Dutch Healthcare Insurance Research Articles

How to measure effects of integrated primary care?

Project description: The project “Added value of Integrated Primary Health Care” aims to study the association between integrated primary health care and quality and costs of health care. It is assumed that integrated primary care is related to more cost-effective care. Empirical evidence for such relationships is scarce up till now because instruments to measure these components are missing. The main aim of this project is to develop an instrument to measure “integration of care” and to relate this to quality of the provided care and the health care costs generated in these practices by patients. In the first stage of the project, instruments to measure the level of integration, the quality, and the costs of health care were developed. In a pilot study, it was tested whether different types of data could be linked on an individual level. In this contribution we present the early progress of the project. Methods: Questionnaires to measure integrated primary care were developed based on literature research and a Delphi method with expert interviews. Indicators for quality of care can be measured by using data from GP’s Electronic Patient Records and with questionnaires among the three most prevalent providers in primary health care (GPs, physical therapists, pharmacists). At the information center Vektis, we have access to health claims data on patient level from all Dutch health care insurance companies. These data include curative and care costs for the whole GP 14th International Conference on Integrated Care, Brussels, April 2-4 2014 International Journal of Integrated Care – Volume 14, 01 October – URN:NBN:NL:UI:10-1-116149– http://www.ijic.org/ population and information about which hospital the patients went to. In a pilot study, curative and care costs of the patient population of 5 GP practices were linked to survey data of over 500 patients by using a Trusted-Third-Party as linking partner. Innovation: The project “Added value of Integrated Primary Health Care” includes a number of innovative elements. First, the development of an integrated care instrument is a novelty. We hope to inspire other researchers to collaborate with us on further improvements of this instrument. We developed measures of quality of care from mono-centered to integrated care. The use of health claims data is still new in health services research and very promising. Next, it was shown that linking data on patient level is possible which is very important for answering the final research question whether integrated primary care produces cost-effective care.

The cost-utility of left ventricular assist devices for end-stage heart failure patients ineligible for cardiac transplantation: a systematic review and critical appraisal of economic evaluations.

A health technology assessment (HTA) of left ventricular assist devices (LVADs) as destination therapy in patients with end-stage heart failure was commissioned by the Dutch Health Care Insurance Board [College voor Zorgverzekeringen (CVZ)]. In this context, a systematic review of the economic literature was performed to assess the procedure's value for money. A systematic search (updated in December 2013) for economic evaluations was performed by consulting various databases: the HTA database produced by the Centre for Reviews and Dissemination (CRD HTA), websites of HTA institutes, CRD's National Health Service Economic Evaluation Database (NHS EED), Medline (OVID) and EMBASE. No time or language restrictions were imposed and pre-defined selection criteria were used. The two-step selection procedure was performed by two people. References of the selected studies were checked for additional relevant citations. Six relevant studies were selected. Four economic evaluations relied on the results of the REMATCH trial to compare a pulsatile-flow LVAD with optimal medical therapy (OMT). These evaluations were performed before the publication of the HeartMate II (HM-II) Destination Therapy Trial which compared a pulsatile-flow with a continuous-flow LVAD. Two more recent economic evaluations combined the results of both trials to make an indirect comparison of a continuous-flow LVAD with OMT. In all studies, the largest part of the incremental cost was due to the reimplantation cost of an LVAD, with a device cost of €58,000-€75,000 and about €55,000 for the surgical procedure. The survival gain was highest with a continuous-flow LVAD, up to about three life-years gained (LYG) versus OMT in the most optimistic study. Quality of life (QoL) was improved but measures with a generic utility instrument were lacking, making estimates on quality-adjusted life-years (QALYs) gained more uncertain. Incremental cost-effectiveness ratios of the two most recent studies were on average €107,600 and $198,184 (ca.€145,800) per QALY gained. Although LVAD destination therapy improves survival and QoL, it remains questionable as to whether it offers value for money. This conclusion may alter if the price of the device/procedure decreases sufficiently, in combination with further improved outcomes for mortality, adverse events and QoL.

Adopting Health Apps, What’s Hindering Doctors and Patients?

