Cost-effectiveness of an urinary biomarker panel in combination with MRI for prostate cancer diagnosis.

PURPOSE: The health impact and cost-effectiveness of the biomarker test SelectMDx were evaluated when used in combination with MRI, in two US populations: biopsy naïve men and men with a previous negative biopsy. METHODS: Using a decision model, the current MRI strategy was compared with two SelectMDx strategies: SelectMDx used before MRI to select men for MRI and SelectMDx used after a negative MRI to select men for biopsy. Parameters were informed by the literature most relevant for both populations. Differences in quality-adjusted life years (QALYs) and costs between the current strategy and the SelectMDx strategies were calculated using two different assumptions regarding PCa-specific mortality (SPCG-4 and PIVOT). RESULTS: In biopsy naïve men, the use of SelectMDx before MRI results in a gain of 0.004 QALY per patient under the SPCG-4 scenario, and a gain of 0.030 QALY under the PIVOT scenario. The cost savings are $1650 per patient. When used after MRI, SelectMDx results in a QALY gain per patient of 0.004 (SPCG-4), and 0.006 (PIVOT) with $262 in cost savings. In the previous negative population, SelectMDx before MRI results in a QALY gain of 0.006 (SPCG-4) and 0.022 (PIVOT), with $1281 in cost savings per patient. SelectMDx after MRI results in a QALY gain of 0.003 (SPCG-4) and 0.004 (PIVOT) with $193 in cost savings. CONCLUSION: Application of SelectMDx results in better health outcomes and cost savings. The value of SelectMDx was highest when used before MRI to select patients for MRI and subsequent biopsy.

Patient-guided dose reduction of tyrosine kinase inhibitors in chronic myeloid leukaemia (RODEO study): study protocol for a prospective, multicentre, single-arm trial.

BACKGROUND: Dose reduction of tyrosine kinase inhibitors (TKI) in patients with chronic myeloid leukaemia (CML) with an optimal response to TKIs may support cost-effective medication use by maintaining therapeutic effectiveness while reducing adverse events and medication costs. As the choice for dose reduction depends on patients' individual needs and preferences, a patient-centred approach is warranted. Therefore, a study to evaluate the effectiveness of patient-guided dose reduction in patients with CML who are in a major or deep molecular response is designed. METHODS: This study is a prospective, multicentre, single-arm study. 147 patients with CML (aged ≥ 18 years) in chronic phase, who are treated with imatinib, bosutinib, dasatinib, nilotinib or ponatinib, and have reached at least major molecular response (defined as having BCR-ABL levels < 0.1% for an uninterrupted period of 6 months) are eligible. Patients will use an online patient decision aid and a shared decision making consultation will be held, after which patients who choose to will receive a personalised, lower TKI dose. Primary outcome is the proportion of patients with intervention failure at 12 months after dose reduction, defined as patients who have restarted their initial dose due to (expected) loss of major molecular response. For this, BCR-ABL1 levels will be analysed from blood samples drawn at baseline, 6 weeks after dose reduction and 3-monthly thereafter. Secondary outcomes include the proportion of patients with intervention failure at 6 and 18 months after dose reduction. Other outcomes include differences before and after dose reduction regarding the number and severity of patient-reported side effects; quality of life; beliefs about medicines; and medication adherence. Patients' level of decisional conflict and regret after choosing dose reduction will be assessed, as will the decisional process experienced by patients and healthcare providers. DISCUSSION: Outcomes of this trial using a personalised approach will provide clinical and patient-reported data to guide future dose reduction of TKIs in CML. If the strategy appears to be effective, it may be implemented as another valid option to offer next to standard of care to prevent potential unnecessary exposure to higher TKI doses in this selected group of patients. TRIAL REGISTRATION: EudraCT number 2021-006581-20.

