Monika Wagner

Systematic review of the incidence and prevalence of genital warts

BackgroundAnogenital warts (AGWs) are a common, highly infectious disease caused by the human papillomavirus (HPV), whose high recurrence rates contribute to direct medical costs, productivity loss and increased psychosocial impact. Because of the lack of a systematic review of the epidemiology of AGWs in the literature, this study reviewed the published medical literature on the incidence and prevalence of AGWs.MethodsA comprehensive literature search was performed on the worldwide incidence and prevalence of AGWs between 2001 and 2012 using the PubMed and EMBASE databases. An additional screening of abstracts from relevant sexual health and infectious disease conferences from 2009 to 2011 was also conducted. Only original studies with general adult populations (i.e., at least including ages 20 through 40 years) were included.ResultsThe overall (females and males combined) reported annual incidence of any AGWs (including new and recurrent) ranged from 160 to 289 per 100,000, with a median of 194.5 per 100,000. New AGW incidence rates among males ranged from 103 to 168 per 100,000, with a median of 137 per 100,000 and among females from 76 to 191 per 100,000, with a median of 120.5 per 100,000 per annum. The reported incidence of recurrent AGWs was as high as 110 per 100,000 among females and 163 per 100,000 among males. Incidence peaked before 24 years of age in females and between 25 and 29 years of age among males. The overall prevalence of AGWs based on retrospective administrative databases or medical chart reviews or prospectively collected physician reports ranged from 0.13% to 0.56%, whereas it ranged from 0.2% to 5.1% based on genital examinations.ConclusionsThe literature suggests that AGWs are widespread and the prevalence depends on study methodology as suggested by higher rates reported from routine genital examinations versus those from treatment records. However, there remains a need for more population-based studies from certain regions including Africa, Latin America and Southern Asia to further elucidate the global epidemiology of this disease.

Evidence and Value: Impact on DEcisionMaking – the EVIDEM framework and potential applications

BackgroundHealthcare decisionmaking is a complex process relying on disparate types of evidence and value judgments. Our objectives for this study were to develop a practical framework to facilitate decisionmaking in terms of supporting the deliberative process, providing access to evidence, and enhancing the communication of decisions.MethodsExtensive analyses of the literature and of documented decisionmaking processes around the globe were performed to explore what steps are currently used to make decisions with respect to context (from evidence generation to communication of decision) and thought process (conceptual components of decisions). Needs and methodologies available to support decisionmaking were identified to lay the groundwork for the EVIDEM framework.ResultsA framework was developed consisting of seven modules that can evolve over the life cycle of a healthcare intervention. Components of decision that could be quantified, i.e., intrinsic value of a healthcare intervention and quality of evidence available, were organized into matrices. A multicriteria decision analysis (MCDA) Value Matrix (VM) was developed to include the 15 quantifiable components that are currently considered in decisionmaking. A methodology to synthesize the evidence needed for each component of the VM was developed including electronic access to full text source documents. A Quality Matrix was designed to quantify three criteria of quality for the 12 types of evidence usually required by decisionmakers. An integrated system was developed to optimize data analysis, synthesis and validation by experts, compatible with a collaborative structure.ConclusionThe EVIDEM framework promotes transparent and efficient healthcare decisionmaking through systematic assessment and dissemination of the evidence and values on which decisions are based. It provides a collaborative framework that could connect all stakeholders and serve the healthcare community at local, national and international levels by allowing sharing of data, resources and values. Validation and further development is needed to explore the full potential of this approach.

From efficacy to equity: Literature review of decision criteria for resource allocation and healthcare decisionmaking.