There are high expectations for Mobile Health to transform health into a sustainable and prevention-based system. Unfortunately it has not reached its scale of adoption many had hoped for, due to the existence of adoption barriers. More insight into these barriers fosters adoption of mHealth and the innovation it can bring to worldwide healthcare. This study investigates the main barriers in the adoption of mHealth, their underlying causes and their breakthrough possibilities. All the data are gathered from an international and multi-stakeholder point of view. First of all we tried to identify the main barriers by doing an international literature study. Second of all we asked Dutch mHealth Key Opinion Leaders (KOLs) to rank the barriers to importance. These KOLs were from different stakeholder groups; policy-makers, users and developers. At last we asked the KOLs in interviews for underlying causes and breakthrough opportunities of the barriers. Eventually twelve main adoption barriers emerged. According to literature and to the KOLs the most important barriers are “Integration and interoperability” and “Business case”. An underlying cause for the barrier “Integration and interoperability” might be the active closed power system of technology suppliers, which exists in the Netherlands. Furthermore there seems to be a difference in the importance of the barriers “Privacy and security” and “Conservative culture” when perceptions of Dutch KOLS and international literature are compared. Within the stakeholders-groups, the KOLs think differently about the importance of the barriers “Visionless development” and “Competing payment mechanism”. The Dutch healthcare insurers could take a more leading role in the fragmented landscape of mHealth in the Netherlands, by strategically funding new initiatives that use open standards and deliver better value for end-users. Other chances might lie in the international cooperation between countries to overcome certain barriers.

Are the Dutch long-term care organizations getting better? A trend study of quality indicators between 2007 and 2009 and the patterns of regional influences on performance

and setting The Dutch long-term care organizations, providing somatic care, psycho-geriatric care and home care, have to measure the quality of care through client-related and professional indicators since 2007. At the same time, competition was introduced with regional stimuli from healthcare insurers. The first aim of this study is to determine the trends of the national performance on client-related and professional quality indicators for the period 2007-09 in long-term care organizations in the Netherlands. The second aim is to determine the influence of the region on the quality performance in 2009. We performed trend analyses on the indicators of clients of 2115 long-term care organizations. We used multivariate analyses to determine the difference in national performance between 2007 and 2009 and to calculate the influence of the region on the performance of 2009. None. Client-related and professional indicators. The national performance on client-related indicators for somatic care and home care increased and for psycho-geriatric care the quality performance became worse. The professional indicators for intramural care improved between 2007 and 2009. Region influences the performance. In general, organizations in the west of the Netherlands performed worse than other regions (with exception of home care). The study suggests that working with quality indicators in long-term care organizations for older people may lead to a better performance on several indicators. The influence of the region on the quality is significant, which could be caused by Dutch healthcare insurers.

Interview: European collaboration in relative effectiveness assessment: the use of patient registries and development of common guidelines

Wim Goettsch is currently the Project Leader of Work Package 5 of the European Network of Health Technology Assessment (EUnetHTA) Joint Action 2 (2012-2015). EUnetHTA is a network of the health technology assessment organizations in Europe responsible for advising or deciding on the national reimbursement of pharmaceuticals and other health technologies. In this work package, rapid joint assessments of the relative effectiveness of pharmaceuticals are piloted between more than 25 health technology assessment organizations around Europe. These pilots are based on the methodology that was developed in a similar work package in EUnetHTA JA1 (2010-2012), of which Dr Goettsch was also the Project Leader. Until the beginning of 2013, Dr Goettsch was the Deputy Secretary of the Medicinal Products Reimbursement Committee at Dutch Healthcare Insurance Board (CVZ). The Dutch Medicinal Products Reimbursement Committee advises the Dutch Minister of Health on whether new drugs need to be included in the basic insurance package. Before joining CVZ, he worked as a research manager for the PHARMO Institute (Utrecht, The Netherlands) and was responsible for the coordination of numerous pharmacoepidemiological and outcomes studies for international offices of pharmaceutical companies, such as AstraZeneca, Novartis, Pfizer and GlaxoSmithKline. Dr Goettsch has approximately 50 publications in peer-reviewed international journals.

