A tese abordou questões relacionadas à economia da saúde, particularmente à visão econômica dos transplantes renais. Foi conduzida uma análise de custo-utilidade para verificar qual tratamento, transplante renal ou hemodiálise, possui menor razão de custo por anos de vida ajustados por qualidade. O resultado obtido corrobora as evidências internacionais, as quais indicam o transplante renal como estratégia mais custo-efetiva. No caso deste estudo, a razão de custo-utilidade para o transplante renal e hemodiálise foi de R$ 18.161,00/AVAQ e R$ 40.872,00/AVAQ, respectivamente. Apesar de o transplante renal ser uma estratégia dominante, a escassez de órgãos impede que essa estratégia seja amplamente utilizada, reduzindo, assim, os ganhos de eficiência na alocação dos recursos escassos. Nesse contexto, também foi alvo desta tese a questão da escassez de órgãos. Pelo levantamento feito, há tendência de aumento do desequilíbrio entre demanda e oferta de órgãos, visto que a primeira cresce rapidamente, enquanto a segunda mostra pequena tendência de crescimento. Assim, alternativas para contornar esse problema foram analisadas, especialmente as relacionadas a mudanças institucionais na lei de doação de órgãos. Entre elas, foi argüido que a lei de consentimento presumido seria a opção mais factível, por não ferir o pressuposto do altruísmo. Objetivando estimar quanto seria o eventual incremento na doação de órgãos por doador cadáver devido à lei de consentimento presumido, fez-se uso do ferramental da econometria da saúde, aplicando, para uma amostra de 34 países ao longo de cinco anos, o método de regressão quantílica para dados de painel. Os resultados obtidos nessa aplicação indicam que há benefício na adoção da lei de consentimento presumido, que tem um efeito positivo sobre a taxa de doação de órgãos, em torno de 21-26%, comparada à lei de consentimento informado. / The thesis broaches questions related to health economics, particularly the economic vision of renal transplants. A cost-utility analysis was conducted to assess which treatment, renal transplant or hemodialysis, has a lower cost rate per quality-adjusted life years. The result obtained corroborates the international evidence, which indicates renal transplant as the most cost effective strategy. In the case of this study, the cost-utility ratio for renal transplant and hemodialysis was US$ 11,157/QALY and US$ 25,110/QALY, respectively. In spite of renal transplant being the dominant strategy, the scarcity of organs hinders this strategy to be widely used, reducing in this way, the efficiency gain in the allocation of scarce resources. Within this context, the organ shortage was also a target issue of this thesis. Through the survey performed, there is a tendency towards the increase of unbalance between the demand and supply of organs, being that the first grows rapidly while the second shows small tendency towards growth. Within this context, the investigation target of this thesis was to look into possible alternatives to by-pass this problem, especially those related to institutional changes in the organ donation law. Among them, it was argued that the law of presumed consent would be the most feasible option, since it does not harm the presupposition of altruism. With the object of estimating what would be the eventual increase in organ donation, per cadaveric donor, due to the law of presumed consent, the health econometric tool of quantile regression method for panel data was used, applied to a sample of 34 countries during a five-year period. The results obtained in this application indicate that there is benefit in adopting the law of presumed consent, which has a positive effect on the organ donation rate, around 21 – 26%, compared to the law of informed consent.

