How real can we get in generating real world evidence? Exploring the opportunities of routinely collected administrative data for evaluation of medical devices.

Real-world data are considered a potentially valuable source of evidence for assessing medical technologies in clinical practice, but their widespread use is hampered by numerous challenges. Using the case of coronary stents in Italy, we investigate the potential of administrative databases for estimating costs and health outcomes associated with the use of medical devices in real world conditions. An administrative dataset was created ad hoc by merging hospital records from patients admitted between 2013 and 2019 for stent implantations with ambulatory records, pharmaceutical use data and vital statistics. Health outcomes were multifold: all-cause and cardiac mortality and myocardial infarction, within 30 days, 1, 2, 5 years. Costs were estimated from the National Health System perspective. We used multivariable Cox models and propensity score (PS) methods (PS matching; stratification on PS; inverse probability of treatment weighting using PS; PS adjustment). 257,907 coronary stents were implanted in 113,912 patients. For all health outcomes and follow-up times, and across all methods, patients receiving drug-eluting stents (DES) presented lower risk. For all-cause mortality, the DES patient advantage over bare-metal stent (BMS) patients declined over time but remained significant even at 5 years. For myocardial infarction, results remained quite stable. The DES group presented lower cumulative total costs (ranging from 3264 to 2363 Euros less depending on methods). Our results confirm the consolidated evidence of the benefits of DES compared to BMS. The consistency of results across methods suggests internal validity of the study, while highlighting strengths and limitations of each depending on research context. Administrative data yield great potential to perform comparative effectiveness and cost-effectiveness analysis of medical devices provided certain conditions are met.

An Analysis of Cost-Effectiveness of Stents Used in the Treatment of Coronary Artery Disease

Background: There is only limited information about the cost-effectiveness of drug-eluting stents compared with bare-metal stents in Turkey. Aims: To evaluate bare-metal and drug-eluting stents used in the treatment of coronary artery disease from the perspective of the reimbursement institution with cost-effectiveness analysis. Study Design: Retrospective cost-effectiveness analysis. Methods: In our study, 329 patients diagnosed with coronary artery disease and treated with bare-metal or drug-eluting stents in the cardiology clinics of a public university hospital between January 1 and December 31, 2016 were investigated. Bare-metal and drug-eluting stents used in the treatment of coronary artery disease were evaluated retrospectively with cost-effectiveness analysis from the perspective of the reimbursement institution. Results: The cost of treatment with a bare-metal stent was 2,131.41 Turkish Liras, and the cost of treatment with a drug-eluting stent was 3,546.14 Turkish Liras; the Quality Adjusted Life Years value of treatment with a bare-metal stent was 0.8371, and the Quality Adjusted Life Years value of treatment with a drug-eluting stent was 0.8924. All these data were analyzed by decision tree. As a result of decision tree analysis, the weighted cost of treatment with a bare-metal stent was 2,340.71 Turkish Liras and weighted Quality Adjusted Life Years value was 0.8332; and the weighted cost of treatment with drug-eluting stent was 3,970.90 Turkish Liras and the weighted Quality Adjusted Life Years value of the treatment with drug-eluting stent was 0.8911. With these values, the additional cost-effectiveness ratio was calculated as 28,179.12 Turkish Liras per acquired Quality Adjusted Life Years. The additional cost-effectiveness ratio is in the first zone in the cost-effectiveness plane and below the very threshold of cost-effectiveness. Conclusion: In our study, it was concluded that drug-eluting stents are cost effective compared with bare-metal stents in the treatment of coronary artery disease. Considering the cost and effectiveness of the drug-eluting stent, it is thought that increasing reimbursement for this technology by the reimbursement agency would be beneficial for the service provider.

Ultra-High-Resolution Computed Tomography Angiography for Assessment of Coronary Artery Stenosis.

