Faculty Bibliography

Measurement of height and weight in large studies may force the use of multiple measurers. The purpose of this study was to evaluate the reliability of height, weight, and body mass index (BMI) measures collected by multiple measurers in a large, statewide BMI surveillance program. A random subsample of schools (n=30) was selected from schools that participated in the 2009 to 2010 Ohio third-grade Oral Health/BMI surveillance program. Children (n=1,189) were measured by multiple volunteer health professional measurers and again by a trained researcher, who was standard across all schools. Mean differences for height, weight, and BMI percentiles were calculated for BMI category classifications. Agreement was estimated by the reliability coefficient, McNemar's test, and Kappa statistic. Sensitivity, specificity, and positive and negative predictive values were estimated using the trained researcher measures as the reference. Overall mean differences (95% confidence interval) were 0.45 (0.41-0.48) cm for height, 0.07 (-0.01-0.15) kg for weight, and 1.37 (1.20-1.53) for BMI. The correlation coefficient for all three measures was over 0.9 (P<0.01), indicating a strong positive association between measures. BMI category classifications showed substantial reliability (Kappa range: 0.94-0.96). Percentage agreement ranged from 98% to 99% for all BMI categories, as did sensitivities and specificities. Positive predictive values for all BMI categories were approximately 97%, and close to 100% for negative predictive values. Reliability for height, weight, BMI percentile, and BMI classification was very high, supporting the use of multiple trained measurers in a statewide BMI surveillance program. Similar methods can be applied to other public health and clinical settings to improve anthropometric measurement reliability.

OBJECTIVE:To assess hypothetical acceptance of the human papillomavirus (HPV) vaccine for themselves and a daughter age 9-12 years among Appalachia Ohio women. METHODS:Women with an abnormal Pap smear and randomly selected women with a normal Pap smear from 17 clinics completed an interview in 2006-2008. RESULTS:From 1131 original study participants, 807 (71%) completed a survey about the HPV vaccine for their daughters and themselves. Nearly half, 380 (47%), of the participants had heard of a vaccine to prevent cancer, and 362 (95%) of respondents had heard of HPV. The participants were then told that the FDA had approved a vaccine to prevent HPV. Only 379 (38%) participants identified girls ages 9-12 years as a group who should get the vaccine. After being given the official HPV vaccine recommendation statement, 252 (31%) wanted the vaccine; 198 (25%) were "not sure"; and 353 (44%) did not want the vaccine for themselves. With respect to giving the HPV vaccine to a daughter ages 9-12 years, participants responded "yes" 445 (55%); "not sure" 163 (20%); or "no" 185 (23%). Numerous reasons were provided supporting and opposing vaccine acceptance for themselves and for a daughter. Their physician's recommendation for the HPV vaccine increased vaccine acceptance to 86% for themselves and 90% for a daughter. CONCLUSION/CONCLUSIONS:Knowledge, acceptance, and barriers about the HPV vaccine vary among women living in Appalachia Ohio. Physician recommendation is a key facilitator for vaccine diffusion in this region.

BACKGROUND:Obesity is a known risk factor and poor prognostic factor for many comorbidities including cancer. However, the influence of body mass index (BMI) on ovarian cancer outcomes is inconclusive. Therefore, the objective of this study was to evaluate the impact of BMI and weight changes on survival in patients with advanced ovarian cancer after primary treatment. METHODS:All patients with a diagnosis of advanced epithelial ovarian cancer from January 2000 to December 2007 undergoing primary cytoreductive surgery and adjuvant chemotherapy were identified. Patients were divided into 3 categories: underweight/normal weight (BMI, <25 kg/m), overweight (BMI, 25-30 kg/m), and obese (BMI, >30 kg/m). Adjusted hazard ratios for progression-free survival (PFS) and overall survival (OS) were calculated via Cox proportional hazards models. RESULTS:One hundred ninety-eight patients met the inclusion criteria. For all patients, the mean BMI was 26 kg/m (range, 16.4-49.1 kg/m), with 43% of patients being classified as normal weight, 29% overweight, and 28% as obese. Median 5-year OS was 48.2 months (95% confidence interval, 16.4-49.1 months), and no differences in OS were noted between BMI groups. Unadjusted median PFS for patients with normal weight was 13.7 months, compared with 15.5 and 17.9 months for the overweight and obese groups. Adjusted analysis of BMI over time indicates a trend of increased risk for patients who gain weight in the 6 months after primary therapy on disease progression (hazard ratio, 1.68; 95% confidence interval, 0.87-3.26). CONCLUSIONS:After adjustment for confounders, such as stage, grade, histology, age, and debulking status, data suggest a trend toward a shorter PFS in patients with a normal BMI. However, OS was not significantly related to BMI, and weight change in the 6 months after completion of treatment had no effect on PFS or OS. Further research should be directed at elucidating relationships between weight and cancer biology.

