Publication and non-publication of clinical trials: longitudinal study of applications submitted to a research ethics committee

BACKGROUND: Not all clinical trials are published, which may distort the evidence that is available in the literature. We studied the publication rate of a cohort of clinical trials and identified factors associated with publication and nonpublication of results. METHODS: We analysed the protocols of randomized clinical trials of drug interventions submitted to the research ethics committee of University Hospital (Inselspital) Bern, Switzerland from 1988 to 1998. We identified full articles published up to 2006 by searching the Cochrane CENTRAL database (issue 02/2006) and by contacting investigators. We analyzed factors associated with the publication of trials using descriptive statistics and logistic regression models. RESULTS: 451 study protocols and 375 corresponding articles were analyzed. 233 protocols resulted in at least one publication, a publication rate of 52%. A total of 366 (81%) trials were commercially funded, 47 (10%) had non-commercial funding. 346 trials (77%) were multi-centre studies and 272 of these (79%) were international collaborations. In the adjusted logistic regression model non-commercial funding (Odds Ratio [OR] 2.42, 95% CI 1.14-5.17), multi-centre status (OR 2.09, 95% CI 1.03-4.24), international collaboration (OR 1.87, 95% CI 0.99-3.55) and a sample size above the median of 236 participants (OR 2.04, 95% CI 1.23-3.39) were associated with full publication. CONCLUSIONS: In this cohort of applications to an ethics committee in Switzerland, only about half of clinical drug trials were published. Large multi-centre trials with non-commercial funding were more likely to be published than other trials, but most trials were funded by industry.

Androgen and gonadotropin patterns differ in HIV-1-infected men who develop lipoatrophy during antiretroviral therapy: a case-control study

OBJECTIVES: We compared androgen and gonadotropin values in HIV-infected men who did and did not develop lipoatrophy on combination antiretroviral therapy (cART). METHODS: From a population of 136 treatment-naïve male Caucasians under successful zidovudine/lamivudine-based cART, the 10 patients developing lipoatrophy (cases) were compared with 87 randomly chosen controls. Plasma levels of free testosterone (fT), dehydroepiandrosterone (DHEA), follicle-stimulating hormone and luteinizing hormone (LH) were measured at baseline and after 2 years of cART. RESULTS: At baseline, 60% of the cases and 71% of the controls showed abnormally low fT values. LH levels were normal or low in 67 and 94% of the patients, respectively, indicating a disturbance of the hypothalamic-pituitary-gonadal axis. fT levels did not significantly change after 2 years of cART. Cases showed a significant increase in LH levels, while controls showed a significant increase in DHEA levels. In a multivariate logistic regression model, lipoatrophy was associated with higher baseline DHEA levels (P=0.04), an increase in LH levels during cART (P=0.001), a lower body mass index and greater age. CONCLUSIONS: Hypogonadism is present in the majority of HIV-infected patients. The development of cART-related lipoatrophy is associated with an increase in LH and a lack of increase in DHEA levels.

Comparison between two caller groups of a medical call centre in Switzerland

OBJECTIVES: The incidence distribution of triage advice in the medical call centre Medi24 and the pattern of service utilisation were analysed with respect to two groups of callers with different insurance schemes. Individuals having contracted insurance of the Medi24 model could use the telephone consultation service of the medical call centre Medi24 (mainly part of the mandatory basic health insurance) voluntarily and free of charge whereas individuals holding an insurance policy of the Telmed model (special contract within the mandatory basic health insurance with a premium discount ranging from 8% to 12%) were obliged to have a telephone consultation before arranging an appointment with a medical doctor. METHODS: A cross-sectional study was carried out in the medical call centre Medi24 based on all triage datasets of the Medi24 and Telmed groups collected during the one year period from July 1st 2005 to June 30th 2006. The distribution of the six different urgency levels within the two groups and their respective pattern of service utilisation was determined. In a multivariable logistic regression model the Odds Ratio for every enquiry originating from the Telmed group versus those originating from the Medi24 group was calculated. RESULTS: During a one-year period 48 388 triage requests reached the medical call centre Medi24, 56% derived from the Telmed group and 44% from the Medi24 group. Within the Medi24 group more than 25% of the individuals received self-care advice, within the Telmed group, on the other hand, only about 18% received such advice. In contrast, 27% of the Telmed triage requests but only 18% of the Medi24 triage requests resulted in the advice to make a routine appointment with a medical doctor. The probability that an individual of the Telmed group obtained the advice to go to the accident and emergency department was lower than for an individual of the Medi24 group (OR 0.77, 95% CI 0.60-0.99). Likewise, the probability of self-care advice was decreased in regard to the Medi24 group (OR 0.80, 95% CI 0.75-0.85). However, regarding the advice to make a routine appointment with a medical doctor, the Telmed group was represented more frequently than the Medi24 group (OR 1.36, 95% CI 1.28-1.44). CONCLUSION: In respect of the triage advice, the Telmed group differed significantly from the Medi24 group within all urgency levels. The differences between the two groups in respect of the advice given were still less pronounced than expected against the background of their different contract conditions and the disparate temporal pattern of utilisation. We interprete this finding with the fact that appraising the urgency of health problems appropriately seems to be very difficult for the majority of people seeking advice.

