Application of statistical and decision-analytic models for evidence synthesis for decision-making in public health and the healthcare sector

With the awareness that healthcare is a limited resource, decision-makers are challenged to allocate it rationally and efficiently. Health economic methods of evidence synthesis for decision-making are useful to quantify healthcare resource utilisation, critically evaluate different interventions and ensure the implementation of the most effective or cost-effective strategy. The nine studies included in the present cumulative doctoral thesis aim to demonstrate the capability of statistical and decision-analytic modelling techniques to inform and support rational healthcare decision-making in Germany. Five studies apply statistical modelling in analyses of public health and health economic data. They show that the developed models are valuable instruments for examining patterns in the data and generating knowledge from observable data which can further be used in devising disease management and care programs as well as economic evaluations. Further, two health economic evaluations, which adopt the decision-analytic-modelling approach, show that decision-analytic modelling is a powerful tool to represent the epidemiology of infectious and non-infectious diseases on a population level, quantify the burden of the diseases, generalise the outcomes of clinical trials, and predict how the interventions can change the impact of the diseases on the health of the population. Additionally, two literature reviews examine the application of decision-analytic modelling in health economic evaluations. The first study reviews and empirically analyses health technology assessments by the German Institute for Medical Documentation and Information and demonstrates that the application of decision-analytic models improves the evidence produced for policy-making in the healthcare sector in Germany. The second systematic review focuses on methodological choices made in constructing decision-analytic models and explains how critically the structural and parametrical assumptions can influence the final message of the economic evaluations and shows that building a validated, reliable model as well as the transparent reporting is of high priority in facilitating the communication and implementation of the most cost-effective course of action. Overall, the present thesis shows the relevance and advantage of the application of models in synthesising evidence for decision-making. The included studies contribute to the current and future development of the methods used to address the problems of health economic efficiency. Further advances in the computational modelling techniques and data collection, from one side, will ease the decision-making process, but, from another side, will require increasing competence and understanding within the decision-making bodies

The Role of decision-analytic modelling in German health technology assessments

BACKGROUND: Decision-analytic modelling (DAM) has become a widespread method in health technology assessments (HTA), but the extent to which modelling is used differs among international HTA institutions. In Germany, the use of DAM is optional within HTAs of the German Institute of Medical Documentation and Information (DIMDI). Our study examines the use of DAM in DIMDI HTA reports and its effect on the quality of information provided for health policies. METHODS: A review of all DIMDI HTA reports (from 1998 to September 2012) incorporating an economic assessment was performed. All included reports were divided into two groups: HTAs with DAM and HTAs without DAM. In both groups, reports were categorized according to the quality of information provided for healthcare decision making. RESULTS: Of the sample of 107 DIMDI HTA reports, 17 (15.9%) used DAM for economic assessment. In the group without DAM, conclusions were limited by the quality of economic information in 51.1% of the reports, whereas we did not find limited conclusions in the group with DAM. Furthermore, 24 reports without DAM (26.7%) stated that using DAM would likely improve the quality of information of the economic assessment. CONCLUSION: The use of DAM techniques can improve the quality of HTAs in Germany. When, after a systematic review of existing literature within a HTA, it is clear that DAM is likely to positively affect the quality of the economic assessment DAM should be used

Assessment of the Effects of Active Immunisation against Respiratory Syncytial Virus (RSV) using Decision-Analytic Models: A Systematic Review with a Focus on Vaccination Strategies, Modelling Methods and Input Data

Background: Several vaccine and antibody candidates are currently in development for the prevention of lower respiratory tract infections caused by the respiratory syncytial virus (RSV). Methods: We searched MEDLINE, Embase, and SCOPUS and included model-based evaluations of RSV vaccinations. Two reviewers performed the selection, data extraction, and quality evaluation with EVIDEM. Cost-effectiveness (CE) estimates were converted to $US purchasing power parity (PPP), year 2018 values. Potential economic and epidemiological outcomes were summarised for maternal, infant, children, and elderly vaccinations. The PROSPERO identifier is CRD42019122570. Results: In total, 22 model-based studies were reviewed. On average, a potential 27$US1766–5857 PPP 2018/disability-adjusted life-years (DALYs) for Global Alliance for Vaccines and Immunisation (Gavi)-eligible countries. For England, the maximum cost-effective price of maternal vaccination was estimated at $US81.5 PPP 2018. Infant vaccination was associated with higher CE ratios in low- and high-income settings. Vaccination of neonates born before the RSV season was the most cost effective in high-income settings. Higher values for vaccine effectiveness, duration of protection, and vaccine uptake increased the benefits. Due to indirect effects, the vaccination of school-age children and a cocooning strategy were effective alternatives to protect infants, and the vaccination of children aged < 5 years had a beneficial impact on the elderly. Conclusion: RSV vaccines with anticipated characteristics may reduce a sizeable proportion of the RSV burden. The results are subject to uncertainty because of the limited epidemiological and clinical data. Data on RSV incidence and hospitalisation risk for granular age strata should be prioritised to facilitate the evaluation of RSV interventions and decision making.Peer Reviewe

