Use of administrative data to increase the practicality of clinical trials: Insights from the Women's Health Initiative.
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ABSTRACT:
SUBMITTER: Anderson GL
PROVIDER: S-EPMC5059108 | biostudies-other | 2016 Oct
REPOSITORIES: biostudies-other
Publications
Use of administrative data to increase the practicality of clinical trials: Insights from the Women's Health Initiative.
Anderson Garnet L GL Burns Carolyn J CJ Larsen Joseph J Shaw Pamela A PA
Clinical trials (London, England) 20160630 5
<h4>Background</h4>To reduce research costs in the context of pragmatic trials, consideration is given to using administrative data (Medicare claims) to ascertain clinical outcomes.<h4>Methods</h4>In the historical context of the Women's Health Initiative, the correspondence between selected cardiovascular events derived from Medicare claims was compared to those documented and adjudicated in this large-scale prevention trial.<h4>Results</h4>Classification performance varies somewhat by type of ...[more]
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Project description:IMPORTANCE:The use of menopausal hormone therapy (HT) continues in clinical practice, but reports are conflicting concerning the longer-term breast cancer effects of relatively short-term use. OBJECTIVE:To report the longer-term influence of menopausal HT on breast cancer incidence in the 2 Women's Health Initiative (WHI) randomized clinical trials. DESIGN, SETTING, AND PARTICIPANTS:A total of 27,347 postmenopausal women aged 50 to 79 years were enrolled at 40 US centers from 1993 to 1998 and followed up for a median of 13 years through September 2010. INTERVENTIONS:A total of 16,608 women with a uterus were randomized to conjugated equine estrogens (0.625 mg/d [estrogen]) plus medroxyprogesterone acetate (2.5 mg/d [progestin]) (E?+?P) or placebo with a median intervention duration of 5.6 years, and 10,739 women with prior hysterectomy were randomized to conjugated equine estrogens alone (0.625 mg/d) or placebo with a median intervention duration of 7.2 years. MAIN OUTCOMES AND MEASURES:Time-specific invasive breast cancer incidence rates and exploratory analyses of breast cancer characteristics by intervention and postintervention phases in the 2 HT trials. RESULTS:In the E?+?P trial, hazard ratios (HRs) for the influence of combined HT on breast cancer were lower than 1 for 2 years (HR, 0.71; 95% CI, 0.47-1.08) and steadily increased throughout intervention, becoming significantly increased for the entire intervention phase (HR, 1.24; 95% CI, 1.01-1.53). In the early postintervention phase (within 2.75 years from intervention), there was a sharp decrease in breast cancer incidence in the combined HT group, though the HR remained higher than 1 (HR, 1.23; 95% CI, 0.90-1.70). During the late postintervention phase (requiring patient re-consent), the HR for breast cancer risk remained higher than 1 through 5.5 years (median) of additional follow-up (HR, 1.37; 95% CI, 1.06-1.77). In the estrogen alone trial, the HR for invasive breast cancer risk was lower than 1 throughout the intervention phase (HR, 0.79; 95% CI, 0.61-1.02) and remained lower than 1 in the early postintervention phase (HR, 0.55; 95% CI, 0.34-0.89), but risk reduction was not observed during the late postintervention follow-up (HR, 1.17; 95% CI, 0.73-1.87). Characteristics of breast cancers diagnosed during early and late postintervention phases differed in both trials. CONCLUSIONS AND RELEVANCE:In the E?+?P trial, the higher breast cancer risk seen during intervention was followed by a substantial drop in risk in the early postintervention phase, but a higher breast cancer risk remained during the late postintervention follow-up. In the estrogen alone trial, the lower breast cancer risk seen during intervention was sustained in the early postintervention phase but was not evident during the late postintervention follow-up.
