
Uwe Siebert, MD, MPH, MSc, ScD
Prof. Uwe Siebert, MD, MPH, MSc, ScD, Professor of Public Health, Medical Decision Making and Health Technology Assessment (HTA), is the Chair of the Department of Public Health, Health Services Research and HTA at UMIT – University for Health Sciences, Medical Informatics and Technology in Austria and the Director of the Division for HTA in the ONCOTYROL – Center for Personalized Cancer Medicine in Austria. He is also Adjunct Professor of Health Policy and Management, and Epidemiology, at the Harvard T.H. Chan School of Public Health and Affiliated Researcher of the Program on Cardiovascular Research at the Institute for Technology Assessment and Department of Radiology at the Massachusetts General Hospital, Harvard Medical School, Boston. He is the course director of the Harvard summer course on ‘Decision Analysis in Clinical Research’ and he has an adjunct teaching appointment at the School of Public Health and Epidemiology at the University of Munich.
After medical school, he worked for several years as a physician in international public health projects in West-Africa, Brazil, and Germany. He then earned an MPH at the Munich School of Public Health, and completed an MSc in Epidemiology and a ScD in Health Policy and Management with a concentration in decision sciences at the Harvard School of Public Health. Before he started his faculty position at Harvard Medical School, he was the Director of the Bavarian Public Health Research and Coordinating Center at the University of Munich, Germany, and completed Visiting Scholarship at the Harvard Center for Risk Analysis.
Prof. Siebert is Past-President of the Society for Medical Decision Making (SMDM), a member of the Latin America Consortium Advisory Committee of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR), member of the Oncology Advisory Council of the Federal Ministry of Health in Austria, member of the Advisory Board of the GÖG – National Austrian Public Health Institute, member of the Austrian Cochrane Collaboration Branch, and a member of several national and international Directors Boards (Austrian Society of Epidemiology, German Network of EbM; German Association for Medical Informatics, Biometry and Epidemiology). He has served as Vice President of SMDM, and member of the ISPOR Board of Directors, the Society for Medical Decision Making Board of Trustees; the Harvard Flagship Initiative in Comparative Effectiveness Research, the ‘National HTA Strategy’ Expert Group of the Austrian Federal Ministry of Health, the Advisory Board of the Ludwig Boltzmann Institute for HTA in Austria, the International Expert Committee Advising the Institute for Quality and Efficiency in Health Care (IQWiG) on the Methods for Economic Evaluations of Health Care Interventions, the Directors Board of the German Competence Network Heart Failure, and the Extended Board of Directors of the German Association of Health Economics.
He is the Clinical Guideline Commissioner for the Association of the Scientific Medical Societies in Germany (AWMF), Authorized Expert in the COVID-19 Prognosis Consortium and the Scientific Platform Screening- and Monitoring Programs for COVID-19 of AGES – Austrian Agency for Health and Food Safety and GÖG advising the Austrian Federal Ministry of Social Affairs, Health, Care and Consumer Protection, Member of the Task Force for COVID-19 Vaccination Implementation of the State Government Tyrol, Chair of the Horizontal Initiative in Causal Inference of the German Society for Epidemiology (DGEpi), Chair of the Working Group “Effectiveness and Side Effects of Non-Pharmaceutical Interventions” of the Competence Network for Public Health for COVID-19, and Chair of the Working Groups ‘Health Economics’ and ‘Medical Decision Making’ of the German Society for Medical Informatics, Biometry and Epidemiology (GMDS). He is Co-Chair of the ISPOR-SMDM Modeling Good Research Practices Task Force, Co-Chair of the ‘Issues in Methodology Section’ of the SMDM Policy Initiative, a Leadership Member of the ISPOR Personalized/Precision Medicine Special Interest Group, and member of the SMDM COVID-19 Modeling Special Committee.
He has worked with several HTA Agencies (e.g., DAHTA@DIMDI/Germany, IQWiG/Germany, NICE/UK, ANVISA/Brazil, IATS/Brazil, CADTH/Canada, LBI-HTA/Austria, GÖG/Austria) and he advises public and government agencies, academic institutions and industry regarding the conduction of HTAs and their impact on policy and reimbursement decisions. He has authored more than 400 publications (> 20,000 citations, H index > 50) including HTA reports, textbook chapters, scientific articles, policy briefs and editorials, and is Editor of the European Journal of Epidemiology, Associate Editor of Public Health Reviews as well as editorial board member of several scientific journals.
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Selected Publications
Juneau, Carl-Etienne; Briand, Anne-Sara; Collazzo, Pablo; Siebert, Uwe; Pueyo, Tomas
Effective contact tracing for COVID-19: A systematic review Journal Article
In: Glob Epidemiol, vol. 5, pp. 100103, 2023, ISSN: 2590-1133.