Infection with human herpesvirus 8 and transplant-associated gammopathy

BACKGROUND: The role of human herpesvirus (HHV)-8 in the pathogenesis of multiple myeloma and its pre-malignant state of monoclonal gammopathy is unclear. HHV-8 is transmitted by organ transplantation, representing a unique model with which to investigate primary HHV-8 infection. METHODS: The authors studied the incidence of clonal gammopathy in renal transplant recipients and correlated it with previous and recent HHV-8 infection. RESULTS: Clonal gammopathy was observed in 31 of 162 (19%) HHV-8-seronegative patients, in 5 of 17 (29%) HHV-8-seropositive patients, and in 9 of 24 (38%) HHV-8 seroconverters within 5 years after transplantation. Gammopathy was often transient, and no progression to myeloma was observed. Two patients with persistent gammopathy developed B-cell lymphoma. In a logistic regression model, HHV-8 serostatus of the graft recipient was significantly associated with subsequent development of gammopathy, with a relative risk (RR) of 1.9 and a 95% confidence interval (CI) of 0.5 to 6.4 for an HHV-8-seropositive recipient and an RR of 2.9 and a 95% CI of 1.01 to 8.0 for seroconverters as compared with baseline (HHV-8 seronegative). Other significant variables were cytomegalovirus (CMV) serostatus and the intensity of immunosuppression (RR of 10.4 and 95% CI of 2.6-41.7 for a CMV-negative recipient with a CMV-positive donor vs. a CMV-negative recipient with a CMV-negative donor and RR of 17.6 and 95% CI of 2.0-150.8 if OKT3 was used vs. no use of antilymphocytic substances). CONCLUSIONS: Transplant recipients with HHV-8 infection are more likely to develop clonal gammopathy. However, this risk is much lower than the risk conferred by CMV infection and antilymphocytic therapy, arguing against a major role of HHV-8 infection in the pathogenesis of clonal plasma cell proliferation.

Expanding the cone location and magnitude index to include corneal thickness and posterior surface information for the detection of keratoconus

PURPOSE To extend the capabilities of the Cone Location and Magnitude Index algorithm to include a combination of topographic information from the anterior and posterior corneal surfaces and corneal thickness measurements to further improve our ability to correctly identify keratoconus using this new index: ConeLocationMagnitudeIndex_X. DESIGN Retrospective case-control study. METHODS Three independent data sets were analyzed: 1 development and 2 validation. The AnteriorCornealPower index was calculated to stratify the keratoconus data from mild to severe. The ConeLocationMagnitudeIndex algorithm was applied to all tomography data collected using a dual Scheimpflug-Placido-based tomographer. The ConeLocationMagnitudeIndex_X formula, resulting from analysis of the Development set, was used to determine the logistic regression model that best separates keratoconus from normal and was applied to all data sets to calculate PercentProbabilityKeratoconus_X. The sensitivity/specificity of PercentProbabilityKeratoconus_X was compared with the original PercentProbabilityKeratoconus, which only uses anterior axial data. RESULTS The AnteriorCornealPower severity distribution for the combined data sets are 136 mild, 12 moderate, and 7 severe. The logistic regression model generated for ConeLocationMagnitudeIndex_X produces complete separation for the Development set. Validation Set 1 has 1 false-negative and Validation Set 2 has 1 false-positive. The overall sensitivity/specificity results for the logistic model produced using the ConeLocationMagnitudeIndex_X algorithm are 99.4% and 99.6%, respectively. The overall sensitivity/specificity results for using the original ConeLocationMagnitudeIndex algorithm are 89.2% and 98.8%, respectively. CONCLUSIONS ConeLocationMagnitudeIndex_X provides a robust index that can detect the presence or absence of a keratoconic pattern in corneal tomography maps with improved sensitivity/specificity from the original anterior surface-only ConeLocationMagnitudeIndex algorithm.