A tese abordou questões relacionadas à economia da saúde, particularmente à visão econômica dos transplantes renais. Foi conduzida uma análise de custo-utilidade para verificar qual tratamento, transplante renal ou hemodiálise, possui menor razão de custo por anos de vida ajustados por qualidade. O resultado obtido corrobora as evidências internacionais, as quais indicam o transplante renal como estratégia mais custo-efetiva. No caso deste estudo, a razão de custo-utilidade para o transplante renal e hemodiálise foi de R$ 18.161,00/AVAQ e R$ 40.872,00/AVAQ, respectivamente. Apesar de o transplante renal ser uma estratégia dominante, a escassez de órgãos impede que essa estratégia seja amplamente utilizada, reduzindo, assim, os ganhos de eficiência na alocação dos recursos escassos. Nesse contexto, também foi alvo desta tese a questão da escassez de órgãos. Pelo levantamento feito, há tendência de aumento do desequilíbrio entre demanda e oferta de órgãos, visto que a primeira cresce rapidamente, enquanto a segunda mostra pequena tendência de crescimento. Assim, alternativas para contornar esse problema foram analisadas, especialmente as relacionadas a mudanças institucionais na lei de doação de órgãos. Entre elas, foi argüido que a lei de consentimento presumido seria a opção mais factível, por não ferir o pressuposto do altruísmo. Objetivando estimar quanto seria o eventual incremento na doação de órgãos por doador cadáver devido à lei de consentimento presumido, fez-se uso do ferramental da econometria da saúde, aplicando, para uma amostra de 34 países ao longo de cinco anos, o método de regressão quantílica para dados de painel. Os resultados obtidos nessa aplicação indicam que há benefício na adoção da lei de consentimento presumido, que tem um efeito positivo sobre a taxa de doação de órgãos, em torno de 21-26%, comparada à lei de consentimento informado. / The thesis broaches questions related to health economics, particularly the economic vision of renal transplants. A cost-utility analysis was conducted to assess which treatment, renal transplant or hemodialysis, has a lower cost rate per quality-adjusted life years. The result obtained corroborates the international evidence, which indicates renal transplant as the most cost effective strategy. In the case of this study, the cost-utility ratio for renal transplant and hemodialysis was US$ 11,157/QALY and US$ 25,110/QALY, respectively. In spite of renal transplant being the dominant strategy, the scarcity of organs hinders this strategy to be widely used, reducing in this way, the efficiency gain in the allocation of scarce resources. Within this context, the organ shortage was also a target issue of this thesis. Through the survey performed, there is a tendency towards the increase of unbalance between the demand and supply of organs, being that the first grows rapidly while the second shows small tendency towards growth. Within this context, the investigation target of this thesis was to look into possible alternatives to by-pass this problem, especially those related to institutional changes in the organ donation law. Among them, it was argued that the law of presumed consent would be the most feasible option, since it does not harm the presupposition of altruism. With the object of estimating what would be the eventual increase in organ donation, per cadaveric donor, due to the law of presumed consent, the health econometric tool of quantile regression method for panel data was used, applied to a sample of 34 countries during a five-year period. The results obtained in this application indicate that there is benefit in adopting the law of presumed consent, which has a positive effect on the organ donation rate, around 21 – 26%, compared to the law of informed consent.

A tese abordou questões relacionadas à economia da saúde, particularmente à visão econômica dos transplantes renais. Foi conduzida uma análise de custo-utilidade para verificar qual tratamento, transplante renal ou hemodiálise, possui menor razão de custo por anos de vida ajustados por qualidade. O resultado obtido corrobora as evidências internacionais, as quais indicam o transplante renal como estratégia mais custo-efetiva. No caso deste estudo, a razão de custo-utilidade para o transplante renal e hemodiálise foi de R$ 18.161,00/AVAQ e R$ 40.872,00/AVAQ, respectivamente. Apesar de o transplante renal ser uma estratégia dominante, a escassez de órgãos impede que essa estratégia seja amplamente utilizada, reduzindo, assim, os ganhos de eficiência na alocação dos recursos escassos. Nesse contexto, também foi alvo desta tese a questão da escassez de órgãos. Pelo levantamento feito, há tendência de aumento do desequilíbrio entre demanda e oferta de órgãos, visto que a primeira cresce rapidamente, enquanto a segunda mostra pequena tendência de crescimento. Assim, alternativas para contornar esse problema foram analisadas, especialmente as relacionadas a mudanças institucionais na lei de doação de órgãos. Entre elas, foi argüido que a lei de consentimento presumido seria a opção mais factível, por não ferir o pressuposto do altruísmo. Objetivando estimar quanto seria o eventual incremento na doação de órgãos por doador cadáver devido à lei de consentimento presumido, fez-se uso do ferramental da econometria da saúde, aplicando, para uma amostra de 34 países ao longo de cinco anos, o método de regressão quantílica para dados de painel. Os resultados obtidos nessa aplicação indicam que há benefício na adoção da lei de consentimento presumido, que tem um efeito positivo sobre a taxa de doação de órgãos, em torno de 21-26%, comparada à lei de consentimento informado. / The thesis broaches questions related to health economics, particularly the economic vision of renal transplants. A cost-utility analysis was conducted to assess which treatment, renal transplant or hemodialysis, has a lower cost rate per quality-adjusted life years. The result obtained corroborates the international evidence, which indicates renal transplant as the most cost effective strategy. In the case of this study, the cost-utility ratio for renal transplant and hemodialysis was US$ 11,157/QALY and US$ 25,110/QALY, respectively. In spite of renal transplant being the dominant strategy, the scarcity of organs hinders this strategy to be widely used, reducing in this way, the efficiency gain in the allocation of scarce resources. Within this context, the organ shortage was also a target issue of this thesis. Through the survey performed, there is a tendency towards the increase of unbalance between the demand and supply of organs, being that the first grows rapidly while the second shows small tendency towards growth. Within this context, the investigation target of this thesis was to look into possible alternatives to by-pass this problem, especially those related to institutional changes in the organ donation law. Among them, it was argued that the law of presumed consent would be the most feasible option, since it does not harm the presupposition of altruism. With the object of estimating what would be the eventual increase in organ donation, per cadaveric donor, due to the law of presumed consent, the health econometric tool of quantile regression method for panel data was used, applied to a sample of 34 countries during a five-year period. The results obtained in this application indicate that there is benefit in adopting the law of presumed consent, which has a positive effect on the organ donation rate, around 21 – 26%, compared to the law of informed consent.

