Development of a national quality framework for palliative care in a mixed generalist and specialist care model: A whole-sector approach and a modified Delphi technique.

In a predominantly biomedical healthcare model focused on cure, providing optimal, person-centred palliative care is challenging. The general public, patients, and healthcare professionals are often unaware of palliative care's benefits. Poor interdisciplinary teamwork and limited communication combined with a lack of early identification of patients with palliative care needs contribute to sub-optimal palliative care provision. We aimed to develop a national quality framework to improve availability and access to high-quality palliative care in a mixed generalist-specialist palliative care model. We hypothesised that a whole-sector approach and a modified Delphi technique would be suitable to reach this aim. Analogous to the international AGREE guideline criteria and employing a whole-sector approach, an expert panel comprising mandated representatives for patients and their families, various healthcare associations, and health insurers answered the main question: 'What are the elements defining high-quality palliative care in the Netherlands?'. For constructing the quality framework, a bottleneck analysis of palliative care provision and a literature review were conducted. Six core documents were used in a modified Delphi technique to build the framework with the expert panel, while stakeholder organisations were involved and informed in round-table discussions. In the entire process, preparing and building relationships took one year and surveying, convening, discussing content, consulting peers, and obtaining final consent from all stakeholders took 18 months. A quality framework, including a glossary of terms, endorsed by organisations representing patients and their families, general practitioners, elderly care physicians, medical specialists, nurses, social workers, psychologists, spiritual caregivers, and health insurers was developed and annexed with a summary for patients and families. We successfully developed a national consensus-based patient-centred quality framework for high-quality palliative care in a mixed generalist-specialist palliative care model. A whole-sector approach and a modified Delphi technique are feasible structures to achieve this aim. The process we reported may guide other countries in their initiatives to enhance palliative care.

Three cases of hearing impairment with surprising subjective improvements after prayer. What can we say when analyzing them?

AIM: to enhance the understanding of documented mismatches between 'subjective' experiences and 'objective' data in three cases of self-reported instantaneous healing of hearing impairment upon prayer. METHOD: description of three cases taken out of a larger retrospective case-based study of prayer healing in the Netherlands. In this larger study multiple reported healings were investigated using both medical files and patients' narratives through in-depth interviews. A subset of three cases with dramatic subjective reduction of hearing impairment upon prayer was studied. These patients underwent extensive additional investigations at the audiology center of the Amsterdam University Medical Centre. All data was evaluated by an interdisciplinary medical assessment team, subsequent analysis was transdisciplinary. RESULTS: the three case histories with self-reported healing after prayer demonstrated a clear mismatch between subjective experiences and objective findings. No measurable improvements were found in four different audiological testing methods. However, in-depth interviews, hetero-anamnesis and a validated questionnaire all confirmed the healings. The medical assessment team could not label these healings as 'medically remarkable' because of absence of measurable 'objective' changes, but they did consider them as 'remarkable in a broader sense'. On expert consultation no equivalents of mismatches to this extent could be found. The healing experiences of our participants involved their entire being with profound positive effects in different domains of their lives, and a perception of a benevolent God who acted upon them. There was a distinctive pattern, labelled by the participants as a healing of mind, soul and body. CONCLUSIONS: The subjective-objective incongruities that were found were not well understood. We noticed a paradox: the 'objective' measurements did not reflect hearing abilities in daily life where-as 'subjective experiential' data did. The latter could be 'objectified' and validated in various ways. In fact, a rigid distinction between 'objective' and 'subjective' was not relevant here, nor a hierarchy among them. A model leaving room for different causations (horizontal epistemology) complied best with the multi dimensionality we came across.

Cost-effectiveness of Novel Treatment Sequences for Transplant-Ineligible Patients With Multiple Myeloma.