Adjudication-related processes are underreported and lack standardization in clinical trials of venous thromboembolism: a systematic review

OBJECTIVES Although the use of an adjudication committee (AC) for outcomes is recommended in randomized controlled trials, there are limited data on the process of adjudication. We therefore aimed to assess whether the reporting of the adjudication process in venous thromboembolism (VTE) trials meets existing quality standards and which characteristics of trials influence the use of an AC. STUDY DESIGN AND SETTING We systematically searched MEDLINE and the Cochrane Library from January 1, 2003, to June 1, 2012, for randomized controlled trials on VTE. We abstracted information about characteristics and quality of trials and reporting of adjudication processes. We used stepwise backward logistic regression model to identify trial characteristics independently associated with the use of an AC. RESULTS We included 161 trials. Of these, 68.9% (111 of 161) reported the use of an AC. Overall, 99.1% (110 of 111) of trials with an AC used independent or blinded ACs, 14.4% (16 of 111) reported how the adjudication decision was reached within the AC, and 4.5% (5 of 111) reported on whether the reliability of adjudication was assessed. In multivariate analyses, multicenter trials [odds ratio (OR), 8.6; 95% confidence interval (CI): 2.7, 27.8], use of a data safety-monitoring board (OR, 3.7; 95% CI: 1.2, 11.6), and VTE as the primary outcome (OR, 5.7; 95% CI: 1.7, 19.4) were associated with the use of an AC. Trials without random allocation concealment (OR, 0.3; 95% CI: 0.1, 0.8) and open-label trials (OR, 0.3; 95% CI: 0.1, 1.0) were less likely to report an AC. CONCLUSION Recommended processes of adjudication are underreported and lack standardization in VTE-related clinical trials. The use of an AC varies substantially by trial characteristics.

Clinical signs of deformed wing virus infection are predictive markers for honey bee colony losses.

The ectoparasitic mite Varroa destructor acting as a virus vector constitutes a central mechanism for losses of managed honey bee, Apis mellifera, colonies. This creates demand for an easy, accurate and cheap diagnostic tool to estimate the impact of viruliferous mites in the field. Here we evaluated whether the clinical signs of the ubiquitous and mite-transmitted deformed wing virus (DWV) can be predictive markers of winter losses. In fall and winter 2007/2008, A.m. carnica workers with apparent wing deformities were counted daily in traps installed on 29 queenright colonies. The data show that colonies which later died had a significantly higher proportion of workers with wing deformities than did those which survived. There was a significant positive correlation between V. destructor infestation levels and the number of workers displaying DWV clinical signs, further supporting the mite's impact on virus infections at the colony level. A logistic regression model suggests that colony size, the number of workers with wing deformities and V. destructor infestation levels constitute predictive markers for winter colony losses in this order of importance and ease of evaluation.

Multifactor effects and evidence of potential interaction between complement factor H Y402H and LOC387715 A69S in age-related macular degeneration.

BACKGROUND: Variants in the complement cascade genes and the LOC387715/HTRA1, have been widely reported to associate with age-related macular degeneration (AMD), the most common cause of visual impairment in industrialized countries. METHODS/PRINCIPAL FINDINGS: We investigated the association between the LOC387715 A69S and complement component C3 R102G risk alleles in the Finnish case-control material and found a significant association with both variants (OR 2.98, p = 3.75 x 10(-9); non-AMD controls and OR 2.79, p = 2.78 x 10(-19), blood donor controls and OR 1.83, p = 0.008; non-AMD controls and OR 1.39, p = 0.039; blood donor controls), respectively. Previously, we have shown a strong association between complement factor H (CFH) Y402H and AMD in the Finnish population. A carrier of at least one risk allele in each of the three susceptibility loci (LOC387715, C3, CFH) had an 18-fold risk of AMD when compared to a non-carrier homozygote in all three loci. A tentative gene-gene interaction between the two major AMD-associated loci, LOC387715 and CFH, was found in this study using a multiplicative (logistic regression) model, a synergy index (departure-from-additivity model) and the mutual information method (MI), suggesting that a common causative pathway may exist for these genes. Smoking (ever vs. never) exerted an extra risk for AMD, but somewhat surprisingly, only in connection with other factors such as sex and the C3 genotype. Population attributable risks (PAR) for the CFH, LOC387715 and C3 variants were 58.2%, 51.4% and 5.8%, respectively, the summary PAR for the three variants being 65.4%. CONCLUSIONS/SIGNIFICANCE: Evidence for gene-gene interaction between two major AMD associated loci CFH and LOC387715 was obtained using three methods, logistic regression, a synergy index and the mutual information (MI) index.