@article{pmid36959868,
title = {Effective contact tracing for COVID-19: A systematic review},
author = {Carl-Etienne Juneau and Anne-Sara Briand and Pablo Collazzo and Uwe Siebert and Tomas Pueyo},
doi = {10.1016/j.gloepi.2023.100103},
issn = {2590-1133},
year = {2023},
date = {2023-12-01},
journal = {Glob Epidemiol},
volume = {5},
pages = {100103},
abstract = {Contact tracing is commonly recommended to control outbreaks of COVID-19, but its effectiveness is unclear. Following PRISMA guidelines, we searched four databases using a range of terms related to contact tracing effectiveness for COVID-19. We found 343 papers; 32 were included. All were observational or modelling studies. Observational studies ( = 14) provided consistent, very-low certainty evidence that contact tracing (alone or in combination with other interventions) was associated with better control of COVID-19 (e.g. in Hong Kong, only 1084 cases and four deaths were recorded in the first 4.5 months of the pandemic). Modelling studies ( = 18) provided consistent, high-certainty evidence that under assumptions of prompt and thorough tracing with effective quarantines, contact tracing could stop the spread of COVID-19 (e.g. by reducing the reproduction number from 2.2 to 0.57). A cautious interpretation indicates that to stop the spread of COVID-19, public health practitioners have 2-3 days from the time a new case develops symptoms to isolate the case and quarantine at least 80% of its contacts.},
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Veličković, Vladica M; Carradice, Daniel; Boyle, Jonathan R; Hamady, Mohamad; Cleveland, Trevor; Neequaye, Simon; Ignjatović, Aleksandra; Bogdanović, Dragana; Savovic, Jelena; Siebert, Uwe
In: Expert Rev Cardiovasc Ther, vol. 21, no. 5, pp. 347–356, 2023, ISSN: 1744-8344.
@article{pmid37128666,
title = {Umbrella review and meta-analysis of reconstructed individual patient data of mortality following conventional endovascular and open surgical repair of infrarenal abdominal aortic aneurysm},
author = {Vladica M Veli\v{c}kovi\'{c} and Daniel Carradice and Jonathan R Boyle and Mohamad Hamady and Trevor Cleveland and Simon Neequaye and Aleksandra Ignjatovi\'{c} and Dragana Bogdanovi\'{c} and Jelena Savovic and Uwe Siebert},
doi = {10.1080/14779072.2023.2207009},
issn = {1744-8344},
year = {2023},
date = {2023-05-01},
journal = {Expert Rev Cardiovasc Ther},
volume = {21},
number = {5},
pages = {347--356},
abstract = {OBJECTIVES: This umbrella review aims to quality assess published meta-analyses, conduct a de-novo meta-analysis of the available randomized control trials (RCTs), and test the hypothesis that there is a long-term difference in mortality between OSR and EVAR.nnMETHODS: A systematic search was conducted in MEDLINE and EMBASE's bibliographic databases (June 2022). Data were extracted using standardized extraction forms. The methodological quality of publications was assessed using the ROBIS tool. Data were analyzed with 'one-stage' and 'two-stage' approaches.nnRESULTS: According to two-stage analysis, EVAR has significantly favorable mortality for up to four years (increasing evidence). Subsequently, until the longest available time period, there is no difference between EVAR and OSR; all the results are statistically non-significant.In one stage analysis, the Cox model demonstrated a non-significant (weak evidence) hazard ratio of 1.03 (95% confidence interval [CI]: 0.94-1.12) in favor of OSR. The best-fitting parametric model (generalized gamma), leads to an hazard ratio of 0.97 (95% CI: 0.93-1.01) in favor of EVAR, with the results approaching significance (weak evidence).nnCONCLUSION: The results of this umbrella systematic review and meta-analysis failed to demonstrate any difference in long-term mortality following planned EVAR, compared with OSR of infrarenal AAA.},
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Gartlehner, Gerald; Schernhammer, Eva; Lax, Sigurd F; Preusser, Matthias; Bachler, Herbert; Tietzer, Harald; Kletecka-Pulker, Maria; Turnher, Helga; Siebert, Uwe
Screening for colorectal cancer : A recommendation statement of the Austrian National Committee for Cancer Screening Journal Article
In: Wien Klin Wochenschr, 2023, ISSN: 1613-7671.