Syfte: Syftet med studien var att undersöka ekonomiska utvärderingar av preventiva metoder som används inom tandvården genom att göra en systematisk litteraturöversikt och besvara frågor om vilka preventiva metoder som analyserats avseende kostnad och effekt samt vilka typer av ekonomiska utvärderingar som analyserats. Material och metod: En sökningsstrategi genomfördes och PubMed, The Cochrane Library och Web of Science utgjorde databaser för litteratursökningen. Inklusions- och exklusionskriterier fastställdes och ett protokoll utgjorde grunden för läsningen av de inkluderade studierna i fulltext. En kritisk granskning av de inkluderade studierna genomfördes genom att använda ett andra protokoll. Resultat: Totalt 38 publikationer om ekonomiska utvärderingar av preventiva metoder som används inom tandvården inkluderades. Studier om kariespreventiva metoder var av övervägande majoritet (n=35) och endast ett fåtal studier utvärderade preventiva metoder för andra sjukdomar (n=3). Den vanligaste preventiva metoden som utvärderades var fissurförsegling (n=8) följt av fluorlackning (n=6) och vattenfluoridering (n=3). Många studier utvärderade kombinerade preventiva metoder (n=12). Typerna av ekonomiska utvärderingar var CEA (n=16) följt av CA/Cost-minimization analysis (n=10), CBA (n=3), en kombination av CEA och CBA (n=5), CUA (n=1) och en kombination av CEA och CA (n=1). Konklusion: Även om studierna om ekonomiska utvärderingar av preventiva metoder som används inom tandvården är betydligt fler än när SBU-rapporterna publicerades så kan ingen generell slutsats beträffande kostnadseffektiviteten dras på grund heterogenitet i design och sätt att analysera. Fler välgjorda studier rekommenderas. / Aims: The aim of this study was to examine economic evaluations of preventive methods used in dentistry by using a systematic review approach and answering questions about which preventive methods used in dentistry that have been analysed regarding costs and effects and what types of economic evaluations that have been conducted. Material and method: A search strategy were conducted and PubMed, The Cochrane Library and Web of Science formed the basis of the literature search. Inclusion- and exclusion criteria were defined and a protocol was made for full-text reading of the included publications. A critical appraisal of the included publications was made using a second protocol. Results: A total of 38 publications on economic evaluations of preventive methods used in dentistry were included. Publications on caries preventive methods were of overwhelming majority (n=35) and only a few publications evaluated preventive methods for other diseases (n=3). The most common evaluated preventive method was pit and fissure sealant (n=8) followed by fluoride varnish (n=6) and water fluoridation (n=3). Most publications evaluated combined preventive methods (n=11). Types of economic evaluations were CEA (n=16) followed by CA/Cost-minimization analysis (n=10), CBA (n=3), a combination of CEA and CBA (n=5), CUA (n=1) and a combination of CEA and CA (n=1). Conclusions: Publications on economic evaluations of preventive methods used in dentistry were considerably more than when the SBU reports were published. Yet, no general conclusions could be drawn regarding cost-effectiveness due to heterogeneity in design and way of analyses. Future well-designed studies are recommended.

