Developing a Standardized and Reusable Method to Link Distributed Health Plan Databases to the National Death Index: Methods Development Study Protocol.

BACKGROUND: Certain medications may increase the risk of death or death from specific causes (eg, sudden cardiac death), but these risks may not be identified in premarket randomized trials. Having the capacity to examine death in postmarket safety surveillance activities is important to the US Food and Drug Administration's (FDA) mission to protect public health. Distributed networks of electronic health plan databases used by the FDA to conduct multicenter research or medical product safety surveillance studies often do not systematically include death or cause-of-death information. OBJECTIVE: This study aims to develop reusable, generalizable methods for linking multiple health plan databases with the Centers for Disease Control and Prevention's National Death Index Plus (NDI+) data. METHODS: We will develop efficient administrative workflows to facilitate multicenter institutional review board (IRB) review and approval within a distributed network of 6 health plans. The study will create a distributed NDI+ linkage process that avoids sharing of identifiable patient information between health plans or with a central coordinating center. We will develop standardized criteria for selecting and retaining NDI+ matches and methods for harmonizing linked information across multiple health plans. We will test our processes within a use case comprising users and nonusers of antiarrhythmic medications. RESULTS: We will use the linked health plan and NDI+ data sets to estimate the incidences and incidence rates of mortality and specific causes of death within the study use case and compare the results with reported estimates. These comparisons provide an opportunity to assess the performance of the developed NDI+ linkage approach and lessons for future studies requiring NDI+ linkage in distributed database settings. This study is approved by the IRB at Harvard Pilgrim Health Care in Boston, MA. Results will be presented to the FDA at academic conferences and published in peer-reviewed journals. CONCLUSIONS: This study will develop and test a reusable distributed NDI+ linkage approach with the goal of providing tested NDI+ linkage methods for use in future studies within distributed data networks. Having standardized and reusable methods for systematically obtaining death and cause-of-death information from NDI+ would enhance the FDA's ability to assess mortality-related safety questions in the postmarket, real-world setting. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/21811.

Randomized trial of a clinic-based weight loss intervention in cancer survivors.

BACKGROUND: This trial examined the efficacy of a clinic-based weight loss intervention in cancer survivors. METHODS: This single-center phase II trial randomized survivors of solid tumors and hematologic malignancies to a 15-week group-based weight loss intervention that included caloric restriction and physical activity (n = 30) or a wait-list control intervention (n = 30). The primary study outcome was body mass. Secondary study outcomes included body composition using dual-energy X-ray absorptiometry, physical fitness using the 6-min walk test (6MWT), and concentrations of serum biomarkers. RESULTS: Participants in the intervention group lost 5.6 ± 4.4% of baseline weight (4.6 ± 3.9 kg), whereas participants in the control group gained 0.2 ± 2.4% of baseline weight (0.2 ± 2.0 kg); intervention effect - 5.8% (95% CI - 7.8, - 3.8); - 4.8 kg (95% CI - 6.6, - 3.0); P = 0.0001. A larger proportion of participants in the intervention group lost ≥ 5% of baseline weight compared to the control group (43 vs 0%; P < 0.0001). The intervention led to reductions in fat mass (- 3.2 ± 0.7 kg; P < 0.0001), improvements in physical fitness (an increase of 22.6 ± 10.8 m on 6MWT; P = 0.03), and reductions in concentrations of insulin (- 7.7 ± 3.5 µU/mL; P = 0.004) and leptin (- 7.3 ± 4.0 ng/mL; P = 0.04). CONCLUSION: A 15-week clinic-based weight loss intervention resulted in significant weight loss and improvements in body composition, physical fitness, and concentrations of serum biomarkers in cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Weight loss programs provide a number of benefits for cancer survivors; survivors should inquire about the availability of lifestyle programs offered at their cancer center and within their local communities.

Effect of the LIVESTRONG at the YMCA exercise program on physical activity, fitness, quality of life, and fatigue in cancer survivors.

BACKGROUND: Physical activity (PA) has been linked to a lower risk of developing and dying of cancer, yet many cancer survivors do not exercise. In the current study, the authors evaluated the impact of the LIVESTRONG at the YMCA exercise program, available at Young Men's Christian Associations (YMCAs) across the United States, on PA, fitness, quality of life, fatigue, body composition, serum biomarkers, and program safety in cancer survivors. METHODS: Cancer survivors were recruited through the Yale Cancer Center and the Dana-Farber Cancer Institute and randomized to a 12-week, twice-weekly LIVESTRONG at the YMCA exercise program at YMCAs in Connecticut or Massachusetts or to a control group. Questionnaires, dual-energy x-ray absorptiometry scans, 6-minute walk tests (6MWTs), and a fasting blood draw were completed at baseline and at 12 weeks. Intervention effects were evaluated using mixed model repeated measures analysis, with changes at 12 weeks in PA and 6MWT as the primary endpoints. RESULTS: A total of 186 participants were randomized (95 to the exercise group and 91 to the control group). The majority of patients were diagnosed with AJCC stage I to II cancer and 53% had breast cancer. Participants randomized to the LIVESTRONG at the YMCA program experienced increases in PA (71% exercising at ≥ 150 minutes/week vs 26% of controls; P<.05) and improvements in the 6MWT (group difference: 28.9 meters [95% confidence interval, 0.3-49.0; P = .004]) and quality of life (group difference: 2.6 [95% confidence interval, 0.1-5.0; P = .04]). No adverse events were reported. CONCLUSIONS: The LIVESTRONG at the YMCA exercise program has the potential to impact thousands of survivors across the YMCA network and could lead to improvements in disease and psychosocial outcomes in the growing population of cancer survivors. Cancer 2017;123:1249-1258. © 2016 American Cancer Society.

