Registry-based trials: a potential model for cost savings?

BACKGROUND/AIMS: Registry-based trials have emerged as a potentially cost-saving study methodology. Early estimates of cost savings, however, conflated the benefits associated with registry utilisation and those associated with other aspects of pragmatic trial designs, which might not all be as broadly applicable. In this study, we sought to build a practical tool that investigators could use across disciplines to estimate the ranges of potential cost differences associated with implementing registry-based trials versus standard clinical trials. METHODS: We built simulation Markov models to compare unique costs associated with data acquisition, cleaning, and linkage under a registry-based trial design versus a standard clinical trial. We conducted one-way, two-way, and probabilistic sensitivity analyses, varying study characteristics over broad ranges, to determine thresholds at which investigators might optimally select each trial design. RESULTS: Registry-based trials were more cost effective than standard clinical trials 98.6% of the time. Data-related cost savings ranged from $4300 to $600,000 with variation in study characteristics. Cost differences were most reactive to the number of patients in a study, the number of data elements per patient available in a registry, and the speed with which research coordinators could manually abstract data. Registry incorporation resulted in cost savings when as few as 3768 independent data elements were available and when manual data abstraction took as little as 3.4 seconds per data field. CONCLUSIONS: Registries offer important resources for investigators. When available, their broad incorporation may help the scientific community reduce the costs of clinical investigation. We offer here a practical tool for investigators to assess potential costs savings.

Electrocardiograms in Healthy North American Children in the Digital Age.

BACKGROUND: Interpretation of pediatric ECGs is limited by lack of accurate sex- and race-specific normal reference values obtained with modern technology for all ages. We sought to obtain contemporary digital ECG measurements in healthy children from North America, to evaluate the effects of sex and race, and to compare our results to commonly used published datasets. METHODS: Digital ECGs (12-lead) were retrospectively collected for children ≤18 years old with normal echocardiograms at 19 centers in the Pediatric Heart Network. Patients were classified into 36 groups: 6 age, 2 sex, and 3 race (white, black, and other/mixed) categories. Standard intervals and amplitudes were measured; mean±SD and 2nd/98th percentiles were determined by age group, sex, and race. For each parameter, multivariable analysis, stratified by age, was conducted using sex and race as predictors. Parameters were compared with 2 large pediatric ECG data sets. RESULTS: Among ECGs from 2400 children, significant differences were found by sex and race categories. The corrected QT interval in lead II was greater for girls compared with boys for age groups ≥3 years (P≤0.03) and for whites compared with blacks for age groups ≥12 years (P<0.05). The R wave amplitude in V6 was greater for boys compared with girls for age groups ≥12 years (P<0.001), for blacks compared with white or other race categories for age groups ≥3 years (P≤0.006), and greater compared with a commonly used public data set for age groups ≥12 years (P<0.0001). CONCLUSIONS: In this large, diverse cohort of healthy children, most ECG intervals and amplitudes varied by sex and race. These differences have important implications for interpreting pediatric ECGs in the modern era when used for diagnosis or screening, including thresholds for left ventricular hypertrophy.

Effects of patient medication requests on physician prescribing behavior: results of a factorial experiment.

BACKGROUND: Because of internet searches, advice from friends, and pharmaceutical advertising, especially direct-to-consumer advertising, patients are increasingly activated to request medications during a physician encounter. OBJECTIVES: To estimate the effect of patient requests for medications on physician-prescribing behavior, unconfounded by patient, physician, and practice-setting factors. RESEARCH DESIGN: Two experiments were conducted among 192 primary care physicians, each using different video-based scenarios: an undiagnosed "patient" with symptoms strongly suggesting sciatica, and a "patient" with already diagnosed chronic knee osteoarthritis. Half of patients with sciatica symptoms requested oxycodone, whereas the other half requested something to help with pain. Similarly, half of knee osteoarthritis patients specifically requested celebrex and half requested something to help with pain. SUBJECTS: To increase generalizability and ensure sufficient numbers were available, we recruited 192 primary care physicians from 6 US states. MEASURES: The primary outcome was whether physicians would accede to a patient's request for a medication. Alternative pain medications prescribed were secondary outcomes. RESULTS: 19.8% of sciatica patients requesting oxycodone would receive a prescription for oxycodone, compared with 1% of those making no specific request (P = 0.001). Fifty-three percent of knee osteoarthritis patients requesting celebrex would receive it, compared with 24% of patients making no request (P = 0.001). Patients requesting oxycodone were more likely to receive a strong narcotic (P = 0.001) and less likely to receive a weak narcotic (P = 0.01). Patients requesting celebrex were much less likely to receive a nonselective nonsteroidal anti-inflammatory drugs (P = 0.008). No patient attributes, physician, or organizational factors influenced a physician's willingness to accede to a patient's medication request. CONCLUSIONS: In both scenarios, activated patient requests for a medication substantially affected physician-prescribing decisions, despite the drawbacks of the requested medications.