Introduction: There are no economic evaluations to determine the value of PRSs. The objective of this study was to determine if the addition of a PRS to traditional risk factors to guide statin therapy is a cost-effective intervention for the prevention of primary MI cases in the Ontario healthcare payer perspective. Methods: A PRS cost-effectiveness model was constructed to produce various statin prescription strategies in conjunction with the FRS. Upper PRS thresholds (between 25% to 70%) were set such that individuals falling into them would be eligible for statins while those in lower PRS thresholds (between 1% to 25%) were deemed protected and removed from consideration. The model determined number of incident MIs saved or not saved by statins, costs, quality of life, and the effect of statins on preventing MIs over a 10-year time horizon, discounted at 1.5% annually. One-way sensitivity analysis and a PSA were performed by varying all model parameters. Non-related participants of white British descent from 96,736 participants in the UK Biobank at intermediate risk for cardiovascular disease, determined using the Canadian Cardiovascular Society dyslipidemia guidelines of 2016, were used for the study. Results: The optimal clinical and economic strategy was one whereby the top 70% PRS individuals are eligible for statins, with the lower 5% PRS excluded. A base-case analysis at a PRS cost of $70 produced an ICER of $747,184.10/QALY, ranging from $525,678.90/QALY to $930,144.40/QALY in a one-way sensitivity analysis. In the PSA, the intervention has approximately a 50% probability of being cost-effective at $750,000/QALY. At a genotyping cost of $0, statin strategies guided by PRS dominated standard care when at least 12% of the lower PRS individuals were withheld from statins. When the predictive performance of the PRS is increased, the ICER drops drastically depending on the cost of genotyping and statin strategy. Conclusion: The cost-effectiveness model considers MI cases exclusively and a short, 10-year time horizon which likely overestimate the ICER. However, this study elucidates that the PRS has the potential to be extremely cost-effective in the future. / Thesis / Master of Science (MSc) / Approximately 1 in 3 Canadians live with at least one genetically linked chronic disease. Together, these diseases constitute a large economic burden on the healthcare system and well-being of individuals. Recent advancements in genetics allow risk prediction of developing complex, but common chronic diseases such as cardiovascular disease. Termed as polygenic risk scores, they have the potential to carry beneficial clinical outcomes such as an improved quality of life. However, the economics is not yet understood. This study determined that when targeting heart attacks, approximately $750,000 is required to gain an additional life-year for an adult. Although this may seem high, the result is closer to an upper-limit estimate than the true cost since polygenic risk scores have more benefits than solely for heart attacks. In the future, when accounting for their entire potential, the cost per life-year is likely to be lower, and perhaps even a money-returning investment.

No description available.

Background: In the ‘Arimidex’, Tamoxifen Alone or in Combination (ATAC) trial, the aromatase inhibitor (AI) anastrozole had a ignificantly better efficacy and safety profile than tamoxifen as initial adjuvant therapy for hormone receptor-positive (HR+) early breast cancer (EBC) in postmenopausal patients. To compare the combined long-term clinical and economic benefits, we carried out a cost-effectiveness analysis (CEA) of anastrozole versus tamoxifen based on the data of the 100- month analysis of the ATAC trial from the perspective of the German public health insurance. Patients and Methods: A Markov model with a 25-year time horizon was developed using the 100-month analysis of the ATAC trial as well as data obtained from published literature and expert opinion. Results: Adjuvant treatment of EBC with anastrozole achieved an additional 0.32 quality-adjusted life-years (QALYs) gained per patient compared with tamoxifen, at an additional cost of D 6819 per patient. Thus, the incremental cost effectiveness of anastrozole versus tamoxifen at 25 years was D 21,069 ($ 30,717) per QALY gained. Conclusions: This is the first CEA of an AI that is based on extended follow-up data, taking into account the carryover effect of anastrozole, which maintains the efficacy benefits beyond therapy completion after 5 years. Adjuvant treatment with anastrozole for postmenopausal women with HR+ EBC is a cost-effective alternative to tamoxifen. / Hintergrund: Bei der adjuvanten Therapie von postmenopausalen Patientinnen mit