Importance: Although the number of treatments for elderly patients with non-transplant-eligible (NTE) multiple myeloma (MM) has increased substantially, evidence is lacking on the clinical effectiveness and cost-effectiveness of novel treatment sequences. Objective: To determine the optimal sequence of treatment for patients with NTE MM from the perspective of the patient, physician, and society. Design, Setting, and Participants: Using data from a Dutch observational registry, this economic evaluation combined evidence from network meta-analyses in a patient-level simulation model and modeled time-to-event and types of events from a hospital perspective with a lifetime horizon. Data analysis was performed from June 2019 to September 2020. Interventions: Thirty treatment sequences, including up to 3 lines of therapy, were compared with bortezomib-melphalan-prednisone (VMP)-lenalidomide-dexamethasone (LenDex)-pomalidomide-dexamethasone (PomDex). Main Outcomes and Measures: The primary outcomes of the model were overall survival (OS), quality-adjusted life-years (QALYs), costs, and cost-effectiveness. Results: Sequences starting with daratumumab-VMP (second line: carfilzomib-lenalidomide-dexamethasone or elotuzumab-lenalidomide-dexamethasone) or bortezomib-melphalan-prednisone-thalidomide-maintenance bortezomib-thalidomide (VMPT-VT) (second line: daratumumab-lenalidomide-dexamethasone) had the largest expected OS (7.5 years), which is 3.5 additional life-years compared with VMP-LenDex-PomDex. Total costs per patient for these sequences ranged between $786 024 and $1 085 794. The sequence VMPT-VT-carfilzomib-lenalidomide-dexamethasone-panobinostat-bortezomib-dexamethasone had the most favorable cost-effectiveness ratio ($98 585 per life-year gained and $132 707 per QALY gained vs VMP-LenDex-PomDex). Conclusions and Relevance: These findings suggest that sequences including novel treatments were highly effective, but the cost-effectiveness ratios were above currently accepted willingness-to-pay thresholds. Treating MM with novel agents necessitates either a large increase in budget or a substantial reduction of drug costs by price negotiations, and these findings can support these reimbursement decisions and price negotiations.

[Fewer cancer diagnoses during the COVID-19 epidemic according to diagnosis, age and region]. / Onderdiagnostiek bij kanker door de COVID-19-crisis naar diagnose, leeftijd en provincie: Een cruciale rol voor eerstelijnszorgverleners.

The COVID-19 crisis and the intelligent lockdown have led to a situation in which the Dutch health care system was locked for months for non-COVID-19 patients. Patients did not dare to go to their general practitioner, general practitioners were reticent about hospital referrals, and diagnostic and treatment trajectories were delayed or adapted. This also concerned cancer patients. The severity of the underdiagnosis for these patients mainly depends on their prognosis. In this study, we evaluated the magnitude of underdiagnosis using data from the Netherlands Cancer Registry and the Dutch registry of histo- and cytopathology (PALGA). From the week of the first COVID-19 diagnosis in the Netherlands, a decrease of 20-40% in the number of cancer diagnosis was noticed. This decrease was observed in nearly all cancer types, including cancers such as lung cancer (average 23%), head-neck cancer (average 36%) and hematology (average 26%), for which a missed or delayed diagnosis can be life threatening. Therefore, we want more attention for the observed underdiagnosis and the role of the primary care givers, including the general practitioner and dentist. Furthermore, it is of crucial importance that patients with symptoms or complaints feel no hesitation to visit their caregivers.

A population-based study on different regimens of R-CHOP in patients with newly diagnosed DLBCL in The Netherlands.

Randomized controlled trials have studied different dose-intensity and dose-interval regimens of R-CHOP for patients with diffuse large B-cell lymphoma (DLBCL). This study was undertaken to confirm these results in a population-based setting, with special emphasis on the value of 6xR-CHOP21 among patients aged 18-64 years. Two thousand three hundred and thirty-eight stage II-IV DLBCL patients, ≥18 years, we confirmed the similar efficacy of six versus eight cycles of R-CHOP and of R-CHOP21 versus R-CHOP14 regimens across all age groups on overall survival (median follow-up 36.4 (1.3-167.6) months). Nevertheless, overall survival decreased with older age. Interestingly, in patients 18-64 years, the adjusted risk of mortality among recipients of 6xR-CHOP21 compared to other R-CHOP regimens seems to be similar (HR 0.62; 95%CI: 0.38-1.02; p= .059). Although this finding might suggest that 6xR-CHOP21 could be considered as first-line regimen for all stage II-IV DLBCL patients, it should be confirmed in forthcoming population-based studies with larger patient numbers and longitudinal follow-up.

