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      Simulating Time-Dependent Patterns of Nonadherence by Patients With Breast Cancer to Adjuvant Oral Endocrine Therapy

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          Abstract

          PURPOSE

          Nearly 40% of patients with breast cancer discontinue their adjuvant oral endocrine treatment (ET). We measured discontinuation rates of ET at a comprehensive cancer center. We then used an iterative approach to model patterns of determinants associated with discontinuation of ET.

          METHODS

          Patients with nonmetastatic breast cancer receiving active adjuvant ET were approached by nurse practitioners to complete an anonymous survey at one time point. We simulated a prospective model by iteratively regressing adverse effects onto adherence status across windowed time periods of 2 to 3 consecutive years, bootstrapping the smaller group of nonadherent patients and subsampling the larger adherent group.

          RESULTS

          From February to April 2013, 216 participants were enrolled in the study. Forty patients (18.5%) reported that they had discontinued ET during the first 5 years of ET, and an additional four patients (1.9%) missed > 20% of their doses. Using two-sided significance tests, simulations showed that all 13 ET adverse effects and reasons for discontinuation were significantly related to discontinuation at some time point during ET. Worry about ET cost (odds ratio [OR], 1.79), emotional distress (OR, 1.72), and bone and joint pain (OR, 1.69) were the three most impactful reasons for discontinuation, with varying patterns of influence over time.

          CONCLUSION

          These analyses provide preliminary evidence that there are varying patterns of discontinuation of ET. Although some reasons for discontinuation exerted a steady influence over the 6-year ET trajectory (ie, bone and joint pain), other reasons, such as cost, cognitive complaints, and general dislike of pills, became more important in the later years of ET.

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          American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: status report 2004.

          To update the 2003 American Society of Clinical Oncology technology assessment on adjuvant use of aromatase inhibitors. Based on results from multiple large randomized trials, adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer should include an aromatase inhibitor in order to lower the risk of tumor recurrence. Neither the optimal timing nor duration of aromatase inhibitor therapy is established. Aromatase inhibitors are appropriate as initial treatment for women with contraindications to tamoxifen. For all other postmenopausal women, treatment options include 5 years of aromatase inhibitors treatment or sequential therapy consisting of tamoxifen (for either 2 to 3 years or 5 years) followed by aromatase inhibitors for 2 to 3, or 5 years. Patients intolerant of aromatase inhibitors should receive tamoxifen. There are no data on the use of tamoxifen after an aromatase inhibitor in the adjuvant setting. Women with hormone receptor-negative tumors should not receive adjuvant endocrine therapy. The role of other biomarkers such as progesterone receptor and HER2 status in selecting optimal endocrine therapy remains controversial. Aromatase inhibitors are contraindicated in premenopausal women; there are limited data concerning their role in women with treatment-related amenorrhea. The side effect profiles of tamoxifen and aromatase inhibitors differ. The late consequences of aromatase inhibitor therapy, including osteoporosis, are not well characterized. The Panel believes that optimal adjuvant hormonal therapy for a postmenopausal woman with receptor-positive breast cancer includes an aromatase inhibitor as initial therapy or after treatment with tamoxifen. Women with breast cancer and their physicians must weigh the risks and benefits of all therapeutic options.
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            Analysis of human immune responses in quasi-experimental settings: tutorial in biostatistics

