Development and validation of a decision model for the evaluation of novel lung cancer treatments in the Netherlands.

Recent discoveries in molecular diagnostics and drug treatments have improved the treatment of patients with advanced (inoperable) non-squamous non-small cell lung cancer (NSCLC) from solely platinum-based chemotherapy to more personalized treatment, including targeted therapies and immunotherapies. However, these improvements come at considerable costs, highlighting the need to assess their cost-effectiveness in order to optimize lung cancer care. Traditionally, cost-effectiveness models for the evaluation of new lung cancer treatments were based on the findings of the randomized control trials (RCTs). However, the strict RCT inclusion criteria make RCT patients not representative of patients in the real-world. Patients in RCTs have a better prognosis than patients in a real-world setting. Therefore, in this study, we developed and validated a diagnosis-treatment decision model for patients with advanced (inoperable) non-squamous NSCLC based on real-world data in the Netherlands. The model is a patient-level microsimulation model implemented as discrete event simulation with five health events. Patients are simulated from diagnosis to death, including at most three treatment lines. The base-model (non-personalized strategy) was populated using real-world data of patients treated with platinum-based chemotherapy between 2008 and 2014 in one of six Dutch teaching hospitals. To simulate personalized care, molecular tumor characteristics were incorporated in the model based on the literature. The impact of novel targeted treatments and immunotherapies was included based on published RCTs. To validate the model, we compared survival under a personalized treatment strategy with observed real-world survival. This model can be used for health-care evaluation of personalized treatment for patients with advanced (inoperable) NSCLC in the Netherlands.

Cost-Effectiveness of Surveillance Scanning Strategies after Curative Treatment of Non-Small-Cell Lung Cancer.

BACKGROUND: After curative treatment of primary non-small-cell lung cancer (NSCLC), patients undergo intensive surveillance with the aim to detect recurrences from the primary tumor or metachronous second primary lung cancer as early as possible and improve overall survival. However, the benefit of surveillance is debated. Available evidence is of low quality and conflicting. Microsimulation modeling facilitates the exploration of the impact of different surveillance strategies and provides insight into the cost-effectiveness of surveillance. METHODS: A microsimulation model was used to simulate a range of computed tomography (CT)-based surveillance schedules, differing in the frequency and duration of CT surveillance. The impact on survival, quality-adjusted life-years, costs, and cost-effectiveness of each schedule was assessed. RESULTS: Ten of 108 strategies formed the cost-effectiveness frontier; that is, these were the strategies with the optimal cost-health benefit balance. Per person, the discounted QALYs of these strategies varied between 5.72 and 5.81 y, and discounted costs varied between €9892 and €19,259. Below a willingness-to-pay threshold of €50,000/QALY, no scanning is the preferred option. For a willingness-to-pay threshold of €80,000/QALY, surveillance scanning every 2 y starting 1 y after curative treatment becomes the best option, with €11,860 discounted costs and 5.76 discounted QALYs per person. The European Society for Medical Oncology guideline strategy was more expensive and less effective than several other strategies. CONCLUSION: Model simulations suggest that limited CT surveillance scanning after the treatment of primary NSCLC is cost-effective, but the incremental health-benefit remains marginal. However, model simulations do suggest that the guideline strategy is not cost-effective.

Trends in Drug Costs and Overall Survival in Patients with Metastatic Non-small Cell Lung Cancer in The Netherlands Diagnosed from 2008 Through 2014.