A conditional model predicting the 10-year annual extra mortality risk compared to the general population: a large population-based study in Dutch breast cancer patients.

OBJECTIVE: Many cancer survivors are facing difficulties in getting a life insurance; raised premiums and declinatures are common. We generated a prediction model estimating the conditional extra mortality risk of breast cancer patients in the Netherlands. This model can be used by life insurers to accurately estimate the additional risk of an individual patient, conditional on the years survived. METHODOLOGY: All women diagnosed with stage I-III breast cancer in 2005-2006, treated with surgery, were selected from the Netherlands Cancer Registry. For all stages separately, multivariable logistic regression was used to estimate annual mortality risks, conditional on the years survived, until 10 years after diagnosis, resulting in 30 models. The conditional extra mortality risk was calculated by subtracting mortality rates of the general Dutch population from the patient mortality rates, matched by age, gender and year. The final model was internally and externally validated, and tested by life insurers. RESULTS: We included 23,234 patients: 10,101 stage I, 9,868 stage II and 3,265 stage III. The final models included age, tumor stage, nodal stage, lateralization, location within the breast, grade, multifocality, hormonal receptor status, HER2 status, type of surgery, axillary lymph node dissection, radiotherapy, (neo)adjuvant systemic therapy and targeted therapy. All models showed good calibration and discrimination. Testing of the model by life insurers showed that insurability using the newly-developed model increased with 13%, ranging from 0%-24% among subgroups. CONCLUSION: The final model provides accurate conditional extra mortality risks of breast cancer patients, which can be used by life insurers to make more reliable calculations. The model is expected to increase breast cancer patients' insurability and transparency among life insurers.

Psychosocial challenges and health-related quality of life of adolescents and young adults with hematologic malignancies.

Adolescents and young adults (AYAs) occupy a unique place within the hematologic malignancy community due to the challenges they face related to their disease biology and physical, psychosocial, and economic circumstances, as well as issues related to access to care and long-term follow-up. Efforts to define age-specific (supportive) care needs and targets for intervention in these areas are evolving. This review discusses the psychosocial issues AYAs with hematologic malignancies are dealing with, how these might affect their health-related quality of life, and the challenges in delivering high-quality supportive care to this underserved population.

MDS classification is improving in an era of the WHO 2016 criteria of MDS: A population-based analysis among 9159 MDS patients diagnosed in the Netherlands.

BACKGROUND: Morphologic and cytogenetic assessments are required to characterize diagnostic and prognostic features of myelodysplastic syndromes (MDS). We assessed whether these assessments were performed among newly diagnosed MDS patients in the Netherlands. METHODS: MDS cases were retrieved from the nationwide Netherlands Cancer Registry (N=9159; period 2001-2014) and the regional PHAROS MDS registry (N=676; period 2008-2011). RESULTS: The proportion of unclassified MDS decreased from 58% in 2001 to 13% in 2014. Data from the more detailed PHAROS registry revealed that the degree of bone marrow dysplasia was only reported in ∼30% of all evaluable bone marrow aspirates. Further, the International Prognostic Scoring System was undetermined in 55% of patients, primarily owing to unperformed cytogenetics in 46% of patients. CONCLUSION: The classification of MDS is improving in the Netherlands. Nevertheless, particular diagnostic and prognostic procedures that are essential for the diagnosis and subsequent treatment decision-making of MDS were not fully utilized in particular patient subsets.

Utilization of supportive care by survivors of colorectal cancer: results from the PROFILES registry.