ObjectivesResource allocation is a challenging issue faced by health policy decisionmakers requiring careful consideration of many factors. Objectives of this study were to identify decision criteria and their frequency reported in the literature on healthcare decisionmaking.MethodAn extensive literature search was performed in Medline and EMBASE to identify articles reporting healthcare decision criteria. Studies conducted with decisionmakers (e.g., focus groups, surveys, interviews), conceptual and review articles and articles describing multicriteria tools were included. Criteria were extracted, organized using a classification system derived from the EVIDEM framework and applying multicriteria decision analysis (MCDA) principles, and the frequency of their occurrence was measured.ResultsOut of 3146 records identified, 2790 were excluded. Out of 356 articles assessed for eligibility, 40 studies included. Criteria were identified from studies performed in several regions of the world involving decisionmakers at micro, meso and macro levels of decision and from studies reporting on multicriteria tools. Large variations in terminology used to define criteria were observed and 360 different terms were identified. These were assigned to 58 criteria which were classified in 9 different categories including: health outcomes; types of benefit; disease impact; therapeutic context; economic impact; quality of evidence; implementation complexity; priority, fairness and ethics; and overall context. The most frequently mentioned criteria were: equity/fairness (32 times), efficacy/effectiveness (29), stakeholder interests and pressures (28), cost-effectiveness (23), strength of evidence (20), safety (19), mission and mandate of health system (19), organizational requirements and capacity (17), patient-reported outcomes (17) and need (16).ConclusionThis study highlights the importance of considering both normative and feasibility criteria for fair allocation of resources and optimized decisionmaking for coverage and use of healthcare interventions. This analysis provides a foundation to develop a questionnaire for an international survey of decisionmakers on criteria and their relative importance. The ultimate objective is to develop sound multicriteria approaches to enlighten healthcare decisionmaking and priority-setting.

Bridging health technology assessment (HTA) and efficient health care decision making with multicriteria decision analysis (MCDA): applying the EVIDEM framework to medicines appraisal.

Background. Health care decision making is complex and requires efficient and explicit processes to ensure transparency and consistency of factors considered. Objectives. To pilot an adaptable decision-making framework incorporating multicriteria decision analysis (MCDA) in health technology assessment (HTA) with a pan-Canadian group of policy and clinical decision makers and researchers appraising 10 medicines covering 6 therapeutic areas. Methods. An appraisal group was convened and participants were asked to express their individual perspectives, independently of the medicines, by assigning weights to each criterion of the MCDA core model: disease severity, size of population, current practice and unmet needs, intervention outcomes (efficacy, safety, patient reported), type of health benefit, economics, and quality of evidence. Participants then assigned performance scores for each medicine using available evidence synthesized in a “by-criterion” HTA report covering each of the MCDA CORE model criteria. MCDA estimates of perceived value were calculated by combining normalized weights and scores. Feedback on the approach was collected through structured discussion. Results. Relative weights on criteria varied widely, reflecting the diverse perspectives of participants. Scores for each criterion provided a performance measure, highlighting strengths and weaknesses of each medicine. MCDA estimates of perceived value ranged from 0.42 to 0.64 across medicines, providing comprehensive measures incorporating a large spectrum of criteria. Participants reported that the framework provided an efficient approach to systematic consideration in a pragmatic format of the multiple elements guiding decision, including criteria and values (MCDA core model) and evidence (HTA “by-criterion” report). Conclusions. This proof-of-concept study demonstrated the usefulness of incorporating MCDA in HTA to support transparent and systematic appraisal of health care interventions. Further research is needed to advance MCDA-based approaches to more effective healthcare decision making.

Clinical and Economic Consequences of Vancomycin and Fidaxomicin for the Treatment of Clostridium difficile Infection in Canada

BACKGROUND Clostridium difficile infection (CDI) represents a public health problem with increasing incidence and severity. OBJECTIVE To evaluate the clinical and economic consequences of vancomycin compared with fidaxomicin in the treatment of CDI from the Canadian health care system perspective. METHODS A decision-tree model was developed to compare vancomycin and fidaxomicin for the treatment of severe CDI. The model assumed identical initial cure rates and included first recurrent episodes of CDI (base case). Treatment of patients presenting with recurrent CDI was examined as an alternative analysis. Costs included were for study medication, physician services and hospitalization. Cost effectiveness was measured as incremental cost per recurrence avoided. Sensitivity analyses of key input parameters were performed. RESULTS In a cohort of 1000 patients with an initial episode of severe CDI, treatment with fidaxomicin led to 137 fewer recurrences at an incremental cost of

Can the EVIDEM Framework Tackle Issues Raised by Evaluating Treatments for Rare Diseases: Analysis of Issues and Policies, and Context-Specific Adaptation

1.81 million, resulting in an incremental cost of

Global availability of data on HPV genotype-distribution in cervical, vulvar and vaginal disease and genotype-specific prevalence and incidence of HPV infection in females