Time to renal disease and end-stage renal disease in PROFILE: a multiethnic lupus cohort.

BACKGROUND: Renal involvement is a serious manifestation of systemic lupus erythematosus (SLE); it may portend a poor prognosis as it may lead to end-stage renal disease (ESRD). The purpose of this study was to determine the factors predicting the development of renal involvement and its progression to ESRD in a multi-ethnic SLE cohort (PROFILE). METHODS AND FINDINGS: PROFILE includes SLE patients from five different United States institutions. We examined at baseline the socioeconomic-demographic, clinical, and genetic variables associated with the development of renal involvement and its progression to ESRD by univariable and multivariable Cox proportional hazards regression analyses. Analyses of onset of renal involvement included only patients with renal involvement after SLE diagnosis (n = 229). Analyses of ESRD included all patients, regardless of whether renal involvement occurred before, at, or after SLE diagnosis (34 of 438 patients). In addition, we performed a multivariable logistic regression analysis of the variables associated with the development of renal involvement at any time during the course of SLE.In the time-dependent multivariable analysis, patients developing renal involvement were more likely to have more American College of Rheumatology criteria for SLE, and to be younger, hypertensive, and of African-American or Hispanic (from Texas) ethnicity. Alternative regression models were consistent with these results. In addition to greater accrued disease damage (renal damage excluded), younger age, and Hispanic ethnicity (from Texas), homozygosity for the valine allele of FcgammaRIIIa (FCGR3A*GG) was a significant predictor of ESRD. Results from the multivariable logistic regression model that included all cases of renal involvement were consistent with those from the Cox model. CONCLUSIONS: Fcgamma receptor genotype is a risk factor for progression of renal disease to ESRD. Since the frequency distribution of FCGR3A alleles does not vary significantly among the ethnic groups studied, the additional factors underlying the ethnic disparities in renal disease progression remain to be elucidated.

Temporal lobe white matter asymmetry and language laterality in epilepsy patients.

Recent studies using diffusion tensor imaging (DTI) have advanced our knowledge of the organization of white matter subserving language function. It remains unclear, however, how DTI may be used to predict accurately a key feature of language organization: its asymmetric representation in one cerebral hemisphere. In this study of epilepsy patients with unambiguous lateralization on Wada testing (19 left and 4 right lateralized subjects; no bilateral subjects), the predictive value of DTI for classifying the dominant hemisphere for language was assessed relative to the existing standard-the intra-carotid Amytal (Wada) procedure. Our specific hypothesis is that language laterality in both unilateral left- and right-hemisphere language dominant subjects may be predicted by hemispheric asymmetry in the relative density of three white matter pathways terminating in the temporal lobe implicated in different aspects of language function: the arcuate (AF), uncinate (UF), and inferior longitudinal fasciculi (ILF). Laterality indices computed from asymmetry of high anisotropy AF pathways, but not the other pathways, classified the majority (19 of 23) of patients using the Wada results as the standard. A logistic regression model incorporating information from DTI of the AF, fMRI activity in Broca's area, and handedness was able to classify 22 of 23 (95.6%) patients correctly according to their Wada score. We conclude that evaluation of highly anisotropic components of the AF alone has significant predictive power for determining language laterality, and that this markedly asymmetric distribution in the dominant hemisphere may reflect enhanced connectivity between frontal and temporal sites to support fluent language processes. Given the small sample reported in this preliminary study, future research should assess this method on a larger group of patients, including subjects with bi-hemispheric dominance.