@article{pmid37256423,
title = {Screening for colorectal cancer : A recommendation statement of the Austrian National Committee for Cancer Screening},
author = {Gerald Gartlehner and Eva Schernhammer and Sigurd F Lax and Matthias Preusser and Herbert Bachler and Harald Tietzer and Maria Kletecka-Pulker and Helga Turnher and Uwe Siebert},
doi = {10.1007/s00508-023-02209-0},
issn = {1613-7671},
year = {2023},
date = {2023-05-01},
journal = {Wien Klin Wochenschr},
abstract = {BACKGROUND: Colorectal cancer is the fourth most common cancer in Austria. To date, colorectal cancer screening in Austria remains opportunistic and includes colonoscopy or stool-based blood tests. The Austrian National Committee for Cancer Screening developed evidence-based recommendations for a nationwide organized colorectal cancer screening program.nnMETHODS: The methodological framework followed the approach of the United States Preventive Services Task Force. The evidence base underlying the newly developed recommendations comprised a review of the existing published evidence and a decision analytic model tailored to the Austrian context. Using a structured process, committee members considered 1) the magnitude of the net benefit of each screening strategy, 2) the certainty of evidence, and 3) the level of acceptance of the interventions among the target population.nnRECOMMENDATIONS: The Austrian National Committee for Cancer Screening recommends the implementation of a nationwide organized colorectal cancer screening program for all adults aged 45-75 years. For persons 65 years or older, screening decisions should occur on an individual basis in accordance with a person's overall health, prior screening history, and preferences. Specifically, the committee recommends either a 10-year screening colonoscopy or biennial fecal immunochemical tests with colonoscopy following a positive result, with both screening strategies considered equivalent. Each citizen should be able to make an informed decision about their preferred screening method. Switching between the two screening strategies should be possible. Following an unremarkable colonoscopy, screening by fecal immunochemical test (FIT) is only required after 10 years. Screening recommendations apply only to asymptomatic persons at average risk for colorectal cancer. The screening program must be pilot tested, and accompanied by a public information campaign, formative evaluation, quality assurance, and data collection.},
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Schnell-Inderst, Petra; Conrads-Frank, Annette; Stojkov, Igor; Krenn, Cornelia; Kofler, Lisa-Maria; Siebert, Uwe
Occupational therapy for persons with cognitive impairments Journal Article
In: Ger Med Sci, vol. 21, pp. Doc02, 2023, ISSN: 1612-3174.
@article{pmid37260919,
title = {Occupational therapy for persons with cognitive impairments},
author = {Petra Schnell-Inderst and Annette Conrads-Frank and Igor Stojkov and Cornelia Krenn and Lisa-Maria Kofler and Uwe Siebert},
doi = {10.3205/000316},
issn = {1612-3174},
year = {2023},
date = {2023-01-01},
journal = {Ger Med Sci},
volume = {21},
pages = {Doc02},
abstract = {BACKGROUND: Damage to the central nervous system can occur in adulthood, for example, due to stroke, trauma, tumours, or chronic diseases. After damage to the central nervous system, cognitive impairments occur in addition to physical limitations. Occupational therapy is most often prescribed for neurological diagnoses, including stroke and traumatic brain injury.nnMETHODS: The health technology assessment (HTA) report this HTA article is based on investigates the clinical effectiveness, cost-effectiveness, and patient-related, social and ethical aspects of occupational therapy for patients with cognitive impairments compared to no occupational therapy. In addition, the effects of different occupational therapy interventions with and without cognitive components were compared in an explorative overview. Patients with moderate or severe dementia are excluded from the assessment. Systematic overviews, that is, systematic reviews of systematic reviews, were conducted.nnRESULTS: For the evaluation of clinical effectiveness, a total of nine systematic reviews were included. No systematic review was identified for the assessment of costs or cost-effectiveness. Five systematic reviews were included for the assessment of patient and social aspects. For the assessment of clinical effectiveness compared with no occupational therapy, five systematic reviews comprising 20 randomised controlled trials with a total of 1,316 subjects reported small positive effects for the outcomes "global cognitive function" and "activities of daily living" as well as a non-quantified positive effect on the outcomes "health-related quality of life" and "behavioural control". No effect was found for individual components of cognition and measures of perception. The quality of the evidence for all outcomes is low due to a high risk of bias. In the supplementary presentations, no positive effects could be demonstrated on the basis of the available evidence. The quality of this evidence was not assessed. For the assessment of patient and social aspects, five systematic reviews on patients with a stroke or a traumatic brain injury - without specification regarding cognitive deficits or studies with their relatives - were included. It was reported that patients and family caregivers go through different phases of rehabilitation in which the discharge home is a decisive turning point. The discharge home represents a crucial breaking point. Regaining an active, self-determining role is a process that requires therapists to find the right level of support for patients and relatives. For the assessment of ethical aspects, nine documents were included. We identified ethical problem-solving models for occupational therapy and 16 ethical aspects in occupational therapy for cognitive deficits. The central theme of the analysis is the limited autonomy due to the consequences of the disease as well as the resulting tensions with those treating the patient.nnCONCLUSIONS: Based on this systematic overview, it can neither be proven nor excluded with certainty that occupational therapy for cognitive impairment is an effective therapy for adult patients with central nervous system injuries compared to no occupational therapy. There is a lack of randomised trials with sufficient sample size, well-defined interventions, and comparable concomitant therapies in the control groups, but there is also a lack of well-designed observational studies in routine care and health economic studies. The identified systematic reviews on patient and social aspects provide information on the needs of patients after stroke or traumatic brain injury and their relatives, but there is a lack of studies on this aspect in German-speaking countries. For the ethical assessment, in addition to the identified theoretical models for solving ethical conflicts in occupational therapy, more empirical studies on ethical aspects with patients with cognitive deficits and their relatives as well as occupational therapists are needed.},
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Haslwanter, Veronika; Rochau, Ursula; Siebert, Uwe; Schönherr, Hans-Robert; Oberaigner, Willi
A population-based cohort of adult patients with diabetes mellitus in a Western District of Austria: The Diabetes Landeck cohort Journal Article
In: Endocrinol Diabetes Metab, pp. e395, 2022, ISSN: 2398-9238.
