The Choquet Integral Applied to Ranking Therapies in Radiation Cystitis

Radiation cystitis is in general rarely occurring, which makes it very difficult to study in a large group of clinical trials. Most available data about radiation cystitis treatment come from a small number of descriptive studies or from expert opinions. As clinical data are considered to have low quality then physicians, who are still facing patients with a disease hugely influencing quality of life, mostly base on their own experience. We thus want to test fuzzy decision-making model, regarded as a valuable tool, to help in selecting a patient-tailored treatment in radiation cystitis. Theoretical fuzzy decision-making models, possessing the utility matrix filled with distinct utilities of pairs (decision, object-state), give rise to own trials of successfully accomplished applications concerning the item of medication. After interpreting pairs (decision, object-state) as (therapy, symptom), we intend to prove decision-making based on the Choquet integral to extract the optimal treatment in radiation cystitis

Can routinely collected electronic health data be used to develop novel healthcare associated infection surveillance tools?

Background: Healthcare associated infections (HCAI) pose a significant burden to health systems both within the UK and internationally. Surveillance is an essential component to any infection control programme, however traditional surveillance systems are time consuming and costly. Large amounts of electronic routine data are collected within the English NHS, yet these are not currently exploited for HCAI surveillance. Aim: To investigate whether routinely collected electronic hospital data can be exploited for HCAI surveillance within the NHS. Methods: This thesis made use of local linked electronic health data from Imperial College Healthcare NHS Trust, including information on patient admissions, discharges, diagnoses, procedures, laboratory tests, diagnostic imaging requests and traditional infection surveillance data. To establish the evidence base on surveillance and risks of HCAI, two literature reviews were carried out. Based on these, three types of innovative surveillance tools were generated and assessed for their utility and applicability. Results: The key findings were firstly the emerging importance of automated and syndromic surveillance in infection surveillance, but the lack of investigation and application of these tools within the NHS. Syndromic surveillance of surgical site infections was successful in coronary artery bypass graft patients; however it was an inappropriate methodology for caesarean section patients. Automated case detection of healthcare associated urinary tract infections, based on electronic microbiology data, demonstrated similar rates of infection to those recorded during a point prevalence survey. Routine administrative data demonstrated mixed utility in the creation of simplified risk scores or infection, with poorly performing risk models of surgical site infections but reasonable model fit for HCA UTI. Conclusion: Whilst in principle routine administrative data can be used to generate novel surveillance tools for healthcare associated infections; in reality it is not yet practical within the IT infrastructure of the NHS

Trial efficacy vs real world effectiveness in first line treatment of multiple myeloma

Background: Large randomized clinical trials (RCT) are the foundation of the registration of newly developed drugs. A potential problem with RCTs is that the inclusion/exclusion criteria will make the population different from the actual population treated in real life. Hence, it is important to understand how the results from the RCT can be generalized to a general population. Aims: The primary aim of the present study was to assess the generalizability of the large 1st line RCTs in Multiple Myeloma (MM) to the Nordic setting and to understand potential difference and magnitude in outcomes between RCTs and patients treated in standard care in the Nordics. Methods: A retrospective analysis was performed on an incident cohort of 2960 MM-patients from 24 hospitals in Denmark, Finland, Norway and Sweden. The database contained information on patient baseline characteristics, treatments and outcomes. Data from relevant 1st line MM RCTs was selected from the treatment MP (Waage, A., et al., Blood. 2010], MPT (Waage, A., et al., Blood. 2010) and VMP (San Miguel, J.F., et al., N Engl J Med, 2008) and baseline characteristics were compared to newly diagnosed Nordic MM treated patients. Potential difference in response and overall survival (OS) was estimated by adjusting the RWE population to the RCT population using matching adjusted indirect comparisons. Patients were matched on age (median approximated to mean), gender, calcium, beta2-microglobulin and ISS score 3. These variables were selected because they were reported in all trials and have previously been identified as having prognostic value. Results: Patients in the Nordic database treated with MP (n=880) had a response rate of (PD, NR, PR, VGPR, ≥nCR) of (13%, 39%, 38%, 6%, 4%). After matching (n=347), the response rate was slightly worse (12%, 43%, 36%, 6%, 3%). This can be compared to the response rate from the RCT of (7%, 53%, 33%, 3%, 4%). OS for Nordic MP treated patients was 2.67 years (2.25-3.17). After matching the OS was 3.37 years (2.86-3.96) and this can be compared to the trial with OS 2.40 years (2.23-2.66). Patients treated with MPT (n=283) in the Nordic countries had a response rate of (5%, 14%, 52%, 20%, 9%). After matching (n=179) the response rate was slightly changed to (6%, 20%, 50%, 13% 11%). The corresponding RCT response results were 14%, 29%, 34%, 10%, and 13% respectively. OS for Nordic MPT treated patients was 4.15 years (3.73- 4.74). After matching the OS was 4.28 years (3.98-NA) years and compared to 2.42 years (2.08-3.17) OS observed in the corresponding trial. Patients treated with VMP (n=59) in the Nordic countries had a response rate of (4%, 5%, 40%, 18%, 33%). After matching (n=31) the response rate was improved to (8%, 11%, 28%, 8%, 45%). This corresponding response rates shown in the trial are 1%, 23%, 33%, 8%, and 33% respectively. OS for Nordic MP treated patients was 4.86 years (3.79-NA). After matching the OS was 4.86 years (4.86-NA) and this can be compared to the trial with OS 4.70 years. Summary and Conclusions: Surprisingly Nordic treated MM patients do very well compared to, and even better than, patients treated in RCTs. Since the OS for all tested treatments improves after matching to the RCT baseline characteristics, patients recruited to the RCTs seems to be a bit better than ordinary Nordic patents. The database used in the present study, and the used method, can be valuable for generalizing the results to the Nordic setting and estimating potential difference for future RCTs and Nordic MM treated patients. Future research should include different data cuts to see whether the analyses are biased by differences subsequent treatments applied in RCTs and clinical practice

Micro-costing study of rituximab subcutaneous injection versus intravenous infusion in dutch setting

Background: Rituximab for subcutaneous (SC) administration has recently been approved for use in common forms of diffuse large B-cell lymphoma (DLBCL). This form of rituximab is supplied in ready-to-use vials that do not require individual dose adjustment. It is expected that SC-injection will shorten the treatment time per administration of rituximab in comparison with currently available intravenous (IV) infusion. Aims: The goal of this study is to identify and compare all direct costs of IV and SC rituximab given to the DLBCL patients in the Netherlands. Methods: Using a prospective, observational, bottom up, micro-costing study we collected primary data on the direct medical costs of the preparation, administration and acquisition of rituximab. Drug costs and spillage, labor costs, material costs and remaining daycare costs were identified using standardized forms, structured using guideline prices and compared for the IV and SC forms of rituximab. Results: Measurements were done on 53 administrations (33 IV and 20 SC). The mean total costs of the IV infusion were €2174, and €1907 for the SC injection. The estimated difference of €267 per administration was mainly due to spillage costs and differences in chair time, related daycare costs and drug costs. Summary and Conclusions: Rituximab administered in the form of SC injection is less costly than its IV form. Taking into account their equal effectiveness, favorable pharmacoeconomic profile of SC rituximab can result in significant savings when transferred to the total DLBCL population in the Netherlands