Administering selected subscales of patient-reported outcome questionnaires to reduce patient burden and increase relevance: a position statement on a modular approach.

Patient-reported outcome (PRO) questionnaires considered in this paper contain multiple subscales, although not all subscales are equally relevant for administration in all target patient populations. A group of measurement experts, developers, license holders, and other scientific-, regulatory-, payer-, and patient-focused stakeholders participated in a panel to discuss the benefits and challenges of a modular approach, defined here as administering a subset of subscales out of a multi-scaled PRO measure. This paper supports the position that it is acceptable, and sometimes preferable, to take a modular approach when administering PRO questionnaires, provided that certain conditions have been met and a rigorous selection process performed. Based on the experiences and perspectives of all stakeholders, using a modular approach can reduce patient burden and increase the relevancy of the items administered, and thereby improve measurement precision and eliminate wasted data without sacrificing the scientific validity and utility of the instrument. The panelists agreed that implementing a modular approach is not expected to have a meaningful impact on item responses, subscale scores, variability, reliability, validity, and effect size estimates; however, collecting additional evidence for the impact of context may be desirable. It is also important to recognize that adequate rationale and evidence (e.g., of fit-for-purpose status and relevance to patients) and a robust consensus process that includes patient perspectives are required to inform selection of subscales, as in any other measurement circumstance, is expected. We believe that the considerations discussed within (content validity, administration context, and psychometric factors) are relevant across multiple therapeutic areas.

Future Role of Health Technology Assessment for Genomic Medicine in Oncology: A Canadian Laboratory Perspective.

Genome-based testing in oncology is a rapidly expanding area of health care that is the basis of the emerging area of precision medicine. The efficient and considered adoption of novel genomic medicine testing is hampered in Canada by the fragmented nature of health care oversight as well as by lack of clear and transparent processes to support rapid evaluation, assessment, and implementation of genomic tests. This article provides an overview of some key barriers and proposes approaches to addressing these challenges as a potential pathway to developing a national approach to genomic medicine in oncology.

Progress toward Health System Readiness for Genome-Based Testing in Canada.

(1) Background: Genomic medicine harbors the real potential to improve the health and healthcare journey of patients, care provider experiences, and improve the health system efficiency-even reducing healthcare costs. There is expected to be an exponential growth in medically necessary new genome-based tests and test approaches in the coming years. Testing can also create scientific research and commercial opportunities beyond healthcare decision making. The purpose of this research is to generate a better understanding of Canada's state of readiness for genomic medicine, and to provide some insights for other healthcare systems. (2) Methods: A mixed-methods approach of a review of the literature and key informant interviews with a purposive sample of experts was used. The health system readiness was assessed using a previously published set of conditions. (3) Results: Canada has created some of the established conditions, but further action needs to be taken to improve the state of readiness for genome-based medicine. The important gaps to be filled are the need for linked information systems and data integration; evaluative processes that are timely and transparent; navigational tools for care providers; dedicated funding to facilitate rapid onboarding and support test development and proficiency testing; and broader engagement with innovation stakeholders beyond care providers and patients. These findings highlight the role of the organizational context, social influence, and other factors that are known to affect the diffusion of innovation within health systems.

Development of a Multi-Criteria Decision Analysis Rating Tool to Prioritize Real-World Evidence Questions for the Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration.

The Canadian Real-world Evidence for Value of Cancer Drugs (CanREValue) collaboration developed an MCDA rating tool to assess and prioritize potential post-market real-world evidence (RWE) questions/uncertainties emerging from public drug funding decisions in Canada. In collaboration with a group of multidisciplinary stakeholders from across Canada, the rating tool was developed following a three-step process: (1) selection of criteria to assess the importance and feasibility of an RWE question; (2) development of rating scales, application of weights and calculating aggregate scores; and (3) validation testing. An initial MCDA rating tool was developed, composed of seven criteria, divided into two groups. Group A criteria assess the importance of an RWE question by examining the (1) drug's perceived clinical benefit, (2) magnitude of uncertainty identified, and (3) relevance of the uncertainty to decision-makers. Group B criteria assess the feasibility of conducting an RWE analysis including the (1) feasibility of identifying a comparator, (2) ability to identify cases, (3) availability of comprehensive data, and (4) availability of necessary expertise and methodology. Future directions include partnering with the Canadian Agency for Drugs and Technology in Health's Provincial Advisory Group for further tool refinement and to gain insight into incorporating the tool into drug funding deliberations.