BACKGROUND: The Value-Based Health Care concept defines patient value as patient-relevant outcomes divided by costs. The aim of the present study was to assess the development of systemic treatment costs over the years compared with changes in overall survival (OS) at the level of a diagnosis of stage IV non-small cell lung cancer (NSCLC). METHODS: All patients diagnosed (in 2008-2014) with stage IV NSCLC and treated with systemic treatment in six Dutch large teaching hospitals (Santeon network) were included. We collected data on OS and amounts of drug units (milligrams) for every drug in the applied systemic cancer treatments, until death. These amounts were multiplied by Dutch unit costs (Euros/mg) expressed in 2018 Euros to construct total drug costs per line of treatment per patient. Costs for day care visits were added for drugs requiring parenteral administration. RESULTS: Data were collected from 1214 patients. Median OS and mean total drug costs showed no significant variation over the years (p = 0.437 and p = 0.693, respectively). Mean total drug costs per 1 year of survival ranged from €20,665 to €26,438 during the period under study. Costs for first-line systemic treatment were significantly higher in 2011-2014 compared with 2008-2010. CONCLUSION: This study shows that overall drug costs were stable over the years, despite a relative increase in first-line treatment costs. Median OS remained at around 8 months from year to year. These trend data are very relevant as background for the assessment of costs and achieved outcomes in the more recent years.

Cost-effectiveness of stereotactic body radiation therapy versus video assisted thoracic surgery in medically operable stage I non-small cell lung cancer: A modeling study.

OBJECTIVES: Stage I non-small cell lung cancer (NSCLC) can be treated with either Stereotactic Body Radiotherapy (SBRT) or Video Assisted Thoracic Surgery (VATS) resection. To support decision making, not only the impact on survival needs to be taken into account, but also on quality of life, costs and cost-effectiveness. Therefore, we performed a cost-effectiveness analysis comparing SBRT to VATS resection with respect to quality adjusted life years (QALY) lived and costs in operable stage I NSCLC. MATERIALS AND METHODS: Patient level and aggregate data from eight Dutch databases were used to estimate costs, health utilities, recurrence free and overall survival. Propensity score matching was used to minimize selection bias in these studies. A microsimulation model predicting lifetime outcomes after treatment in stage I NSCLC patients was used for the cost-effectiveness analysis. Model outcomes for the two treatments were overall survival, QALYs, and total costs. We used a Dutch health care perspective with 1.5 % discounting for health effects, and 4 % discounting for costs, using 2018 cost data. The impact of model parameter uncertainty was assessed with deterministic and probabilistic sensitivity analyses. RESULTS: Patients receiving either VATS resection or SBRT were estimated to live 5.81 and 5.86 discounted QALYs, respectively. Average discounted lifetime costs in the VATS group were €29,269 versus €21,175 for SBRT. Difference in 90-day excess mortality between SBRT and VATS resection was the main driver for the difference in QALYs. SBRT was dominant in at least 74 % of the probabilistic simulations. CONCLUSION: Using a microsimulation model to combine available evidence on survival, costs, and health utilities in a cost-effectiveness analysis for stage I NSCLC led to the conclusion that SBRT dominates VATS resection in the majority of simulations.

Comparing survival predicted by the diagnosis-specific Graded Prognostic Assessment (DS-GPA) to actual survival in patients with 1-10 brain metastases treated with stereotactic radiosurgery.

BACKGROUND AND PURPOSE: Multiple prognostic models for predicting survival after treatment for brain metastases have been developed. One of them, the diagnosis-specific Graded Prognostic Assessment (DS-GPA), has been developed to predict the median survival for brain metastases from the most frequent primary sites: lung carcinoma, breast cancer, melanoma, renal cell cancer and gastrointestinal tumours. In this study we aim to compare the survival predicted by the DS-GPA to actual survival, and to assess this models performance on both population and individual levels. METHODS: We identified a consecutive cohort of patients treated with SRS for brain metastases in our institute. DS-GPA scores were calculated for each patient, and the median survival for each DS-GPA group was calculated. Differences in survival between DS-GPA groups were tested with Wilcoxon Signed Rank tests and log-rank tests. RESULTS: In total 367 patients were included in the analysis. Median survival in our cohort is largely comparable to corresponding DS-GPA cohorts, but some notable differences are present. There was a significantly shorter median survival (15.4 months, compared to 26.5 months) in the adenocarcinoma NSCLC subgroup with a GPA score of 2.3-3. We confirmed the significant differences in survival time for most cancer-specific subgroups. CONCLUSION: DS-GPA seems to be a reliable tool to classify patients with brain metastases treated with SRS into prognostic subgroups. However, we found some aberrations from predicted median survival times, which may be due to specific characteristics of the populations of patients treated with SRS versus other patients.