BACKGROUND: Limitations of coronary computed tomography (CTA) include false-positive stenosis at calcified lesions and assessment of in-stent patency. A prototype of ultra-high resolution computed tomography (U-HRCT: 1,792 channels and 0.25-mm slice thickness×128 rows) with improved spatial resolution was developed. We assessed the diagnostic accuracy of coronary artery stenosis using U-HRCT.Methods and Results:Seventy-nine consecutive patients who underwent CTA using U-HRCT were prospectively included. Coronary artery stenosis was graded from 0 (no plaque) to 5 (occlusion). Stenosis grading at 102 calcified lesions was compared between U-HRCT and conventional-resolution CT (CRCT: 896 channels and 0.5-mm slice thickness×320 rows). Median stenosis grading at calcified plaque was significantly improved on U-HRCT compared with CRCT (1; IQR, 1-2 vs. 2; IQR, 1-3, P<0.0001). Assessability of in-stent lumen was evaluated on U-HRCT in 79 stents. Stent strut thickness and luminal diameter were quantitatively compared between U-HRCT and CRCT. Of 79 stents, 83.5% were assessable on U-HRCT; 80% of stents with diameter 2.5 mm were regarded as assessable. On U-HRCT, stent struts were significantly thinner (median, 0.78 mm; IQR, 0.7-0.83 mm vs. 0.83 mm; IQR, 0.75-0.92 mm, P=0.0036), and in-stent lumens were significantly larger (median, 2.08 mm; IQR, 1.55-2.51 mm vs. 1.74 mm; IQR, 1.31-2.06 mm, P<0.0001) than on CRCT. CONCLUSIONS: U-HRCT with improved spatial resolution visualized calcified lesions with fewer artifacts. The in-stent lumen of stents with diameter ≥2.5 mm was assessable on U-HRCT.

Can Patients Select the Best Hospital for Carotid Revascularization?

BACKGROUND: Public reporting of cardiac surgery outcomes has been available for many years in the USA. Whether public information regarding carotid endarterectomy or stenting outcomes is available has not been studied previously. METHODS: The Medicare Hospital Compare website was analyzed for carotid endarterectomy and stenting volume and complications data. RESULTS: Within a large metropolitan area, endarterectomy volume data was provided in less than half of hospitals, with no information provided on morbidity or mortality. No information was available on carotid stenting. CONCLUSIONS: The quality of information available to patients in the USA contemplating a carotid revascularization procedure is suboptimal. Considering the volume of these procedures, greater transparency with regard to outcomes is desirable. Adoption of carotid procedure reporting practices as used in the UK should be considered.

An internet-based method to elicit experts' beliefs for Bayesian priors: a case study in intracranial stent evaluation.

RATIONALE: Bayesian methods provide an interesting approach to assessing an implantable medical device (IMD) that has evolved through successive versions because they allow for explicit incorporation of prior knowledge into the analysis. However, the literature is sparse on the feasibility and reliability of elicitation in cases where expert beliefs are used to form priors. OBJECTIVES: To develop an Internet-based method for eliciting experts' beliefs about the success rate of an intracranial stenting procedure and to assess their impact on the estimated benefit of the latest version. STUDY DESIGN AND SETTING: The elicitation questionnaire was administered to a group of nineteen experts. Elicited experts' beliefs were used to inform the prior distributions of a Bayesian hierarchical meta-analysis model, allowing for the estimation of the success rate of each version. RESULTS: Experts believed that the success rate of the latest version was slightly higher than that of the previous one (median: 80.8 percent versus 75.9 percent). When using noninformative priors in the model, the latest version was found to have a lower success rate (median: 83.1 percent versus 86.0 percent), while no difference between the two versions was detected with informative priors (median: 85.3 percent versus 85.6 percent). CONCLUSIONS: We proposed a practical method to elicit experts' beliefs on the success rates of successive IMD versions and to explicitly combine all available evidence in the evaluation of the latest one. Our results suggest that the experts were overoptimistic about this last version. Nevertheless, the proposed method should be simplified and assessed in larger, representative samples.

Health Technology Assessment in the UK.