Pre-existing health conditions and severe COVID-19 outcomes: an umbrella review approach and meta-analysis of global evidence

Background This study applies an umbrella review approach to summarise the global evidence on the risk of severe COVID-19 outcomes in patients with pre-existing health conditions. Methods Systematic reviews (SRs) were identified in PubMed, Embase/Medline and seven pre-print servers until December 11, 2020. Due to the absence of age-adjusted risk effects stratified by geographical regions, a re-analysis of the evidence was conducted. Primary studies were extracted from SRs and evaluated for inclusion in the re-analysis. Studies were included if they reported risk estimates (odds ratio (OR), hazard ratio (HR), relative risk (RR)) for hospitalisation, intensive care unit admission, intubation or death. Estimated associations were extracted from the primary studies for reported pre-existing conditions. Meta-analyses were performed stratified for each outcome by regions of the World Health Organization. The evidence certainty was assessed using GRADE. Registration number CRD42020215846. Results In total, 160 primary studies from 120 SRs contributed 464 estimates for 42 pre-existing conditions. Most studies were conducted in North America, European, and Western Pacific regions. Evidence from Africa, South/Latin America, and the Eastern Mediterranean region was scarce. No evidence was available from the South-East Asia region. Diabetes (HR range 1.2–2.0 (CI range 1.1–2.8)), obesity (OR range 1.5–1.75 (CI range 1.1–2.3)), heart failure (HR range 1.3–3.3 (CI range 0.9–8.2)), COPD (HR range 1.12–2.2 (CI range 1.1–3.2)) and dementia (HR range 1.4–7.7 (CI range 1.2–39.6)) were associated with fatal COVID-19 in different regions, although the estimates varied. Evidence from Europe and North America showed that liver cirrhosis (OR range 3.2–5.9 (CI range 0.9–27.7)) and active cancer (OR range 1.6–4.7 (CI range 0.5–14.9)) were also associated with increased risk of death. Association between HIV and undesirable COVID-19 outcomes showed regional heterogeneity, with an increased risk of death in Africa (HR 1.7 (CI 1.3–2.2)). GRADE certainty was moderate to high for most associations. Conclusion Risk of undesirable COVID-19 health outcomes is consistently increased in certain patient subgroups across geographical regions, showing high variability in others. The results can be used to inform COVID-19 vaccine prioritisation or other intervention strategies.Peer Reviewe

Einfluss von Impfungen und Kontaktreduktionen auf die dritte Welle der SARS-CoV-2-Pandemie und perspektivische Rückkehr zu prä-pandemischem Kontaktverhalten

Das im Epidemiologischen Bulletin 13/2021 vorgestellte mathematische Modell schätzt die voraussichtlichen Effekte der COVID-19-Impfung in der Bevölkerung in Deutschland und vergleicht mögliche Strategien zur Priorisierung einzelner Bevölkerungsgruppen bei Knappheit der verfügbaren Impfstoffdosen. Das Modell ermöglicht nicht nur die Abbildung des aktuellen Infektionsgeschehens, sondern kann über Fragestellungen zur Impfstrategie hinaus auch Strategien zur Lockerung der bestehenden bzw. die Wiederaufnahme von Kontaktbeschränkungen analysieren. Dabei können saisonale Effekte auf die Übertragung von SARS-CoV-2 sowie der Einfluss neuer Virusvarianten berücksichtigt werden

Die Impfung gegen COVID-19 in Deutschland zeigt eine hohe Wirksamkeit gegen SARS-CoV-2-Infektionen, Krankheitslast und Sterbefälle

