A (Latent) Class of Their Own: Response Patterns in Trading Off Quantity and Quality of Life in Time Trade-Off Exercises.

BACKGROUND: Conflicting results regarding associations of time trade-off (TTO) valuations with respondent characteristics have been reported, mostly on the basis of regression analyses. Alternative approaches, such as the latent class analysis (LCA), may add to the further understanding of variations in TTO responses. OBJECTIVES: To identify whether subgroups of respondents can be identified on the basis of their responses to TTO exercises and to investigate which respondent characteristics are associated with membership of the identified subgroups. METHODS: Members of the Dutch general public, aged 18 to 65 years, completed a Web-based questionnaire concerning sociodemographic characteristics, three TTO exercises valuing health states described using the domains of the EuroQol five-dimensional questionnaire, and preference for quality versus quantity of life. LCA was used to identify patterns in the responses. Predictive variables were included in the final LCA model to identify the particular respondent characteristics that predict subgroup membership. RESULTS: The sample consisted of 1067 respondents. Four latent classes were identified in the responses to TTO exercises. Two were high traders, focusing on quality of life and trading off a relatively high number of years. The other two were low traders, focusing on length of life. Predictive analyses revealed significant differences between subgroups in terms of age, sex, subjective life expectancy, and preference for quantity over quality of life. CONCLUSIONS: We showed that distinct classes of respondents can be discerned in TTO responses from the general public, distinguishing subgroups of low and high traders. More research in this area should confirm our findings and investigate their implications for health state valuation exercises.

Uncoiling collagen: a multidimensional mass spectrometry study.

Mass spectrometry can be used to determine structural information about ions by activating precursors and analysing the resulting series of fragments. Two-dimensional Fourier transform ion cyclotron resonance mass spectrometry (2D FT-ICR MS) is a technique that correlates the mass-to-charge (m/z) ratio of fragment and precursor ions in a single spectrum. 2D FT-ICR MS records the fragmentation of all ions in a sample without the need for isolation. To analyse specific precursors, horizontal cross-sections of the spectrum (fragment ion scans) are taken, providing an alternative to conventional tandem mass spectrometry (MS/MS) experiments. In this work, 2D FT-ICR MS has been used to study the tryptic digest of type I collagen, a large protein. Fragment ion scans have been extracted from the 2D FT-ICR MS spectrum for precursor m/z ratios: 951.81, 850.41, 634.34, and 659.34, and 2D FT-ICR MS spectra are compared with a set of 1D MS/MS spectra using different fragmentation methods. The results show that two-dimensional mass spectrometry excells at MS/MS of complex mixtures, simplifying spectra by eliminating contaminant peaks, and aiding the identification of species in the sample. Currently, with desktop computers, 2D FT-ICR MS is limited by data processing power, a limitation which should be alleviated using cluster parallel computing. In order to explore 2D FT-ICR MS for collagen, with reasonable computing time, the resolution in the fragment ion dimension is limited to 256k data points (compared to 4M data points in 1D MS/MS spectra), but the vertical precursor ion dimension has 4096 lines, so the total data set is 1G data points (4 Gbytes). The fragment ion coverage obtained with a blind, unoptimized 2D FT-ICR MS experiment was lower than conventional MS/MS, but MS/MS information is obtained for all ions in the sample regardless of selection and isolation. Finally, although all 2D FT-ICR MS peak assignments were made with the aid of 1D FT-ICR MS data, these results demonstrate the promise of 2D FT-ICR MS as a technique for studying complex protein digest mixtures.

[Cost-effectiveness in Dutch mental health care: future because of ROM?]. / Doelmatigheid in de ggz: toekomst dankzij ROM?