Plasma DNA is Elevated in Patients with Deep Vein Thrombosis

OBJECTIVE To investigate if plasma DNA is elevated in patients with deep vein thrombosis (DVT) and to determine whether there is a correlation with other biomarkers of DVT. BACKGROUND Leukocytes release DNA to form extracellular traps (ETs), which have recently been linked to experimental DVT. In baboons and mice, extracellular DNA co-localized with von Willebrand factor (VWF) in the thrombus and DNA appeared in circulation at the time of thrombus formation. ETs have not been associated with clinical DVT. SETTING From December 2008 to August 2010, patients were screened through the University of Michigan Diagnostic Vascular Unit and were divided into three distinct groups: 1) the DVT positive group, consisting of patients who were symptomatic for DVT, which was confirmed by compression duplex ultrasound (n=47); 2) the DVT negative group, consisting of patients that present with swelling and leg pain but had a negative compression duplex ultrasound, (n=28); and 3) a control group of healthy non-pregnant volunteers without signs or symptoms of active or previous DVT (n=19). Patients were excluded if they were less than 18 years of age, unwillingness to consent, pregnant, on an anticoagulant therapy, or diagnosed with isolated calf vein thrombosis. METHODS Blood was collected for circulating DNA, CRP, D-dimer, VWF activity, myeloperoxidase (MPO), ADAMTS13 and VWF. The Wells score for a patient's risk of DVT was assessed. The Receiver Operating Characteristic (ROC) curve was generated to determine the strength of the relationship between circulating DNA levels and the presence of DVT. A Spearman correlation was performed to determine the relationship between the DNA levels and the biomarkers and the Wells score. Additionally the ratio of ADAMTS13/VWF was assessed. RESULTS Our results showed that circulating DNA (a surrogate marker for NETs) was significantly elevated in DVT patients, compared to both DVT negative patients (57.7±6.3 vs. 17.9±3.5ng/mL, P<.01) and controls (57.7±6.3 vs. 23.9±2.1ng/mL, P<.01). There was a strong positive correlation with CRP (P<.01), D-dimer (P<.01), VWF (P<.01), Wells score (P<.01) and myeloperoxidase (MPO) (P<.01), along with a strong negative correlation with ADAMTS13 (P<.01) and the ADAMTS13/VWF ratio. The logistic regression model showed a strong association between plasma DNA and the presence of DVT (ROC curve was determined to be 0.814). CONCLUSIONS Plasma DNA is elevated in patients with deep vein thrombosis and correlates with biomarkers of DVT. A strong correlation between circulating DNA and MPO suggests that neutrophils may be a source of plasma DNA in patients with DVT.

BAYESIAN PHASE I DOSE FINDING IN CANCER TRIALS

This dissertation explores phase I dose-finding designs in cancer trials from three perspectives: the alternative Bayesian dose-escalation rules, a design based on a time-to-dose-limiting toxicity (DLT) model, and a design based on a discrete-time multi-state (DTMS) model. We list alternative Bayesian dose-escalation rules and perform a simulation study for the intra-rule and inter-rule comparisons based on two statistical models to identify the most appropriate rule under certain scenarios. We provide evidence that all the Bayesian rules outperform the traditional ``3+3'' design in the allocation of patients and selection of the maximum tolerated dose. The design based on a time-to-DLT model uses patients' DLT information over multiple treatment cycles in estimating the probability of DLT at the end of treatment cycle 1. Dose-escalation decisions are made whenever a cycle-1 DLT occurs, or two months after the previous check point. Compared to the design based on a logistic regression model, the new design shows more safety benefits for trials in which more late-onset toxicities are expected. As a trade-off, the new design requires more patients on average. The design based on a discrete-time multi-state (DTMS) model has three important attributes: (1) Toxicities are categorized over a distribution of severity levels, (2) Early toxicity may inform dose escalation, and (3) No suspension is required between accrual cohorts. The proposed model accounts for the difference in the importance of the toxicity severity levels and for transitions between toxicity levels. We compare the operating characteristics of the proposed design with those from a similar design based on a fully-evaluated model that directly models the maximum observed toxicity level within the patients' entire assessment window. We describe settings in which, under comparable power, the proposed design shortens the trial. The proposed design offers more benefit compared to the alternative design as patient accrual becomes slower.

Cement volume is the most important modifiable predictor for pain relief in BKP: results from SWISSspine, a nationwide registry