“Sharing is caring”

PurposeThe effects of corporate social responsibility (CSR) communication on external stakeholders' perceptions and behaviours have been studied extensively; however, researchers have largely overlooked the effects of CSR communication on internal stakeholders. This study seeks to propose that, by enhancing employee awareness of the organisation's CSR activities (aimed at society, the government, customers, and employees), organisational communication can increase affective commitment.Design/methodology/approachData were collected at a Dutch healthcare insurance company, using a web‐based questionnaire (n=301). The proposed model was tested with structural equation modelling (SEM) using Amos.FindingsThe bootstrapping results showed a positive association between information flow and affective commitment, with a mediating effect for CSR aimed at employees and customers. CSR projects aimed at the government and society at large did not mediate the relationship between information flow and affective commitment.Originality/valueThe impact of CSR towards employees and customers can be explained by social exchange theory. When employees feel that their organisation values their well‐being and that of their customers, they reciprocate what they receive from the organisation by committing themselves to the organisation. As such, this study provides an important argument for the implementation of CSR activities: it increases the emotional attachment of employees towards their organisation.

Cost-Effectiveness Assessment of Orphan Drugs

In September 2012, the Dutch Healthcare Insurance Board issued advice not to reimburse orphan drugs that target lysosomal storage disorders: agalsidase alfa and agalsidase beta for Fabry disease and alglucosidase alfa for Pompe disease [1, 2].With respect to the former, the Healthcare Insurance Board concluded that enzyme replacement therapy offered an added therapeutic value compared with symptomatic treatment of Fabry disease [1]. However, enzyme replacement therapy was not cost effective at an incremental cost of euro3.3 million per quality-adjusted life-year gained. The unfavourable cost effectiveness originated from the limited additional therapeutic value (as a result of the slow progression of the disease) and high costs: enzyme replacement therapy costs euro200,000 per patient per year, resulting in a total budget impact of euro11 million per year for the Netherlands. The Healthcare Insurance Board argued that continued reimbursement of enzyme replacement therapy for Fabry disease would imply that limited resources are not available to reimburse other, more cost effective health technologies.With respect to the latter, the Healthcare Insurance Board recommended to restrict reimbursement of alglucosidase alfa for Pompe disease to patients who suffer from the classic form of the disease and to patients who show symptoms of the (non-)classic disease during their infancy [2]. Alglucosidase alfa was found to generate an added therapeutic value over best supportive care, was cost effective at an incremental cost of euro0.3-0.9 million per quality-adjusted life-year gained in the classic form of Pompe disease, but was not cost effective at an incremental cost of euro15 million per quality-adjusted life-year gained in the non-classic form of Pompe disease. The annual cost of treating a patient with alglucosidase alfa amounted to euro0.4-0.7 million.1 A Scientific ConundrumThese two examples highlight some of the scientific challenges involved in assessing the cost effectiveness of orphan drugs.Uncertainty tends to surround the safety and effectiveness of orphan drugs at the time of market launch. This clinical uncertainty may result from difficulties involved in recruiting a sufficient number of patients across countries, the lack of randomized controlled trials, and the use of surrogate efficacy measures [3]. As a result, there is an urgent need for the development of methodological guidelines about the assessment of the (cost) effectiveness of orphan drugs for (ultra-)rare diseases. In England and Wales, the National Institute for Health and Clinical Excellence (NICE) will be responsible for assessing orphan drugs from April 2013 onwards and has committed itself to developing methods to guide such an assessment [4].Dutch physicians who are involved in treating patients with these lysosomal storage disorders have argued that the Healthcare Insurance Board is not able to issue an informed advice due to the lack of long-term data on safety and effectiveness [5]. For instance, on the occasion of the public hearing of the Dutch Healthcare Insurance Board on 21 September 2012, Professor Hollak stressed that the main challenge with enzyme replacement therapy is that effectiveness is different across patient subgroups [6]. While a clear benefit was shown in some patients, in others, such as those with end-renal or cardiac disease, a lesser benefit was observed. No conclusions can nonetheless be drawn as the overall amount of data remains too small, resulting from the low number of Dutch patients. To address this issue, the idea has been proposed to launch a compulsory Europeanwide registry following marketing authorization of an orphan drug [5]. The establishment of such registries for rare diseases is supported by the European Medicines Agency and by many member states, although registries are not without methodological limitations [3].The ethical principle underlying economic evaluation is that scarce resources are allocated to the most cost-effective health technologies with a view to maximizing population health. …