13,202 per recurrence avoided. Among 1000 patients with recurrent CDI, 113 second recurrences were avoided at an incremental cost of

Economic evaluation of high-dose (80 mg/day) atorvastatin treatment compared with standard-dose (20 mg/day to 40 mg/day) simvastatin treatment in Canada based on the Incremental Decrease in End-Points Through Aggressive Lipid-Lowering (IDEAL) trial

18,190 per second recurrence avoided. Incremental costs per recurrence avoided increased with increasing proportion of cases caused by the NAP1/B1/027 strain. Results were sensitive to variations in recurrence rates and treatment duration but were robust to variations in other parameters. CONCLUSIONS The use of fidaxomicin is associated with a cost increase for the Canadian health care system. Clinical benefits of fidaxomicin compared with vancomycin depend on the proportion of cases caused by the NAP1/B1/027 strain in patients with severe CDI.

Associations of Anogenital Low-Risk Human Papillomavirus Infection With Cancer and Acquisition of HIV.

BackgroundThe multiplicity of issues, including uncertainty and ethical dilemmas, and policies involved in appraising interventions for rare diseases suggests that multicriteria decision analysis (MCDA) based on a holistic definition of value is uniquely suited for this purpose. The objective of this study was to analyze and further develop a comprehensive MCDA framework (EVIDEM) to address rare disease issues and policies, while maintaining its applicability across disease areas.MethodsSpecific issues and policies for rare diseases were identified through literature review. Ethical and methodological foundations of the EVIDEM framework v3.0 were systematically analyzed from the perspective of these issues, and policies and modifications of the framework were performed accordingly to ensure their integration.ResultsAnalysis showed that the framework integrates ethical dilemmas and issues inherent to appraising interventions for rare diseases but required further integration of specific aspects. Modification thus included the addition of subcriteria to further differentiate disease severity, disease-specific treatment outcomes, and economic consequences of interventions for rare diseases. Scoring scales were further developed to include negative scales for all comparative criteria. A methodology was established to incorporate context-specific population priorities and policies, such as those for rare diseases, into the quantitative part of the framework. This design allows making more explicit trade-offs between competing ethical positions of fairness (prioritization of those who are worst off), the goal of benefiting as many people as possible, the imperative to help, and wise use of knowledge and resources. It also allows addressing variability in institutional policies regarding prioritization of specific disease areas, in addition to existing uncertainty analysis available from EVIDEM.ConclusionThe adapted framework measures value in its widest sense, while being responsive to rare disease issues and policies. It provides an operationalizable platform to integrate values, competing ethical dilemmas, and uncertainty in appraising healthcare interventions.

Appraising the holistic value of Lenvatinib for radio-iodine refractory differentiated thyroid cancer: A multi-country study applying pragmatic MCDA

BackgroundCountry-level HPV genotyping data may be sought by decision-makers to gauge the genotype-specific burden of HPV-related diseases in their jurisdiction and assess the potential impact of HPV vaccines. We investigated, by country, the availability of published literature on HPV genotypes in cervical, vaginal and vulvar cancers and intraepithelial neoplasms (CINs, VaINs and VINs) and on prevalence and incidence of genital HPV infections among women without clinically manifest disease.FindingsPrimary sources of publications were the PubMed/Medline and EMBASE databases. Original studies or meta-analyses published from 2000, covering genotypes 16 and 18 and at least one of genotypes 31/33/45/52/58, were included. Key exclusion criteria were language not English, cervical lesions not histologically confirmed (cytology only), special populations (e.g., immunocompromised) and, for cervical studies, small population (<50). A total of 727 studies reporting HPV genotype-specific data were identified: 366 for cervical cancers and CINs, 43 for vulvar or vaginal cancers and VINs/VaINs, and 395 and 21 for infection prevalence and incidence, respectively, in general female population samples. A large proportion of studies originated from a small set of countries. Cervical cancer/CIN typing data was scarce for several regions with the highest cervical cancer burden, including Eastern, Middle and Western Africa, Central America, South-East Asia, South Asia, and Eastern Europe. Data for vulvar/vaginal disease was limited outside of Europe and North America.ConclusionsAlthough a large body of published HPV genotype-specific data is currently available, data gaps exist for genotype-specific infection incidence and several world regions with the highest cervical cancer burden.