BACKGROUND: The document reporting Dutch mental health care negotiations for 2014-2017 calls for a cost decrease based on cost-effectiveness. Thanks to ROM, the Dutch mental health care seems well prepared for cost-effectiveness research. AIM: Evaluate how valid cost-effectiveness research should be established in mental health care and the role of rom therein. METHOD: Evaluation of requirements of cost-effectiveness research, trends, and a translation to Dutch mental health care. RESULTS: Valid cost-effectiveness research in mental health care requires the application of a societal perspective, a long time-horizon and an adequate evaluation of quality of life of patients. Healthcare consumption, outcome of care and characterisation of the patient population should be measured systematically and continuously. Currently, rom-data are not suitable to serve as a basis for cost-effectiveness research, although a proper basis is present. Further development of rom could lead to a situation in which mental health care is purchased on the basis of cost-effectiveness. However, cost-effectiveness will only really be improved if quality of care is rewarded, rather than rewarding activities that are not always related to outcome of care. CONCLUSION: Cost-effectiveness research in mental health care should focus on societal costs and benefits, quality of life and a long time-horizon. If developed further, rom has the potential to be a basis for cost-effectiveness research in the future.

Access to expensive cancer drugs in Dutch daily practice: should we be concerned?

BACKGROUND: To investigate whether equal access to bortezomib has been achieved under the Dutch policy regulations that guarantee equal access to expensive inpatient drugs. METHODS: We investigated accessibility to bortezomib treatment at national and regional levels by (i) conducting interviews with stakeholders in the Dutch healthcare system to explore prescription barriers and (ii) tabulating sales data from 2004-2009 and trial participation rates. RESULTS: Interviews revealed awareness of the high treatment costs, although prescription barriers were not encountered. National use of bortezomib increased slowly (treating 2% of patients in 2004 to 17% in 2009), indicating a long adjustment period. Furthermore, use remains below the rate estimated by the professional association of haematologists (27%). Regional differences were found for both daily practice use (e.g. ranging from 13-27% in 2009) and clinical trial participation (e.g. ranging from 1-12% in 2006). CONCLUSION: Our results were somewhat conflicting: interviews did not reveal any prescription barriers, but quantitative methods showed regional differences, signs of underutilisation, and access inequality. Investigating use and accessibility, based on data triangulation, provides valuable feedback which can enhance evidence-based decision making for both physicians and policymakers. This could improve appropriate and efficient use and ensure equal access to expensive drugs.

Free radial forearm flap versus pectoralis major myocutaneous flap reconstruction of oral and oropharyngeal defects: a cost analysis.

OBJECTIVES: The free radial forearm flap has replaced the pedicled pectoralis major myocutaneous flap and it has become the 'workhorse flap' used by many head and neck reconstructive surgeons for soft tissue reconstructions. Cost implications of radial forearm flap reconstruction within the context of the overall health care in a particular system need to be investigated particularly before it is labelled as 'costly only'. DESIGN AND SETTING: Forty patients who underwent immediate free radial forearm flap reconstruction for oral or oropharyngeal soft tissue defects were matched with patients who underwent pectoralis major myocutaneous flap reconstruction for similar defects. The 2 years of which the overall management costs according to the hospital perspective were calculated were divided into four periods: operative period, the postoperative phase, follow-up during first year and follow-up during second year after discharge. RESULTS: The total costs within the first 2 years were comparable at approximately 50,000 Euros. The lower costs of hospital admission (24 days versus 28 days; P = 0.005) in the postoperative phase outweighed the higher costs of the surgical procedure (692 min versus 462 min; P < 0.005) in radial forearm flap patients when compared with pectoralis major flap patients. CONCLUSIONS: Oral and oropharyngeal reconstruction with radial forearm flap is not more costly than pectoralis major flap reconstruction. Given the better functional outcome and the present cost analysis, reconstruction of oral and oropharyngeal defects is preferably performed using free tissue transfer.

A cost-utility analysis comparing intensive chemotherapy alone to intensive chemotherapy followed by myeloablative chemotherapy with autologous stem-cell rescue in newly diagnosed patients with stage II/III multiple myeloma; a prospective randomised phase III study.

A prospective randomised phase III study in patients < or =65 years old with previously untreated multiple myeloma (MM), intensive chemotherapy followed by myeloablative chemotherapy and autologous stem-cell rescue was compared with intensive chemotherapy alone. This economic evaluation was based on detailed data from patient charts and hospital information systems. In the intention-to-treat analysis, mean total treatment and follow-up costs of the myeloablative treatment arm were 81,643 euros compared to 68,802 euros for the chemotherapy arm (P=0.09). Costs per quality-adjusted life year were 51,357 euros versus 37,328 euros. In the clinical study, no significant differences were found in overall survival after a median follow-up of 33 months from randomisation. Intensive chemotherapy is regarded as standard therapy for younger patients with previously untreated MM. Cost-effectiveness of myeloma therapy after 3 years of follow up seems not to be favoured by myeloablative treatment with autologous stem-cell rescue.