OBJECTIVES/OBJECTIVE:Multiple baseline designs (MBDs) have been suggested as alternatives to group-randomized trials (GRT). We reviewed structural features of MBDs and considered their potential effectiveness in public health research. We also reviewed the effect of staggered starts on statistical power. METHODS:We reviewed the MBD literature to identify key structural features, recent suggestions that MBDs be adopted in public health research, and the literature on power in GRTs with staggered starts. We also computed power for MBDs and GRTs. RESULTS:The features that have contributed to the success of small MBDs in some fields are not likely to translate well to public health research. MBDs can be more powerful than GRTs under some conditions, but those conditions involve assumptions that require careful evaluation in practice. CONCLUSIONS:MBDs will often serve better as a complement of rather than as an alternative to GRTs. GRTs may employ staggered starts for logistical or ethical reasons, but this will always increase their duration and will often increase their cost.

PURPOSE/OBJECTIVE:Multiple myeloma (MM) is an incurable plasma-cell neoplasm for which most treatments involve a therapeutic agent combined with dexamethasone. The preclinical combination of lenalidomide with the mTOR inhibitor CCI-779 has displayed synergy in vitro and represents a novel combination in MM. PATIENTS AND METHODS/METHODS:A phase I clinical trial was initiated for patients with relapsed myeloma with administration of oral lenalidomide on days 1 to 21 and CCI-779 intravenously once per week during a 28-day cycle. Pharmacokinetic data for both agents were obtained, and in vitro transport and uptake studies were conducted to evaluate potential drug-drug interactions. RESULTS:Twenty-one patients were treated with 15 to 25 mg lenalidomide and 15 to 20 mg CCI-779. The maximum-tolerated dose (MTD) was determined to be 25 mg lenalidomide with 15 mg CCI-779. Pharmacokinetic analysis indicated increased doses of CCI-779 resulted in statistically significant changes in clearance, maximum concentrations, and areas under the concentration-time curves, with constant doses of lenalidomide. Similar and significant changes for CCI-779 pharmacokinetics were also observed with increased lenalidomide doses. Detailed mechanistic interrogation of this pharmacokinetic interaction demonstrated that lenalidomide was an ABCB1 (P-glycoprotein [P-gp]) substrate. CONCLUSION/CONCLUSIONS:The MTD of this combination regimen was 25 mg lenalidomide with 15 mg CCI-779, with toxicities of fatigue, neutropenia, and electrolyte wasting. Pharmacokinetic and clinical interactions between lenalidomide and CCI-779 seemed to occur, with in vitro data indicating lenalidomide was an ABCB1 (P-gp) substrate. To our knowledge, this is the first report of a clinically significant P-gp-based drug-drug interaction with lenalidomide.

Public health interventions are often designed to target communities defined either geographically (e.g. cities, counties) or socially (e.g. schools or workplaces). The group randomized trial (GRT) is regarded as the gold standard for evaluating these interventions. However, community leaders may object to randomization as some groups may be denied a potentially beneficial intervention. Under a regression discontinuity design (RDD), individuals may be assigned to treatment based on the levels of a pretest measure, thereby allowing those most in need of the treatment to receive it. In this article, we consider analysis, power, and sample size issues in applying the RDD and related cutoff designs in community-based intervention studies. We examine the power of these designs as a function of intraclass correlation, number of groups, and number of members per group and compare results to the traditional GRT.

