Estimating the cost effectiveness ratio for those suffering from lung cancer in Greece: a new methodological approach for economic evaluation and its practical application for the public health

Introduction: Economic evaluation compares the costs and health effects of an intervention in order to maximize health benefits from available resources. Aim: The scope of this doctoral thesis was twofold. The primary scope was to develop a new methodological model of cost-effectiveness analysis for lung cancer patients in Greece. The second aim was to estimate the cost-effectiveness ratio for competitive interventions based on a real data set. Hence, an economic evaluation was also conducted alongside a prospective, multicenter, randomized, trial, to evaluate pemetrexed relative to erlotinib in pre-treated patients with metastatic non small cell lung cancer (NSCLC) in Greece. Methods: We developed a new model which combines the cost-effectiveness and budget impact analysis in a unique model. The proposed model relaxed the simplified constant-return-on-scale assumption of willingness to pay (λ) for innovative interventions introducing a log-sigmoid function derived from Weibull family. In our model, it was assumed that the budget is exogenous and has been set by the budget holders in a small disease-specific area. Moreover, in an attempt to practically describe the real world, the proposed model allows a flexible -upper bounded- budget. Frequently, budget allocation amongst therapeutic areas lies on historical, political and social criteria and thus, the application of prominent instruments such as mathematical programming seems difficult to be practically implemented for the optimum allocation of the health care budgets. In our case, a far less ambiguous approach was adopted to estimate the local equilibrium which is driven by the de facto budget availability in a disease specific context. Results: The model allows the determination of λ to be different across different therapeutic areas, taking into account the differences in the “production” of a QALY amongst patient groups. The model demonstrates how willingness to pay changes, as we hold the budget fixed and allows the incremental effectiveness to vary, how the budget must be expanded to afford an innovative technology given a specific willingness to pay path -fixed or not-, or a combination of the above. Concerning the second part, statistical analysis showed that pemetrexed and erlotinib had comparable effectiveness and thus a cost minimization analysis was conducted to assess and find the least costly option. Patient-level resource utilization data were combined with unit cost data and they were then aggregated to compute total treatment cost for each patient. Conclusion: The model which developed is in accordance with the principles of microeconomic theory and can be used to estimate the equilibrium in the context of lung cancer patients. Concerning the second part, the evidence did not support any survival or cost difference between pemetrexed and erlotinib, and thus, they can be deemed equivalent, except if any other relevant parameter such as quality of life makes a difference.