In this Review, we discuss the UK's Health Technology Assessment programme, which is 20 years old in 2013. We situate the programme in the context of the UK landscape for evidence-based medicine, including in relation to the National Institute for Health and Care Excellence and as guidance to the National Health Service. We identify features that might be of value to other health systems as they confront the challenges of rapid innovation and rising costs. We use examples of recent studies to show the strengths and weaknesses of the programme.

Bayesian hierarchical meta-analysis model for medical device evaluation: application to intracranial stents.

OBJECTIVES: The aim of this study was to propose a statistical model that takes into account clinical data on earlier versions when evaluating the latest version of an implantable medical device (IMD). METHODS: We compared the performances of a bayesian three-level hierarchical meta-analysis model with those of a bayesian random-effects model through a simulation study. Posterior mean estimates of the success rate for each IMD version were computed as well as the probability that the latest version improved in effectiveness. Models were compared using the Deviance Information Criterion (DIC), the estimated bias and the standard deviation of the mean success rates. Sensitivity analyses to the choice of the priors were performed. These methods were applied to the evaluation of an intracranial stent used to treat wide-necked aneurysms. RESULTS: When IMD versions did not differ in effectiveness, the best-fitting model was the random-effects model. By contrast, when there was a version effect, the hierarchical model was selected in more than 95 percent of the cases. It provided precise estimations of success rates of each IMD version and allowed detecting an improvement in effectiveness of the latest version, with a low influence of the choice of the priors. No evidence of benefit from the latest version of the intracranial stent was found. CONCLUSIONS: In the setting of IMD assessment, comparison of DIC between the two proposed models appeared useful for detecting version effects. In that case, bayesian hierarchical meta-analysis model may help the decision maker by providing useful information on the latest version of IMD compared with the previous versions.

Stent for Life Initiative placed at the forefront in Egypt 2011.

AIMS: Myocardial infarction is a medical emergency in which 25 to 35% of patients will die before receiving medical attention. The Stent for Life registry was launched to access the current situation of the Egyptian population presenting with STEMI, and to determine what were the barriers to providing patients with cardiac problems appropriate care. METHODS AND RESULTS: This registry was conducted at 14 centres covered all the Egyptian regions including 1,324 consecutive patients presenting with STEMI during the period between January 1st, 2011 to November, 2011. Fourteen centres and 38 interventionalists participated in this registry; only six centres are Pilot Centres (fulfilling the criteria for a primary PCI centre) and were assigned at the end of 2011. Cardiovascular risk factors were mainly smoking (60.5%), dyslipidaemia (46.0%), diabetes (51.4%) and hypertension (56.0%). The mean age at presentation was 56.01±10.61years and 75.0% were male. Only 5% of the STEMI patients arrived via the emergency medical system. Thrombus aspiration was done in 42.7% of patients in primary PCI group and 25.9% in rescue PCI group. Bare metal stents (BMS) were used in 80.7% of the stented patients while drug eluting stents (DES) were used in 19.3% of the stented patients. In-hospital mortality was 2.9% (1.4% in primary PCI group, 1.1% in patients treated with thrombolysis and 0.4% in patients receiving no reperfusion therapy). CONCLUSION: Despite the logistical difficulties, excellent outcomes for acute interventional reperfusion strategy in STEMI can be achieved in our country, possibly similar to those seen in the West. There is a strong need for making the practice of PCI in STEMI more widespread in developing regions.

Stent for Life Initiative--the Greek experience.

Primary percutaneous coronary intervention (p-PCI) is considered the gold standard reperfusion strategy for patients with ST-elevation myocardial infarction (STEMI). In the last two years, the Stent for Life (SFL) Initiative has aimed at expanding the use of p-PCI in Greece and several other European countries. During this short period of time, intensive efforts towards propagating the main objectives of the programme in Greece and important actions on the organisation and activation of two p-PCI networks in Athens, the Greek capital, and Patras in south-western Greece, have led to a dramatic nationwide increase of p-PCI rates among STEMI patients (from 9% to 32%). Especially in Athens, p-PCI is implemented in almost 60% of the cases with a diagnosis of STEMI. Recent data from the Greek national registry on acute coronary syndromes underscore the need to improve p-PCI time delays which are partially attributed to inter-hospital delays from hospitals with no p-PCI facilities to p-PCI hospitals. A national public campaign for the promotion of p-PCI is progressing very fast, while specific planning for the recruitment of additional hospitals in urban and rural areas to join old, or to form new p-PCI networks is still developing.