Adjuvant surgical oophorectomy is an effective and remarkably cost effective treatment for premenopausal women with hormone receptor positive operable breast cancer. Previously published secondary analyses indicated a survival benefit for patients whose surgery was performed in the luteal phase of the menstrual cycle as opposed to the follicular. This study utilizes additional follow-up and more fully examines this hypothesis and the general implications of long-term follow-up on trial design. Beginning in 1993 we recruited women to a multicenter randomized clinical trial of adjuvant surgical oophorectomy and tamoxifen for 5 years. We recorded the reported day 1 of the patients' last menstrual cycle on the day of their adjuvant surgery. We conducted secondary analyses of the association of history-estimated luteal or follicular phase oophorectomy surgery with disease-free and overall survival. In multivariable Cox analyses, disease-free survival (DFS) exhibited a positive trend and overall survival (OS) showed a significant improvement in patients whose surgery was estimated to have occurred in the luteal phase of the menstrual cycle compared to the follicular (HR for DFS: 0.66, 95% CI: 0.37-1.16; HR for OS: 0.49, 95% CI: 0.27-0.88). From the hazard function plots, it appears that the luteal phase surgery effect on DFS diminishes after 6 years of follow-up. In conclusion, adjuvant surgical oophorectomy during the luteal phase of the menstrual cycle resulted in a reduced hazard of recurrence as compared to oophorectomy in the follicular phase during the first 5.5 years of follow-up. The practical and biological implications of these findings deserve rigorous evaluation in clinical trials.

BACKGROUND:During the recruitment phase of a randomized breast cancer trial, investigating the time to recurrence, we found a strong suggestion that the failure probabilities used at the design stage were too high. Since most of the methodological research involving sample size re-estimation has focused on normal or binary outcomes, we developed a method which preserves blinding to re-estimate sample size in our time to event trial. PURPOSE/OBJECTIVE:A mistakenly high estimate of the failure rate at the design stage may reduce the power unacceptably for a clinically important hazard ratio. We describe an ongoing trial and an application of a sample size re-estimation method that combines current trial data with prior trial data or assumes a parametric model to re-estimate failure probabilities in a blinded fashion. METHODS:Using our current blinded trial data and additional information from prior studies, we re-estimate the failure probabilities to be used in sample size re-calculation. We employ bootstrap re-sampling to quantify uncertainty in the re-estimated sample sizes. RESULTS:At the time of re-estimation data from 278 patients were available, averaging 1.2 years of follow up. Using either method, we estimated a sample size increase of zero for the hazard ratio because the estimated failure probabilities at the time of re-estimation differed little from what was expected. We show that our method of blinded sample size re-estimation preserves the type I error rate. We show that when the initial guess of the failure probabilities are correct, the median increase in sample size is zero. LIMITATIONS/CONCLUSIONS:Either some prior knowledge of an appropriate survival distribution shape or prior data is needed for re-estimation. CONCLUSIONS:In trials when the accrual period is lengthy, blinded sample size re-estimation near the end of the planned accrual period should be considered. In our examples, when assumptions about failure probabilities and HRs are correct the methods usually do not increase sample size or otherwise increase it by very little. Clinical Trials 2010; 7: 219. http://ctj.sagepub.com.

OBJECTIVE:We describe factors, in the context of the Social Determinants of Health model, associated with receiving Pap smears within risk-appropriate guidelines (i.e., guidelines that specify screening intervals based upon a woman's individual risk of developing cervical cancer). METHODS:Completed in June 2006, we conducted a cross-sectional survey of women from 14 health clinics in Ohio Appalachia pertaining to psychosocial, demographic, biological, and health-related factors. A logistic regression model was constructed to predict whether or not a woman was within risk-appropriate cervical cancer screening guidelines. RESULTS:Of 562 women with a date of last Pap smear, 380 (68%) were within risk-appropriate guidelines. Logistic regression showed that, compared to women with low-level SES, women with middle- and high-level SES had 3.39 [1.85, 6.21] and 3.86 [2.03, 7.34] times the odds, respectively, of being within risk-appropriate guidelines. Odds of being within guidelines increased 1.09 [1.04, 1.15] fold for each decrease of one major life event. Additionally, women that were financially better off or financially worse off than their parents at the same age had lower odds (0.41 [0.23, 0.73] and 0.49 [0.24, 0.98], respectively) of being within guidelines than women who reported their finances were the same as their parents. Results also showed an interaction between marital status and age at first intercourse (p=0.001). CONCLUSION/CONCLUSIONS:The results suggest an impact of psychosocial factors on Pap smear testing behaviors, and illustrate the need to examine risk-appropriate interventions to improve screening.