PURPOSE: In an equitable healthcare system, healthcare utilization should be predominantly explained by patient-perceived need and clinical need factors. This study aims to analyze whether predisposing, enabling, and need factors are associated with the utilization of supportive care (i.e., dietary care, oncological nursing care, physical therapy, psychological care, or participation in a rehabilitation program consisting of an exercise component and a psycho-educational component) among survivors of colorectal cancer in the Netherlands. METHODS: Cross-sectional data of 3957 survivors of colorectal cancer (1-11 years after diagnosis) were used. Clinical data from the Eindhoven Cancer Registry were linked to questionnaire data from the PROFILES registry. Regression analyses were used to examine which predisposing, enabling, and need factors were associated with self-reported utilization of supportive care. RESULTS: Utilization of supportive care was primarily associated with younger age, patient-perceived need (i.e., lower physical health, anxious mood, depressive mood, and fatigue), and clinical need (i.e., tumor stage, radiotherapy, chemotherapy, comorbidity, having a stoma and lower BMI) factors. CONCLUSIONS: In the Netherlands, utilization of supportive care by survivors of colorectal cancer is primarily associated with younger age, patient-perceived need, and clinical need factors. Apart from the association with younger age, the utilization of supportive care services seems to be quite equitable. Further research is needed to determine whether there is indeed inequity in the provision of supportive care to older survivors, or whether older survivors are less in need of supportive care.

A cost-effectiveness analysis of real-world treatment for elderly patients with multiple myeloma using a full disease model.

OBJECTIVES: To study the impact of novel treatments for elderly (≥66 yr) patients with multiple myeloma (MM) in daily practice by comparing real-world effects [overall survival (OS) and quality-adjusted life years (QALYs)] and costs over time. Also, we calculate cost-effectiveness of treatment sequences commonly prescribed to predict effects and costs if patients had received a different treatment sequence. METHODS: Real-world data including patient and disease characteristics, treatment information and resource use were collected from 1054 elderly patients with MM. Patients received first-line treatment during 2004-2007 (cohort 1) and 2008-2013 (cohort 2). The two cohorts were compared using a patient-level simulation (PLS) model comprising regression models which used patient and disease characteristics to estimate time to next treatment and death. Effects and costs from cohort 2 were compared to 4 commonly prescribed real-world sequences. RESULTS: Utilisation of novel agents was higher for cohort 2 compared to cohort 1. Modelled average OS for cohort 1 was 38 months (median 25) and total costs €44,200. OS for cohort 2 was 42 months (median 28) and total costs €69,017. The model identified potential OS gains if all patients were to be treated using combinations containing thalidomide, lenalidomide and bortezomib in that particular order. This sequence had, compared to real-world treatment, the most favourable incremental cost-effectiveness ratio, €24,618 per life year gained and €34,875 per QALY. CONCLUSIONS: Our patient-level model enabled to study the effects and costs of entire treatment sequences and to compare real-world treatment patterns over time. Increased utilisation of novel agents improved survival and increased costs for real-world patients with MM in the Netherlands.

Trends in incidence, treatment and survival of aggressive B-cell lymphoma in the Netherlands 1989-2010.

Only a small number of patients with aggressive B-cell lymphoma take part in clinical trials, and elderly patients in particular are under-represented. Therefore, we studied data of the population-based nationwide Netherlands Cancer Registry to determine trends in incidence, treatment and survival in an unselected patient population. We included all patients aged 15 years and older with newly diagnosed diffuse large B-cell lymphoma or Burkitt lymphoma in the period 1989-2010 and mantle cell lymphoma in the period 2001-2010, with follow up until February 2013. We examined incidence, first-line treatment and survival. We calculated annual percentage of change in incidence and carried out relative survival analyses. Incidence remained stable for diffuse large B-cell lymphoma (n=23,527), while for mantle cell lymphoma (n=1,634) and Burkitt lymphoma (n=724) incidence increased for men and remained stable for women. No increase in survival for patients with aggressive B-cell lymphoma was observed during the period 1989-1993 and the period 1994-1998 [5-year relative survival 42% (95%CI: 39%-45%) and 41% (38%-44%), respectively], but increased to 46% (43%-48%) in the period 1999-2004 and to 58% (56%-61%) in the period 2005-2010. The increase in survival was most prominent in patients under 65 years of age, while there was a smaller increase in patients over 75 years of age. However, when untreated patients were excluded, patients over 75 years of age had a similar increase in survival to younger patients. In the Netherlands, survival for patients with aggressive B-cell lymphoma increased over time, particularly in younger patients, but also in elderly patients when treatment had been initiated. The improvement in survival coincided with the introduction of rituximab therapy and stem cell transplantation into clinical practice.