@article{pmid36527244,
title = {A population-based cohort of adult patients with diabetes mellitus in a Western District of Austria: The Diabetes Landeck cohort},
author = {Veronika Haslwanter and Ursula Rochau and Uwe Siebert and Hans-Robert Sch\"{o}nherr and Willi Oberaigner},
doi = {10.1002/edm2.395},
issn = {2398-9238},
year = {2022},
date = {2022-12-16},
urldate = {2022-12-01},
journal = {Endocrinol Diabetes Metab},
pages = {e395},
abstract = {INTRODUCTION: Diabetes mellitus (DM) has become an important and exacerbating health epidemic, with severe consequences for both patients and health systems. The National Diabetes Strategy of Austria addresses the lack of high-quality data on DM in Austria and the need for developing a national data network. The aims of our study are to establish a cohort including all adult diabetes patients in a district in western Austria, describe the demographic and clinical characteristics of this cohort, and provide an estimation of diabetes prevalence.
METHODS: We recruited a population-based cohort of adult patients with a diagnosis of DM in cooperation with a network of all caregivers. Data collection was based on a case report form, including patient characteristics, clinical parameters and long-term complications.
RESULTS: In total, 1845 patients with DM were recruited and analysed. We observed an overall prevalence of 5.3% [95% CI: 5.0%-5.5%]. For the subsequent main analysis, we included 1755 patients with DM after excluding 90 patients with gestational DM. There were significant differences between genders in the distribution of specific clinical parameters, patient characteristics, and the long-term complications diabetic foot, amputation and cardiovascular disease.
CONCLUSION: To the best of our knowledge, we established the first diabetes cohort study in Austria. Prevalence and the proportion of specific long-term complications were lower when compared to the international context. We assume that the Diabetes Landeck Cohort has reached a high degree of completeness; however, we were not able to identify independent data sources for a valid check of completeness.},
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METHODS: We recruited a population-based cohort of adult patients with a diagnosis of DM in cooperation with a network of all caregivers. Data collection was based on a case report form, including patient characteristics, clinical parameters and long-term complications.
RESULTS: In total, 1845 patients with DM were recruited and analysed. We observed an overall prevalence of 5.3% [95% CI: 5.0%-5.5%]. For the subsequent main analysis, we included 1755 patients with DM after excluding 90 patients with gestational DM. There were significant differences between genders in the distribution of specific clinical parameters, patient characteristics, and the long-term complications diabetic foot, amputation and cardiovascular disease.
CONCLUSION: To the best of our knowledge, we established the first diabetes cohort study in Austria. Prevalence and the proportion of specific long-term complications were lower when compared to the international context. We assume that the Diabetes Landeck Cohort has reached a high degree of completeness; however, we were not able to identify independent data sources for a valid check of completeness.
Steigenberger, Caroline; Flatscher-Thoeni, Magdalena; Siebert, Uwe; Leiter, Andrea M
Determinants of willingness to pay for health services: a systematic review of contingent valuation studies Journal Article
In: Eur J Health Econ, vol. 23, no. 9, pp. 1455–1482, 2022, ISSN: 1618-7601.
@article{pmid35166973,
title = {Determinants of willingness to pay for health services: a systematic review of contingent valuation studies},
author = {Caroline Steigenberger and Magdalena Flatscher-Thoeni and Uwe Siebert and Andrea M Leiter},
doi = {10.1007/s10198-022-01437-x},
issn = {1618-7601},
year = {2022},
date = {2022-12-01},
journal = {Eur J Health Econ},
volume = {23},
number = {9},
pages = {1455--1482},
abstract = {INTRODUCTION: Stated preference studies are a valuable tool to elicit respondents' willingness to pay (WTP) for goods or services, especially in situations where no market valuation exists. Contingent valuation (CV) is a widely used approach among stated-preference techniques for eliciting WTP if prices do not exist or do not reflect actual costs, for example, when services are covered by insurance. This review aimed to provide an overview of relevant factors determining WTP for health services to support variable selection.
