Estimating power for clinical trials with Patient Reported Outcomes - using Item Response Theory.

OBJECTIVES: Patient reported outcomes (PRO) are widely used in quality of life (QOL) studies, health outcomes research, and clinical trials. The importance of PRO has been advocated by health authorities. Patient Reported Outcomes Measurement Information System (PROMIS) is a collection of standardized measures of PROs using Item Response Theory (IRT). However, in clinical trials with PROs as endpoints, observed scores are routinely used for power estimation rather than IRT scores. This paper aims to fill this gap and estimate power in a two-arm clinical trials with PROMIS measures as endpoints with IRT model. STUDY DESIGN AND SETTING: We conducted a series of simulations to study the IRT power with validated PROMIS measures controlling factors including sample size, effect size, number of items, and missing data proportion. RESULTS: Our results showed that sample size, effect size, and number of items are important indicators of IRT based power estimation for PROMIS measures. When effect size is small and sample size is limited, IRT model provides higher power than the closed form formula. CONCLUSION: IRT based simulation should be used for power estimation in two-armed clinical, especially when there is small effect size or small sample size.

The need to study rural cancer outcome disparities at the local level: a retrospective cohort study in Kansas and Missouri.

BACKGROUND: Rural residence is commonly thought to be a risk factor for poor cancer outcomes. However, a number of studies have reported seemingly conflicting information regarding cancer outcome disparities with respect to rural residence, with some suggesting that the disparity is not present and others providing inconsistent evidence that either urban or rural residence is associated with poorer outcomes. We suggest a simple explanation for these seeming contradictions: namely that rural cancer outcome disparities are related to factors that occur differentially at a local level, such as environmental exposures, lack of access to care or screening, and socioeconomic factors, which differ by type of cancer. METHODS: We conducted a retrospective cohort study examining ten cancers treated at the University of Kansas Medical Center from 2011 to 2018, with individuals from either rural or urban residences. We defined urban residences as those in a county with a U.S. Department of Agriculture Urban Influence Code (UIC) of 1 or 2, with all other residences defines a rural. Inverse probability of treatment weighting was used to create a pseudo-sample balanced for covariates deemed likely to affect the outcomes modeled with cumulative link and weighted Cox-proportional hazards models. RESULTS: We found that rural residence is not a simple risk factor but rather appears to play a complex role in cancer outcome disparities. Specifically, rural residence is associated with higher stage at diagnosis and increased survival hazards for colon cancer but decreased risk for lung cancer compared to urban residence. CONCLUSION: Many cancers are affected by unique social and environmental factors that may vary between rural and urban residents, such as access to care, diet, and lifestyle. Our results show that rurality can increase or decrease risk, depending on cancer site, which suggests the need to consider the factors connected to rurality that influence this complex pattern. Thus, we argue that such disparities must be studied at the local level to identify and design appropriate interventions to improve cancer outcomes.

A framework for personalized mammogram screening.

Breast cancer screening guidelines serve as crucial evidence-based recommendations in deciding when to begin regular screenings. However, due to developments in breast cancer research and differences in research interpretation, screening guidelines can vary between organizations and within organizations over time. This leads to significant lapses in adopting updated guidelines, variable decision making between physicians, and unnecessary screening for low to moderate risk patients (Jacobson and Kadiyala, 2017; Corbelli et al., 2014). For analysis, risk factors were assessed for patient screening behaviors and results. The outcome variable for the first analysis was whether the patient had undergone screening. The risk factors considered were age, marital status, education level, rural versus urban residence, and family history of breast cancer. The outcome variable for the second analysis was whether patients who had undergone breast cancer screening presented abnormal results. The risk factors considered were age, Body Mass Index, family history, smoking and alcohol status, hormonal contraceptive use, Hormone Replacement Therapy use, age of first pregnancy, number of pregnancies (parity), age of first menses, rural versus urban residence, and whether or not patients had at least one child. Logistic regression analysis displayed strong associations for both outcome variables. Risk of screening nonattendance was negatively associated with age as a continuous variable, age as a dichotomous variable, being married, any college education, and family history. Risk of one or more abnormal mammogram findings was positively associated with family history, and hormonal contraceptive use. This procedure will be further developed to incorporate additional risk factors and refine the analysis of currently implemented risk factors.

Optimizing Retrieval of Biospecimens Using the Curated Cancer Clinical Outcomes Database (C3OD).