Methodological Quality of Economic Evaluations of New Pharmaceuticals in the Netherlands

In the Netherlands, decisions about the reimbursement of new pharmaceuticals are based on cost effectiveness, as well as therapeutic value and budget impact. Since 1 January 2005, drug manufacturers are formally required to substantiate the cost effectiveness of drugs that have therapeutic added value in comparison with existing ones through pharmacoeconomic evaluations. Dutch guidelines for pharmacoeconomic research provide methods guidance, ensuring consistency in both the evidence and the decision-making process about drug reimbursement. This study reviewed the methodological quality of all 21 formally required pharmacoeconomic evaluations of new pharmaceuticals between 1 January 2005 and 1 October 2008, and verified whether these evaluations complied with pharmacoeconomic guidelines. Data on the quality of the pharmacoeconomic evaluations were extracted from the pharmacoeconomic reports published by the Dutch Health Care Insurance Board (CVZ). The Board's newsletters provided information on the advice to, and reimbursement decisions made by, the Dutch Minister of Health. All data extraction was carried out by two independent reviewers, and descriptive analyses were conducted. The methodological quality was sound in only 8 of the 21 pharmacoeconomic evaluations. In most cases, the perspective of analysis, the comparator drugs, and the reporting of both total and incremental costs and effects were correct. However, drug indication, form (i.e. cost utility/cost effectiveness) and time horizon of the evaluations were frequently flawed. Moreover, the costs and effects of the pharmaceuticals were not always analysed correctly, and modelling studies were often non-transparent. Twelve drugs were reimbursed, and nine were not. The compliance with pharmacoeconomic guidelines in economic evaluations of new pharmaceuticals can be improved. This would improve the methodological quality of the pharmacoeconomic evaluations and ensure consistency in the evidence and the decision-making process for drug reimbursement in the Netherlands.

Use and costs of oral anticancer agents in the Netherlands in the period 2000–2008

In recent years, the number of oral anticancer agents has increased substantially. Although these agents have quickly been incorporated in the treatment of a variety of malignancies, data on their incidence, prevalence and costs are lacking. The objective of the present study was to obtain insight into the use and the costs of oral anticancer agents (with Anatomical Therapeutic Chemical classification system (World Health Organisation) code L01) in the Netherlands between 2000 and 2008. Incidence and prevalence were determined using community pharmacy dispensing records obtained from the PHARMO Record Linkage System database. The data of costs were provided by the Genees- en hulpmiddelen Informatie Project of the Dutch Health Care Insurance Board (CVZ, Diemen, The Netherlands). In the years 2000-2008, the use of oral anticancer agents has more than doubled from 64 to 140 users per 100 000 inhabitants. The increase is mainly caused by the prescription of capecitabine for various indications. There was a 50-fold rise in costs on oral anticancer agents from €2 m in 2000 to approximately €100 m in 2008. The share in the costs of tyrosine kinase inhibitors (TKIs) in 2008 was 67% (€70 m) with the oldest TKI, imatinib, having a share of more than 50% within the group of TKIs. The increased use of oral anticancer agents is mainly due to the frequent prescription of capecitabine. The increased costs are caused by the registration of a variety of TKIs, in particular imatinib. The costs of new agents with an orphan drug status are very high as compared with those of capecitabine, a newer agent for which there are alternative treatment options.

Triptan overuse in the Dutch general population: A nationwide pharmaco-epidemiology database analysis in 6.7 million people