The European Society for Vascular Surgery guidelines for carotid intervention: an updated independent assessment and literature review.

BACKGROUND AND PURPOSE: Many medical societies now recommend carotid stenting as an alternative to endarterectomy which raises the question of whether the ESVS guidelines are still valid. This review addresses the validity of the ESVS guidelines that refer to carotid stenting based on the evidence available today. METHODS: We conducted a review and meta-analysis based on the original ESVS guidelines paper and articles published over the past 2 years. RESULTS: For symptomatic patients, surgery remains the best option, since stenting is associated with a 61% relative risk increase of periprocedural stroke or death compared to endarterectomy. However, centres of excellence in carotid stenting may achieve comparable results. In asymptomatic patients, there is still no good evidence for any intervention because the stroke risk from an asymptomatic stenosis is very low, especially with the best modern medical treatment. CREST and CAVATAS have verified that mid-term stroke prevention after successful stenting is similar to endarterectomy. EVA-3S, SPACE, ICSS and CREST have provided additional evidence regarding the role of age in choosing therapeutic modality. The role of the cerebral protection devices is challenged by the imaging findings of small randomised trials but supported by large systematic reviews. CONCLUSIONS: The ESVS guidelines that refer to carotid stenting not only remain valid but also have been further strengthened by the latest available clinical data. An update of these guidelines including all of the recent evidence is needed to provide an objective and up-to-date interpretation of the data.

Symptomatic intracranial arterial disease: incidence, natural history, diagnosis, and management.

Symptomatic intracranial arterial disease is associated with a high rate of recurrent ischemic events. The management of this condition is controversial, with some advocating medical therapy as a sole means of treatment and others recommending endovascular therapy in addition to best medical management. In rare cases, surgical intervention is considered. A thorough review of the available literature was performed, and treatment recommendations based on these data are provided.

Call for standards in technical documentation of intracoronary stents.

At present, the product information of intracoronary stents provided by the industry contains only limited technical data restricting judgments on the in vivo performance of individual products. Available experimental and clinical evidence suggests that interventional target sites display highly heterogeneous biomechanical behavior needed to be matched by specific stent and stent delivery system characteristics. To allow individualized stent-lesion matching, both, understanding of biomechanical properties of the atherosclerotic coronary artery lesions and expert knowledge of the intracoronary stent systems, are required. Here, the authors review some of the initial data on mechanical properties of coronary artery lesions potentially relevant to stenting and suggest standards for technical documentation of intracoronary stents.

Therapeutic approach to the malignant tumors of the biliary tract.

Cholangiocarcinomas (CCA) are malignant tumors that originate in the cholangiocytes, occur at any level of the biliary tract, are very aggressive and have a 5-year survival rate of 7-8%. Their diagnosis is late and difficult, and the prognosis is very poor. The only curative treatment of these tumors is the complete surgical resection. Signs of unresectability can be detected in most patients with CCA when establishing the diagnosis. Thus, only certain palliative measures can be employed in most cases. The ideal palliative method should be minimally invasive, accompanied by few complications, should offer an increased quality of life, require reduced hospitalization and the lowest costs. The palliative treatment of the obstructive jaundice may be achieved by means of surgical bypass, endoscopic insertion of biliary stents, percutaneous stents, transhepatic stents, photodynamic therapy and/or radio-chemotherapy.

Reporting standards for angioplasty and stent-assisted angioplasty for intracranial atherosclerosis.