Filgotinib for Treating Moderately to Severely Active Ulcerative Colitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence invited the manufacturer (Galapagos) of filgotinib (Jyseleca®), as part of the Single Technology Appraisal process, to submit evidence for the clinical effectiveness and cost effectiveness of filgotinib for treating moderately to severely active ulcerative colitis in adults who have had an inadequate response, loss of response or were intolerant to a previous biologic agent or conventional therapy. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre+, was commissioned to act as the independent Evidence Review Group. This paper summarises the company submission, presents the Evidence Review Group's critical review on the clinical and cost-effectiveness evidence in the company submission, highlights the key methodological considerations and describes the development of the National Institute for Health and Care Excellence guidance by the Appraisal Committee. The company submission included one relevant study for the comparison of filgotinib versus placebo: the SELECTION trial. As there was no head-to-head evidence with any of the comparators, the company performed two separate network meta-analyses, one for the biologic-naïve population and one for the biologic-experienced population, and for both the induction and maintenance phases. The Evidence Review Group questioned the validity of the maintenance network meta-analysis because it assumed all active treatments to be comparators in this phase, which is not in line with clinical practice. The economic analysis used a number of assumptions that introduced substantial uncertainty, which could not be fully explored, for instance, the assumption that a risk of loss of response would be independent of health state and constant over time. Company and Evidence Review Group results indicate that at its current price, and disregarding confidential discounts for comparators and subsequent treatments, filgotinib dominates some comparators (golimumab and adalimumab in the company base case, all but intravenous and subcutaneous vedolizumab in the Evidence Review Group's base case) in the biologic-naïve population. In the biologic-experienced population, filgotinib dominates all comparators in both the company and the Evidence Review Group's base case. Results should be interpreted with caution as some important uncertainties were not included in the modelling. These uncertainties were mostly centred around the maintenance network meta-analysis, loss of response, health-related quality-of-life estimates and modelling of dose escalation. The National Institute for Health and Care Excellence recommended filgotinib within its marketing authorisation, as an option for treating moderately to severely active ulcerative colitis in adults when conventional or biological treatment cannot be tolerated, or if the disease has not responded well enough or has stopped responding to these treatments, and if the company provides filgotinib according to the commercial arrangement.

Intelligent digital tools for screening of brain connectivity and dementia risk estimation in people affected by mild cognitive impairment: the AI-Mind clinical study protocol.

More than 10 million Europeans show signs of mild cognitive impairment (MCI), a transitional stage between normal brain aging and dementia stage memory disorder. The path MCI takes can be divergent; while some maintain stability or even revert to cognitive norms, alarmingly, up to half of the cases progress to dementia within 5 years. Current diagnostic practice lacks the necessary screening tools to identify those at risk of progression. The European patient experience often involves a long journey from the initial signs of MCI to the eventual diagnosis of dementia. The trajectory is far from ideal. Here, we introduce the AI-Mind project, a pioneering initiative with an innovative approach to early risk assessment through the implementation of advanced artificial intelligence (AI) on multimodal data. The cutting-edge AI-based tools developed in the project aim not only to accelerate the diagnostic process but also to deliver highly accurate predictions regarding an individual's risk of developing dementia when prevention and intervention may still be possible. AI-Mind is a European Research and Innovation Action (RIA H2020-SC1-BHC-06-2020, No. 964220) financed between 2021 and 2026. First, the AI-Mind Connector identifies dysfunctional brain networks based on high-density magneto- and electroencephalography (M/EEG) recordings. Second, the AI-Mind Predictor predicts dementia risk using data from the Connector, enriched with computerized cognitive tests, genetic and protein biomarkers, as well as sociodemographic and clinical variables. AI-Mind is integrated within a network of major European initiatives, including The Virtual Brain, The Virtual Epileptic Patient, and EBRAINS AISBL service for sensitive data, HealthDataCloud, where big patient data are generated for advancing digital and virtual twin technology development. AI-Mind's innovation lies not only in its early prediction of dementia risk, but it also enables a virtual laboratory scenario for hypothesis-driven personalized intervention research. This article introduces the background of the AI-Mind project and its clinical study protocol, setting the stage for future scientific contributions.