The use of medical claims to assess incidence, diagnostic procedures and initial treatment of myelodysplastic syndromes and chronic myelomonocytic leukemia in the Netherlands.

Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) may be underreported in cancer registries such as the Netherlands Cancer Registry (NCR). Analysis of Dutch medical claims can complement NCR data on MDS and CMML. We analyzed data on 3681 MDS patients and 235 CMML patients aged ≥18 years with initial claims for MDS or CMML from the Dutch nationwide medical claims-based Diagnosis Treatment Combination Information System (DIS) between 2008 and 2010. Clinical information was available in the DIS. MDS and CMML were diagnosed without a bone marrow (BM) examination in almost half of the patients. The age-standardized incidence rate (ASR) per 100,000 in the cohort that underwent BM examinations compared with NCR data was 2.8 vs. 3.3 for MDS and 0.2 vs. 0.4 for CMML in 2008-2010. A conservative treatment approach was associated with increasing age and absence of BM examination in MDS (p<0.001 for both) and CMML patients (p<0.033 for both). In conclusion, the ASR of MDS in the cohort that underwent BM examinations was comparable with the NCR. The majority of elderly patients, either with or without BM examinations, received no therapy. Together, MDS and CMML may be misdiagnosed and inappropriately managed without a BM confirmation.

Perceived need for information among patients with a haematological malignancy: associations with information satisfaction and treatment decision-making preferences.

For patients with haematological malignancies, information on disease, prognosis, treatment and impact on quality of life is of the utmost importance. To gain insight into the perceived need for information in relation to sociodemographic and clinical parameters, comorbidity, quality of life (QoL) and information satisfaction, we compiled a questionnaire based on existing validated questionnaires. A total of 458 patients diagnosed with a haematological malignancy participated. The perceived need for information was moderate to high (40-70%). Multivariate regression analyses showed that a higher need for information was related to younger age, worse QoL, being member of a patient society and moderate comorbidity. The need for disease and treatment-related information was higher than the need for psychosocial information. A higher need for disease and treatment-related information was associated to being diagnosed with multiple myeloma. A higher need for psychosocial information was related to a lower educational level. The information provision could be improved according to 41% of the patients. Higher satisfaction with provided information was associated with better QoL. Most patients (62%) reported that they wanted to be fully informed about their illness and actively involved in treatment decision-making. The results contribute to improving patient-tailored information provision and shared decision-making in clinical practice.

Perceived need for information of patients with haematological malignancies: a literature review.

AIMS AND OBJECTIVES: To provide insight into the perceived need for information of patients with haematological malignancies. BACKGROUND: Providing timely and accurate information to patients diagnosed with a haematological malignancy is a challenge in clinical practice; treatment often has to start promptly, with little time to inform patients. DESIGN: Literature review. METHODS: A comprehensive literature search was conducted from all available literature to May 2013 in the databases: Cumulative Index to Nursing and Allied Health Literature, PsycINFO and PubMed (Medline). Relevant studies were reviewed regarding the perceived need for information on various topics, sources of information and satisfaction with information provided. RESULTS: The initial search revealed 215 articles, fourteen of which were relevant. Patients need basic information on the disease (diagnosis and diagnostics), treatment (various treatment options, side effects and duration), prognosis (curability and prolonging life) and all other topics (recovery, self-care and psychosocial functioning). Need for detailed information varied between studies. Patients expressed a higher need for medical than for psychosocial information. Patients preferred to receive information from their doctors the most, followed by nurses. Most studies described patients' satisfaction with the information provided. CONCLUSION: Based on the limited number of data available, medical information is for patients of higher priority compared to psychosocial information. Patients need basic information on diagnosis, treatment, prognosis and all other topics. Need for detailed information varied between studies. Patients were satisfied with the provided information, preferably offered by doctors and nurses. RELEVANCE TO CLINICAL PRACTICE: The perceived need for information and satisfaction with the information provided differs strongly between patients. In clinical practice, more attention is needed for information tailored to the patient, taking into account important moderating factors such as age, type of cancer, time since diagnosis, treatment modality and coping style.