[The role of cost analysis in the evaluation of the development of medical technology. The case of allogenic stem-cell transplantation]. / Der rol van kostenanalysen in de evaluatie van de ontwikkeling van medische technologieën. De casus allogene stamceltransplantaties.

OBJECTIVE: To estimate the real costs of allogeneic haematopoetic stem-cell transplantation and to compare these with the historically determined budgets that are made available for this purpose ([symbol: see text] 70,038 for genetically related donors and [symbol: see text] 76,826 for unrelated donors). DESIGN: Cost analysis. METHODS: In the period 1994-1999, the direct medical costs (price level of 1998) of bone-marrow transplantation from related donors (BMT), stem-cell transplantation from unrelated donors (VUD-SCT) and allogeneic peripheral-blood stem-cell transplantation (PBSCT) from related donors were determined on the basis of data on adult patients with either acute myeloid leukaemia (n = 66) or acute lymphocytic leukaemia (n = 31). First, the medical resource use by these patients was determined and multiplied by the unit costs of each of the items. Second, a structural programme for allogeneic stem-cell transplantation brings along costs that are not evident from the registration of the medical resource use (e.g., the costs of pretransplantation screening and the selection of the donor). The costs of these items were calculated by taking inventory in the hospitals and assessed by experts. RESULTS: The average costs per transplanted patient were [symbol: see text] 98,334 (BMT), [symbol: see text] 151,754 (VUD-SCT) and [symbol: see text] 98,977 (PBSCT) during the first two years after transplantation. The greater part of the costs was incurred in the transplantation phase. In VUD-SCT, one-third of the total cost was due to the costs of finding a suitable donor. CONCLUSION: The current budget for allogeneic stem-cell transplantation is insufficient to perform the transplantations adequately. Periodic evaluation of the budgets for complicated procedures based on cost analyses has added value for the evaluation of the development of these procedures in time and can thereby contribute to the quality and continuity of care.

[Survival of patients with aggressive non-hodgkin's lymphoma: no difference between first line treatment in a prospective randomised phase III clinical trial and first line treatment according to routine clinical practice]. / Overleving van patiënten met agressief non-hodgkinlymfoom: geen verschil tussen eerstelijnsbehandeling in klinisch prospectief gerandomiseerd fase-III-onderzoek en eerstelijnsbehandeling buiten studieverband.

OBJECTIVE: To compare survival of patients with disseminated aggressive non-Hodgkin's lymphoma (NHL) who were treated either as part of a clinical trial or in routine clinical practice. DESIGN: Retrospective. METHOD: The survival was studied of patients with disseminated NHL of an intermediate or high degree of malignancy who were treated in the Meander Medical Centre, Amersfoort, the Netherlands, in the years 1994-2001 with chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). This took place either in routine clinical practice (RCP) or as part of a clinical trial where patients < or = 60 years of age received intensified CHOP and patients > 60 years received CHOP with growth factors. Treatment data, the response to therapy, survival and prognostic factors according to the International Prognostic Index for aggressive NHL were collected by a review of the patient records. RESULTS: Fifty-nine patients were eligible for this analysis: 32 men and 27 women with a median age of 63 years (range 30-83). Of these, 35 were treated within a clinical trial and 24 were treated in RCP. The patient characteristics in the two groups were comparable. There was no difference in median survival between the trial and RCP groups, this being 27 months for all patients, 34 months for the younger patients, 20 months for the elderly patients, and 42 months for patients who achieved complete remission following chemotherapy. CONCLUSION: No difference in overall survival was found between patients with disseminated aggressive NHL who underwent treatment according to either RCP or as part of a clinical trial. It demonstrates that both patients in clinical trials and patients treated according to RCP received equally effective therapy. Recent developments in NHL treatments are promising, and therefore participation in clinical trials should be encouraged.

CHOP compared with CHOP plus granulocyte colony-stimulating factor in elderly patients with aggressive non-Hodgkin's lymphoma.