METHODS: A comprehensive systematic literature search and review of CV studies assessing determinants of WTP for health services was conducted, including 11 electronic databases. Two of the authors made independent decisions on the eligibility of studies. We extracted all determinants used and related p values for the effect sizes (e.g. reported in regression models with WTP for a health service as outcome variable). Determinants were summarised in systematic evidence tables and structured by thematic domains.
RESULTS: We identified 2082 publications, of which 202 full texts were checked for eligibility. We included 62 publications on 61 studies in the review. Across all studies, we identified 22 WTP determinants and other factors from 5 thematic domains: sociodemographic characteristics, perceived threat, perceived benefit, perceived barriers, and other information.
CONCLUSION: Our review provides evidence on 22 relevant determinants of WTP for health services, which may be used for variable selection and as guidance for planning CV surveys. Endogeneity should be carefully considered before interpreting these determinants as causal factors and potential intervention targets.},
keywords = {},
pubstate = {published},
tppubtype = {article}
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METHODS: A comprehensive systematic literature search and review of CV studies assessing determinants of WTP for health services was conducted, including 11 electronic databases. Two of the authors made independent decisions on the eligibility of studies. We extracted all determinants used and related p values for the effect sizes (e.g. reported in regression models with WTP for a health service as outcome variable). Determinants were summarised in systematic evidence tables and structured by thematic domains.
RESULTS: We identified 2082 publications, of which 202 full texts were checked for eligibility. We included 62 publications on 61 studies in the review. Across all studies, we identified 22 WTP determinants and other factors from 5 thematic domains: sociodemographic characteristics, perceived threat, perceived benefit, perceived barriers, and other information.
CONCLUSION: Our review provides evidence on 22 relevant determinants of WTP for health services, which may be used for variable selection and as guidance for planning CV surveys. Endogeneity should be carefully considered before interpreting these determinants as causal factors and potential intervention targets.
Rainer, Lukas; Bachner, Florian; Eglau, Karin; Ostermann, Herwig; Siebert, Uwe; Zuba, Martin
Comorbidities and COVID-19 hospitalization, ICU admission and hospital mortality in Austria : A retrospective cohort study Journal Article
In: Wien Klin Wochenschr, vol. 134, no. 23-24, pp. 856–867, 2022, ISSN: 1613-7671.
@article{pmid35608673,
title = {Comorbidities and COVID-19 hospitalization, ICU admission and hospital mortality in Austria : A retrospective cohort study},
author = {Lukas Rainer and Florian Bachner and Karin Eglau and Herwig Ostermann and Uwe Siebert and Martin Zuba},
doi = {10.1007/s00508-022-02036-9},
issn = {1613-7671},
year = {2022},
date = {2022-12-01},
journal = {Wien Klin Wochenschr},
volume = {134},
number = {23-24},
pages = {856--867},
abstract = {BACKGROUND: The protection of vulnerable populations is a central task in managing the Coronavirus disease 2019 (COVID-19) pandemic to avoid severe courses of COVID-19 and the risk of healthcare system capacity being exceeded. To identify factors of vulnerability in Austria, we assessed the impact of comorbidities on COVID-19 hospitalization, intensive care unit (ICU) admission, and hospital mortality.
METHODS: A retrospective cohort study was performed including all patients with COVID-19 in the period February 2020 to December 2021 who had a previous inpatient stay in the period 2015-2019 in Austria. All patients with COVID-19 were matched to population controls on age, sex, and healthcare region. Multiple logistic regression was used to estimate adjusted odds ratios (OR) of included factors with 95% confidence intervals (CI).
RESULTS: Hemiplegia or paraplegia constitutes the highest risk factor for hospitalization (OR 1.61, 95% CI 1.44-1.79), followed by COPD (OR 1.48, 95% CI 1.43-1.53) and diabetes without complications (OR 1.41, 95% CI 1.37-1.46). The highest risk factors for ICU admission are renal diseases (OR 1.76, 95% CI 1.61-1.92), diabetes without complications (OR 1.57, 95% CI 1.46-1.69) and COPD (OR 1.53, 95% CI 1.41-1.66). Hemiplegia or paraplegia, renal disease and COPD constitute the highest risk factors for hospital mortality, with ORs of 1.5. Diabetes without complications constitutes a significantly higher risk factor for women with respect to all three endpoints.