Experience with outcomes research into the real-world effectiveness of novel therapies in Dutch daily practice from the context of conditional reimbursement.

Policymakers more often request outcomes research for expensive therapies to help resolve uncertainty of their health benefits and budget impact at reimbursement. Given the limitations of observational data, we assessed its usefulness in evaluating clinical outcomes for bortezomib in advanced multiple myeloma patients. Data were retrospectively collected from patients included in the pivotal Assessment of Proteasome Inhibition for Extending Remissions trial (APEX; n=333) and two groups of daily practice patients treated with bortezomib following progression from upfront therapy (n=201): real-world patients treated as of May 2009 (RW-1; n=72) and June 2012 (RW-2; n=129). Prognosis, treatment, and effectiveness were compared. Outcomes research was useful for policymakers for addressing to whom and how bortezomib was administered in daily practice. It was limited however in generating robust evidence on real-world safety and effectiveness. The quality of real-world evidence on effectiveness was low due to missing data in patient charts, existing treatment variation and the dynamics in care during the novel drug's initial market uptake period. Policymakers requesting real-world evidence on clinical outcomes for reimbursement decisions should be aware of these limitations and advised to carefully consider beforehand the type of evidence that best addresses their needs for the re-assessment phase.

Cognitive coping style (monitoring and blunting) and the need for information, information satisfaction and shared decision making among patients with haematological malignancies.

OBJECTIVE: A haematological malignancy is a serious, life-altering disease and may be characterised as an uncontrollable and unpredictable stress situation. In dealing with potentially threatening information, individuals generally utilise two main cognitive coping styles: monitoring (the tendency to seek threat-relevant information) and blunting (avoiding threatening information and seeking distraction). The aim of this study was to obtain insight into the association between cognitive coping style and (a) need for information, (b) satisfaction with information, (c) involvement in decision making, and (d) quality of life (QoL). METHODS: In this cross-sectional study, coping style was assessed among adult patients diagnosed with a haematological malignancy, using an adapted version of the Threatening Medical Situations Inventory. Information need, information satisfaction, decision-making preference and QoL were measured with validated questionnaires. RESULTS: In total, 458 patients returned the questionnaire (66%). A monitoring coping style was positively related to need for both general and specific information. Blunting was positively and QoL was negatively related to need for information. Monitoring was positively related to involvement in decision-making and negatively to information satisfaction. Using multivariate analysis, this relation between monitoring and information satisfaction disappeared, and for blunting, we found a negatively significant relation. QoL was not related to coping style. CONCLUSIONS: Among patients with haematological malignancies, coping style is related to a need for information, information satisfaction, and involvement in treatment decision-making. Therefore, it is important for health care professionals to be aware of individual differences in cognitive coping style.

Health-related quality of life and persistent symptoms in relation to (R-)CHOP14, (R-)CHOP21, and other therapies among patients with diffuse large B-cell lymphoma: results of the population-based PHAROS-registry.

The increasing number of longer-living patients with diffuse large B-cell lymphoma (DLBCL) and serious side effects of treatment urged us to study the health-related quality of life (HRQoL) and persistent (treatment-related) symptoms in unselected patients after different treatment modalities and compare HRQoL of patients with a normative population. The population-based Eindhoven Cancer Registry was used to select all patients diagnosed with DLBCL from 2004 to 2010. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) was completed twice, with a 1-year interval. Detailed data on treatment were extracted from the Population-based HAematological Registry for Observational Studies. Two hundred fifty-six patients responded (84 %, T1). Compared to patients treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days ((R-)CHOP21), those who underwent (R-)CHOP14 more often reported tingling in the hands and feet (27 vs 42 %, p = 0.02) and fatigue (35 vs 46 %, p = 0.03) and reported a lower global health status/HRQoL. Mean HRQoL was statistically and clinically relevantly lower among DLBCL patients compared to a normative population (p < 0.01). Persistent tingling in hands/feet was reported more often by older patients and patients treated with (R-)CHOP14 independently of the other characteristics. Furthermore, patients who reported symptoms exhibited significantly lower HRQoL compared to patients without symptoms/worries. Patients treated with (R-)CHOP14 reported more neuropathic symptoms, more fatigue, and a lower HRQoL than patients treated with (R-)CHOP21. Alertness for persistent symptoms that occur during and after treatment of DLBCL patients is needed and may help to avoid lasting negative influence on their HRQoL.