Development of a decision analytical framework to prioritise operating room capacity: lessons learnt from an empirical example on delayed elective surgeries during the COVID-19 pandemic in a hospital in the Netherlands.

OBJECTIVE: To develop a prioritisation framework to support priority setting for elective surgeries after COVID-19 based on the impact on patient well-being and cost. DESIGN: We developed decision analytical models to estimate the consequences of delayed elective surgical procedures (eg, total hip replacement, bariatric surgery or septoplasty). SETTING: The framework was applied to a large hospital in the Netherlands. OUTCOME MEASURES: Quality measures impacts on quality of life and costs were taken into account and combined to calculate net monetary losses per week delay, which quantifies the total loss for society expressed in monetary terms. Net monetary losses were weighted by operating times. RESULTS: We studied 13 common elective procedures from four specialties. Highest loss in quality of life due to delayed surgery was found for total hip replacement (utility loss of 0.27, ie, 99 days lost in perfect health); the lowest for arthroscopic partial meniscectomy (utility loss of 0.05, ie, 18 days lost in perfect health). Costs of surgical delay per patient were highest for bariatric surgery (€31/pp per week) and lowest for arthroscopic partial meniscectomy (-€2/pp per week). Weighted by operating room (OR) time bariatric surgery provides most value (€1.19/pp per OR minute) and arthroscopic partial meniscectomy provides the least value (€0.34/pp per OR minute). In a large hospital the net monetary loss due to prolonged waiting times was €700 840 after the first COVID-19 wave, an increase of 506% compared with the year before. CONCLUSIONS: This surgical prioritisation framework can be tailored to specific centres and countries to support priority setting for delayed elective operations during and after the COVID-19 pandemic, both in and between surgical disciplines. In the long-term, the framework can contribute to the efficient distribution of OR time and will therefore add to the discussion on appropriate use of healthcare budgets. The online framework can be accessed via: https://stanwijn.shinyapps.io/priORitize/.

Cost-effectiveness of artificial intelligence aided vessel occlusion detection in acute stroke: an early health technology assessment.

BACKGROUND: Limited evidence is available on the clinical impact of artificial intelligence (AI) in radiology. Early health technology assessment (HTA) is a methodology to assess the potential value of an innovation at an early stage. We use early HTA to evaluate the potential value of AI software in radiology. As a use-case, we evaluate the cost-effectiveness of AI software aiding the detection of intracranial large vessel occlusions (LVO) in stroke in comparison to standard care. We used a Markov based model from a societal perspective of the United Kingdom predominantly using stroke registry data complemented with pooled outcome data from large, randomized trials. Different scenarios were explored by varying missed diagnoses of LVOs, AI costs and AI performance. Other input parameters were varied to demonstrate model robustness. Results were reported in expected incremental costs (IC) and effects (IE) expressed in quality adjusted life years (QALYs). RESULTS: Applying the base case assumptions (6% missed diagnoses of LVOs by clinicians, $40 per AI analysis, 50% reduction of missed LVOs by AI), resulted in cost-savings and incremental QALYs over the projected lifetime (IC: - $156, - 0.23%; IE: + 0.01 QALYs, + 0.07%) per suspected ischemic stroke patient. For each yearly cohort of patients in the UK this translates to a total cost saving of $11 million. CONCLUSIONS: AI tools for LVO detection in emergency care have the potential to improve healthcare outcomes and save costs. We demonstrate how early HTA may be applied for the evaluation of clinically applied AI software for radiology.

A cost-effectiveness analysis of three approaches for lymph node assessment in patients with low- and intermediate-risk endometrial cancer.