Randomized trial of a physical activity intervention in women with metastatic breast cancer.

BACKGROUND: Exercise interventions improve fitness, functional capacity, and quality of life in patients with early-stage breast cancer, but to the authors' knowledge there are few data regarding the feasibility or potential benefits of exercise in women with metastatic breast cancer. METHODS: Individuals with metastatic breast cancer were randomized 1:1 to a 16-week moderate-intensity exercise intervention or wait-list control group. Intervention goals included 150 minutes of moderate-intensity aerobic exercise per week. The baseline and 16-week evaluations included a modified Bruce Ramp treadmill test, 7-day Physical Activity Recall interview, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C-30) questionnaire. RESULTS: A total of 101 participants were randomized (48 to the intervention group and 53 to the control group). The median age of the participants was 49 years, the median time since the diagnosis of metastatic breast cancer was 1.1 years, and approximately 42% of participants were undergoing chemotherapy at the time of enrollment. Study attrition was higher in the intervention arm (14 participants vs 8 participants; P = .15). Women randomized to the exercise intervention experienced a nonsignificant increase with regard to minutes of weekly exercise (62.4 minutes vs 46.0 minutes; P = .17) and physical functioning (EORTC QLQ C30: 4.79 vs 0.93 [P = .23] and Bruce Ramp Treadmill test: 0.61 minutes vs 0.37 minutes [P = .35]) compared with control participants. CONCLUSIONS: Participation in an exercise intervention did not appear to result in significant improvements in physical functioning in a heterogeneous group of women living with advanced breast cancer. Given the significant benefits of exercise in women with early-stage breast cancer, more work is needed to explore alternative interventions to determine whether exercise could help women with metastatic disease live more fully with fewer symptoms from disease and treatment.

Impact of a telephone-based physical activity intervention upon exercise behaviors and fitness in cancer survivors enrolled in a cooperative group setting.

Observational studies demonstrate an association between physical activity and improved outcomes in breast and colon cancer survivors. To test these observations with a large, randomized clinical trial, an intervention that significantly impacts physical activity in these patients is needed. The Active After Cancer Trial (AACT) was a multicenter pilot study evaluating the feasibility of a telephone-based exercise intervention in a cooperative group setting. Sedentary (engaging in <60 min of recreational activity/week) breast and colorectal cancer survivors were randomized to a telephone-based exercise intervention or usual care control group. The intervention was delivered through the University of California at San Diego; participants received ten phone calls over the course of the 16-week intervention. All participants underwent assessment of physical activity, fitness, physical functioning, fatigue and exercise self-efficacy at baseline and after the 16-week intervention. One hundred and twenty-one patients were enrolled through ten Cancer and Leukemia Group B (CALGB) institutions; 100 patients had breast cancer and 21 had colorectal cancer. Participants randomized to the exercise group increased physical activity by more than 100 versus 22% in controls (54.5 vs. 14.6 min, P = 0.13), and experienced significant increases in fitness (increased 6-min walk test distance by 186.9 vs. 81.9 feet, P = 0.006) and physical functioning (7.1 vs. 2.6, P = 0.04) as compared to the control group. Breast and colorectal cancer survivors enrolled in a multicenter, telephone-based physical activity intervention increased physical activity and experienced significant improvements in fitness and physical functioning. Lifestyle intervention research is feasible in a cooperative group setting.

Physical and psychological outcomes among women in a telephone-based exercise intervention during adjuvant therapy for early stage breast cancer.

BACKGROUND: Many women gain weight after breast cancer diagnosis. Weight gain has been associated with poor quality of life (QOL), dissatisfaction with one's body, increased risk of postoperative complications, and possibly even an increased risk of breast cancer recurrence. Studies have suggested that decreases in physical activity during treatment may contribute to weight gain in breast cancer patients. METHODS: In this single-arm pilot study, 41 sedentary women with early stage breast cancer participated in a 12-week, moderate-intensity aerobic exercise intervention during adjuvant chemotherapy and/or radiation. The target exercise goal was 150 minutes of activity/week. Participants underwent evaluation of exercise behaviors, fitness, and psychological and anthropometric measures at baseline and after the 12-week intervention. RESULTS: Most participants were premenopausal, and 80% were treated with intensive chemotherapy regimens that included both an anthracycline and a taxane. In the 34 patients for whom baseline and week 12 measures were available, weekly exercise increased from 13 minutes to 116 minutes at week 12 (p < 0.001). Cardiorespiratory fitness and QOL improved significantly (p < 0.003 and p = 0.001, respectively), and there was a trend toward improvements in fatigue (p = 0.08). Participants also avoided weight gain and increases in body fat over the course of the 12-week protocol. CONCLUSIONS: Women participating in a home-based exercise intervention during adjuvant therapy significantly increased activity and avoided weight gain, which has been associated with poor QOL and cancer outcomes in early stage breast cancer.