A population-based observational study was used to assess the prevalence, demographics, risk factors, and costs of triptan overuse, defined as more than 30 (International Headache Society criteria) or 54 (stringent criteria) defined daily doses per 3 months. Analysis of the Dutch Health Care Insurance Board Database for 2005, which included prescriptions for 6.7 million people (46% of the total Dutch population). Triptans were used by 85,172 (1.3%) people; of these, 8,844 (10.4%; 95% CI 10.2-10.6) were overusers by International Headache Society and 2,787 (3.3%; 95% CI 3.2-3.4) were overusers by stringent criteria. The triptan-specific odds ratios for the rate of International Headache Society overuse compared with sumatriptan were: 0.26 (95% CI 0.19-0.36) for frovatriptan; 0.34 (95% CI 0.32-0.37) for rizatriptan; 0.76 95% CI 0.68-0.85) for naratriptan; 0.86 (95% CI 0.72-1.02) for eletriptan; 0.97 (95% CI 0.88-1.06) for zolmitriptan; and 1.49 (95% CI 1.31-1.72) for almotriptan. Costs for overuse were 29.7 million euros; for the International Headache Society criteria this was 46% of total costs and for stringent criteria it was 23%. In the Dutch general population, 1.3% used a triptan in 2005, of which 10.3% were overusers and accounted for half of the total costs of triptans. Users of frovatriptan, rizatriptan and naratriptan had a lower level of overuse.

Answer to the letter to the editor of Carl Hans Fürstenberg et al. (2010) concerning manuscript “transforaminal endoscopic surgery for lumbar stenosis: a systematic review” by Jorm Nellensteijn, Raymond Ostelo, Ronald Bartels, Wilco Peul, Barend Van Royen, Maurits Van Tulder. Eur Spine J 19:879–886

In the letter to the editor it is suggested that we might have missed relevant evidence. Not including ‘discectomy’ in the search strategy is pointed out as the main reason. But apparently there is confusion regarding the fact that we published two systematic reviews, both on transforaminal endoscopic surgery. One focuses on symptomatic lumbar disc herniations [1] and the second one on lumbar stenosis [2]. We combined the search strategy for these two reviews for efficiency reasons. The keywords were used as MESH headings and free text words; discectomy was included in the search strategy [1]. The full search strategy is available upon request. In the present review we focus on stenosis. The SCIATICA-Med trial [3, 4] included patients with lumbar disc herniation and was therefore not eligible for this review. Moreover, it clearly uses a different technique than the transforaminal endoscopic surgery. Therefore, this study was also excluded from our systematic review on symptomatic lumbar disc herniations [1]. The German health technology assessment report [5] focuses on the treatment of disc prolapse and not stenosis. The study by Hermantin et al. [6] met the inclusion criteria for review on symptomatic lumbar disc herniations [1] and was included (see Ref. 11 of that review). The report by the Dutch Health Care Insurance also focuses on lumbar disc herniation and was based on our review [1]. The three key publications [7–9] that we reportedly ‘omitted’ were included in our review on symptomatic lumbar disc herniations [1] as they included patients with lumbar disc herniation. The study by Molyneux was not found as our search strategy was up to November 2009. Conference proceedings did not meet our definition of ‘published papers’ and therefore Lewandrowski [10] and Iprenburg [11] were not included. The reference by Morgenstern [12] could not be retrieved, as the European Musculoskeletal Review seems not to be indexed in the databases we searched. The study by Hoogland [13] includes patients with recurrent lumbar disc herniation, not stenosis. In assessing the risk of bias, we followed the guidelines of the Cochrane Back Review Group and, therefore, we think that the doubt the authors convey regarding ‘the publication quality assessment criteria’ is without any foundation. In conclusion, no randomized controlled trial, but only seven observational studies were identified and no relevant papers are missed. All these studies had a high risk of bias. Consequently, the conclusion that there is no valid evidence on the effectiveness of transforaminal endoscopic surgery for lumbar stenosis is supported by the data.

Letter to the editor concerning “Transforaminal endoscopic surgery for lumbar stenosis: a systematic review” (Nellensteijn et al.)