OBJECTIVE: To assess the cost-effectiveness of sentinel lymph node mapping compared to risk factor assessment and routine full lymph node dissection for the assessment of lymph nodes in patients with low- and intermediate-risk endometrioid endometrial cancer. METHODS: A decision-analytic model was designed to compare three lymph node assessment strategies in terms of costs and effects: 1) sentinel lymph node mapping; 2) post-operative risk factor assessment (adjuvant therapy based on clinical and histological risk factors); 3) full lymph node dissection. Input data were derived from systematic literature searches and expert opinion. QALYs were used as measure of effectiveness. The model was built from a healthcare perspective and the impact of uncertainty was assessed with sensitivity analyses. RESULTS: Base-case analysis showed that sentinel lymph node mapping was the most effective strategy for lymph node assessment in patients with low- and intermediate-risk endometrial cancer. Compared to risk factor assessment it was more costly, but the incremental cost effectiveness ratio stayed below a willingness-to-pay threshold of €20,000 with a maximum of €9637/QALY. Sentinel lymph node mapping was dominant compared to lymph node dissection since it was more effective and less costly. Sensitivity analyses showed that the outcome of the model was robust to changes in input values. With a willingness-to-pay threshold of €20,000 sentinel lymph node mapping remained cost-effective in at least 74.3% of the iterations. CONCLUSION: Sentinel lymph node mapping is the most cost-effective strategy to guide the need for adjuvant therapy in patients with low and intermediate risk endometrioid endometrial cancer.

Potential Value of Haptic Feedback in Minimally Invasive Surgery for Deep Endometriosis.

Introduction. Laparoscopic treatment of deep endometriosis (DE) is associated with intra- and post-operative morbidity. New technological developments, such as haptic feedback in laparoscopic instruments, could reduce the rate of complications. The aim of this study was to assess the room for improvement and potential cost-effectiveness of haptic feedback instruments in laparoscopic surgery. Methods. To assess the potential value of haptic feedback, a decision analytical model was constructed. Complications that could be related to the absence of haptic feedback were included in the model. Costs of complications were based on the additional length of hospital stay, operating time, outpatient visits, reinterventions, and/or conversions to laparotomy. The target population consists of women who are treated for DE in the Netherlands. A headroom analysis was performed to estimate the maximum value of haptic feedback in case it would be able to prevent all selected intra- and post-operative complications. Results. A total of 9.7 intraoperative and 47.0 post-operative complications are expected in the cohort of 636 patients annually treated for DE in the Netherlands. Together, these complications cause an additional length of hospital stay of 432.1 days, 10.2 additional outpatient visits, 73.9 reinterventions, and 4.2 conversions. Most consequences are related to post-operative complications. The total additional annual costs due to complications were €436 623, amounting to €687 additional costs per patient. Discussion. This study demonstrated that the potential value for improvement in DE laparoscopic surgery by using haptic feedback instruments is considerable, mostly caused by the potential prevention of major post-operative complications.

The potential health gain and cost savings of improving adherence in chronic myeloid leukemia.

Healthcare costs are rising due to an increase in chronic diseases, including chronic myeloid leukemia (CML) due to improved survival. In CML care, patient adherence and physician adherence are key elements. We assessed the potential health gain and cost savings when both are improved, using a decision analytic model that integrated various sources of evidence. The current situation was compared to a theoretical situation in which either patient or physician adherence is improved, in terms of costs and quality-adjusted life years (QALYs). Current patient adherence rate is 74%, improvement to 100% resulted in 0.1031 QALYs gained and a saving of €17,509 per patient over a 25-year period. Improving physician adherence from 72% to 100%, resulted in 0.0380 QALYs and €7606. Enhancement of either adherence results in substantial health gain and cost savings. Regarding the rising healthcare costs, new strategies should focus on improving adherence to keep healthcare affordable in the future.

Cost-effectiveness of SelectMDx for prostate cancer in four European countries: a comparative modeling study.