Pilot study on the effectiveness and students' attitude towards undergraduate training provided by industry.

INTRODUCTION: Rapid developments in CAD/CAM technology necessitate the adaptation of curriculum content. Limited resources hinder institutions in holding state of the art equipment available for student training. MATERIALS AND METHODS: A workshop given by an industry partner was organised as part of the final pre-clinical course in prosthodontics for the academic years 2015 and 2016. The workshop on dental ceramics and CAD/CAM technology comprised of lectures and practical demonstrations. Multiple-choice examinations prior to and after the workshop as well as questionnaires were used for assessing effectiveness and students' perception. The test scores and evaluation results were compared using Fisher's exact test of homogeneity (α = 0.05). RESULTS: The workshop improved students' performance in the written examination. With the exception of 1 question, students having attended the workshop performed significantly better (P < .05). The majority of students felt that the workshop fostered their knowledge in the field of dental ceramics and CAD/CAM. Whilst only a small portion (<10%) disapproved industry-supported education, up to 45% of the participants considered the workshop as sales promotion. The students were undecided on whether or not competitor companies should be invited to present on the same topic and whether or not more industry-supported courses would be beneficial. DISCUSSION: Industry-supported education appears to be a necessity in the field of CAD/CAM dentistry, but care has to be taken to select adequate partners, and the content of courses has to be controlled.

Quantitative and qualitative assessment of real world data comparative effectiveness research of systemic therapies in lung oncology: A systematic review.

INTRODUCTION: The growing interest in comparative effectiveness research (CER) based on data from routine clinical practice also extends towards lung oncology. Although CER studies using real world data (RWD) have the potential to assist clinical decision-making, concerns about the quality and validity of studies with observational data subsist. The primary objective of the present study is to assess the current status of observational CER in the field of lung oncology, both quantitatively as qualitatively. METHODS: We performed a systematic electronic literature database search in MEDLINE and EMBASE (up to 1 July 2015). The quality of all selected studies was assessed according to the Good ReseArch for Comparative Effectiveness (GRACE) checklist. RESULTS: The first selection included 657 publications. After screening the corresponding abstracts and full-text papers, 38 studies remained. A total of 36 studies included patients with advanced NSCLC. The comparison of the effectiveness of gefitinib versus erlotinib was the main objective in 22% of the studies. The median number of patients per study was 202 (range 21-10064). The number of publications increased over the years whereas the quality score remained stable over the years with several common shortcomings (checklist items M5, D1, D4, D6). DISCUSSION: The growing interest in clinical oncology CER studies using RWD is reflected in an increasing number of publications in the recent years. The studies have several common methodological shortcomings possibly limiting their applicability in clinical decision-making. To fulfil the promise of RWD CER in lung oncology effort should be continued to overcome these shortcomings.

Assessment of DFT for Computing Sum Frequency Generation Spectra of an Epoxydiol and a Deuterated Isotopologue at Fused Silica/Vapor Interfaces.