A Guide to Selecting Flexible Survival Models to Inform Economic Evaluations of Cancer Immunotherapies.

OBJECTIVES: Parametric models are routinely used to estimate the benefit of cancer drugs beyond trial follow-up. The advent of immune checkpoint inhibitors has challenged this paradigm, and emerging evidence suggests that more flexible survival models, which can better capture the shapes of complex hazard functions, might be needed for these interventions. Nevertheless, there is a need for an algorithm to help analysts decide whether flexible models are required and, if so, which should be chosen for testing. This position article has been produced to bridge this gap. METHODS: A virtual advisory board comprising 7 international experts with in-depth knowledge of survival analysis and health technology assessment was held in summer 2021. The experts discussed 24 questions across 6 topics: the current survival model selection procedure, data maturity, heterogeneity of treatment effect, cure and mortality, external evidence, and additions to existing guidelines. Their responses culminated in an algorithm to inform selection of flexible survival models. RESULTS: The algorithm consists of 8 steps and 4 questions. Key elements include the systematic identification of relevant external data, using clinical expert input at multiple points in the selection process, considering the future and the observed hazard functions, assessing the potential for long-term survivorship, and presenting results from all plausible models. CONCLUSIONS: This algorithm provides a systematic, evidence-based approach to justify the selection of survival extrapolation models for cancer immunotherapies. If followed, it should reduce the risk of selecting inappropriate models, partially addressing a key area of uncertainty in the economic evaluation of these agents.

Delivering precision oncology to patients with cancer.

With the increasing use of genomic profiling for diagnosis and therapy guidance in many tumor types, precision oncology is rapidly reshaping cancer care. However, the current trajectory of drug development in oncology results in a paradox: if patients cannot access advanced diagnostics, we may be developing drugs that will reach few patients. In this Perspective, we outline the major challenges to the implementation of precision oncology and discuss critical steps toward resolving these, including facilitation of equal access to genomics tests, ensuring that clinical studies provide robust evidence for new drugs and technologies, enabling physicians to interpret genomics data, and empowering patients toward shared decision-making. A multi-stakeholder approach to evidence generation, value assessment, and healthcare delivery is necessary to translate advances in precision oncology into benefits for patients with cancer globally.

Pharmacologic treatment of attention deficit hyperactivity disorder in adults: A systematic review and network meta-analysis.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) affects approximately 3% of adults globally. Many pharmacologic treatments options exist, yet the comparative benefits and harms of individual treatments are largely unknown. We performed a systematic review and network meta-analysis to assess the relative effects of individual pharmacologic treatments for adults with ADHD. METHODS: We searched English-language published and grey literature sources for randomized clinical trials (RCTs) involving pharmacologic treatment of ADHD in adults (December 2018). The primary outcome was clinical response; secondary outcomes were quality of life, executive function, driving behaviour, withdrawals due to adverse events, treatment discontinuation, serious adverse events, hospitalization, cardiovascular adverse events, and emergency department visits. Data were pooled via pair-wise meta-analyses and Bayesian network meta-analyses. Risk of bias was assessed by use of Cochrane's Risk of Bias tool, and the certainty of the evidence was assessed by use of the GRADE framework. RESULTS: Eighty-one unique trials that reported at least one outcome of interest were included, most of which were at high or unclear risk of at least one important source of bias. Notably, only 5 RCTs were deemed at overall low risk of bias. Included pharmacotherapies were methylphenidate, atomoxetine, dexamfetamine, lisdexamfetamine, guanfacine, bupropion, mixed amphetamine salts, and modafinil. As a class, ADHD pharmacotherapy improved patient- and clinician-reported clinical response compared with placebo (range: 4 to 15 RCTs per outcome); however, these findings were not conserved when the analyses were restricted to studies at low risk of bias, and the certainty of the finding is very low. There were few differences among individual medications, although atomoxetine was associated with improved patient-reported clinical response and quality of life compared with placebo. There was no significant difference in the risk of serious adverse events or treatment discontinuation between ADHD pharmacotherapies and placebo; however, the proportion of participants who withdrew due to adverse events was significantly higher among participants who received any ADHD pharmacotherapy. Few RCTs reported on the occurrence of adverse events over a long treatment duration. CONCLUSIONS: Overall, despite a class effect of improving clinical response relative to placebo, there were few differences among the individual ADHD pharmacotherapies, and most studies were at risk of at least one important source of bias. Furthermore, the certainty of the evidence was very low to low for all outcomes, and there was limited reporting of long-term adverse events. As such, the choice between ADHD pharmacotherapies may depend on individual patient considerations, and future studies should assess the long-term effects of individual pharmacotherapies on patient-important outcomes, including quality of life, in robust blinded RCTs. REGISTRATION: PROSPERO no. CRD 42015026049.