To fully support their role in translational and personalized medicine, biorepositories and biobanks must continue to advance the annotation of their biospecimens with robust clinical and laboratory data. Translational research and personalized medicine require well-documented and up-to-date information, but the infrastructure used to support biorepositories and biobanks can easily be out of sync with the host institution. To assist researchers and provide them with accurate pathological, epidemiological, and bio-molecular data, the Biospecimen Repository Core Facility (BRCF) at the University of Kansas Medical Center (KUMC) merges data from medical records, the tumor registry, and pathology reports using the Curated Cancer Clinical Outcomes Database (C3OD). In this report, we describe the utilization of C3OD to optimally retrieve and dispense biospecimen samples using these 3 data sources and demonstrate how C3OD greatly increases the efficiency of obtaining biospecimen samples for the researchers.

Relevant Word Order Vectorization for Improved Natural Language Processing in Electronic Health Records.

Electronic health records (EHR) represent a rich resource for conducting observational studies, supporting clinical trials, and more. However, much of the data contains unstructured text, presenting an obstacle to automated extraction. Natural language processing (NLP) can structure and learn from text, but NLP algorithms were not designed for the unique characteristics of EHR. Here, we propose Relevant Word Order Vectorization (RWOV) to aid with structuring. RWOV is based on finding the positional relationship between the most relevant words to predicting the class of a text. This facilitates machine learning algorithms to use the interaction of not just keywords but positional dependencies (e.g. a relevant word occurs 5 relevant words before some term of interest). As a proof-of-concept, we attempted to classify the hormone receptor status of breast cancer patients treated at the University of Kansas Medical Center, comparing RWOV to other methods using the F1 score and AUC. RWOV performed as well as, or better than other methods in all but one case. For F1 score, RWOV had a clear edge on most tasks. AUC tended to be closer, but for HER2, RWOV was significantly better for most comparisons. These results suggest RWOV should be further developed for EHR-related NLP.

A Curated Cancer Clinical Outcomes Database (C3OD) for accelerating patient recruitment in cancer clinical trials.

Data used to determine patient eligibility for cancer clinical trials often come from disparate sources that are typically maintained by different groups within an institution, use differing technologies, and are stored in different formats. Collecting data and resolving inconsistencies across sources increase the time it takes to screen eligible patients, potentially delaying study completion. To address these challenges, the Biostatistics and Informatics Shared Resource at The University of Kansas Cancer Center developed the Curated Cancer Clinical Outcomes Database (C3OD). C3OD merges data from the electronic medical record, tumor registry, bio-specimen and data registry, and allows querying through a single unified platform. By centralizing access and maintaining appropriate controls, C3OD allows researchers to more rapidly obtain detailed information about each patient in order to accelerate eligibility screening. This case report describes the design of this informatics platform as well as initial assessments of its reliability and usability.

Laparoscopic supracervical hysterectomy with transcervical morcellation and sacrocervicopexy for the treatment of uterine prolapse.

INTRODUCTION AND HYPOTHESIS: The objective is to describe our surgical approach for management of uterine prolapse using 5-mm skin incisions and transcervical morcellation. METHODS: This video presents a novel approach for laparoscopic supracervical hysterectomy, bilateral salpingectomy, and sacrocervicopexy using only 5-mm skin incisions and transcervical morcellation. The procedure begins with a laparoscopic supracervical hysterectomy with bilateral salpingectomy. A classic intrafascial supracervical hysterectomy (CISH) instrument is then used transvaginally to core the endocervical canal. A disposable morcellator is placed through the remaining cervix to morcellate the uterus and fallopian tubes. Following morcellation, the handle of the morcellator is removed, and it is used during the remainder of the surgery as an access cannula for the sacrocervicopexy. The polypropylene mesh is introduced through this cannula. It is secured to the anterior and posterior vaginal fascia with a suture that is also introduced through the transcervical port. At the conclusion of the surgery, a previously placed 0 Vicryl purse-string suture at the ectocervix is tied down as a cerclage around the cervix once the cannula is removed. CONCLUSIONS: The transcervical morcellation technique demonstrated in this video allows the surgeon to maintain 5-mm skin incisions and core the endocervical canal during a laparoscopic supracervical hysterectomy with sacrocervicopexy.

p27 deficiency desensitizes Rb-/- cells to signals that trigger apoptosis during pituitary tumor development.

Low p27 expression in many human cancers is a prognostic indicator for poor outcome. While analysing the mechanism by which p27 deficiency contributed to tumor development in the Rb+/- mouse model, we identified a role for p27 as a proapoptotic tumor suppressor. We examined the cell cycle and apoptotic response of these pituitary tumor cells to the dopamine analog bromocriptine as well as the expression of Arf and other cell cycle and apoptotic regulators in these tumors. We also examined the expression of Arf and its function in mouse embryo fibroblasts either singly or doubly deficient for Rb and p27. From these studies, we concluded that the absence of p27 disabled the trigger for an Arf-dependent apoptotic response in Rb-/- tumor cells. This suggests a novel mechanism by which the loss of p27 may impact on tumor development.