CONCLUSION: We contribute to the literature by identifying sex-specific risk factors. In general, our results are consistent with the literature, particularly regarding diabetes as a risk factor for severe courses of COVID-19. Due to the observational nature of our data, caution is warranted regarding causal interpretation. Our results contribute to the protection of vulnerable populations and may be used for targeting further pharmaceutical interventions.},
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METHODS: A retrospective cohort study was performed including all patients with COVID-19 in the period February 2020 to December 2021 who had a previous inpatient stay in the period 2015-2019 in Austria. All patients with COVID-19 were matched to population controls on age, sex, and healthcare region. Multiple logistic regression was used to estimate adjusted odds ratios (OR) of included factors with 95% confidence intervals (CI).
RESULTS: Hemiplegia or paraplegia constitutes the highest risk factor for hospitalization (OR 1.61, 95% CI 1.44-1.79), followed by COPD (OR 1.48, 95% CI 1.43-1.53) and diabetes without complications (OR 1.41, 95% CI 1.37-1.46). The highest risk factors for ICU admission are renal diseases (OR 1.76, 95% CI 1.61-1.92), diabetes without complications (OR 1.57, 95% CI 1.46-1.69) and COPD (OR 1.53, 95% CI 1.41-1.66). Hemiplegia or paraplegia, renal disease and COPD constitute the highest risk factors for hospital mortality, with ORs of 1.5. Diabetes without complications constitutes a significantly higher risk factor for women with respect to all three endpoints.
CONCLUSION: We contribute to the literature by identifying sex-specific risk factors. In general, our results are consistent with the literature, particularly regarding diabetes as a risk factor for severe courses of COVID-19. Due to the observational nature of our data, caution is warranted regarding causal interpretation. Our results contribute to the protection of vulnerable populations and may be used for targeting further pharmaceutical interventions.
Efficace, Fabio; Koinig, Karin; Cottone, Francesco; Bowen, David; Mittelman, Moshe; Sommer, Kathrin; Langemeijer, Saskia; Culligan, Dominic; Filanovsky, Kalman; Storck, Michael; Smith, Alexandra; van Marrewijk, Corine; Dugas, Martin; Stojkov, Igor; Siebert, Uwe; de Witte, Theo; Stauder, Reinhard
In: Cancer Med, 2022, ISSN: 2045-7634.
@article{pmid36533415,
title = {Raising the standards of patient-centered outcomes research in myelodysplastic syndromes: Clinical utility and validation of the subscales of the QUALMS from the MDS-RIGHT project},
author = {Fabio Efficace and Karin Koinig and Francesco Cottone and David Bowen and Moshe Mittelman and Kathrin Sommer and Saskia Langemeijer and Dominic Culligan and Kalman Filanovsky and Michael Storck and Alexandra Smith and Corine van Marrewijk and Martin Dugas and Igor Stojkov and Uwe Siebert and Theo de Witte and Reinhard Stauder},
doi = {10.1002/cam4.5487},
issn = {2045-7634},
year = {2022},
date = {2022-12-01},
journal = {Cancer Med},
abstract = {BACKGROUND: Clinical decision-making for patients with myelodysplastic syndromes (MDS) is challenging, and both disease and treatment effects heavily impact health-related quality of life (HRQoL) of these patients. Therefore, disease-specific HRQoL measures can be critical to harness the patient voice in MDS research.
METHODS: We report a prospective international validation study of the Quality of Life in Myelodysplasia Scale (QUALMS) with a main focus on providing information on the psychometric characteristics of its three subscales: physical burden (QUALMS-P), emotional burden (QUALMS-E), and benefit finding (QUALMS-BF). The analysis is based on patients enrolled from three European countries and Israel, participating to the MDS-RIGHT Project. The scale structure and psychometric properties of the QUALMS were assessed.
RESULTS: Overall, 270 patients with a median age of 74 years were analyzed and the majority of them (60.3%) had a low MDS-Comorbidity Index score. Results of the confirmatory factor analysis supported the underlying scale structure of the QUALMS, which, in addition to a total score, includes three subscales: QUALMS-P, QUALMS-E, and the QUALMS-BF. The QUALMS-P exhibited the highest Cronbach's alpha coefficients. Discriminant validity analysis indicated good results with the QUALMS-P and QUALMS-E distinguishing between patients with different performance status, comorbidity, anemia, and transfusion dependency status. No floor and ceiling effects were observed. Responsiveness to change analysis supported the validity of the measure. Patients with a hemoglobin (Hb) level of <11 g/dL at study entry, who subsequently showed an improvement in their Hb levels, also reported a mean score change of 9 and 8 points (scales ranging between 0 and 100) in the expected direction of the QUALMS-E and QUALMS-P, respectively.