Value assessment of oncology drugs using a weighted criterion-based approach.

BACKGROUND: Globally, the rising cost of anticancer therapy has motivated efforts to quantify the overall value of new cancer treatments. Multicriteria decision analysis offers a novel approach to incorporate multiple criteria and perspectives into value assessment. METHODS: The authors recruited a diverse, multistakeholder group who identified and weighted key criteria to establish the drug assessment framework (DAF). Construct validity assessed the degree to which DAF scores were associated with past pan-Canadian Oncology Drug Review (pCODR) funding recommendations and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS; version 1.1) scores. RESULTS: The final DAF included 10 criteria: overall survival, progression-free survival, response rate, quality of life, toxicity, unmet need, equity, feasibility, disease severity, and caregiver well-being. The first 5 clinical benefit criteria represent approximately 64% of the total weight. DAF scores ranged from 0 to 300, reflecting both the expected impact of the drug and the quality of supporting evidence. When the DAF was applied to the last 60 drugs (with reviewers blinded) reviewed by pCODR (2015-2018), those drugs with positive pCODR funding recommendations were found to have higher DAF scores compared with drugs not recommended (103 vs 63; Student t test P = .0007). DAF clinical benefit criteria mildly correlated with ESMO-MCBS scores (correlation coefficient, 0.33; 95% CI, 0.009-0.59). Sensitivity analyses that varied the criteria scores did not change the results. CONCLUSIONS: Using a structured and explicit approach, a criterion-based valuation framework was designed to provide a transparent and consistent method with which to value and prioritize cancer drugs to facilitate the delivery of affordable cancer care.

Health Utility Book (HUB)-Cancer: Protocol for a Systematic Literature Review of Health State Utility Values in Cancer.

Background. Treatment options in oncology are rapidly advancing, and public payer systems are increasingly under pressure to adopt new but expensive cancer treatments. Cost-utility analyses (CUAs) are used to estimate the relative costs and effects of competing interventions, where health outcomes are measured using quality-adjusted life years (QALYs). Health state utility values (HSUVs) are used to reflect health-related quality of life or health status in the calculation of QALYs. To support reimbursement agencies in the appraisal of oncology drug submissions, which typically include a CUA component, we have proposed a systematic literature review of published HSUV estimates in the field of oncology. Methods. The following databases will be searched: MEDLINE, EMBASE, EconLit, and CINAHL. A team of reviewers, working independently and in duplicate, will evaluate abstracts and full-text publications for eligibility against broad inclusion criteria. Studies using a direct, indirect, or combination approach to eliciting preferences related to cancer or cancer treatments are eligible. Data extraction will capture details of study methodology, participants, health states, and corresponding HSUVs. We will summarize our findings with descriptive analyses at this stage. A pilot review in thyroid cancer is presented to illustrate the proposed methods. Discussion. This systematic review will generate a comprehensive summary of the oncology HSUV literature. As a component of the Health Utility Book (HUB) project, we anticipate that this work will assist both health economic modelers as well as critical reviewers in the development and appraisal of CUAs in oncology.

Variability in aneurysm sac regression after endovascular aneurysm repair based on a comprehensive registry of patients in Eastern Ontario.