Εισαγωγή: Η οικονομική αξιολόγηση συγκρίνει το κόστος και το όφελος που προκύπτει από μια νέα θεραπευτική παρέμβαση, προκειμένου να μεγιστοποιήσει την υγεία του πληθυσμού με βάση τους διαθέσιμους πόρους. Σκοπός: Ο σκοπός της παρούσας διατριβής ήταν διττός. Πρωταρχικά, στόχευε στο να αναπτύξει ένα νέο μοντέλο κόστους- αποτελεσματικότητας για τους ασθενείς με καρκίνο του πνεύμονα στην Ελλάδα. Ο δεύτερος στόχος ήταν να εκτιμηθεί ο λόγος κόστους-αποτελεσματικότητας για την ερλοτινίμπη και την πεμετρεξίδη με βάση πραγματικά δεδομένα ασθενών. Έτσι διενεργήθηκε μια οικονομική αξιολόγηση, παράλληλα με μια προοπτική, πολυκεντρική, τυχαιοποιημένη κλινική δοκιμή σε προ-θεραπευμένους ασθενείς με μη-μικροκυταρικό καρκίνο του πνεύμονα. Μέθοδος: Αναπτύχθηκε ένα νέο υπόδειγμα που συνδυάζει την ανάλυση κόστους-αποτελεσματικότητας με την ανάλυση επίπτωσης προϋπολογισμού σε ένα μοναδιαίο υπόδειγμα. Το προτεινόμενο υπόδειγμα ανασκευάζει την απλοποιητική υπόθεση των σταθερών αποδόσεων κλίμακας σε σχέση με την οριακή-διάθεση-πληρωμής (λ) για καινοτόμες θεραπείες, εισάγοντας μια λογαριθμο-σιγμοειδή συνάρτηση προερχόμενη από την οικογένεια κατανομών Weibull. Στο υπόδειγμα υποτέθηκε ότι ο προϋπολογισμός είναι εξωγενής και τίθεται από την κεντρική εξουσία σε μια μικρή θεραπευτική περιοχή. Συχνά, ο καταμερισμός του προϋπολογισμού προσδιορίζεται με βάση ιστορικά, πολιτικά και κοινωνικά κριτήρια και επομένως η πρακτική χρήση σημαντικών εργαλείων όπως ο μαθηματικός προγραμματισμός είναι πολύ δύσκολη προκειμένου να κατανείμουμε τους διαθέσιμους πόρους. Στην περίπτωση μας, υιοθετήθηκε μια αρκετά λιγότερη φιλόδοξη προσέγγιση, προκειμένου να εκτιμηθεί η ισορροπία του συστήματος με βάση το διαθέσιμο προϋπολογισμό στους συγκεκριμένους ασθενείς. Επιπρόσθετα εκπονήθηκε ανάλυση ελαχιστοποίησης κόστους προκειμένου να εκτιμηθεί η εξοικονόμηση από τη χορήγηση των εναλλακτικών τεχνολογιών υγείας. Αποτελέσματα: To νέο υπόδειγμα επιτρέπει την διαφοροποίηση στον προσδιορισμό του λ, λαμβάνοντας υπόψη τις διαφορές στην παραγωγή ενός QALY μεταξύ ασθενών που προέρχονται από διαφορετικές θεραπευτικές κατηγορίες. Το υπόδειγμα επιδεικνύει πως η οριακή-διάθεση-πληρωμής αλλάζει καθώς διατηρούμε σταθερό τον προϋπολογισμό και επιτρέπουμε στην οριακή αποτελεσματικότητα να διαφοροποιείται, πως ο προϋπολογισμός πρέπει να επεκταθεί προκειμένου να καλύψει την καινοτομία με βάση ένα συγκεκριμένο πρότυπο για το λ (σταθερό ή μεταβλητό) ή έναν συνδυασμό των παραπάνω. Αναφορικά με το δεύτερο σκέλος, η στατιστική ανάλυση έδειξε ότι η πεμετρεξίδη και ερλοτινίμπη είχαν συγκρίσιμη αποτελεσματικότητα και έτσι πραγματοποιήθηκε ανάλυση ελαχιστοποίησης κόστους, προκειμένου να προσδιορισθεί η λιγότερη δαπανηρή θεραπεία, ως προτιμότερη. Tα δεδομένα χρήσης πόρων και μοναδιαίου κόστους συνδυάστηκαν, για να βρεθεί το κόστος για κάθε ασθενή ξεχωριστά. Συμπεράσματα: To υπόδειγμα που αναπτύχθηκε είναι ευθυγραμμισμένο με τις αρχές της μικροοικονομικής θεωρίας και μπορεί να χρησιμοποιηθεί για να προσδιοριστεί η ισορροπία του συστήματος στα πλαίσια διαχείρισης των ασθενών με καρκίνο του πνεύμονα. Αναφορικά με το δεύτερο μέρος, η ανάλυση δεν υποστηρίζει διαφοροποιήσεις μεταξύ των θεραπειών και έτσι μπορούν να θεωρηθούν ισοδύναμες, εκτός αν άλλοι παράγοντες –όπως η ποιότητα ζωής- προκαλούν μια διαφορά