We assess the capabilities of eight popular density functional theory (DFT) functionals, in combination with several basis sets, as applied to calculations of vibrational sum frequency generation (SFG) spectra of the atmospherically relevant isoprene oxidation product trans-ß-isoprene epoxydiol (IEPOX) and one of its deuterated isotopologues at the fused silica/vapor interface. We use sum of squared differences (SSD) and total absolute error (TAE) calculations to estimate the performance of each functional/basis set combination in producing SFG spectra that match experimentally obtained spectra from trans-ß-IEPOX and one of its isotopologues. Our joined SSD/TAE analysis shows that while the twist angle of the methyl C3v symmetry axis of trans-ß-IEPOX relative to the surface is sensitive to the choice of DFT functional, the calculated tilt angle relative to the surface normal is largely independent of the functional and basis set. Moreover, we report that hybrid functionals such as B3LYP, ωB97X-D, PBE0, and B97-1 in combination with a modest basis set, such as 6-311G(d,p), provides good agreement with experimental data and much better performance than pure functionals such as PBE and BP86. However, improving the quality of the basis set only improves agreement with experimental data for calculations based on pure functionals. A conformational analysis, based on comparisons of calculated and experimental SFG spectra, suggests that trans-ß-IEPOX points all of its oxygen atoms toward the silica/vapor interface.

[Memorandum on sustainable reinforcement of prevention and health promotion: challenges at the federal, state and local level]. / Memorandum--Prävention und Gesundheitsförderung nachhaltig stärken: Herausforderungen auf Bundes-, Landes- und kommunaler Ebene.

Research-based evidence and practice-based experience are core requirements for the effective implementation of preventive interventions. The knowledge gained in the Prevention Research Funding Initiative of the German Federal Ministry of Education and Research (2004-2013) was therefore amalgamated, reflected and consolidated in the Cooperation for Sustainable Prevention Research (KNP) meta-project. In annual strategy meetings, researchers and practitioners from the field and other experts developed 3 memoranda providing recommendations for the further development of research and practice in the field of prevention and health promotion. Memorandum III is primarily aimed at decision-makers in politics and administration at the federal, state and local level, in civil society and in the workplace. Its recommendations show that structuring efforts are urgently needed to achieve sustainable policy, particularly in the fields of health, education, employment and social affairs. Memorandum III brings together the knowledge extracted and problems identified in research projects. More so than its 2 predecessors, Memorandum III abstracts knowledge from the individual projects and attempts to derive guidance for action and decision-making, as shown by the 7 recommendations that appear to useful for consensus-building in practice and research. Value judgments are inevitable. Prevention and health promotion are an investment in the future: of social health, social capital and social peace. Improvement of the framework conditions is needed to achieve the harmonized awareness and the sustained effectiveness of these structure-building efforts in different policy areas, spheres of life, fields of action, and groups of actors. This includes the implementation of an overall national strategy as well as the expansion of sources of funding, extension of the legal framework, overarching coordination, and the establishment of a National Center of Excellence to develop and safeguard prevention and health promotion. The memorandum is intended to stimulate a discourse resulting in structure-building and stabilizing measures designed to ensure the sustainability of prevention and health promotion.

Assessment of cardiovascular disease risk in patients with schizophrenia spectrum disorders in German psychiatric hospitals: results of the pharmacoepidemiologic CATS study.

PURPOSE: Patients with severe mental illness are at high risk for metabolic and cardiac disorders. Thus, monitoring of cardiovascular risks is imperative and schedules for screening for lipids, glucose, body mass index (BMI), waist-hip ratio and blood pressure have been developed. We intended to analyze screening for metabolic disorders in German patients with schizophrenia spectrum disorders in routine psychiatric care. METHODS: We included 674 patients with any F2 diagnosis in out- and inpatient settings and analyzed metabolic screening procedures as practiced under conditions of usual care. RESULTS: Except BMI (54 %), all other values were documented only in a minority of patients: waist circumference (23 %), cholesterol (28 %), fasting glucose (19 %), triglycerides (25 %) and blood pressure (37 %). We found evidence for less than perfect quality of blood pressure measures. The group of patients who met the individual metabolic syndrome ATP III criteria was comparable to the US CATIE trial. CONCLUSIONS: We conclude that frequency and quality of metabolic monitoring in German in- and outpatients settings are not in accordance with the respective recommendations. Similar to previous reports we found evidence for a high prevalence of metabolic disturbances in German patients with schizophrenia spectrum disorders.

First steps towards a fast-neutron therapy planning program.