Methodological considerations with the use of urine samples for assessment of mercury excretion and markers of renal damage.

OBJECTIVE: To provide recommendations for design and analysis of studies using urine specimens to evaluate renal function or mercury excretion in children. METHODS: An analysis of mercury, albumin, γ-glutamyl transpeptidase (γ-GT) and N-acetyl-ß-D-glucosaminidase (NAG) concentrations was carried out. RESULTS: Mercury concentration and creatinine-corrected renal markers were higher in daytime compared with overnight samples. Excretion rates increased with urinary flow rate. γ-GT and NAG concentrations decreased with storage time at -20°C. Differences by age, sex and race were noted. CONCLUSIONS: We recommend use of these creatinine-corrected markers and collection of timed overnight urine samples, stored at -70°C, with control for urinary flow rate, age, sex and race in statistical models.

Effect of storage time at -20°C on markers used for assessment of renal damage in children: albumin, γ-glutamyl transpeptidase, N-acetyl-ß-D-glucosaminidase and α1-microglobulin.

OBJECTIVE: The objective of this study is to examine the influence of storage time at -20°C on the concentration of albumin, γ-glutamyl transpeptidase (γ-GT), N-acetyl-ß-D-glucosaminidase (NAG), α(1)-microglobulin (A1M) and creatinine in a large sample of healthy children. MATERIAL AND METHODS: The New England Children's Amalgam Trial followed 534 children, aged 6-10 at baseline, for 5 years, with annual urine collections. Urine samples were analysed for creatinine, albumin, γ-GT, NAG and A1M concentrations. Repeated measures analysis of covariance was used to model the effect of storage time on these concentrations. RESULTS: The γ-GT concentration decreased significantly with storage time at -20°C. There was also a limited decrease in NAG. Albumin, A1M and creatinine concentrations did not appear to be affected by storage time at -20°C. CONCLUSIONS: If it is necessary to interpret results from samples stored for a long time at -20°C, it is advisable to account for storage time in statistical models.

Neuropsychological function in school-age children with low mercury exposures.

The EPA reference dose for methylmercury (MeHg) was established using data from populations with greater exposures than those typical of the US. Few data are available on potential adverse health effects at lower levels. We examined relationships between hair mercury (Hg) levels and neuropsychological outcomes in a population of US children. This study included data from 355 children ages 6-10 enrolled in the New England Children's Amalgam Trial. Data on total hair Hg levels, sociodemographic information and neuropsychological function were collected. We evaluated associations between hair Hg and neuropsychological test scores with linear regression methods and used generalized additive models to determine the shape of associations that departed from linearity. Models controlled for relevant covariates, including the potential beneficial effects of consuming fish. In adjusted models, we observed no significant linear relationships between hair Hg level and any test score. Significant departures from linearity were identified for WIAT Math Reasoning and WRAMVA Visual-Motor Composite scores. The association was positive for hair Hg levels below 0.5 microg/g and negative for levels between 0.5 and 1.0 microg/g. Overall, test scores of children with hair Hg levels 1.0 microg/g appeared to be lower than those of children with levels < 1.0 microg/g, but few children had levels in this upper range and these differences did not reach statistical significance. Hair Hg levels below 1.0 microg/g in US school-age children were not adversely related to neuropsychological function.