            Background Human immunology is a growing field of research in which experimental, clinical, and analytical methods of many life science disciplines are utilized. Classic epidemiological study designs, including observational longitudinal birth cohort studies, offer strong potential for gaining new knowledge and insights into immune response to pathogens in humans. However, rigorous discussion of methodological issues related to designs and statistical analysis that are appropriate for longitudinal studies is lacking. Methods In this communication we address key questions of quality and validity of traditional and recently developed statistical tools applied to measures of immune responses. For this purpose we use data on humoral immune response (IR) associated with the first cryptosporidial diarrhea in a birth cohort of children residing in an urban slum in south India. The main objective is to detect the difference and derive inferences for a change in IR measured at two time points, before (pre) and after (post) an event of interest. We illustrate the use and interpretation of analytical and data visualization techniques including generalized linear and additive models, data-driven smoothing, and combinations of box-, scatter-, and needle-plots. Results We provide step-by-step instructions for conducting a thorough and relatively simple analytical investigation, describe the challenges and pitfalls, and offer practical solutions for comprehensive examination of data. We illustrate how the assumption of time irrelevance can be handled in a study with a pre-post design. We demonstrate how one can study the dynamics of IR in humans by considering the timing of response following an event of interest and seasonal fluctuation of exposure by proper alignment of time of measurements. This alignment of calendar time of measurements and a child's age at the event of interest allows us to explore interactions between IR, seasonal exposures and age at first infection. Conclusions The use of traditional statistical techniques to analyze immunological data derived from observational human studies can result in loss of important information. Detailed analysis using well-tailored techniques allows the depiction of new features of immune response to a pathogen in longitudinal studies in humans. The proposed staged approach has prominent implications for future study designs and analyses.
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              Association between prescription co-payment amount and compliance with adjuvant hormonal therapy in women with early-stage breast cancer.

              Noncompliance with adjuvant hormonal therapy among women with breast cancer is common. Little is known about the impact of financial factors, such as co-payments, on noncompliance. We conducted a retrospective cohort study by using the pharmacy and medical claims database at Medco Health Solutions. Women older than age 50 years who were taking aromatase inhibitors (AIs) for resected breast cancer with two or more mail-order prescriptions, from January 1, 2007, to December 31, 2008, were identified. Patients who were eligible for Medicare were analyzed separately. Nonpersistence was defined as a prescription supply gap of more than 45 days without subsequent refill. Nonadherence was defined as a medication possession ratio less than 80% of eligible days. Of 8110 women younger than age 65 years, 1721 (21.1%) were nonpersistent and 863 (10.6%) were nonadherent. Among 14,050 women age 65 years or older, 3476 (24.7%) were nonpersistent and 1248 (8.9%) were nonadherent. In a multivariate analysis, nonpersistence (ever/never) in both age groups was associated with older age, having a non-oncologist write the prescription, and having a higher number of other prescriptions. Compared with a co-payment of less than $30, a co-payment of $30 to $89.99 for a 90-day prescription was associated with less persistence in women age 65 years or older (odds ratio [OR], 0.69; 95% CI, 0.62 to 0.75) but not among women younger than age 65, although a co-payment of more than $90 was associated with less persistence both in women younger than age 65 (OR, 0.82; 95% CI, 0.72 to 0.94) and those age 65 years or older (OR, 0.72; 95% CI, 0.65 to 0.80). Similar results were seen with nonadherence. We found that higher prescription co-payments were associated with both nonpersistence and nonadherence to AIs. This relationship was stronger in older women. Because noncompliance is associated with worse outcomes, future policy efforts should be directed toward interventions that would help patients with financial difficulties obtain life-saving medications.
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                Author and article information

                Journal
                JCO Clin Cancer Inform
                JCO Clin Cancer Inform
                cci
                cci
                CCI
                JCO Clinical Cancer Informatics
                American Society of Clinical Oncology
                2473-4276
                2019
                19 April 2019
                : 3
                : CCI.18.00091
                Affiliations
                [ 1 ]University of Texas MD Anderson Cancer Center, Houston, TX
                [ 2 ]Rochester Institute of Technology, Rochester, NY
                Author notes
                Eileen H. Shinn, PhD, Department of Behavioral Science, University of Texas MD Anderson Cancer Center, 1155 Herman Pressler, Unit 1330, P.O. Box 301439, Houston, TX 77230-1330; e-mail: eshinn@ 123456mdanderson.org .
                Article
                1800091
                10.1200/CCI.18.00091
                6873985
                31002563
                50bc8542-1b20-4d95-b159-9d7eda4a215e
                © 2019 by American Society of Clinical Oncology

                Licensed under the Creative Commons Attribution 4.0 License: https://creativecommons.org/licenses/by/4.0/

                History
                : 7 December 2018
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 18, Pages: 9
                Categories
                Original Report
                Custom metadata
                v1

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