BACKGROUND: The Monte Carlo code GEANT4 was used to implement first steps towards a treatment planning program for fast-neutron therapy at the FRM II research reactor in Garching, Germany. Depth dose curves were calculated inside a water phantom using measured primary neutron and simulated primary photon spectra and compared with depth dose curves measured earlier. The calculations were performed with GEANT4 in two different ways, simulating a simple box geometry and splitting this box into millions of small voxels (this was done to validate the voxelisation procedure that was also used to voxelise the human body). RESULTS: In both cases, the dose distributions were very similar to those measured in the water phantom, up to a depth of 30 cm. In order to model the situation of patients treated at the FRM II MEDAPP therapy beamline for salivary gland tumors, a human voxel phantom was implemented in GEANT4 and irradiated with the implemented MEDAPP neutron and photon spectra. The 3D dose distribution calculated inside the head of the phantom was similar to the depth dose curves in the water phantom, with some differences that are explained by differences in elementary composition. The lateral dose distribution was studied at various depths. The calculated cumulative dose volume histograms for the voxel phantom show the exposure of organs at risk surrounding the tumor. CONCLUSIONS: In order to minimize the dose to healthy tissue, a conformal treatment is necessary. This can only be accomplished with the help of an advanced treatment planning system like the one developed here. Although all calculations were done for absorbed dose only, any biological dose weighting can be implemented easily, to take into account the increased radiobiological effectiveness of neutrons compared to photons.

Cell biology assessment of glucokinase mutations V62M and G72R in pancreatic beta-cells: evidence for cellular instability of catalytic activity.

Mutations in the glucokinase (GK) gene cause defects in blood glucose homeostasis. In some cases (V62M and G72R), the phenotype cannot be explained by altered enzyme kinetics or protein instability. We used transient and stable expression of green fluorescent protein (GFP) GK chimaeras in MIN6 beta-cells to study the phenotype defect of V62M and G72R. GK activity in lysates of MIN6 cell lines stably expressing wild-type or mutant GFP GK showed the expected affinity for glucose and response to pharmacological activators, indicating the expression of catalytically active enzymes. MIN6 cells stably expressing GFP V62M or GFP G72R had a lower GK activity-to-GK immunoreactivity ratio and GK activity-to-GK mRNA ratio but not GK immunoreactivity-to-GK mRNA ratio than wild-type GFP GK. Heterologous expression of liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK2/FDP2) in cell lines increased GK activity for wild-type GK and V62M but not for G72R, whereas expression of liver GK regulatory protein (GKRP) increased GK activity for wild type but not V62M or G72R. Lack of interaction of these mutants with GKRP was also evident in hepatocyte transfections from the lack of nuclear accumulation. These results suggest that cellular loss of GK catalytic activity rather than impaired translation or enhanced protein degradation may account for the hyperglycemia in subjects with V62M and G72R mutations.

[The process of deinstitutionalization in German State Mental Hospitals. Critical overview of empirical research studies]. / Enthospitalisierungsprozesse in deutschen psychiatrischen Grosskrankenhäusern. Eine kritische Ubersicht zur durchgeführten Begleitforschung.

The process of discharging previously long-term hospitalized patients from German state mental hospitals, and of transferring these patients to other forms of supported housing has meanwhile come to its end. Therefore, this paper presents an overview of the scientific evaluation of this process. By using clearly defined research methodological criteria, eight empirical studies from several German federal states are assessed focusing on the meaningfulness of their results. Because of the heterogeneity of the aims regarding contents of this transformation process, of the research methodological approaches, and of the characteristics of the assessed patient groups, only few general results could be identified. Chronically mentally ill patients (mostly suffering from schizophrenic disorders) who had been successfully discharged to the community were younger, and showed shorter periods of illness and hospitalization than control patients. After discharge they might have experienced positive changes of their objective and subjective quality of life and of their perceived needs of care. Referred to several other outcome domains, no homogeneous tendencies concerning clinically relevant improvement or deterioration were found. In particular, changes related to psychopathological symptoms and social competencies were generally small. However, mortality and re-hospitalization rates of de-hospitalized patients were considerably high, and ranged between 3-24 %, and 4-46 %, respectively. The assessed studies could not identify replicated predictors of successful de-hospitalization. Female sex and long-term last hospitalization seemed to be important for stable placement in forms of supported housing requiring a higher level of autonomy. From the generally unclear procedural quality of the German deinstitutionalization process, the authors deduce implications for the scientific evaluation of future projects of restructuring mental health care services. Besides the clear definition of empirically assessable aims which should be based on theoretical considerations, it is of utmost priority to guarantee high performance quality of research methodological standards.