Extent of tooth decay in the mouth and increased need for replacement of dental restorations: the New England Children's Amalgam Trial.

PURPOSE: The purpose of this study was to assess the relationship between baseline caries experience and the restoration replacement rate in children. METHODS: The 5-year New England Children's Amalgam Trial recruited 534 6- to 10-year-old children with 2 or more carious posterior teeth. The association between decoy and longevity of restorations was assessed. Restorations with no follow-up (N = 391) were excluded from analysis. RESULTS: The average follow-up was 3.0 +/- 1.6 years in 489 children. Restorations with follow-up (N = 3,604) were placed in mouths with a median of 15 dfs/DFS and 8 dft/DFT. The need for replacement increased significantly (P < or = .001) with increasing numbers of dfs/DFS and dft/DFT. After 5 years of follow-up, at least 15% of restorations in a mouth with > or = 14 dfs/DFS needed replacement, compared to 9% for 2 to 5 dfs/DFS. Comparing dft/DFT after 5 years of follow-up, there was a 23% replacement rate for > or = 12 dft/DFT compared to 10% for 2 to 3 dft/DFT. Decoy in the mouth had a greater association with the need for replacement due to new caries compared to replacement due to recurrent caries. CONCLUSION: Children with more decoy at the time of restoration placement were at higher risk for replacement of restorations.

Underutilization of dental care when it is freely available: a prospective study of the New England Children's Amalgam Trial.

OBJECTIVE: This study aims to prospectively examine the trends and reasons for the underutilization of free semiannual preventive dental care provided to children with unmet dental needs who participated in the 5-year New England Children's Amalgam Trial. METHODS: Children aged 6 to 10 at baseline (1997-99) with > or = 2 posterior carious teeth were recruited from rural Maine (n = 232) and urban Boston (n = 266). Interviewer-administered questionnaires assessed demographic and personal characteristics. Reasons for missed appointments were recorded during follow-up and are descriptively presented. We used an ordinal logistic regression to analyze the utilization of semiannual dental visits. RESULTS: On average, urban children utilized 69 percent of the visits and rural children utilized 82 percent of the visits. For both sites, utilization steadily decreased until the end of the 5-year trial. Significant predictors of underutilization in the multivariate model for urban children were non-White race, household welfare use, deep debt, and distance to dental clinic. Among the relatively less-diverse rural children, caregiver education level and a greater number of decayed tooth surfaces at baseline (i.e., need for care) were significantly associated with underutilization. Among all children, the common reasons for missed visits included guardian scheduling and transportation difficulties; reasons among urban participants also indicated a low priority for dental care. CONCLUSIONS: Among these children with unmet dental needs, the provision of free preventive dental care was insufficient to remove the disparities in utilization and did not consistently result in high utilization through follow-up. Differences between educational levels, ethnicities, and rural/urban location suggest that public health programs need to target the social settings in which financial burdens exist.

Oral health disparities in children of immigrants: dental caries experience at enrollment and during follow-up in the New England Children's Amalgam Trial.

OBJECTIVES: Previous research shows increased dental decay among immigrants, but little is known about the oral health of the growing population of children of immigrants. We compared the children of immigrants to the children of US-born caregivers in their caries experience at enrollment and their new caries increments during the 5-year New England Children's Amalgam Trial (NECAT). METHODS: NECAT recruited 283 Boston-area children aged 6 to 10 with untreated caries and offered free semiannual preventive and restorative dental care during the trial. Sociodemographic factors and caregiver immigrant status were assessed through interviews. Multivariate negative binomial models evaluated the association between caregiver immigrant status and clinically assessed carious surfaces. RESULTS: Forty percent of these Boston-area children had immigrant caregivers. At baseline, the children of immigrants had more carious surfaces (11.5 versus 9.4, adjusted for race/ethnicity, age, gender, and caregiver smoking status). Caregiver language preference explained some of this association. Immigrant status and language preference were not associated with 5-year caries increments. CONCLUSIONS: Prevalent disparities in the unmet dental needs of the immigrants' children were quickly ameliorated during participation in NECAT Dental initiatives that target neighborhoods and are sensitive to acculturation levels may help improve and maintain the oral health of immigrant families.