Hormonrezeptor-positivem (HR+) Mammakarzinom belegen die ATAC-100-Monatsdaten (ATAC-Studie: ‘Arimidex’, Tamoxifen Alone or in Combination) einen signifikanten Vorteil von Anastrozol gegenüber Tamoxifen in Bezug auf Rezidivrisiko und Verträglichkeit. Es wurde eine Kosten-Nutzwert-Analyse von Anastrozol im Vergleich zu Tamoxifen aus der Sicht des deutschen Gesundheitssystems durchgeführt. Material und Methoden: Als Berechnungsbasis wurde ein Markov- Modell zur Abschätzung der Kosteneffektivität entwickelt. Der Modellierungszeitraum umfasste 25 Jahre. Die Daten wurden anhand der ATAC-100-Monatsdaten, vorliegender Literatur und durch ein interdisziplinäres Expertenteam ermittelt. Ergebnisse: Eine adjuvante Therapie mit Anastrozol erzielte 0,32 quality-adjusted life-years (QALYs) pro Patientin mehr, verglichen mit einer adjuvanten Tamoxifentherapie. Die zusätzlichen Kosten der Therapie mit Anastrozol lagen bei 6819 D pro Patientin. Im Vergleich mit Tamoxifen erzielte Anastrozol einen ICER (Incremental Cost-Effectiveness Ratio) von 21 069 D (30 717 $)/QALY über den gesamten Modellierungszeitraum. Schlussfolgerung: Diese Kosten- Nutzwert-Analyse eines Aromatasehemmers basiert erstmals auf einer Datenanalyse, die auch das Follow-Up und den sogenannten Carryover- Effekt nach einer abgeschlossenen 5-Jahres-Therapie beinhaltet. Anastrozol ist auch nach dieser Analyse aus der Sicht des deutschen Gesundheitssystems eine kosteneffektive Therapieoption für postmenopausale Patientinnen mit einem HR+ frühen Mammakarzinom. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Background: In the ‘Arimidex’, Tamoxifen Alone or in Combination (ATAC) trial, the aromatase inhibitor (AI) anastrozole had a ignificantly better efficacy and safety profile than tamoxifen as initial adjuvant therapy for hormone receptor-positive (HR+) early breast cancer (EBC) in postmenopausal patients. To compare the combined long-term clinical and economic benefits, we carried out a cost-effectiveness analysis (CEA) of anastrozole versus tamoxifen based on the data of the 100- month analysis of the ATAC trial from the perspective of the German public health insurance. Patients and Methods: A Markov model with a 25-year time horizon was developed using the 100-month analysis of the ATAC trial as well as data obtained from published literature and expert opinion. Results: Adjuvant treatment of EBC with anastrozole achieved an additional 0.32 quality-adjusted life-years (QALYs) gained per patient compared with tamoxifen, at an additional cost of D 6819 per patient. Thus, the incremental cost effectiveness of anastrozole versus tamoxifen at 25 years was D 21,069 ($ 30,717) per QALY gained. Conclusions: This is the first CEA of an AI that is based on extended follow-up data, taking into account the carryover effect of anastrozole, which maintains the efficacy benefits beyond therapy completion after 5 years. Adjuvant treatment with anastrozole for postmenopausal women with HR+ EBC is a cost-effective alternative to tamoxifen. / Hintergrund: Bei der adjuvanten Therapie von postmenopausalen Patientinnen mit Hormonrezeptor-positivem (HR+) Mammakarzinom belegen die ATAC-100-Monatsdaten (ATAC-Studie: ‘Arimidex’, Tamoxifen Alone or in Combination) einen signifikanten Vorteil von Anastrozol gegenüber Tamoxifen in Bezug auf Rezidivrisiko und Verträglichkeit. Es wurde eine Kosten-Nutzwert-Analyse von Anastrozol im Vergleich zu Tamoxifen aus der Sicht des deutschen Gesundheitssystems durchgeführt. Material und Methoden: Als Berechnungsbasis wurde ein Markov- Modell zur Abschätzung der Kosteneffektivität entwickelt. Der Modellierungszeitraum umfasste 25 Jahre. Die Daten wurden anhand der ATAC-100-Monatsdaten, vorliegender Literatur und durch ein interdisziplinäres Expertenteam ermittelt. Ergebnisse: Eine adjuvante Therapie mit Anastrozol erzielte 0,32 quality-adjusted life-years (QALYs) pro Patientin mehr, verglichen mit einer adjuvanten Tamoxifentherapie. Die zusätzlichen Kosten der Therapie mit Anastrozol lagen bei 6819 D pro Patientin. Im Vergleich mit Tamoxifen erzielte Anastrozol einen ICER (Incremental Cost-Effectiveness Ratio) von 21 069 D (30 717 $)/QALY über den gesamten Modellierungszeitraum. Schlussfolgerung: Diese Kosten- Nutzwert-Analyse eines Aromatasehemmers basiert erstmals auf einer Datenanalyse, die auch das Follow-Up und den sogenannten Carryover- Effekt nach einer abgeschlossenen 5-Jahres-Therapie beinhaltet. Anastrozol ist auch nach dieser Analyse aus der Sicht des deutschen Gesundheitssystems eine kosteneffektive Therapieoption für postmenopausale Patientinnen mit einem HR+ frühen Mammakarzinom. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