Psychological distress and socioeconomic status in single mothers and their children in a German city.

BACKGROUND: The proportion of single mothers in western countries is continuously growing. In contrast to other western countries, support programs in Germany especially for single mothers are rare. This study identifies for the first time in Germany within a large epidemiological sample different subgroups of higher distressed single mothers as important potential target groups for psychosocial support interventions. Facing limited resources, data about these subgroups are helpful to develop and establish specific support programs. METHOD: In a cross-section study, family status of a complete cohort of school beginners in Duesseldorf (N = 5178 children, aged 5-7 years) was screened within the school eligibility test (recruitment rate 97.5 %, N = 5048). Out of a total of 891 single mothers, 531 fulfilling inclusion criteria (speaking fluent German, not married, living together with the tested child, informed consent) were compared to a control group of married mothers out of the same sample (N = 278). Socioeconomic status, social network and psychological distress of mothers (SCL-90-R) and children (CBCL) were investigated. RESULTS: Socioeconomic status (income, education) of single mothers was lower while psychological distress (SCL-90-R) was elevated compared to the control group. Single mothers without additional personal support for their child, younger, as well as poor single mothers showed higher values of psychological distress. In sons of single mothers, increased behavior problems were found (CBCL). Of all children screened, 907 (18 %) lived in single-parent families. CONCLUSION: An increased psychological distress of single mothers and their sons could be shown for the first time in Germany within a large epidemiologic sample. This has implications for the planning of preventive interventions and evaluation of associations, e. g., between social variables and distress of single mothers and their children within longitudinal study designs.

Responsiveness of subjective quality of life assessment in schizophrenic patients: a quasi-experimental pilot study.

Responsiveness of quality of life (QOL) assessments in chronic schizophrenic patients was investigated by a quasi-experimental pilot study. Satisfaction ratings were assessed over five time points with an externally imposed disturbing stimulus at the second time point. Despite a markedly high stability, the disturbance provoked a temporally limited decrease in QOL.

[Not Available]. / Der Zusammenhang von sozialer Schicht und psychogener Erkrankung im Langzeitverlauf/ Correlation between social class and neurotic impairment in long term course.

Using the data basis of the Mannheim Cohort Study the present paper investigates the correlation between socio-economic Status and psychogenic impairment due to predominantly psychosocially influenced ("psychogenic") disorders (neurotic spectrum disorders, personality disorders, stress reactions and somatoform disorders) in a representative adult Community sample. The period of observation amounted up to 11,1 years. Subjects investigated within our follow-up study for this interval (n=301) were drawn from an representative adult Community population sample (N=600). Within the three step class model members of the lower class were at all investigation time points significantly stronger impaired compared to the members of the middleand upper class. Investigating the clinical impairment related to the intragenerative class mobility those subjects, which could achieve a social rise between two points of investigation were even prior, to the first investigation time point, less affected compared to the ones remaining in their social class. Vice versa subjects in the process of an social decline presented a stronger psychogenic impairment prior to their decline compared to those, which remained stable in their social class. These dynamic correlations offer evidence for the effect of the socalled "drift-hypothesis", which postulates, that persons due to their disease decline in their social Status respectively after improving rise to a higher social class.