CONCLUSIONS: Our study provides additional validation data on the QUALMS from the international MDS-RIGHT Project. The use of this disease-specific HRQoL measure may contribute to raise quality standards of patient-centered outcomes research in MDS.},
keywords = {},
pubstate = {published},
tppubtype = {article}
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METHODS: We report a prospective international validation study of the Quality of Life in Myelodysplasia Scale (QUALMS) with a main focus on providing information on the psychometric characteristics of its three subscales: physical burden (QUALMS-P), emotional burden (QUALMS-E), and benefit finding (QUALMS-BF). The analysis is based on patients enrolled from three European countries and Israel, participating to the MDS-RIGHT Project. The scale structure and psychometric properties of the QUALMS were assessed.
RESULTS: Overall, 270 patients with a median age of 74 years were analyzed and the majority of them (60.3%) had a low MDS-Comorbidity Index score. Results of the confirmatory factor analysis supported the underlying scale structure of the QUALMS, which, in addition to a total score, includes three subscales: QUALMS-P, QUALMS-E, and the QUALMS-BF. The QUALMS-P exhibited the highest Cronbach's alpha coefficients. Discriminant validity analysis indicated good results with the QUALMS-P and QUALMS-E distinguishing between patients with different performance status, comorbidity, anemia, and transfusion dependency status. No floor and ceiling effects were observed. Responsiveness to change analysis supported the validity of the measure. Patients with a hemoglobin (Hb) level of <11 g/dL at study entry, who subsequently showed an improvement in their Hb levels, also reported a mean score change of 9 and 8 points (scales ranging between 0 and 100) in the expected direction of the QUALMS-E and QUALMS-P, respectively.
CONCLUSIONS: Our study provides additional validation data on the QUALMS from the international MDS-RIGHT Project. The use of this disease-specific HRQoL measure may contribute to raise quality standards of patient-centered outcomes research in MDS.
Kuehne, Felicitas; Arvandi, Marjan; Hess, Lisa M; Faries, Douglas E; Gothe, Raffaella Matteucci; Gothe, Holger; Beyrer, Julie; Zeimet, Alain Gustave; Stojkov, Igor; Mühlberger, Nikolai; Oberaigner, Willi; Marth, Christian; Siebert, Uwe
In: J Clin Epidemiol, vol. 152, pp. 269-280, 2022, ISSN: 1878-5921.
@article{pmid36252741,
title = {Causal analyses with target trial emulation for real-world evidence removed large self-inflicted biases: Systematic bias assessment of ovarian cancer treatment effectiveness},
author = {Felicitas Kuehne and Marjan Arvandi and Lisa M Hess and Douglas E Faries and Raffaella Matteucci Gothe and Holger Gothe and Julie Beyrer and Alain Gustave Zeimet and Igor Stojkov and Nikolai M\"{u}hlberger and Willi Oberaigner and Christian Marth and Uwe Siebert},
doi = {10.1016/j.jclinepi.2022.10.005},
issn = {1878-5921},
year = {2022},
date = {2022-12-01},
urldate = {2022-10-01},
journal = {J Clin Epidemiol},
volume = {152},
pages = {269-280},
abstract = {BACKGROUND: Drawing causal conclusions from real-world data (RWD) poses methodological challenges and risk of bias. We aimed to systematically assess the type and impact of potential biases that may occur when analyzing RWD using the case of progressive ovarian cancer.
METHODS: We retrospectively compared overall survival with and without second-line chemotherapy using electronic medical records. Potential biases were determined using directed acyclic graphs. We followed a stepwise analytic approach ranging from crude analysis and multivariable-adjusted Cox model up to a full causal analysis using a marginal-structural-Cox-model (MSCM) with replicates emulating a reference randomized controlled trial. To assess biases, we compared effect estimates (hazard ratios [HRs]) of each approach to the HR of the reference trial.
RESULTS: The reference trial showed a HR for second-line versus delayed-therapy of 1.01 (95% confidence interval [95%CI]: 0.82-1.25). The corresponding HRs from the RWD analysis ranged from 0.51 for simple baseline adjustments to 1.41 (95%CI 1.22-1.64) accounting for immortal time bias with time-varying covariates. Causal trial emulation yielded a HR of 1.12 (95%CI: 0.96-1.28).
CONCLUSIONS: Our study, using ovarian cancer as an example, shows the importance of a thorough causal design and analysis if one is expecting RWD to emulate clinical trial results.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
METHODS: We retrospectively compared overall survival with and without second-line chemotherapy using electronic medical records. Potential biases were determined using directed acyclic graphs. We followed a stepwise analytic approach ranging from crude analysis and multivariable-adjusted Cox model up to a full causal analysis using a marginal-structural-Cox-model (MSCM) with replicates emulating a reference randomized controlled trial. To assess biases, we compared effect estimates (hazard ratios [HRs]) of each approach to the HR of the reference trial.