Purpose The effectiveness of vertebral augmentation techniques is a currently highly debated issue. The biomechanical literature suggests that cement filling volumes may play an important role in the ‘‘dosage’’ of vertebral augmentation and its pain alleviating effect. Good clinical data about filling volumes are scarce and most patient series are small. Therefore, we investigated the predictors of pain alleviation after balloon kyphoplasty in the nationwide SWISSspine registry where cement volumes are also recorded. Methods All single-level vertebral fractures with no additional fracture stabilization and availability of at least one follow-up within 6 months after surgery were included. The following potential predictors were assessed in a multivariate logistic regression model with the group’s average pain alleviation of 41 points on VAS as the desired outcome: patient age, patient sex, diagnosis, preoperative pain, level of fracture, type of fracture, age of fracture, segmental kyphotic deformity, cement volume, vertebral body filling volume, and cement extrusions. Results There were 194 female and 82 males with an average age of 70.4 and 65.3 years, respectively. Female patients were about twice as likely for achieving the average pain relief compared to males (p = 0.04). The preoperative pain level was the strongest predictor in that the likelihood for achieving an at least 41-point pain relief increased by about 8 % with each additional point of preoperative pain (p\0.001). A thoraco-lumbar fracture had a three times higher odds for the average pain relief compared with a lumbar fracture (p = 0.03). An A.3.1 fracture only had about a third of the probability for average pain relief compared with an A.1.1 fracture (p = 0.004). Cement volumes up to 4.5 ml only had an approximately 40 % chance for a minimum 41-point pain alleviation as compared with cement volumes of at least 4.5 ml (p = 0.007). In addition, the relationship between cement volume and pain alleviation followed a dose-dependent pattern. Conclusions Cement volume was revealed as a significant predictor for pain relief in BKP. Cement volume was the third most important influential covariate and the most important modifiable and operator dependent one. The clear dose-outcome relationship between cement filling volumes and pain relief additionally supports these findings. Cement volumes of [4.5 ml seem to be recommendable for achieving relevant pain alleviation. Patient sex and fracture type and location were further significant predictors and all these covariates should be recorded and reported in future studies about the pain alleviating effectiveness of vertebral augmentation procedures.

Outcomes assessment of a pediatric practice guideline

Objective. This study examines the structure, processes, and data necessary to assess the outcome variables, length of stay and total cost, for a pediatric practice guideline. The guideline was developed by a group of physicians and ancillary staff members representing the services that most commonly provide treatment for asthma patients at Texas Children's Hospital, as a means of standardizing care. Outcomes have needed to be assessed to determine the practice guideline's effectiveness.^ Data sources and study design. Data for the study were collected retrospectively from multiple hospital data bases and from inpatient chart reviews. All patients in this quasi-experimental study had a diagnosis of Asthma (ICD-9-CM Code 493.91) at the time of admission.^ The study examined data for 100 patients admitted between September 15, 1995 and November 15, 1995, whose physician had elected to apply the asthma practice guideline at the time of the patient's admission. The study examined data for 66 inpatients admitted between September 15, 1995 and November 15, 1995, whose physician elected not to apply the asthma practice guideline. The principal outcome variables were identified as "Length of Stay" and "Cost".^ Principal findings. The mean length of stay for the group in which the practice guideline was applied was 2.3 days, and 3.1 days for the comparison group, who did not receive care directed by the practice guideline. The difference was statistically significant (p value = 0.008). There was not a demonstrable difference in risk factors, health status, or quality of care between the groups. Although not showing statistical significance in the univariate analysis, private insurance showed a significant difference in the logistic regression model presenting an elevated odds ratio (odds ratio = 2.2 for a hospital stay $\le$2 days to an odds ratio = 4.7 for a hospital stay $\le$3 days) showing that patients with private insurance experienced greater risk of a shorter hospital stay than the patients with public insurance in each of the logistic regression models. Public insurance included; Medicaid, Medicare, and charity cases. Private insurance included; private insurance policies whether group, individual, or managed care. The cost of an admission was significantly less for the group in which the practice guideline was applied, with a mean difference between the two groups of $1307 per patient.^ Conclusion. The implementation and utilization of a pediatric practice guideline for asthma inpatients at Texas Children's Hospital has a significant impact in terms of reducing the total cost of the hospital stay and length of the hospital stay for asthma patients admitted to Texas Children's Hospital. ^

A nonparametric method of comparing the partial areas under two correlated receiver operating characteristic curves

A non-parametric method was developed and tested to compare the partial areas under two correlated Receiver Operating Characteristic curves. Based on the theory of generalized U-statistics the mathematical formulas have been derived for computing ROC area, and the variance and covariance between the portions of two ROC curves. A practical SAS application also has been developed to facilitate the calculations. The accuracy of the non-parametric method was evaluated by comparing it to other methods. By applying our method to the data from a published ROC analysis of CT image, our results are very close to theirs. A hypothetical example was used to demonstrate the effects of two crossed ROC curves. The two ROC areas are the same. However each portion of the area between two ROC curves were found to be significantly different by the partial ROC curve analysis. For computation of ROC curves with large scales, such as a logistic regression model, we applied our method to the breast cancer study with Medicare claims data. It yielded the same ROC area computation as the SAS Logistic procedure. Our method also provides an alternative to the global summary of ROC area comparison by directly comparing the true-positive rates for two regression models and by determining the range of false-positive values where the models differ. ^