Biomedical subjects

Neal L Oden

Publications and source records attributed to Neal L Oden.

4 recordsLinked to original sources

PubMed2006

Influence of prior assignment on refusal rates in a trial of supplemental oxygen for retinopathy of prematurity.

Investigators aware of prior treatment assignments may deliberately or subliminally influence rates of subsequent consent in randomised trials, thus introducing the possibility of bias. As a trial of Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP) was not masked to health professionals other than ophthalmologists, this possibility was evaluated by comparing the incidence of refusal to participate in relation to the previous assignment. Over 5 years, the STOP-ROP trial enrolled 649 infants, while 394 eligible subjects refused. Enrolled infants were assigned to supplemental oxygen or control groups at 30 centres including 71 hospitals, and stratified into two severity strata of their retinopathy of prematurity. We studied whether the assignment of the previously enrolled infant to either the supplemental arm or the control arm of the study affected the incidence of refusal to participate in the study by the next eligible infant. We also evaluated the possibility that refusal based on the preceding assignment could have influenced either the baseline balance of eye severity and pulmonary status between the two arms of the study or the final outcome of the randomised trial. There was a significantly higher incidence of refusal if the prior enrollee had been assigned to the supplemental oxygen group (44%) as compared with the control group (34%, P = 0.004). This effect from the prior assignment was larger in the later half of the study. Irrespective of the prior enrollee's assignment, refusal was more likely for more mature infants and those with milder baseline disease. Selection bias did not influence the ophthalmic or pulmonary findings at baseline, or the study outcomes. In incompletely masked studies, monitoring the distribution of refusers in relation to the previous assignment can reveal selection bias. Despite evidence of unequal refusal rates, the results of the STOP-ROP trial were not affected.

Age Factors↗

PubMed2005

A pulmonary score for assessing the severity of neonatal chronic lung disease.

BACKGROUND: Limited data are available to describe the spectrum of severity of neonatal chronic lung disease. In the multicenter Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity trial, all infants had some degree of pulmonary dysfunction, because eligibility required a median oxygen saturation of < or =94% with room air. Infants randomized to the supplemental oxygen group (oxygen saturation target of 96-99%) had more pulmonary morbidity than did those in the conventional group (oxygen saturation target of 88-94%). This prompted the retrospective development of a pulmonary severity score to compare the baseline status of the 2 groups. OBJECTIVES: To describe a pulmonary score that reflects the severity of neonatal lung disease and to evaluate the association of the score and its components with subsequent pulmonary morbidity through 3 months of corrected age. DESIGN AND METHODS: A pulmonary score was developed empirically by a consensus panel of 3 neonatologists and was defined as the fraction of inspired oxygen (Fio2) x (support) + (medications), where Fio2 is the actual or "effective" (for nasal cannula) Fio2; support is 2.5 for a ventilator, 1.5 for nasal continuous positive airway pressure, or 1.0 for nasal cannula or hood oxygen; and medications is 0.20 for systemic steroids for bronchopulmonary dysplasia, 0.10 each for regular diuretics or inhaled steroids, and 0.05 each for methylxanthines or intermittent diuretics. The scores could range from 0.21 to 2.95. Pulmonary morbidity was defined as any of the following occurring from randomization at a mean of 35.4 weeks' postmenstrual age through 3 months of corrected age: death or rehospitalization with a pulmonary cause; an episode of pneumonia/sepsis/exacerbation of chronic lung disease; or continued hospitalization, supplemental oxygen therapy, diuretic treatment, or systemic steroid therapy at 3 months. Between-group differences were tested with the Kruskal-Wallis or chi2 test. RESULTS: Data through death or the 3-month corrected age examination were available for 588 infants. Enrolled infants represented a wide spectrum of severity of chronic lung disease, with baseline pulmonary scores at randomization ranging from 0.21 to 2.6. The median pulmonary score at enrollment did not differ between the conventional and supplemental groups (0.42 and 0.45, respectively). However, higher baseline pulmonary scores were observed for infants who did versus did not develop subsequent pulmonary morbidity (0.48 vs 0.38). The pulmonary score was associated with subsequent pulmonary morbidity. Regression analyses adjusting for Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity group assignment, gestational age at birth, race, gender, and postmenstrual age at randomization revealed that the score was a significant independent predictor of subsequent pulmonary morbidity (odds ratio: 7.2; 95% confidence interval: 3.6-14.4). CONCLUSIONS: The pulmonary score, calculated near term, reflects a wide spectrum of bronchopulmonary dysplasia severity and is associated with subsequent pulmonary morbidity through corrected age of 3 months. This simple score could prove useful in clinical and research settings. Validation of the score requires additional study.

Bronchopulmonary Dysplasia↗

PubMed2003

Statistical issues related to early closure of STOP-ROP, a group-sequential trial.

The Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity trial used the group-sequential alpha-spending approach with asymmetrical tails to investigate whether supplemental oxygen therapy would reduce the proportion of infants progressing from prethreshold retinopathy of prematurity (ROP) to threshold ROP from 30% to 20%. Three years of enrollment were predicted. After 4 years, the data and safety monitoring committee (DSMC), faced with a projected delay of 2-3 more years, opted to terminate the trial after 1 further year of enrollment despite a continually borderline test statistic. We discuss factors relating to the DSMC decision and its effect upon the conclusions that may be drawn from the trial.

Clinical Trials Data Monitoring Committees↗

PubMedDate not supplied

A new protocol for evaluating putative causes for multiple variables in a spatial setting, illustrated by its application to European cancer rates.

We introduce a statistical protocol for analyzing spatially varying data, including putative explanatory variables. The procedures comprise preliminary spatial autocorrelation analysis (from an earlier study), path analysis, clustering of the resulting set of path diagrams, ordination of these diagrams, and confirmatory tests against extrinsic information. To illustrate the application of these methods, we present incidence and mortality rates of 31 organ- and sex-specific cancers in Europe; these rates vary markedly with geography and type of cancer. Additionally, we investigated three factors (ethnohistory, genetics, and geography) putatively affecting these rates. The five variables were correlated separately for the 31 cancers over European reporting stations. We analyzed the correlations by path analysis, k-means clustering, and nonmetric multidimensional scaling; coefficients of the 31 path diagrams modeling the correlations vary substantially. To simplify interpretation, we grouped the diagrams into five clusters, for which we describe the differential effects of the three putative causes on incidence and mortality. When scaled, the path coefficients intergrade without marked gaps between clusters. Ethnic differences make for differences in cancer rates, even when the populations tested are ancient and complex mixtures. Path analysis usefully decomposes a structural model involving effects and putative causes, and estimates the magnitude of the model's components. Smooth intergradation of the path coefficients suggests the putative causes are the results of multiple forces. Despite this continuity of the path diagrams of the 31 cancers, clustering offers a useful segmentation of the continuum. Etiological and other extrinsic information on the cancers map significantly into the five clusters, demonstrating their epidemiological relevance.

Biometry↗