministry of Health, regional centers of healthcare and NGOs. These responses were accompanied by supplementary materials that fulfilled the authors' requests. Overall, the findings of the assessment provide a thorough understanding of the current state of palliative care in Kazakhstan presented in this study along with areas that require attention for future development. Cost-effectiveness analysis revealed that after 14 days of inpatient palliative care, patients’ median POS score was 5 points better in the hospice group compared to the cancer center group. Family caregiver burden was also 2.5 points lower in favour of the hospice group. The median cost of palliative care per patient over 14 days was $31 lower for the hospice group. There was a statistically significant correlation between the cost of palliative care and patients’ 7 quality of life (r = 0.58). Probabilistic sensitivity analysis showed that hospice-based care has better outcomes and lower costs than care provided in cancer centers in 80% of tested scenarios. Discovering the challenges of palliative care stakeholders, our analysis identified seven main themes that were initially brought forward by different groups of stakeholders. The most common challenges highlighted by family caregivers were high out-of-pocket expenditures; the lack of mobile palliative care services; and shortages of opioids to prevent pain suffering. Health professionals highlighted poor palliative care education and lack of medication, especially opioids for pain relief as the major challenges they encounter in their daily practice. Major challenges for administrators included lack of societal awareness about palliative care, and lack of financial support from the State. Within the analysis of the universal genetinc testing for Lynch syndrome, the incremental cost- effectiveness ratio of this strategy was CHF65,058 per QALY saved, which is cost-effective in the Swiss context. Moreover, the universal testing correctly identifies all colorectal cancer patients with Lynch syndrome, prevents 17 deaths and prevents 19 colorectal cancer cases compared to the currently applied tumor-based testing. Conclusion: Despite recent progress, Kazakhstan faces ongoing challenges such as restricted opioid availability, insufficient education, and low public awareness about palliative care services. Hospice-based palliative care can be a cost-effective alternative in resource-limited settings of Kazakhstan. Implementation of further national palliative care strategies and policies require a large-scale coordinated involvement of all stakeholders. Family caregivers play a crucial role in providing palliative care, yet, they have been completely unsupported by they system in their tasks. Our recommendations are based on the idea that coordinated targeted and tailored stakeholder engagement is preferred to a one-size-fits-all strategy. In the Swiss healthcare context, universal genetic testing has demonstrated both cost- effectiveness and significant health advantages. However, the ICER of CHF 65,058 (USD 70,000) surpasses the cost-effectiveness threshold of most low-to middle-income countries, including Kazakhstan where the GDP per capita is USD 11,000. Hence, the authors underline the critical necessity for locally viable, low-cost cancer screening options in resource-restricted settings. The introduction of more affordable cancer preventive measures, such as mammography, Pap smear test, and fecal occult blood test, among others, could be considered as more financially viable options for population-based cancer screening