| S-EPMC6871651 | biostudies-literature
Project description:The effects of dietary protein on bone health are controversial.We examined the relation between protein intake with fracture and bone mineral density (BMD) within the Women's Health Initiative (WHI).This prospective analysis included 144,580 women aged 50-79 y at baseline in the WHI clinical trials (CTs) and observational study (OS) that recruited participants in 1993-1998 with follow-up through 2011. Self-reported clinical fractures were collected semiannually through the original end of the trials (WHI CTs) and annually (WHI OS) by questionnaires. Hip fracture was adjudicated by a central review of radiology reports. BMDs for total body, hip, and spine were measured at baseline and 3 and 6 y in 9062 women at 3 WHI clinics by using dual-energy X-ray absorptiometry. Protein intake was assessed via food-frequency questionnaire and calibrated by using biomarkers of energy and protein intakes. Associations between protein intake and fracture were estimated by using Cox proportional hazards regression, and the relation between protein intake and BMD was estimated by using linear regression.Median biomarker-calibrated protein intake was 15% of energy intake. Per 20% increase in calibrated protein intake (percentage of energy), there was no significant association with total fracture (HR: 0.99; 95% CI: 0.97, 1.02) or hip fracture (HR: 0.91; 95% CI: 0.84, 1.00), but there was an inverse association with forearm fracture (HR: 0.93; 95% CI: 0.88, 0.98). Each 20% increase in calibrated protein intake was associated with a significantly higher BMD for total body (mean 3-y change: 0.003 g/cm²; 95% CI: 0.001, 0.005 g/cm²) and hip (mean 3-y change: 0.002 g/cm²; 95% CI: 0.001, 0.004 g/cm²).Higher biomarker-calibrated protein intake within the range of usual intake was inversely associated with forearm fracture and was associated with better maintenance of total and hip BMDs. These data suggest higher protein intake is not detrimental to bone health in postmenopausal women.
| S-EPMC3953886 | biostudies-literature
Project description:BACKGROUND:Randomized trials can compare economic as well as clinical outcomes, but economic data are difficult to collect. Linking clinical trial data with Medicare claims could provide novel information on health care utilization and cost. METHODS:We linked data from Medicare claims of women ?65 years old who had Medicare fee-for-service coverage with their clinical data from the Women's Health Initiative trials of conjugated equine estrogens plus medroxyprogesterone acetate (CEE+MPA) versus placebo and of CEE-alone versus placebo. The primary outcome was total Medicare spending during the intervention phase of the trial, and the secondary outcomes were spending on diseases hypothesized a priori to be sensitive to the effects of hormone therapy. RESULTS:In the CEE+MPA trial, 4,557 participants ?65 years old were included. Women randomly assigned to CEE+MPA had 4% higher mean Medicare spending overall ($45,690 vs $43,920, P = .08) but 0.5% lower spending for hormone-sensitive diseases ($3,526 vs $3,547, P = .07), with 73% higher spending for coronary heart disease (P = .045) and 122% higher spending for pulmonary embolism (P = .026). In the CEE-alone trial, 3,107 participants were included. Total spending among women randomly assigned to CEE was 3.3% higher ($75,411 vs $72,997, P = .16), and 1.7% higher spending for hormone-sensitive diseases ($5,213 vs $5,127, P = .57), but with 39% lower spending for hip fracture (p<0.03). CONCLUSIONS:Menopausal hormone therapy increased spending for some diseases, but decreased spending for others. These offsetting effects led to modest (3%-4%), nonsignificant increases in overall spending among women aged 65 years and older.
| S-EPMC5901884 | biostudies-literature
Project description:Debate and controversy surrounding the benefits and risks of menopausal hormone therapy (MHT) for prevention of cardiovascular disease has continued in the decade since the cessation of the Women's Health Initiative (WHI) hormone therapy interventions. As a result, many women and their physicians have been reluctant to turn to MHT for relief of vasomotor and other menopausal symptoms. However, several follow-up studies of WHI participants provide additional insight into clinical characteristics of women who are more likely to have favorable outcomes and lower rates of adverse events associated with MHT. This report focuses on those studies that identify characteristics and biomarkers helpful in stratifying risk for an individual. Incorporation of these factors into a benefit:risk model could assist in patient-oriented decision making regarding use of MHT. Personalizing treatment offers the potential to minimize risk and improve health outcomes.