De nos jours, il est de plus en plus fréquent de recourir à des mesures intermédiaires d’efficacité telles que la survie sans progression (SSP) et le temps avant la progression de la tumeur (TPT) afin d’estimer l’efficacité d’un nouvel agent anticancéreux. Cependant, l’absence de mesures finales comme la survie globale (SG) complexifie la prise de décision par rapport au remboursement des nouveaux traitements anticancéreux. Ainsi, cette thèse se concentre sur différents aspects de l’intégration des mesures intermédiaires d’efficacité dans les évaluations économiques en oncologie, spécifiquement en cancer du sein métastatique. Une première étude a évalué la relation entre la SSP/TPT et la SG dans le contexte du cancer du sein métastatique. Une revue systématique de la littérature a identifié les études cliniques randomisées portant sur l’efficacité d’un traitement anticancéreux chez les femmes atteintes d’un cancer du sein métastatique et rapportant des données de SSP/TPT et de SG. Les résultats de cette étude ont démontré qu’il existe une relation statistiquement significative, d’une part, entre la SSP/TPT médiane et la SG médiane (r = 0.428; p ≤ 0,01), et d’autre part, entre l’effet de traitement sur la SSP/TPT et l’effet de traitement sur la SG (r = 0.427; p ≤ 0,01). Selon les résultats obtenus, la SSP/TPT pourrait être considérée comme un substitut valide de la SG, justifiant ainsi son utilisation dans les évaluations économiques en cancer du sein métastatique. Une deuxième étude a évalué l’utilisation des mesures intermédiaires de survie dans les évaluations économiques en cancer avancé et identifié les méthodes utilisées pour intégrer ces mesures en l’absence de données de SG. Une revue systématique de la littérature a été réalisée pour recenser les évaluations économiques de type coût-efficacité et coût-utilité ayant intégré des mesures intermédiaires de survie. Cette étude a démontré l’ampleur de l’utilisation des mesures intermédiaires de survie dans les évaluations économiques en cancer avancé. Par ailleurs, plusieurs approches ont été identifiées pour pallier l’absence de données de SG, notamment l’utilisation d’un risque de décès post-progression équivalent pour les groupes à l’étude, le recours à des comparaisons indirectes basées sur de nombreuses hypothèses, l’utilisation d’une mesure intermédiaire comme proxy de la SG, le recours à l’opinion d’experts et l’utilisation de données associées à un traitement différent ou une ligne de traitement différente. Enfin, une troisième étude s’est penchée sur le développement d’un modèle pharmacoéconomique générique canadien intégrant les mesures intermédiaires de survie en cancer du sein métastatique. Ce modèle de Markov inclut des paramètres spécifiques aux traitements sous évaluations (coût de traitement, données de survie et incidence des effets indésirables) de même que des paramètres globaux qui ne dépendent pas des traitements évalués (caractéristiques des patientes, valeurs d’utilité associées aux états de santé du modèle, pertes d’utilité et coûts des effets indésirables, coûts d’administration des traitements, coûts de suivi médical et coûts des soins prodigués en fin de vie). Le modèle a été validé en évaluant sa capacité à répliquer des résultats d’études existantes. Ce modèle permet d’uniformiser l’évaluation économique des nouveaux traitements en cancer du sein métastatique et pourrait par conséquent, devenir un outil d’aide à la décision de référence pour les organismes responsables du remboursement des médicaments au Canada. Bref, les résultats de ces trois études répondent à une problématique importante dans l’évaluation économique des traitements en oncologie et pourront contribuer à faciliter la prise de décision en santé. / Nowadays, intermediate endpoints such as progression-free survival (PFS) and time to progression (TTP) are frequently used in clinical trials of advanced cancer. However, use of such endpoints instead of overall survival (OS) poses a significant challenge in the economic evaluation of anticancer drugs. This thesis focuses on different aspects of the integration of intermediate endpoints in the economic evaluation of anticancer drugs, especially in the context of metastatic breast cancer. A first study assessed the relationship between PFS/TPT and OS in metastatic breast cancer using a trial-based approach. A systematic review of the literature was performed to identify randomized clinical trials of metastatic breast cancer therapy reporting both PFS/TTP and OS data. Results of this study indicated a statistically significant relationship between the median PFS/TTP and the median OS (r = 0.428; p < 0.01), and between the treatment effect on PFS/TTP and the treatment effect on OS (r = 0.427; p < 0.01). Findings of this study suggest that PFS/TTP may be considered as a potential surrogate for