BACKGROUND: Low specificity of prostate-specific antigen results in a considerable number of unnecessary prostate biopsies in current practice. SelectMDx® predicts significant prostate cancer upon biopsy and is used to reduce the number of unnecessary initial prostate biopsies. Furthermore, potential overtreatment of insignificant prostate cancer can be reduced. Besides the diagnostic accuracy of the test, also the context in a specific country determines the potential health benefit and cost-effectiveness. Therefore, the health benefit and cost-effectiveness of SelectMDx were assessed in France, Germany, Italy, and Spain. SUBJECT AND METHODS: A decision model was used to compare the current standard of care in which men undergo initial prostate biopsy in case of an elevated prostate-specific antigen, to a strategy in which SelectMDx was used to select men for biopsy. Model inputs most relevant to each of the four countries were obtained. With use of the model long-term quality-adjusted life years (QALYs) and healthcare costs were calculated for both strategies. RESULTS: In all four countries, the SelectMDx resulted in QALY gain and cost savings compared with the current standard of care. In France, SelectMDx resulted in 0.022 QALYs gained and cost savings of €1217 per patient. For Germany, the model showed a QALY gain of 0.016 and a cost saving of €442. In Italy, the QALY gain and cost savings were 0.031 and €762. In Spain 0.020 QALYs were gained and €250 costs were saved. CONCLUSIONS: The results of the model showed that with SelectMDx, QALYs could be gained while saving healthcare costs in the initial diagnosis of prostate cancer. The significant presence of overtreatment in the current standard of care in all four countries was the main factor that resulted in the beneficial outcomes with SelectMDx.

Integrated prediction and decision models are valuable in informing personalized decision making.

OBJECTIVES: To show how prediction models can be incorporated into decision models, to allow for personalized decisions, and to assess the value of this approach using the management of the neck in early-stage oral cavity squamous cell carcinoma as an example. STUDY DESIGN AND SETTING: In a decision model, three approaches were compared: a "population-based" approach in which patients undergo the strategy that is optimal for the population; a "perfectly predicted" approach, in which each patient receives the optimal strategy for that specific patient; and a "prediction model" approach in which each patient receives the strategy that is optimal based on prediction models. The average differences in costs and quality-adjusted life years (QALYs) for the population between these approaches were studied. RESULTS: The population-based approach resulted on average in 4.9158 QALYs with €8,675 in costs, per patient. The perfectly predicted approach yielded 0.21 more QALYs and saved €1,024 per patient. The prediction model approach yielded 0.0014 more QALYs and saved €152 per patient compared with the population-based approach. CONCLUSION: The perfectly predicted approach shows that personalized care is worthwhile. However, current prediction models in the field of oral cavity squamous cell carcinoma have limited value. Incorporating prediction models into decision models appears to be a valuable method to assess the value of personalized decision making.

Cost-Effectiveness of Urinary Biomarker Panel in Prostate Cancer Risk Assessment.

PURPOSE: SelectMDx (MDxHealth®) is a panel of urinary biomarkers used in conjunction with traditional risk factors to individualize risk prediction for clinically significant prostate cancer. In this study we sought to characterize the effectiveness of SelectMDx in a population of American men with elevated prostate specific antigen. MATERIALS AND METHODS: We developed a Markov decision analytical model to simulate the chain of events and downstream outcomes associated with ultrasound guided prostate biopsy and a strategy in which the biomarker panel is implemented prior to biopsy. The primary outcome was health outcomes, measured in QALYs (quality-adjusted life years). The secondary outcome was health care costs from the Medicare payer perspective. Multiple 1-way sensitivity analyses were performed to characterize model robustness. RESULTS: The expected mean QALYs per patient under the current standard was 10.796 at a cost of $11,060 during an 18-year horizon. Incorporating the urinary biomarker panel resulted in an expected mean of 10.841 QALYs per patient and a mean cost of $9,366, representing an average of 0.045 QALYs gained at a cost savings of $1,694 per patient. When extrapolating these data to a conservative estimate of 311,879 men per year undergoing biopsy, one would expect that the biomarker panel would result in an incremental 14,035 QALYs gained at a cost savings of $528,323,026 in each yearly cohort. The biomarker panel strategy dominated the current standard across a wide range of sensitivity analyses. CONCLUSIONS: Routine use of the SelectMDx urinary biomarker panel to guide biopsy decision making improved health outcomes and lowered costs in American men at risk for prostate cancer. This strategy may optimize the value of prostate cancer risk assessment in an era of increasing financial accountability.