PURPOSE: To investigate whether the relative dose-intensity of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy could be improved by prophylactic administration of granulocyte colony-stimulating factor (G-CSF) in elderly patients with aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patients aged 65 to 90 years (median, 72 years) with stage II to IV aggressive NHL were randomly assigned to receive standard CHOP every 3 weeks or CHOP plus G-CSF every 3 weeks on days 2 to 11 of each cycle. RESULTS: In 389 eligible patients, the relative dose intensities (RDIs) of cyclophosphamide (median, 96.3% v 93.9%; P =.01) and doxorubicin (median, 95.4% v 93.3%; P =.04) were higher in patients treated with CHOP plus G-CSF. The complete response rates were 55% and 52% for CHOP and CHOP plus G-CSF, respectively (P =.63). The actuarial overall survival at 5 years was 22% with CHOP alone, compared with 24% with CHOP plus G-CSF (P =.76), with a median follow-up of 33 months. Patients treated with CHOP plus G-CSF had an identical incidence of infections, with World Health Organization grade 3 to 4 (34 of 1,191 cycles v 36 of 1,195 cycles). Only the cumulative days with antibiotics were fewer with CHOP plus G-CSF (median, 0 v 6 days; P =.006) than with CHOP alone. The number of hospital admissions and the number of days in hospital were not different. CONCLUSION: In elderly patients, G-CSF improved the RDI of CHOP, but this did not lead to a higher complete response rate or better overall survival. G-CSF did not prevent serious infections.

[CO2-laser decortication: an efficient alternative to radiotherapy in the treatment of T1a carcinomas of the glottis]. / Decorticatie met CO2-laser; een doelmatig alternatief voor radiotherapie in de behandeling van T1a-carcinomen van de glottis.

OBJECTIVE: Given that CO2-laser decortication and radiotherapy are equally effective in the treatment of T1a glottic carcinomas, to determine which of the two is most efficient with respect to treatment costs. DESIGN: Retrospective analysis. METHOD: The costs of both treatment modalities from the first visit to the Free University Medical Centre, Amsterdam, the Netherlands, until two years after the start of the treatment were calculated, based on the medical consumption of 89 patients who were treated with curative intent for a T1a glottic carcinoma in the years 1995-1999. RESULTS: The total costs from diagnosis until two years after the start of treatment were [symbol: see text] 7,253,- for radiotherapy and [symbol: see text] 3,864,- for CO2-laser decortication. These amounts included the costs of diagnosis and treatment of any recurrence or benign laryngeal disorders occurring within the two-year interval. The difference was statistically significant. CONCLUSION: Radiotherapy was significantly more expensive than CO2-laser decortication. Therefore CO2-laser decortication is an efficient alternative to radiotherapy in the treatment of eligible patients with T1a glottic carcinoma.

Cost analysis of CHOP (-like) chemotherapy regimens for patients with newly diagnosed aggressive non-Hodgkin's lymphoma.

Many cost analyses of stem-cell transplantations are available, which is in sharp contrast to the level of cost analyses on first-line chemotherapy for aggressive non-Hodgkin's lymphoma (NHL). Given the scarcity of cost analyses of first-line chemotherapy for NHL, it is difficult to assess the economic impact of upcoming new treatment modalities. Therefore we performed an analysis on costs of diagnosis and treatment of patients with newly diagnosed NHL who were treated with standard CHOP (-like) chemotherapy. As many NHL patients are treated in trials and the economic effects of the trial participation are unknown, our analysis included both patients treated according to trial protocols and patients treated according to standard local practice (SLP). The cost analysis was based on the total medical consumption of the patients. It was found that costs of the trial and SLP groups are within comparable ranges, although costs of diagnostic tests were somewhat higher within the trials. In elderly patients, SLP chemotherapy was discontinued more frequently in case of leucocytopenia or thrombocytopenia. This analysis provides basic information about the costs of first-line standard chemotherapy for patients with newly diagnosed aggressive NHL and the plausible ranges in which these costs may vary. Given the results, we will initiate larger studies to investigate whether trial treatments (showing more or less similar costs as SLP treatments) are more cost-effective for patients with aggressive NHL.

Cost analysis of HLA-identical sibling and voluntary unrelated allogeneic bone marrow and peripheral blood stem cell transplantation in adults with acute myelocytic leukaemia or acute lymphoblastic leukaemia.