BACKGROUND AND PURPOSE: Intracranial cerebral atherosclerosis causes ischemic stroke in a significant number of patients. Technological advances over the past 10 years have enabled endovascular treatment of intracranial atherosclerotic stenosis. The number of patients treated with angioplasty or stent-assisted angioplasty for this condition is increasing. Given the lack of universally accepted definitions, the goal of this document is to provide consensus recommendations for reporting standards, terminology, and written definitions when reporting clinical and radiological evaluation, technique, and outcome of endovascular treatment using angioplasty or stent-assisted angioplasty for stenotic and occlusive intracranial atherosclerosis. SUMMARY OF REPORT: This article was written under the auspices of Joint Writing Group of the Technology Assessment Committee, Society of Neurolnterventional Surgery, Society of Interventional Radiology; Joint Section on Cerebro-vascular Neurosurgery of the American Association of Neurological Surgeons and Congress of Neurological Surgeons; and the Section of Stroke and Interventional Neurology of the American Academy of Neurology. A computerized search of the National Library of Medicine database of literature (PubMed) from January 1997 to December 2007 was conducted with the goal to identify published endovascular cerebrovascular interventional data in stenotic intracranial atherosclerosis that could be used as benchmarks for quality assessment. We sought to identify those risk adjustment variables that affect the likelihood of success and complications. This document offers the rationale for different clinical and technical considerations that may be important during the design of clinical trials for endovascular treatment of intracranial stenotic and occlusive atherosclerosis. Included in this guidance document are suggestions for uniform reporting standards for such trials. These definitions and standards are primarily intended for research purposes; however, they should also be helpful in clinical practice and applicable to all publications. CONCLUSION: In summary, the definitions proposed represent recommendations for constructing useful research data sets. The intent is to facilitate production of scientifically rigorous results capable of reliable comparisons between and among similar studies. In some cases, the definitions contained here are recommended by consensus of a panel of experts in this writing group for consistency in reporting and publication. These definitions should allow different groups to publish results that are directly comparable.

Reporting standards for angioplasty and stent-assisted angioplasty for intracranial atherosclerosis.

BACKGROUND AND PURPOSE: Intracranial cerebral atherosclerosis causes ischemic stroke in a significant number of patients. Technological advances over the past 10 years have enabled endovascular treatment of intracranial atherosclerotic stenosis. The number of patients treated with angioplasty or stent-assisted angioplasty for this condition is increasing. Given the lack of universally accepted definitions, the goal of this document is to provide consensus recommendations for reporting standards, terminology, and written definitions when reporting clinical and radiological evaluation, technique, and outcome of endovascular treatment using angioplasty or stent-assisted angioplasty for stenotic and occlusive intracranial atherosclerosis. SUMMARY OF REPORT: This article was written under the auspices of Joint Writing Group of the Technology Assessment Committee, Society of NeuroInterventional Surgery, Society of Interventional Radiology; Joint Section on Cerebrovascular Neurosurgery of the American Association of Neurological Surgeons and Congress of Neurological Surgeons; and the Section of Stroke and Interventional Neurology of the American Academy of Neurology. A computerized search of the National Library of Medicine database of literature (PubMed) from January 1997 to December 2007 was conducted with the goal to identify published endovascular cerebrovascular interventional data in stenotic intracranial atherosclerosis that could be used as benchmarks for quality assessment. We sought to identify those risk adjustment variables that affect the likelihood of success and complications. This document offers the rationale for different clinical and technical considerations that may be important during the design of clinical trials for endovascular treatment of intracranial stenotic and occlusive atherosclerosis. Included in this guidance document are suggestions for uniform reporting standards for such trials. These definitions and standards are primarily intended for research purposes; however, they should also be helpful in clinical practice and applicable to all publications. CONCLUSION: In summary, the definitions proposed represent recommendations for constructing useful research data sets. The intent is to facilitate production of scientifically rigorous results capable of reliable comparisons between and among similar studies. In some cases, the definitions contained here are recommended by consensus of a panel of experts in this writing group for consistency in reporting and publication. These definitions should allow different groups to publish results that are directly comparable.