OS, thus justifying its use in cost-effectiveness or cost-utility analyses of metastatic breast cancer therapy. A second study evaluated the use of intermediate endpoints in the economic evaluation of new treatments for advanced cancer and the methodological approaches adopted when OS data are unavailable or of limited use. A systematic review of the literature was conducted to identify cost-effectiveness and cost-utility analyses using an intermediate endpoint as an outcome measure. This study showed that intermediate endpoints are widely used in the economic evaluation of new treatments for advanced cancer. Several approaches are used in the absence of OS data such as assuming an equal risk of death for all treatment groups, using indirect comparison based on numerous assumptions, using of a proxy for OS, using unpublished external information (consultation with clinical experts), and using published external information from different treatment settings. Finally, a third study aimed to develop a global economic model to assess the cost-effectiveness of new treatments for metastatic breast cancer in Canada. This Markov model, which integrates intermediate endpoints, includes parameters specific to the treatments under evaluation (drug treatment, survival outcomes, and incidence of treatment-related adverse events (AEs)), as well as global parameters that are consistent regardless of the treatment under evaluation (patient characteristics, health states utilities, disutilities and costs associated with treatment-related AEs, as well as costs associated with drug administration, medical follow-up, and end-of-life care). The model was validated by assessing its ability to replicate results of existing studies. This model standardizes the economic evaluation of new therapies for metastatic breast cancer, and could thus be used as a benchmark by drug reimbursement authorities in Canada. In summary, the results of these three studies address an important challenge encountered in the economic evaluation of anticancer drugs, and therefore, can be very valuable for decision-making purposes.

Die Dissertation beschreibt am Beispiel einer Längsschnittstudie in der Papierindustrie, wie Effekte von Maßnahmen der betrieblichen Gesundheitsförderung in geschätzten ökonomischen Nutzen übertragen werden können. Ausgangspunkt der Untersuchung ist das Variablen-Modell nach Locke und Latham (1990). Darauf aufbauend wurden geeignete Indikatoren und Messinstrumente ausgewählt und in mehreren Voruntersuchungen überprüft. Hauptinstrument ist ein Fragebogen, der im quasiexperimentellen Design zur Ist-Analyse und nach Umsetzung der Maßnahmen eingesetzt wurde. An der ersten Befragung im Oktober 2000 nahmen 320 Gewerbliche und Angestellte des Unternehmens (Rücklauf 89%), an der zweiten drei Jahre später 402 Mitarbeiter (Rücklauf 91%) teil. Für den Längsschnitt standen die Fragebögen von 118 Mitarbeitern zur Verfügung. Neben den Fragebogendaten wurden personbezogene Daten zum Krankenstand erhoben, die auf freiwilliger Basis mit den Fragebogendaten verknüpft wurden, worauf sich 71% der im Jahr 2000 Befragten und 80% der im Jahr 2003 Befragten einlassen konnten. Zur Absicherung der Validität kamen weitere Untersuchungsmethoden zum Einsatz: für 19 Tätigkeiten wurde eine objektive arbeitspsychologische Tätigkeitsanalyse (Pohlandt, Schulze, Jordan &amp;amp; Richter, 2002) durchgeführt, die beteiligten Bereiche wurden in einem Rankingverfahren durch betriebliche Experten eingeschätzt, die organisationale Einbindung der betrieblichen Gesundheitsförderung wurde zu beiden Untersuchungszeitpunkten mit Hilfe des Fragebogens von Breucker (Prävention online, 2000) erfasst, es fanden 22 strukturierte Interviews mit den Beschäftigten zur Einschätzung der durchgeführten Maßnahmen statt. Die Ergebnisse der ersten Mitarbeiterbefragung wurden zurückgemeldet, diskutiert und zu 12 Maßnahmen verdichtet. Diese 12 Maßnahmen wurden in die Zweitbefragung mit aufgenommen, wobei die aktive Beteiligung an ihnen und die Zufriedenheit mit ihrer Umsetzung eingeschätzt werden sollten. Zur Ermittlung der Effizienz wurden eine erweiterte Kosten-Nutzen-Analyse (nach Schmidt, Hunter &amp;amp; Pearlman, 1982) und eine Kosten-Nutzwert-Analyse (nach Rinza &amp;amp; Schmitz, 1992) durchgeführt. Fast alle im Fragebogen erfassten Variablen hatten sich zwischen der ersten und zweiten Befragung signifikant verbessert (Arbeitsintensität, Tätigkeitsspielraum, Motivationspotenzial der Tätigkeit, soziale Unterstützung, sozialen Stressoren, Commitment, Arbeitszufriedenheit, allgemeines Befinden, psychosomatische Beschwerden). Nicht signifikant waren die Änderungen beim (multimodal beeinflussten) Krankenstand, sowie bei der Einschätzung der Führung. Bezüglich der Effektstärke