The recently published systematic review by Nellensteijn et al. [1] has identified seven observational studies on the effectiveness of transforaminal endoscopic surgery for lumbar stenosis. The authors conclude that there is a lack of valid evidence supporting the intervention. We believe that there is more evidence in the literature than that found. Probably, this is due to the authors not including discectomy as a major key word in their search strategy (Table 1). First and foremost, there are at least three systematic reviews that provide additional data. Gibson and Waddell [2] refer to the SCIATICA-Med Trial [3, 4] and a German health technology assessment report [5] identified three RCTs and 12 case series between 1998 and 2004 focusing on endoscopically assisted minimally invasive disc surgery. None of these is duplicated in the Nellensteijn review and, most interestingly, a former review with the same title and group of authors funded by the Dutch Health Care Insurance Board, yielded 8 controlled studies and 31 cohort studies [6]. The 2010 Nellensteijn review has also omitted three key publications on the grounds of lacking focus on lumbar stenosis [7–9] and data from several observational studies focusing on foraminal treatment access [10–15]. These data should at least have been referred to when considering the potential effectiveness of transforaminal endoscopic surgery in a full text evaluation. In addition to criticisms regarding missing data, there is some doubt about whether or not the publication quality assessment criteria used by the authors are appropriate and state of the art, as there are established instruments [16, 17] for this purpose. It should also be noted that the Prisma Flow diagram is not used in the review [18], which further impairs the quality of the paper. We respectfully suggest that there should be better documentation of the study selection process with detailed reporting of reasons for inclusions and exclusions.

Palliative care is not yet a well-defined product within the Dutch healthcare insurance system

In the Netherlands, the quality and availability of palliative care has improved markedly within the last decade. However, many open questions remain concerning the position of palliative care as an insurable product on the Dutch healthcare market. Therefore, we analysed the policies of all private Dutch healthcare insurance companies as well as the public insurance policy for extraordinary medical costs. We studied how and which parts of palliative care were reimbursed in 2007. We observed a huge variability in costs and reimbursement regulations reflecting a rapid turnover of products for palliative care due to various new developments on this specific field of medical care. We conclude that a better definition of the product 'palliative care' is necessary for patients, health care providers and insurance companies.

Involving stakeholders in policy research should not imply that they control the problem definition: lessons from a case study on new analgesics

The Dutch Health Care Insurance Board (HCIB) commissions research to guide their policy recommendations. However, the studies conducted do not always yield relevant information. This may result from differences in problem definitions held by the HCIB and target populations. To compensate these problems, researchers were asked to analyse the problems from the perspective of the policy's target populations. We analysed the HCIB's commissioning approach when used in a tender for research proposals on new analgesics. The HCIB considered off-label use of these drugs to be problematic. Researchers, however, were reluctant to adopt the HCIB's problem definition, questioning whether it would be shared by 'the field'. Although most of the physicians did not consider their prescribing patterns to be problematic, one of the new drugs had to be withdrawn from the market because of severe side effects. These findings emphasise that involving target populations in policy research should not imply that they control the problem definition.

Innovatief werkgedrag en stress als reacties op roloverlading en rolambiguïteit

Innovative working behavior and stress as a response to role overload and role ambiguity Innovative working behavior and stress as a response to role overload and role ambiguity Simon B. de Jong & Onne Janssen, Gedrag & Organisatie, Volume 18, April 2005, nr. 2, pp. 66-82 This research develops and tests the hypothesis that role ambiguity strengthens the positive relationship between role overload and innovative work behavior, whereas role clarity (i.e. less role ambiguity) weakens this relationship. Furthermore, it is presumed that role overload is positively related to stress regardless of the level of role ambiguity. The results of a survey study, involving 101 employees of a Dutch healthcare insurance company, showed that role overload was indeed positively related with innovative work behavior when employees experience a high level of role ambiguity, whereas this relationship did not occur when employees experienced the role clarity. In addition, role ambiguity did not appear to have a moderating influence on the positive relationship between role overload and stress. The results are discussed in the context of the Job Demand-Control-model and recent findings in literature on innovation.

Strategies for improving the diagnostic specificity of the frequency doubling perimeter

To evaluate various strategies designed to improve the specificity of the interpretation of results obtained with the frequency doubling technology perimeter (FDT) used in the full-threshold mode. Three different strategies were compared using data from 452 glaucoma patients and 237 healthy subjects: combining several FDT parameters from a single test, combining the FDT test with a GDx test, and confirming an abnormal FDT test result with a repeat test. Confirming an abnormal FDT test result with a repeat test yielded a specificity increase of 0.10, from 0.80 to 0.90, at the expense of some loss of sensitivity for early but not for moderate or severe glaucoma. Combining several FDT parameters from a single test and combining FDT with GDx did not yield any noticeable increase in diagnostic performance. A modest increase in FDT diagnostic performance can be obtained by the confirmation of an abnormal test result with a repeat test.