Cost-effectiveness of a new urinary biomarker-based risk score compared to standard of care in prostate cancer diagnostics - a decision analytical model.

OBJECTIVE: To assess the cost-effectiveness of a new urinary biomarker-based risk score (SelectMDx; MDxHealth, Inc., Irvine, CA, USA) to identify patients for transrectal ultrasonography (TRUS)-guided biopsy and to compare this with the current standard of care (SOC), using only prostate-specific antigen (PSA) to select for TRUS-guided biopsy. MATERIALS AND METHODS: A decision tree and Markov model were developed to evaluate the cost-effectiveness of SelectMDx as a reflex test vs SOC in men with a PSA level of >3 ng/mL. Transition probabilities, utilities and costs were derived from the literature and expert opinion. Cost-effectiveness was expressed in quality-adjusted life years (QALYs) and healthcare costs of both diagnostic strategies, simulating the course of patients over a time horizon representing 18 years. Deterministic sensitivity analyses were performed to address uncertainty in assumptions. RESULTS: A diagnostic strategy including SelectMDx with a cut-off chosen at a sensitivity of 95.7% for high-grade prostate cancer resulted in savings of €128 and a gain of 0.025 QALY per patient compared to the SOC strategy. The sensitivity analyses showed that the disutility assigned to active surveillance had a high impact on the QALYs gained and the disutility attributed to TRUS-guided biopsy only slightly influenced the outcome of the model. CONCLUSION: Based on the currently available evidence, the reduction of over diagnosis and overtreatment due to the use of the SelectMDx test in men with PSA levels of >3 ng/mL may lead to a reduction in total costs per patient and a gain in QALYs.

Cost-Effectiveness Comparison of Imaging-Guided Prostate Biopsy Techniques: Systematic Transrectal Ultrasound, Direct In-Bore MRI, and Image Fusion.

OBJECTIVE: Three commonly used prostate biopsy approaches are systematic transrectal ultrasound guided, direct in-bore MRI guided, and image fusion guided. The aim of this study was to calculate which strategy is most cost-effective. MATERIALS AND METHODS: A decision tree and Markov model were developed to compare cost-effectiveness. Literature review and expert opinion were used as input. A strategy was deemed cost-effective if the costs of gaining one quality-adjusted life year (incremental cost-effectiveness ratio) did not exceed the willingness-to-pay threshold of €80,000 (≈$85,000 in January 2017). A base case analysis was performed to compare systematic transrectal ultrasound- and image fusion-guided biopsies. Because of a lack of appropriate literature regarding the accuracy of direct in-bore MRI-guided biopsy, a threshold analysis was performed. RESULTS: The incremental cost-effectiveness ratio for fusion-guided biopsy compared with systematic transrectal ultrasound-guided biopsy was €1386 ($1470) per quality-adjusted life year gained, which was below the willingness-to-pay threshold and thus assumed cost-effective. If MRI findings are normal in a patient with clinically significant prostate cancer, the sensitivity of direct in-bore MRI-guided biopsy has to be at least 88.8%. If that is the case, the incremental cost-effectiveness ratio is €80,000 per quality-adjusted life year gained and thus cost-effective. CONCLUSION: Fusion-guided biopsy seems to be cost-effective compared with systematic transrectal ultrasound-guided biopsy. Future research is needed to determine whether direct in-bore MRI-guided biopsy is the best pathway; in this study a threshold was calculated at which it would be cost-effective.