Assessment of QT dispersion for prediction of mortality or arrhythmic events after myocardial infarction: results of a prospective, long-term follow-up study.

BACKGROUND: Risk stratification by means of analysis of QT dispersion (QTD) in the 12-lead surface ECG is under intense investigation in various patient populations. The aim of the present prospective study was to evaluate the prognostic value of QTD and other ECG variables reflecting dispersion of ventricular repolarization in comparison with established risk stratifiers during long-term follow-up in a large cohort of post-myocardial infarction patients treated according to contemporary therapeutic guidelines. METHODS AND RESULTS: In 280 consecutive infarct survivors, the 12-lead ECG was optically scanned and digitized for analysis of QTD (QTmax-QTmin) and 25 other repolarization variables, including recently developed and validated parameters such as the T peak-to-T end interval and the area under the T wave. In addition, a variety of established risk stratifiers were assessed. After a mean follow-up period of 32+/-10 months, 30 patients reached one of the prospectively defined study end points (death, ventricular tachycardia, or resuscitated ventricular fibrillation). Comparisons between event and nonevent patients by means of Kaplan-Meier event probability analyses revealed that none of the ECG dispersion variables were of discriminative value. In contrast, variables such as left ventricular ejection fraction (P=0.007), mean 24-hour heart rate (P=0.022), or heart rate variability (P=0.007) proved to be potentially useful risk stratifiers in this patient population. On multivariate analysis, only LVEF, heart rate variability, and a history of thrombolysis were independent predictors of outcome. CONCLUSIONS: Determination of QTD from the surface ECG even when performed with the best available methodology failed to predict subsequent risk in this large series of infarct survivors.

Cost-effectiveness of medical nutrition therapy provided by dietitians for persons with non-insulin-dependent diabetes mellitus.

OBJECTIVE: To conduct a cost analysis and cost-effectiveness study based on a randomized clinical trial of basic nutrition care (BC) and practice guidelines nutrition care (PGC) provided by dietitians in outpatient clinics. DESIGN: Subjects with non-insulin-dependent diabetes mellitus (NIDDM) from three states (Minnesota, Florida, Colorado) were randomly assigned to a group receiving BC or a group receiving PGC for a 6-month clinical trial. Along with data about medical and clinical outcomes, data about cost resources were collected. The cost-effectiveness of PGC compared with BC was calculated using per-patient costs and glycemic outcomes for the 6 months of the study. A net cost-effectiveness ratio comparing BC and PGC, including the cost savings resulting from changes in medical therapy, was also calculated. SUBJECTS: The study reports on a sample of 179 subjects with NIDDM between the ages of 38 and 76 years who completed the clinical trial. RESULTS: Patients in the PGC group experienced a mean 1.1 +/- 2.8 mmol/L decrease in fasting plasma glucose level 6 months after entry to the study, for a total per-patient cost of $112. PGC costs included one glycated hemoglobin assay used by the dietitian to evaluate nutrition outcomes. Patients in the BC group experienced a mean 0.4 +/- 2.7 mmol/L decrease, for a total per-patient cost of $42. In the PGC group, 17 persons had changes in therapy, which yielded an average 12-month cost savings prorated for all patients of $31.49. In contrast, in the BC group, 9 persons had changes in therapy, for an average 12-month prorated cost savings of $3.13. Each unit of change in fasting plasma glucose level from entry to the 6-month follow-up can be achieved with an investment of $5.75 by implementing BC or of $5.84 by implementing PGC. If net costs are considered (per-patient costs--cost savings due to therapy changes), the cost-effectiveness ratios become $5.32 for BC and $4.20 for PGC, assuming the medical changes in therapy were maintained for 12 months. APPLICATIONS: These findings suggest that individualized nutrition interventions can be delivered by experienced dietitians with a reasonable investment of resources. Cost-effectiveness is enhanced when dietitians are engaged in active decision making about intervention alternatives based on the patient's needs.