| S-EPMC3652473 | biostudies-literature
Project description:We re-evaluate the Women's Health Initiative findings and their implications for clinical practice. Menopausal hormone therapy (HT) was effective for relief of vasomotor symptoms, and the risk of coronary heart disease (CHD) tended to be reduced in women close to menopause compared with the increased risk in women more distant from menopause. In recently menopausal women, short-term absolute risks of stroke and venous thromboembolism were small. Estrogen plus progestin therapy, but not estrogen therapy, increased the risk of breast cancer with a suggestion of greater risk when initiated close to the menopause. Menopausal HT increased the risk of CHD in women more than 20 years distant from menopause, particularly in women with vasomotor symptoms. It remains unknown whether the suggestive benefit for CHD in younger women will translate into benefits or harms if menopausal HT is continued into older ages. Based on Women's Health Initiative data, the use of menopausal HT for fewer than 5 years is a reasonable option for the relief of moderate to severe vasomotor symptoms. The risks seen with estrogen plus progestin therapy suggest careful periodic reassessment of the ongoing therapy needs for women taking estrogen plus progestin therapy. The more favorable profile of estrogen therapy allows for individualized management with respect to duration of use when symptoms persist. For both estrogen therapy and estrogen plus progestin therapy, the baseline risk profile of the individual woman needs to be taken into account. Menopausal HT is not suitable for long-term prevention of CHD given risks of stroke, venous thromboembolism, and breast cancer (for estrogen plus progestin therapy) found in both clinical trials and in observational studies.
| S-EPMC3547645 | biostudies-other
Project description:Data collected as part of routine clinical practice could be used to detect cardiovascular outcomes in pragmatic clinical trials or clinical registry studies. The reliability of claims data for documenting outcomes is unknown.We linked records of Women's Health Initiative (WHI) participants aged ?65 years to Medicare claims data and compared hospitalizations that had diagnosis codes for acute myocardial infarction or coronary revascularization with WHI outcomes adjudicated by study physicians. We then compared the hazard ratios for active versus placebo hormone therapy based solely on WHI-adjudicated events with corresponding hazard ratios based solely on claims data for the same hormone trial participants. Agreement between WHI-adjudicated outcomes and Medicare claims was good for the diagnosis of myocardial infarction (?, 0.71-0.74) and excellent for coronary revascularization (?, 0.88-0.91). The hormone:placebo hazard ratio for clinical myocardial infarction was 1.31 (95% confidence interval, 1.03-1.67) based on WHI outcomes and 1.29 (95% confidence interval, 1.00-1.68) based on Medicare data. The hazard ratio for coronary revascularization was 1.09 (95% confidence interval, 0.88-1.35) based on WHI outcomes and 1.10 (95% confidence interval, 0.89-1.35) based on Medicare data. The differences between hazard ratios derived from WHI and Medicare data were not significant in 1000 bootstrap replications.Medicare claims may provide useful data on coronary heart disease outcomes among patients aged ?65 years in clinical research studies.URL: www.clinicaltrials.gov. Unique identifier: NCT00000611.
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Project description:NHLBI TOPMed: The Women's Health Initiative
| PRJNA352302 | ENA
Project description:BackgroundWe examined common patterns of home environmental modification (HEM) use and associated major (including disability-, cardiovascular-, and cancer-related) health conditions and events among older women.MethodsWomen, aged 78.6 ± 6.3 years (n = 71,257), self-reported utilization of nine types of HEMs (hand rails, grab bars, ramps, nonslip surfaces, tacking carpets/rugs, decreasing clutter, increasing lighting, raised sink/counter heights, other). Concurrent history of major health conditions and events was collected. Odds ratios (ORs) were estimated based on overall HEM use and four latent classes (low HEM use [56%], rails/grab bars [20%], lighting/decluttering [18%], high HEM use [5%]), adjusted for age, marital status, race/ethnicity, education, depression, and obesity.ResultsFifty-five percent of women reported using any HEM (overall), with strongest associations among disability-related conditions. Activities of daily living limitations were strongly associated with high HEM use (OR = 8.16, 95% confidence interval [CI] = 6.62-10.05), railing/grab bar use (OR = 4.02, 95% CI = 3.26-4.95), and lighting/declutter use (OR = 1.87, 95% CI = 1.40-2.50) versus low HEM use. Recent falls were positively associated with overall HEM use (OR = 1.79, 95% CI = 1.72-1.87); high HEM use (OR = 2.89, 95% CI = 2.64-3.16), railings/grab bars use (OR = 2.32, 95% CI = 2.18-2.48), and lighting/declutter use (OR = 1.93, 95% CI = 1.79-2.08) were positively associated with recent falls. Modest associations were observed between HEM use and select (ie, atrial fibrillation, heart valve disease, stroke) cardiovascular outcomes.ConclusionsAmong older women, disability-related conditions, including functional limitations and recent falls, were strongly associated with overall HEM use, high HEM use, and railings/grab bar use.