BACKGROUND: Although the absence of aneurysm-related mortality, postimplantation rupture, and reintervention after endovascular aneurysm repair (EVAR) is desirable, it may not necessarily reflect successful aneurysm sac exclusion. Sac regression may be a more sensitive marker for EVAR success and may be influenced by factors beyond the presence or absence of an endoleak. The objective of this study is to determine the rate of overall long-term sac regression after EVAR and the influence of nonanatomic factors, and endograft devices used at our center. METHODS: This retrospective cohort study included all EVARs performed for intact and ruptured abdominal aortic aneurysms (AAAs) at a university teaching hospital. Preoperative, operative, and follow-up data were collected using clinical and radiologic institutional databases. Preoperative and post-EVAR sac diameters were determined by a blinded observer in accordance with Society for Vascular Surgery guidelines. Absolute and relative sac regression was determined at the following intervals: 0 to 6 months, 6 to 12 months, 12 to 18 months, 18 months to 2 years, 2 to 5 years, 5 to 10 years, and more than 10 years. RESULTS: From 1999 to 2015, 1060 patients underwent EVAR for an AAA at the Ottawa Hospital. Procedures were performed using a total of nine unique endograft devices, with five devices (Cook Zenith, n = 398; Medtronic Endurant, n = 375; Medtronic Talent, n = 183; Cook Zenith LP, n = 52; and Terumo Anaconda, n = 23) used in 97% of the procedures. The mean preoperative AAA diameter was 61.2 mm, with no detectable differences between endograft devices with respect to age, preoperative AAA diameter, or rupture diagnosis. Overall mean sac regression increased from -1.3 mm at 6 months, to -14.9 mm beyond 10 years. The majority of sac regression was achieved within 2 years. Only 90 of the 1060 patients (8.5%) experienced sac expansion of greater than 5 mm at some point during their follow-up period. Kaplan-Meier analyses revealed statistically significant device-specific variability in sac regression rates, even in the absence of an endoleak. Cox proportional hazard modeling demonstrated that age less than 75 years (hazard ratio [HR], 1.4; P = .001), female sex (HR, 1.4; P = .003), absence of type I endoleak (HR, 4.6; P < .0001), AAA greater than 70 mm (HR, 1.6; P < .0001), and both the Zenith (HR, 2.0; P < .0001) and Endurant (HR, 1.7; P = .001) devices were associated with shorter time to more than 5 mm sac regression. CONCLUSIONS: This study demonstrated a pattern of sac diameter change after EVAR, with the majority of sac regression occurring within the first 2 years. Variability in sac regression was influenced by nonanatomic variables including age, sex, original AAA diameter, and specific endograft device, even after controlling for the presence or absence of an endoleak. The biophysical relationship between specific endograft design and materials, and sac regression is yet to be determined.

Oncology Modeling for Fun and Profit! Key Steps for Busy Analysts in Health Technology Assessment.

In evaluating new oncology medicines, two common modeling approaches are state transition (e.g., Markov and semi-Markov) and partitioned survival. Partitioned survival models have become more prominent in oncology health technology assessment processes in recent years. Our experience in conducting and evaluating models for economic evaluation has highlighted many important and practical pitfalls. As there is little guidance available on best practices for those who wish to conduct them, we provide guidance in the form of 'Key steps for busy analysts,' who may have very little time and require highly favorable results. Our guidance highlights the continued need for rigorous conduct and transparent reporting of economic evaluations regardless of the modeling approach taken, and the importance of modeling that better reflects reality, which includes better approaches to considering plausibility, estimating relative treatment effects, dealing with post-progression effects, and appropriate characterization of the uncertainty from modeling itself.

Using Phase-Based Costing of Real-World Data to Inform Decision-Analytic Models for Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) poses a significant economic burden. An increasing number of interventions for AF require cost-effectiveness analysis with decision-analytic modeling to demonstrate value. However, high-quality cost estimates of AF that can be used to inform decision-analytic models are lacking. OBJECTIVES: The objectives of this study were to determine whether phase-based costing methods are feasible and practical for informing decision-analytic models outside of oncology. METHODS: Patients diagnosed with AF between 1 January 2003 and 30 June 2011 in Ontario, Canada were identified based on a hospital admission for AF using administrative data housed at the Institute for Clinical Evaluative Sciences. Patient observations were then divided into phases based on clinical events typically used for decision-analytic modeling (i.e., minor stroke/transient ischemic attack [TIA], moderate to severe ischemic stroke, myocardial infarction, extracranial hemorrhage [ECH], intracranial hemorrhage [ICH], multiple events, death from an event, or death from other causes). First 30-day and greater than 30-day costs of healthcare resources in each health state were estimated based on a validated methodology. All costs are reported in 2013 Canadian dollars (Can$) and from a healthcare payer perspective. RESULTS: Patients (n = 109,002) with AF who did not experience a clinical event incurred costs of Can$1566 per 30 days, on average. The average 30-day cost of experiencing a fatal clinical event was Can$42,871, but the cost of dying from all other causes was much smaller (Can$12,800). The clinical events associated with the highest short-term costs were ICH (Can$22,347) and moderate to severe ischemic stroke (Can$19,937). The lowest short-term costs were due to minor ischemic stroke/TIA (Can$12,515) and ECH (Can$12,261). Patients who had experienced a moderate to severe ischemic stroke incurred the highest long-term costs. CONCLUSIONS: Real-world Canadian data and a phase-based costing approach were used to estimate short- and long-term costs associated with AF-related major clinical events. The results of this study can also inform decision-analytic models for AF.