Societal and Economic Effect of Meniscus Scaffold Procedures for Irreparable Meniscus Injuries.

BACKGROUND: Meniscus scaffolds are currently evaluated clinically for their efficacy in preventing the development of osteoarthritis as well as for their efficacy in treating patients with chronic symptoms. Procedural costs, therapeutic consequences, clinical efficacy, and future events should all be considered to maximize the monetary value of this intervention. PURPOSE: To examine the socioeconomic effect of treating patients with irreparable medial meniscus injuries with a meniscus scaffold. STUDY DESIGN: Economic and decision analysis; Level of evidence, 2. METHODS: Two Markov simulation models for patients with an irreparable medial meniscus injury were developed. Model 1 was used to investigate the lifetime cost-effectiveness of a meniscus scaffold compared with standard partial meniscectomy by the possibility of preventing the development of osteoarthritis. Model 2 was used to investigate the short-term (5-year) cost-effectiveness of a meniscus scaffold compared with standard partial meniscectomy by alleviating clinical symptoms, specifically in chronic patients with previous meniscus surgery. For both models, probabilistic Monte Carlo simulations were applied. Treatment effectiveness was expressed as quality-adjusted life-years (QALYs), while costs (estimated in euros) were assessed from a societal perspective. We assumed €20,000 as a reference value for the willingness to pay per QALY. Next, comprehensive sensitivity analyses were performed to identify the most influential variables on the cost-effectiveness of meniscus scaffolds. RESULTS: Model 1 demonstrated an incremental cost-effectiveness ratio of a meniscus scaffold treatment of €54,463 per QALY (€5991/0.112). A threshold analysis demonstrated that a meniscus scaffold should offer a relative risk reduction of at least 0.34 to become cost-effective, assuming a willingness to pay of €20,000. Decreasing the costs of the meniscus scaffold procedure by 33% (€10,160 instead of €15,233; an absolute change of €5073) resulted in an incremental cost-effectiveness ratio of €7876 per QALY. Model 2 demonstrated an incremental cost-effectiveness ratio of a meniscus scaffold treatment of €297,727 per QALY (€9825/0.033). On the basis of the current efficacy data, a meniscus scaffold provides a relative risk reduction of "limited benefit" postoperatively of 0.37 compared with standard treatment. A threshold analysis revealed that assuming a willingness to pay of €20,000, a meniscus scaffold would not be cost-effective within a period of 5 years. Most influential variables on the cost-effectiveness of meniscus scaffolds were the cost of the scaffold procedure, cost associated with osteoarthritis, and quality of life before and after the scaffold procedure. CONCLUSION: Results of the current health technology assessment emphasize that the monetary value of meniscus scaffold procedures is very much dependent on a number of influential variables. Therefore, before implementing the technology in the health care system, it is important to critically assess these variables in a relevant context. The models can be improved as additional clinical data regarding the efficacy of the meniscus scaffold become available.

An international comparison of the management of the neck in early oral squamous cell carcinoma in the Netherlands, UK, and USA.

BACKGROUND: Early oral cavity squamous cell carcinoma (OCSCC) management appears to vary both within and between countries. Variation in practice can be an indicator of absence of evidence-based management and may negatively influence survival and morbidity. The exact variation and the relationship to differences in guidelines are unknown. This study aimed to report on these variations in the Netherlands, UK, and USA, and to evaluate them. METHODS: Information regarding the variation in OCSCC management strategies was obtained from a questionnaire sent to representatives of head and neck cancer centers in the Netherlands, UK, and USA. Within-country and between-country variations were also assessed in light of the different guidelines. RESULTS: In total, representatives of 45 centers completed the questionnaire; 10 from the Netherlands, 26 from the UK and 9 from the USA. Our results demonstrate a distinct variation in the diagnoses, treatment and follow-up of OCSCC, both within and between countries. Only a small amount of variation between countries could be linked to differences in guidelines. CONCLUSIONS: There is high variation in the management of the neck in OCSCC. There seem to be a need for direct evidence about optimal management decisions to establish more evidence-based management and uniform practice.