| S-EPMC7566318 | biostudies-literature
Project description:More than two-thirds of US women are overweight or obese, placing them at increased risk for postmenopausal breast cancer.To investigate in this secondary analysis the associations of overweight and obesity with risk of postmenopausal invasive breast cancer after extended follow-up in the Women's Health Initiative (WHI) clinical trials.The WHI clinical trial protocol incorporated measured height and weight, baseline and annual or biennial mammography, and adjudicated breast cancer end points in 67?142 postmenopausal women ages 50 to 79 years at 40 US clinical centers. The women were enrolled from 1993 to 1998 with a median of 13 years of follow-up through 2010; 3388 invasive breast cancers were observed.Height and weight were measured at baseline, and weight was measured annually thereafter. Data were collected on demographic characteristics, personal and family medical history, and personal habits (smoking, physical activity). Women underwent annual or biennial mammograms. Breast cancers were verified by medical records reviewed by physician adjudicators.Women who were overweight and obese had an increased invasive breast cancer risk vs women of normal weight. Risk was greatest for obesity grade 2?plus?3 (body mass index [BMI], calculated as weight in kilograms divided by height in meters squared, >35.0) (hazard ratio [HR] for invasive breast cancer, 1.58; 95% CI, 1.40-1.79). A BMI of 35.0 or higher was strongly associated with risk for estrogen receptor-positive and progesterone receptor-positive breast cancers (HR, 1.86; 95% CI, 1.60-2.17) but was not associated with estrogen receptor-negative cancers. Obesity grade 2?plus?3 was also associated with advanced disease, including larger tumor size (HR, 2.12; 95% CI, 1.67-2.69; P?=?.02), positive lymph nodes (HR, 1.89; 95% CI, 1.46-2.45; P?=?.06), regional and/or distant stage (HR, 1.94; 95% CI, 1.52-2.47; P?=?.05), and deaths after breast cancer (HR, 2.11; 95% CI, 1.57-2.84; P?<?.001). Women with a baseline BMI of less than 25.0 who gained more than 5% of body weight over the follow-up period had an increased breast cancer risk (HR, 1.36; 95% CI, 1.1-1.65), but among women already overweight or obese we found no association of weight change (gain or loss) with breast cancer during follow-up. There was no effect modification of the BMI-breast cancer relationship by postmenopausal hormone therapy, and the direction of association across BMI categories was similar for never, past, and current hormone therapy use.Obesity is associated with increased invasive breast cancer risk in postmenopausal women. These clinically meaningful findings should motivate programs for obesity prevention.clinicaltrials.gov Identifier: NCT00000611.
| S-EPMC5070941 | biostudies-literature
Project description:The associations between breast tenderness during use of conjugated equine estrogen (CEE) therapy with or without medroxyprogesterone (MPA) therapy and subsequent breast cancer risk are unknown. We analyzed data from the Women's Health Initiative Estrogen plus Progestin (N = 16,608, 5.6 years intervention) and estrogen-alone (N = 10,739, 6.8 years intervention) clinical trials until trial close-out (Spring 2005). At baseline and annually, participants underwent mammography and clinical breast exam. Self-reported breast tenderness was assessed at baseline and 12 months. Invasive breast cancer was confirmed by medical record review. The risk of new-onset breast tenderness after 12 months was significantly higher among women assigned to active therapy than placebo (CEE-alone vs. placebo risk ratio [RR] 2.15, 95% confidence interval [CI] 1.97-2.35; CEE + MPA vs. placebo RR 3.07, 95% CI 2.85-3.30). CEE + MPA doubled the risk of invasive breast cancer among women with baseline breast tenderness (hazard ratio [HR] 2.16, 95% CI 1.29-3.74), but had a smaller effect among women without baseline breast tenderness (HR 1.17; 95% CI 0.97-1.41). New-onset breast tenderness was associated with a higher risk of breast cancer among women assigned to CEE + MPA (HR 1.33, 95% CI 1.02-1.72, P = 0.03), but not among women assigned to CEE-alone (HR 0.98, 95% CI 0.62-1.53). New-onset breast tenderness during use of CEE + MPA was associated with increased subsequent breast cancer risk. The association of CEE + MPA therapy with increased breast cancer risk was especially pronounced among women with baseline breast tenderness.
| S-EPMC3697872 | biostudies-literature