Trends in the utilization of endovascular therapy for elective and ruptured abdominal aortic aneurysm procedures in Canada.

OBJECTIVE: While randomized trials have shown improved operative mortality with endovascular aneurysm repair (EVAR) but similar long-term mortality rates, enthusiasm for EVAR persists, and rates of EVAR use continue to increase. Currently, knowledge of utilization rates of EVAR in Canada is limited. METHODS: Patients who underwent nonruptured abdominal aortic aneurysm (AAA) and ruptured AAA (RAAA) repair, by either open surgical repair (OSR) or EVAR, in Canada were identified from hospital discharge abstract data. Trends in rates for OSR and EVAR were calculated by province and by year, and standardized per 100,000 persons over 65 years of age (per capita). RESULTS: Between April 2004 and March 2009, 15,960 AAA procedures were performed in Canada, either by OSR (n=12,204) or EVAR (n=3756). The proportion of all elective AAA procedures by EVAR increased from 11.5% in 2005 to 35.5% in 2009, the highest current proportion of EVAR utilization in British Columbia (45.0%) and the lowest in Manitoba (15.8%). After standardization, the national rate of total procedures was steady, but the rate of RAAAs declined over the entire study period. Alberta consistently had the highest per capita rates of EVAR use (38.9), whereas Prince Edward Island had the lowest (8.4). Provincial variations in EVAR use did not correlate with differences in comorbidities. Compared with Canadian averages, Atlantic Provinces performed the most AAA procedures per capita (137.5 vs 93.4), had the highest rate of RAAAs per capita (29.7 vs 22.2), and had the lowest proportional rates of EVAR use. CONCLUSIONS: Use of EVAR in Canada for AAAs has increased in the past 5 years, without affecting overall AAA procedure volumes. Large discrepancies in EVAR use exist across Canada. The Atlantic Provinces had the highest rates of RAAAs despite having the highest rates for total AAA procedures, suggesting a population with higher susceptibility for AAAs. This region may also have the largest potential for future increased use of EVAR.

Guidelines for health technologies: specific guidance for oncology products in Canada.

OBJECTIVE: Specific methodological challenges are often encountered during cancer-related economic evaluations. The objective of this study was to provide specific guidance to analysts on the methods for the conduct of high-quality economic evaluations in oncology by building on the Canadian Agency for Drugs and Technologies in Health Guidelines for the Economic Evaluation of Health Technologies (third edition). METHODS: Fifteen oncologists, health economists, health services researchers, and decision makers from across Canada identified sections in Canadian Agency for Drugs and Technologies in Health guidelines that would benefit from oncology-specific guidance. Fifteen sections of the guidelines were reviewed to determine whether 1) Canadian Agency for Drugs and Technologies in Health guidelines were sufficient for the conduct of oncology economic evaluations without further guidance specific for oncology products or 2) additional guidance was necessary. A scoping review was conducted by using a comprehensive and replicable search to identify relevant literature to inform recommendations. Recommendations were reviewed by representatives of academia, government, and the pharmaceutical industry in an iterative and formal review of the recommendations. RESULTS: Major adaptations for guidance related to time horizon, effectiveness, modeling, costs, and resources were required. Recommendations around the use of final outcomes over intermediate outcomes to calculate quality-adjusted life-years and life-years gained, the type of evidence, the source of evidence, and the use of time horizon and modeling were made. CONCLUSIONS: This article summarizes key recommendations for the conduct of economic evaluations in oncology and describes methods required to ensure that economic assessments in oncology are conducted in a standardized manner.

Wait times among patients with symptomatic carotid artery stenosis requiring carotid endarterectomy for stroke prevention.