Allogeneic stem cell transplantation (SCT) is one of the most expensive medical procedures. However, only a few studies to date have addressed the costs of HLA-identical sibling transplantation and only one study has reported costs of unrelated transplantation. No recent cost analysis with a proper follow-up period and donor identification expenses is available on related or voluntary matched unrelated donor (MUD) SCT for adult AML or ALL. Therefore, we calculated direct medical (hospital) costs based on 97 adults who underwent HLA-identical sibling bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT), and patients who received a graft from a MUD between 1994 and 1999. The average costs per transplanted patient were Euro 98,334 (BMT), Euro 151,754 (MUD), and Euro 98,977 (PBSCT), including donor identification expenses, 2 years follow-up and costs of patients who were not transplanted after they had been planned to receive an allograft. The majority of these costs was generated during the hospitalisation for graft infusion. For MUD transplants, nearly one-third of these costs was spent on the search for a suitable donor. For patients who were alive after 2 years, cumulative expenses were calculated to be Euro 103,509 (BMT), Euro 173,587 (MUD), and Euro 105,906 (PBSCT).

Cost analysis of regular and filgrastim treatment in patients with refractory chronic rhinosinusitis.

In this double blind randomized placebo controlled clinical trial of filgrastim in chronic sinusitus, we analyzed costs of a 24-week interval in which filgrastim was administered. Since we hypothesized that the scheduled preventive visits within the trial might cause savings as compared to the regular situation in which these patients have a strong tendency to visit the outpatient clinic immediately in case of complications, direct medical costs within the trial were also compared to costs of regular treatment. The difference in costs between both trial groups was driven by the filgrastim costs (Euro 5108). If filgrastim costs were left out of consideration, no significant difference in direct medical costs remained between the filgrastim and placebo groups (Euro 2904 and Euro 2765, respectively). Indirect medical costs also showed no significant differences. Within a regular situation, costs of a 24-week interval were Euro 896. As filgrastim treatment had already been shown not to improve the quality of life, its cost-effectiveness in these patients can only be favourable in case of major clinical improvements. Furthermore, scheduled preventive visits in chronic sinusitis patients appear not to cause savings as compared to the situation in which patients are only seen in case of recurrences.

The costs of head and neck oncology: primary tumours, recurrent tumours and long-term follow-up.

We retrospectively calculated the costs of head and neck oncology for reimbursement purposes. This analysis was based on 854 head and neck cancer patients treated between 1994 and 1996 in two major Dutch university hospitals. To anticipate future care costs, costs of required improvements in the quality of care were added. Costs of diagnosis, treatment and 2 years of follow-up of patients with a primary tumour were (euro) 21 858. For patients with a recurrent tumour, this amount was (euro) 27 629. The costs of 10 years of follow-up were (euro) 423 after discounting and correction for survival. In total, average costs per new patient were (euro) 31 829, which covered discounted costs of treating the primary tumour, costs of treating recurrent tumours in 40% of all patients and the costs of 10 years of follow-up. Costs of improving the quality of care were estimated to be (euro) 1598 per new patient.

Quality of life of patients with refractory chronic rhinosinusitis: effects of filgrastim treatment.

In this double-blind placebo-controlled randomized clinical trial, we investigated the influence of filgrastim administration on the quality of life (QOL) of refractory chronic sinusitis patients who did not respond to regular treatments. QOL was considered to be an important outcome measurement because apart from classic sinusitis parameters, it measures the overall burden of the symptomatology of chronic sinusitis patients caused by general malaise, tiredness, and social impediments. The QOL of 56 patients was assessed five times during the 24-week trial with the EuroQol, the Short Form (SF)-36, and the McGill pain questionnaire (MPQ). The QOL scores were all well below population norm scores and scores in a group of patients with chronic sinusitis who had sinus surgery. QOL scores of the filgrastim group suggested a better QOL than the placebo group, although none of the differences were statistically significant. There were indications that it might be possible to determine a subpopulation in which the results are better. Although the QOL measurements were not able to show a significant treatment effect of filgrastim in this group of patients with refractory chronic sinusitis, these measurements are important in studying chronic sinusitis because they enable the comparison of the burden of illness of patients with chronic sinusitis with other patient groups.