Um die Bevölkerung vor den akuten und langfristigen Auswirkungen einer COVID-19-Infektion zu schützen und die Pandemie langfristig einzudämmen, sind zum einen nicht-pharmakologische Präventionsmaßnahmen und zum anderen eine Schutzimpfung notwendig. Basierend auf den Ergebnissen einer mathematischen Modellierung wurden Effekte der Impfung gegen COVID-19 auf den Pandemieverlauf in Deutschland im Zeitraum Januar bis Juli 2021 quantifiziert. Die Analysen zeigen, dass die Impfungen gegen COVID-19 bisher geschätzt 706.000 Meldefälle, 76.600 stationäre und etwa 19.600 intensiv-medizinische Fälle sowie mehr als 38.300 Sterbefälle verhindert hat. Insbesondere in der Altersgruppe ≥ 60 Jahre wurde die Anzahl der zu erwartenden Fälle für jeden der genannten Endpunkte um mehr als 40% reduziert.Peer Reviewe

Effect of risk status for severe COVID-19 on individual contact behaviour during the SARS-CoV-2 pandemic in 2020/2021-an analysis based on the German COVIMOD study.

BACKGROUND: One of the primary aims of contact restriction measures during the SARS-CoV-2 pandemic has been to protect people at increased risk of severe disease from the virus. Knowledge about the uptake of contact restriction measures in this group is critical for public health decision-making. We analysed data from the German contact survey COVIMOD to assess differences in contact patterns based on risk status, and compared this to pre-pandemic data to establish whether there was a differential response to contact reduction measures. METHODS: We quantified differences in contact patterns according to risk status by fitting a generalised linear model accounting for within-participant clustering to contact data from 31 COVIMOD survey waves (April 2020-December 2021), and estimated the population-averaged ratio of mean contacts of persons with high risk for a severe COVID-19 outcome due to age or underlying health conditions, to those without. We then compared the results to pre-pandemic data from the contact surveys HaBIDS and POLYMOD. RESULTS: Averaged across all analysed waves, COVIMOD participants reported a mean of 3.21 (95% confidence interval (95%CI) 3.14,3.28) daily contacts (truncated at 100), compared to 18.10 (95%CI 17.12,19.06) in POLYMOD and 28.27 (95%CI 26.49,30.15) in HaBIDS. After adjusting for confounders, COVIMOD participants aged 65 or above had 0.83 times (95%CI 0.79,0.87) the number of contacts as younger age groups. In POLYMOD, this ratio was 0.36 (95%CI 0.30,0.43). There was no clear difference in contact patterns due to increased risk from underlying health conditions in either HaBIDS or COVIMOD. We also found that persons in COVIMOD at high risk due to old age increased their non-household contacts less than those not at such risk after strict restriction measures were lifted. CONCLUSIONS: Over the course of the SARS-CoV-2 pandemic, there was a general reduction in contact numbers in the German population and also a differential response to contact restriction measures based on risk status for severe COVID-19. This differential response needs to be taken into account for parametrisations of mathematical models in a pandemic setting

Hierarchisierung von Risikofaktoren für schwere COVID-19-Erkrankungsverläufe im Kontext der COVID-19-Schutzimpfungen

Angesichts der derzeitigen Impfstoffknappheit geht mit den bundesweiten Schutzimpfungen gegen COVID-19 die Notwendigkeit einer Priorisierung bestimmter Bevölkerungsgruppen einher. Basierend auf den Empfehlungen der STIKO sollen zunächst Personen mit besonders hohem Risiko für schwere oder tödliche COVID-19-Verläufe oder beruflicher Exposition geimpft werden. Diese Empfehlungen stützen sich überwiegend auf internationale Studien - für den deutschen Versorgungskontext steht nur begrenzt Evidenz zur Bedeutung relevanter Risikofaktoren für einen schweren COVID-19-Verlauf zur Verfügung. Das Ziel der im Epidemiologischen Bulletin 19/2021 vorgestellten Studie war es, die Relevanz ausgewählter Vorerkrankungen für einen schweren COVID-19-Verlauf in der in Deutschland lebenden Bevölkerung empirisch zu überprüfen, Erkrankungen hinsichtlich ihres Risikos für einen schweren COVID-19-Verlauf zu ordnen und damit eine einfache, im Versorgungsalltag unkompliziert umsetzbare und dabei möglichst effektive Grundlage für die Impfrangfolge in der ambulanten ärztlichen Versorgung bilden