BACKGROUND: Current Canadian and international guidelines suggest patients with transient ischemic attack (TIA) or nondisabling stroke and ipsilateral internal carotid artery stenosis of 50% to 99% should be offered carotid endarterectomy (CEA) ≤ 2 weeks of the incident TIA or stroke. The objective of the study was to identify whether these goals are being met and the factors that most influence wait times. METHODS: Patients who underwent CEA at the Ottawa Hospital for symptomatic carotid artery stenosis from 2008 to 2010 were identified. Time intervals based on the dates of initial symptoms, referral to and visit with a vascular surgeon, the decision to operate, and the date of surgery were recorded for each patient. The influence of various factors on wait times was explored, including age, sex, type of index event, referring physician, distance from the surgical center, degree of stenosis, and surgeon assigned. RESULTS: Of the 117 patients who underwent CEA, 92 (78.6%) were symptomatic. The median time from onset of symptoms to surgery for all patients was 79 days (interquartile range [IQR], 34-161). The shortest wait times were observed in stroke patients (49 [IQR, 27-81] days) and inpatient referrals (66 [IQR, 25-103] days). Only 7 of the 92 symptomatic patients (8%) received care within the recommended 2 weeks. The median surgical wait time for all patients was 14 days (IQR, 8-25 days). In the multivariable analysis, significant predictors of longer wait times included retinal TIA (P = .003), outpatient referrals (P = .004), and distance from the center (P = .008). Patients who presented to the emergency department had the shortest delays in seeing a vascular surgeon and subsequently undergoing CEA (P < .0001). There was no difference between surgeons for wait times to be seen in the clinic; however, there were significant differences among surgeons once the decision was made to proceed with CEA. CONCLUSIONS: Our wait times for CEA currently do not fall within the recommended 2-week guideline nor does it appear feasible within the current system. Important factors contributing to delays include outpatient referrals, living farther from the hospital, and presenting with a retinal TIA (amaurosis fugax). Our findings also suggest better scheduling practices once a decision is made to operate can modestly improve overall and surgical wait times for CEA.

Efficacy of statins for primary prevention in people at low cardiovascular risk: a meta-analysis.

BACKGROUND: Statins were initially used to improve cardiovascular outcomes in people with established coronary artery disease, but recently their use has become more common in people at low cardiovascular risk. We did a systematic review of randomized trials to assess the efficacy and harms of statins in these individuals. METHODS: We searched MEDLINE and EMBASE (to Jan. 28, 2011), registries of health technology assessments and clinical trials, and reference lists of relevant reviews. We included trials that randomly assigned participants at low cardiovascular risk to receive a statin versus a placebo or no statin. We defined low risk as an observed 10-year risk of less than 20% for cardiovascular-related death or nonfatal myocardial infarction, but we explored other definitions in sensitivity analyses. RESULTS: We identified 29 eligible trials involving a total of 80,711 participants. All-cause mortality was significantly lower among patients receiving a statin than among controls (relative risk [RR] 0.90, 95% confidence interval [CI] 0.84-0.97) for trials with a 10-year risk of cardiovascular disease < 20% [primary analysis] and 0.83, 95% CI 0.73-0.94, for trials with 10-year risk < 10% [sensitivity analysis]). Patients in the statin group were also significantly less likely than controls to have nonfatal myocardial infarction (RR 0.64, 95% CI 0.49-0.84) and nonfatal stroke (RR 0.81, 95% CI 0.68-0.96). Neither metaregression nor stratified analyses suggested statistically significant differences in efficacy between high-and low-potency statins, or larger reductions in cholesterol. INTERPRETATION: Statins were found to be efficacious in preventing death and cardiovascular morbidity in people at low cardiovascular risk. Reductions in relative risk were similar to those seen in patients with a history of coronary artery disease.

Health technology assessment: a review of international activity and examples of approaches with computed tomographic colonography.

The growth of health technology assessment (HTA) internationally is currently reflected in the growing membership of the International Network of Agencies for Health Technology Assessment. Many national and regional HTA institutions emerged in the 1980s and 1990s, and more recently, HTA has emerged in newly industrialized countries and in European Union member states in transition. Health technology assessment activities are becoming an increasingly important part of health care culture, with the appearance of HTA units in hospitals and hospital departments. This article provides a brief overview of who conducts HTA internationally and looks at how HTA is conducted and how this information is used. To highlight the different structures, processes, and methods available, a portion of this article is dedicated to describing different approaches that have been observed with respect to the assessment of computed tomographic colonography in North America for population-based colorectal cancer screening.

Imatinib mesylate for chronic myeloid leukemia: what do we really know?

Imatinib mesylate (GleevecTM) is a tyrosine kinase inhibitor, one of a new class of anticancer drugs called signal transduction inhibitors. A systematic review of case-series reports shows imatinib, when indirectly compared to conventional therapy, improves overall 12-month survival, but not surrogate outcomes, in individuals with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in myeloid-blast crisis, and accelerated phase. Surrogate outcomes, but not overall survival, were improved in chronic phase disease. Preliminary data from one randomized controlled trial suggest imatinib has a greater impact on surrogate outcomes compared to the combination of interferonalpha and cytarabine in patients undergoing treatment for chronic phase Ph+CML, however, it is not yet known whether it prolongs or improves quality of life.