Rural and urban disparities in caries prevalence in children with unmet dental needs: the New England Children's Amalgam Trial.

OBJECTIVES: To compare the prevalence of caries between rural and urban children with unmet dental health needs who participated in the New England Children's Amalgam Trial. METHODS: Baseline tooth and surface caries were clinically assessed in children from rural Maine (n = 243) and urban Boston (n = 291), who were aged 6 to 10 years, with two or more posterior carious teeth and no previous amalgam restorations. Statistical analyses used negative binomial models for primary dentition caries and zero-inflated models for permanent dentition caries. RESULTS: Urban children had a higher mean number of carious primary surfaces (8.5 versus 7.4) and teeth (4.5 versus 3.9) than rural children. The difference remained statistically significant after adjusting for sociodemographic factors and toothbrushing frequency. In permanent dentition, urban children were approximately three times as likely to have any carious surfaces or teeth. However, rural/urban dwelling was not statistically significant in the linear analysis of caries prevalence among children with any permanent dentition caries. Covariates that were statistically significant in all models were age and number of teeth. Toothbrushing frequency was also important for permanent teeth. CONCLUSIONS: Within this population of New England children with unmet oral health needs, significant differences were apparent between rural and urban children in the extent of untreated dental decay. Results indicate that families who agree to participate in programs offering reduced cost or free dental care may present with varying amounts of dental need based on geographic location.

The influence of urinary flow rate in children on excretion of markers used for assessment of renal damage: albumin, gamma-glutamyl transpeptidase, N-acetyl-beta-D -glucosaminidase, and alpha1-microglobulin.

The aim of the present study was to examine the influence of urinary flow rate on markers of renal function in children. A sub-study of the New England Children's Amalgam Trial collected 82 pairs of urine samples from children aged 10-16 years: a timed overnight collection and a spot daytime sample collected the following day. These samples were analyzed for albumin, gamma-glutamyl transpeptidase (gamma-GT), N-acetyl-beta-D-glucosaminidase (NAG), alpha1-microglobulin (A1M), and creatinine concentration. Regression analysis was used to model the effect of urinary flow rate in the timed overnight samples. A paired t-test compared concentrations and creatinine-corrected renal markers between overnight and daytime samples. Albumin, gamma-GT, NAG, and A1M excretion rates increased significantly with urinary flow rate. Their corresponding creatinine-corrected markers did not vary significantly with urinary flow rate, but the creatinine-corrected excretions of albumin, gamma-GT, and NAG were significantly higher in daytime samples than in overnight samples, with the same (non-significant) trend for A1M. The influence of urinary flow rate on creatinine-corrected markers of renal function was markedly less than its influence on excretion rates. Therefore, the use of creatinine-corrected markers seems to be a good choice in practice, with the caveat that daytime and overnight samples are not comparable.

Development of abbreviated measures to assess patient trust in a physician, a health insurer, and the medical profession.

BACKGROUND: Despite the recent proliferation in research on patient trust, it is seldom a primary outcome, and is often a peripheral area of interest. The length of our original scales to measure trust may limit their use because of the practical needs to minimize both respondent burden and research cost. The objective of this study was to develop three abbreviated scales to measure trust in: (1) a physician, (2) a health insurer, and (3) the medical profession. METHODS: Data from two samples were used. The first was a telephone survey of English-speaking adults in the United States (N = 1117) and the second was a telephone survey of English-speaking adults residing in North Carolina who were members of a health maintenance organization (N = 1024). Data were analyzed to examine data completeness, scaling assumptions, internal consistency properties, and factor structure. RESULTS: Abbreviated measures (5-items) were developed for each of the three scales. Cronbach's alpha was 0.87 for trust in a physician (test-retest reliability = 0.71), 0.84 for trust in a health insurer (test-retest reliability = 0.73), and 0.77 for trust in the medical profession. CONCLUSION: Assessment of data completeness, scale score dispersion characteristics, reliability and validity test results all provide evidence for the soundness of the abbreviated 5-item scales.