RESULTS: The reference trial showed a HR for second-line versus delayed-therapy of 1.01 (95% confidence interval [95%CI]: 0.82-1.25). The corresponding HRs from the RWD analysis ranged from 0.51 for simple baseline adjustments to 1.41 (95%CI 1.22-1.64) accounting for immortal time bias with time-varying covariates. Causal trial emulation yielded a HR of 1.12 (95%CI: 0.96-1.28).
CONCLUSIONS: Our study, using ovarian cancer as an example, shows the importance of a thorough causal design and analysis if one is expecting RWD to emulate clinical trial results.
Herzog, Chiara; Sundström, Karin; Jones, Allison; Evans, Iona; Barrett, James E; Wang, Jiangrong; Redl, Elisa; Schreiberhuber, Lena; Costas, Laura; Paytubi, Sonia; Dostalek, Lukas; Zikan, Michal; Cibula, David; Sroczynski, Gaby; Siebert, Uwe; Dillner, Joakim; Widschwendter, Martin
In: Clin Epigenetics, vol. 14, no. 1, pp. 150, 2022, ISSN: 1868-7083.
@article{pmid36414968,
title = {DNA methylation-based detection and prediction of cervical intraepithelial neoplasia grade 3 and invasive cervical cancer with the WID™-qCIN test},
author = {Chiara Herzog and Karin Sundstr\"{o}m and Allison Jones and Iona Evans and James E Barrett and Jiangrong Wang and Elisa Redl and Lena Schreiberhuber and Laura Costas and Sonia Paytubi and Lukas Dostalek and Michal Zikan and David Cibula and Gaby Sroczynski and Uwe Siebert and Joakim Dillner and Martin Widschwendter},
doi = {10.1186/s13148-022-01353-0},
issn = {1868-7083},
year = {2022},
date = {2022-11-01},
journal = {Clin Epigenetics},
volume = {14},
number = {1},
pages = {150},
abstract = {BACKGROUND: Cervical screening using primary human papilloma virus (HPV) testing and cytology is being implemented in several countries. Cytology as triage for colposcopy referral suffers from several shortcomings. HPV testing overcomes some of these but lacks specificity in women under 30. Here, we aimed to develop and validate an automatable triage test that is highly sensitive and specific independently of age and sample heterogeneity, and predicts progression to CIN3+ in HPV+ patients.
RESULTS: The WID™-qCIN, assessing three regions in human genes DPP6, RALYL, and GSX1, was validated in both a diagnostic (case-control) and predictive setting (nested case-control), in a total of 761 samples. Using a predefined threshold, the sensitivity of the WID™-qCIN test was 100% and 78% to detect invasive cancer and CIN3, respectively. Sensitivity to detect CIN3+ was 65% and 83% for women < and ≥ 30 years of age. The specificity was 90%. Importantly, the WID™-qCIN test identified 52% of ≥ 30-year-old women with a cytology negative (cyt-) index sample who were diagnosed with CIN3 1-4 years after sample donation.
CONCLUSION: We identified suitable DNAme regions in an epigenome-wide discovery using HPV+ controls and CIN3+ cases and established the WID™-qCIN, a PCR-based DNAme test. The WID™-qCIN test has a high sensitivity and specificity that may outperform conventional cervical triage tests and can in an objective, cheap, and scalable fashion identify most women with and at risk of (pre-)invasive cervical cancer. However, evaluation was limited to case-control settings and future studies will assess performance and generalisability in a randomised controlled trial.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
RESULTS: The WID™-qCIN, assessing three regions in human genes DPP6, RALYL, and GSX1, was validated in both a diagnostic (case-control) and predictive setting (nested case-control), in a total of 761 samples. Using a predefined threshold, the sensitivity of the WID™-qCIN test was 100% and 78% to detect invasive cancer and CIN3, respectively. Sensitivity to detect CIN3+ was 65% and 83% for women < and ≥ 30 years of age. The specificity was 90%. Importantly, the WID™-qCIN test identified 52% of ≥ 30-year-old women with a cytology negative (cyt-) index sample who were diagnosed with CIN3 1-4 years after sample donation.
CONCLUSION: We identified suitable DNAme regions in an epigenome-wide discovery using HPV+ controls and CIN3+ cases and established the WID™-qCIN, a PCR-based DNAme test. The WID™-qCIN test has a high sensitivity and specificity that may outperform conventional cervical triage tests and can in an objective, cheap, and scalable fashion identify most women with and at risk of (pre-)invasive cervical cancer. However, evaluation was limited to case-control settings and future studies will assess performance and generalisability in a randomised controlled trial.