Policymaker, please consider your needs carefully: does outcomes research in relapsed or refractory multiple myeloma reduce policymaker uncertainty regarding value for money of bortezomib?

INTRODUCTION: Dutch policy regulations require outcomes research for the assessment of appropriate drug use and cost-effectiveness after 4 years of temporary reimbursement. We investigated whether outcomes research reduced policymaker uncertainty regarding the question whether the costs are worth public funding. METHODS: Our cohort study included 139 patients with relapsed/refractory multiple myeloma who were treated outside of a clinical study; 72 received bortezomib and 67 did not receive bortezomib. Detailed data were retrospectively collected from medical records in 38% of Dutch hospitals. RESULTS: All patients received second-line treatment; 65%, 40%, and 14%, received three, four, or five or more lines of therapy. Neither a specific treatment sequence nor an appropriate comparator could be identified because of large variation in regimes. Kaplan-Meier curves showed an increased overall survival (mean [median] 29.5 [33.2] vs. 28.0 [21.6] months) for patients treated with bortezomib (Wilcoxon P = 0.01). Total mean costs were €81,626 (range €17,793-€229,783) and €52,760 (range €748-€179,571) for patients receiving bortezomib and patients not receiving bortezomib, respectively. Patients treated with bortezomib, however, were not comparable to other patients despite attempts to correct for confounding. Therefore, it was impossible to develop a feasible model to obtain a valid incremental cost-effectiveness estimate. CONCLUSIONS: It was possible to develop evidence on bortezomib's use, effects, and costs in everyday practice. Much uncertainty, however, remained regarding its cost-effectiveness. Policymakers should carefully consider whether outcomes research sufficiently decreases uncertainty or whether other options (e.g., finance- and/or outcomes-based risk-sharing arrangements) are more appropriate to ensure sufficient value for money of expensive drugs.

Trends in incidence, initial treatment and survival of myelodysplastic syndromes: a population-based study of 5144 patients diagnosed in the Netherlands from 2001 to 2010.

BACKGROUND: Studies with long-term follow-up of patients with myelodysplastic syndromes (MDS) based on data from nationwide population-based cancer registries are lacking. We conducted a nationwide population-based study to assess trends in incidence, initial treatment and survival in MDS patients diagnosed in the Netherlands from 2001 to 2010. METHODS: We identified 5144 MDS patients (median age, 74 years) from the Netherlands Cancer Registry (NCR). The NCR only includes MDS cases that were confirmed by bone marrow examinations. Information regarding initial treatment decisions was available in the NCR. RESULTS: The age-standardised incidence rate of MDS was 2.3/100,000 in 2001-2005 and 2.8/100,000 in 2006-2010. The incidence increased with older age, with the highest incidence among those aged ≥80 years (32.1/100,000 in 2006-2010). Forty-nine percent of all MDS cases were unspecified. Of all patients, 89% receive no treatment or only supportive care and 8% were started on intensive therapy as initial treatment. Survival did not improve over time. The 5-year relative survival was 53%, 58%, 48%, 38% and 18% in patients with refractory anaemia (RA), RA with ringed sideroblasts, 5q-syndrome, refractory cytopenia with multilineage dysplasia, and RA with excess blasts, respectively. CONCLUSION: The incidence of MDS increased over time due to improved notification and better disease awareness, and has stabilised since 2007. The classification of MDS seems challenging as almost half of the pathologically confirmed cases were unspecified. The lack of improvement in survival might be explained by the limited availability of therapeutic agents. Therefore, ameliorated management and new treatment options are warranted.