konnte bei 9 der 12 Maßnahmen mindestens ein positiver Unterscheidungseffekt aufgezeigt werden. Bei der Ermittlung des (subjektiv erlebten) Nutzwertes der Maßnahmen kamen alle 12 Maßnahmen in den positiven Bereich. Mit der Kosten-Nutzen-Analyse wurde ein positives Kosten-Nutzen-Verhältnis für 6 der 9 verbleibenden Maßnahmen (zwischen 1:71 und 1:1,5) ermittelt. Diese Ergebnisse wurden kritisch hinterfragt und durch Einbeziehung von Diskontierung, spezifischen Effizienzkriterien, Sensitivitätsanalysen und Worst-Case-Berechnung relativiert (vgl. Anforderungen nach Drummond, O´Brien, Stoddart &amp;amp; Torrance, 1987/1997). Im Vergleich zur Kosten-Nutzen-Analyse wurden bei der Kosten-Nutzwert-Analyse deutlich andere Rangreihen ermittelt. Die kritische Gesamtschau der Ergebnisse ermöglicht spezifische Empfehlungen für fünf Maßnahmengruppen. Es zeigte sich, dass die gemeinsame Erörterung von Kosten-Nutzen-Analyse und Nutzwert zusätzliche und bisher nicht erfasste Aspekte beim Umgang mit den Maßnahmen eröffnet. / The thesis illustrates a longitudinal study in the paper industry. It shows how effects resulting from measures of occupational health promotion may be translated into an estimated economic advantage. The starting point of the study is the high performance cycle (Locke &amp;amp; Latham: 1990). Proceeding from that, appropriate indicators and measuring instruments were selected and tested in several pre-studies. The main instrument is a questionnaire, used in a comparative design before and after the translation of the measures into practice. 320 white- and blue-collar workers took part in the first survey in October 2000 (response rate 89%), whereas 402 workers participated in the second survey which was conducted three years later (response rate 91%). After all, complete data sets for the longitudinal analysis were available from 118 participants. Apart from that personal data concerning absenteeism were used, which were then connected to the questionnaire data on a voluntary basis. Whereas in 2000, in the first survey, 71% of the participants agreed to the connection of their personal data with the questionnaire, 80% agreed to it in the second survey, in 2003. To guarantee the questionnaire?s validity an array of additional methods was used: an objective occupational job analysis (Pohlandt, Schulze, Jordan &amp;amp; Richter, 2002) of 19 different occupations was carried out and the company?s experts evaluated the branches involved by ranking. Furthermore the organizational embedding of occupational health promotion measures was investigated in both surveys with the help of Breucker?s questionnaire (Prevention online, 2000) and additionally 22 structured interviews with the employees took place in order to evaluate the acceptance of the measures conducted. The results of the first employee survey were reported back, discussed and condensed into 12 measures. These 12 measures were then included in the second survey when the employees? active participation in the measures? implementation and their satisfaction with the measures? effects should be evaluated. To determine the measures? actual efficiency an extended cost-benefit-analysis (with reference to Schmidt, Hunter &amp;amp; Pearlman: 1982) and a cost-utility-analysis (with reference to Rinza &amp;amp; Schmitz: 1992) were conducted. Nearly all variables investigated in the questionnaire had significantly improved between the first and the second survey (indicators of job demands, occupational scope, motivational potential of occupation, social support, social stressors, commitment, job satisfaction, well-being, psychosomatic complaints). Changes in (multi-modally influenced) absenteeism and in the evaluation of the management?s style of leadership were not significant. Referring to the effects? impact 9 out of 12 measures proved to be positively significant in at least one criterion, whereas referring to (subjectively felt) utility all 12 measures turned out to be positively significant. In six of the remaining nine measures the cost-benefit-analysis resulted in a positive cost-benefit-relation (between 1:71 and 1:1,5). These results were critically discussed and taking into account discounting, specific result-criteria, sensitivity analyses and worst case assessment (see quality principles by Drummond, O´Brien, Stoddart &amp;amp; Torrance, 1987/1997) finally adjusted. Comparing the cost-benefit and cost-utility analyses resulted in significantly different rankings. The critical overall view allows for specific recommendations for five measure-groups. Finally, the joint discussion of the cost-benefit analysis and utility turned out to open up additional aspects of how to conduct the measures in future, which have not been described so far.