Cost-effectiveness of selective neck dissection versus modified radical neck dissection for treating metastases in patients with oral cavity cancer: A modelling study.

BACKGROUND: Choosing between a more or less extensive neck dissection implies a tradeoff between survival, quality of life, and costs. The purpose of this study was to determine if selective neck dissection (level I-III or I-IV) is cost-effective compared with modified radical neck dissection (level I-V) in patients with cT1-2 oral squamous cell carcinoma (OSCC) with singular nodal disease confined to level I or II. METHODS: A decision-analytic model was developed to model quality-adjusted life years (QALYs) and costs over a lifetime horizon, based on literature. RESULTS: The selective neck dissection strategy resulted in an expected health loss of 0.06 QALY and savings of €1351 per patient compared to modified radical neck dissection. The results were sensitive to differences in regional failure probabilities between the strategies. CONCLUSION: With the evidence used in this model, selective neck dissection was not cost-effective compared to modified radical neck dissection. Prospective research on regional failure is needed to provide optimal treatment for patients with OSCC.

Management of the N0 neck in early stage oral squamous cell cancer: a modeling study of the cost-effectiveness.

OBJECTIVES: To assess the cost-effectiveness of five strategies for diagnosing and treating cT1-2N0 oral squamous cell cancer. MATERIALS AND METHODS: A Markov decision analytic model was used to evaluate the cost-effectiveness of (1) elective neck dissection (END), (2) watchful waiting (WW), (3) gene expression profiling (GEP) followed by neck dissection (ND) or WW, (4) sentinel lymph node (SLN) procedure followed by ND or WW, and (5) GEP and SLN (for positive GEP) followed by ND or WW. Uncertainty was addressed using one-way and probabilistic sensitivity analyses. RESULTS: Base-case analysis showed that SLN procedure followed by ND or WW was the most effective and most cost effective strategy. Compared with direct END the incremental cost effectiveness ratio was €3356 per QALY gained. Uncertainty analysis showed that the model was sensitive to changes in assumed occult metastases incidence and utility values. SLN was found to have the highest probability (66%) of being cost-effective of the five strategies, at a willingness to pay of €80,000 per QALY. CONCLUSIONS: Given the current evidence and costs the SLN procedure followed by ND or WW appears to be the most cost effective strategy for diagnosing and treating oral squamous cell cancer patients. Our model provides the foundation for future diagnostic and therapeutic research in this field and shows that further information on quality of life in this population is highly valuable.

Sentinel node biopsy for squamous cell carcinoma of the oral cavity and oropharynx: a diagnostic meta-analysis.

BACKGROUND: The aim of the study was to systematically assess the accuracy of a sentinel lymph node biopsy (SLNB) in cT1/T2N0 oral cavity and oropharyngeal squamous cell carcinoma patients. METHODS: We searched electronic databases, including EMBASE and MEDLINE (Pubmed) up to November 7 2012, by combining oral cancer keywords with sentinel node biopsy keywords. We included diagnostic accuracy studies which used neck dissection as a reference test for the sentinel node biopsy. Study characteristics and measures of accuracy were extracted. Diagnostic accuracy was calculated from 2 × 2 tables. RESULTS: 21 Studies (847 patients) could be included. Most of these patients had oral cavity squamous cell carcinoma (OCSCC). The pooled data showed an overall sensitivity of 0.93 [95% CI 0.90-0.95]. Subgroup analysis showed no significant differences in subgroups. CONCLUSION: The high sensitivity of SLNB supports a role in the diagnostic work-up of OCSCC.