Prevention of chemotherapy-induced febrile neutropenia (FN) by antibiotics (AB) versus antibiotics plus granulocyte-colony stimulating factor (G-CSF) in small cell lung cancer (SCLC): A randomized phase III study

8002 Background: FN is a major complication of chemotherapy in patients (pts) with SCLC. G-CSF is used to prevent FN, but its primary use is only recommended in pts with a considerable (>40%) risk of FN (ASCO guidelines, JCO 2000). AB are also effective in preventing FN, even reduce infection-related mortality and are cost-effective (Tjan-Heijnen, Ann Oncol 2001). In this multicenter randomised phase III trial the role of combined primary prophylaxis with AB plus G-CSF in pts with SCLC at increased risk of FN was determined. Methods: Pts with SCLC-limited disease and performance status (PS) 2–3, or age over 60 years or judged not suitable for concurrent chemo/radiotherapy and pts with SCLC-extensive disease were considered at increased risk of FN. Pts were stratified for age (</≥ 60 years), PS (0–1/2), extend of disease (LD/ED) and line of therapy (1st/2nd) and randomised for primary prophylaxis with AB (ciprofloxacin 500mg + roxithromycin 150mg, bid, days 4–13) alone or in combination with G-CSF (filgrastim 5 μ g/kg/day days 4–13). Chemotherapy consisted of cyclophosphamide 1000mg/m2 day 1, doxorubicin 45mg/m2 day 1 and etoposide 100mg/m2 days 1,2,3, i.v., q 3 weeks, × 5. Primary endpoint: incidence of FN in first cycle, targeted accrual: N=156 pts (78/ arm). Results: See table;171 pts were eligible. Patient characteristics were well balanced. Conclusion: The addition of primary prophylactic G-CSF to prophylactic antibiotics significantly reduced the incidence of chemotherapy-related FN in SCLC patients at increased risk of FN, especially in the first cycle by 50%. Supported by a research grant of Dutch Healthcare Insurance Board. No significant financial relationships to disclose.

Prevention of chemotherapy-induced febrile neutropenia (FN) by antibiotics (AB) versus antibiotics plus granulocyte-colony stimulating factor (G-CSF) in small cell lung cancer (SCLC): A randomized phase III study

8002 Background: FN is a major complication of chemotherapy in patients (pts) with SCLC. G-CSF is used to prevent FN, but its primary use is only recommended in pts with a considerable (>40%) risk of FN (ASCO guidelines, JCO 2000). AB are also effective in preventing FN, even reduce infection-related mortality and are cost-effective (Tjan-Heijnen, Ann Oncol 2001). In this multicenter randomised phase III trial the role of combined primary prophylaxis with AB plus G-CSF in pts with SCLC at increased risk of FN was determined. Methods: Pts with SCLC-limited disease and performance status (PS) 2–3, or age over 60 years or judged not suitable for concurrent chemo/radiotherapy and pts with SCLC-extensive disease were considered at increased risk of FN. Pts were stratified for age (</≥ 60 years), PS (0–1/2), extend of disease (LD/ED) and line of therapy (1st/2nd) and randomised for primary prophylaxis with AB (ciprofloxacin 500mg + roxithromycin 150mg, bid, days 4–13) alone or in combination with G-CSF (filgrastim 5 μ g/kg/day days 4–13). Chemotherapy consisted of cyclophosphamide 1000mg/m2 day 1, doxorubicin 45mg/m2 day 1 and etoposide 100mg/m2 days 1,2,3, i.v., q 3 weeks, × 5. Primary endpoint: incidence of FN in first cycle, targeted accrual: N=156 pts (78/ arm). Results: See table;171 pts were eligible. Patient characteristics were well balanced. Conclusion: The addition of primary prophylactic G-CSF to prophylactic antibiotics significantly reduced the incidence of chemotherapy-related FN in SCLC patients at increased risk of FN, especially in the first cycle by 50%. Supported by a research grant of Dutch Healthcare Insurance Board. No significant financial relationships to disclose.