Self-reported prevalence of atherothrombosis in a general population sample of adults in Greece; A telephone survey

Background: The aim of this study was to estimate the prevalence of selected atherothrombotic risk factors and several clinical manifestations of atherothrombosis, as well as the utilization rates of selected vascular interventions in Greece. Methods: During December 2009, 3,007 adults (aged 47 +/- 16 years, 48.3% men and 51.7% women) recruited in a random-digit dialed telephone survey (response rate: 16%). The sample size was selected following a multistage and stratified by gender, age group, and Greek region procedure in order to be more representative. Data regarding medical history and socio-demographic characteristics of the participants were collected. Results: Overall, 6.5%, 17.7% and 14.0% of participants reported that they had been diagnosed with diabetes mellitus, hypertension and hypercholesterolemia, respectively. In the overall sample, 2.5% of participants reported that they had been diagnosed with angina, 2.0% with myocardial infarction, 1.6% with stroke and 2.5% with peripheral artery disease. Overall, 1.5% of participants reported that they had undergone percutaneous coronary intervention, 1.4% coronary artery bypass grafting, 0.6% angioplasty of a peripheral vessel, and 0.7% surgery of a peripheral vessel. Conclusion: Despite the limitations may occur due to the sampling procedure, the findings of the present study indicate that atherothrombosis affects a large portion of the population in Greece and it is expected to impose a significant economic burden. The data of the current study could contribute in obtaining an accurate estimation of the economic burden of atherothrombosis in Greece because people who are aware of their condition/disease are those who use health care resources

A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study

© 2023Background: The benefit of pharmacogenetic testing before starting drug therapy has been well documented for several single gene–drug combinations. However, the clinical utility of a pre-emptive genotyping strategy using a pharmacogenetic panel has not been rigorously assessed. Methods: We conducted an open-label, multicentre, controlled, cluster-randomised, crossover implementation study of a 12-gene pharmacogenetic panel in 18 hospitals, nine community health centres, and 28 community pharmacies in seven European countries (Austria, Greece, Italy, the Netherlands, Slovenia, Spain, and the UK). Patients aged 18 years or older receiving a first prescription for a drug clinically recommended in the guidelines of the Dutch Pharmacogenetics Working Group (ie, the index drug) as part of routine care were eligible for inclusion. Exclusion criteria included previous genetic testing for a gene relevant to the index drug, a planned duration of treatment of less than 7 consecutive days, and severe renal or liver insufficiency. All patients gave written informed consent before taking part in the study. Participants were genotyped for 50 germline variants in 12 genes, and those with an actionable variant (ie, a drug–gene interaction test result for which the Dutch Pharmacogenetics Working Group [DPWG] recommended a change to standard-of-care drug treatment) were treated according to DPWG recommendations. Patients in the control group received standard treatment. To prepare clinicians for pre-emptive pharmacogenetic testing, local teams were educated during a site-initiation visit and online educational material was made available. The primary outcome was the occurrence of clinically relevant adverse drug reactions within the 12-week follow-up period. Analyses were irrespective of patient adherence to the DPWG guidelines. The primary analysis was done using a gatekeeping analysis, in which outcomes in people with an actionable drug–gene interaction in the study group versus the control group were compared, and only if the difference was statistically significant was an analysis done that included all of the patients in the study. Outcomes were compared between the study and control groups, both for patients with an actionable drug–gene interaction test result (ie, a result for which the DPWG recommended a change to standard-of-care drug treatment) and for all patients who received at least one dose of index drug. The safety analysis included all participants who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03093818 and is closed to new participants. Findings: Between March 7, 2017, and June 30, 2020, 41 696 patients were assessed for eligibility and 6944 (51·4 % female, 48·6% male; 97·7% self-reported European, Mediterranean, or Middle Eastern ethnicity) were enrolled and assigned to receive genotype-guided drug treatment (n=3342) or standard care (n=3602). 99 patients (52 [1·6%] of the study group and 47 [1·3%] of the control group) withdrew consent after group assignment. 652 participants (367 [11·0%] in the study group and 285 [7·9%] in the control group) were lost to follow-up. In patients with an actionable test result for the index drug (n=1558), a clinically relevant adverse drug reaction occurred in 152 (21·0%) of 725 patients in the study group and 231 (27·7%) of 833 patients in the control group (odds ratio [OR] 0·70 [95% CI 0·54–0·91]; p=0·0075), whereas for all patients, the incidence was 628 (21·5%) of 2923 patients in the study group and 934 (28·6%) of 3270 patients in the control group (OR 0·70 [95% CI 0·61–0·79]; p <0·0001). Interpretation: Genotype-guided treatment using a 12-gene pharmacogenetic panel significantly reduced the incidence of clinically relevant adverse drug reactions and was feasible across diverse European health-care system organisations and settings. Large-scale implementation could help to make drug therapy increasingly safe. Funding: European Union Horizon 2020