Prospective Benefit-Risk Monitoring of New Drugs for Rapid Assessment of Net Favorability in Electronic Health Care Data.

BACKGROUND: Benefit-risk assessment (BRA) methods can combine measures of benefits and risks into a single value. OBJECTIVES: To examine BRA metrics for prospective monitoring of new drugs in electronic health care data. METHODS: Using two electronic health care databases, we emulated prospective monitoring of three drugs (rofecoxib vs. nonselective nonsteroidal anti-inflammatory drugs, prasugrel vs. clopidogrel, and denosumab vs. bisphosphonates) using a sequential propensity score-matched cohort design. We applied four BRA metrics: number needed to treat and number needed to harm; incremental net benefit (INB) with maximum acceptable risk; INB with relative-value-adjusted life-years; and INB with quality-adjusted life-years (QALYs). We determined whether and when the bootstrapped 99% confidence interval (CI) for each metric excluded zero, indicating net favorability of one drug over the other. RESULTS: For rofecoxib, all four metrics yielded a negative value, suggesting net favorability of nonselective nonsteroidal anti-inflammatory drugs over rofecoxib, and the 99% CI for all but the number needed to treat and number needed to harm excluded the null during follow-up. For prasugrel, only the 99% CI for INB-QALY excluded the null, but trends in values over time were similar across the four metrics, suggesting overall net favorability of prasugrel versus clopidogrel. The 99% CI for INB-relative-value-adjusted life-years and INB-QALY excluded the null in the denosumab example, suggesting net favorability of denosumab over bisphosphonates. CONCLUSIONS: Prospective benefit-risk monitoring can be used to determine net favorability of a new drug in electronic health care data. In three examples, existing BRA metrics produced qualitatively similar results but differed with respect to alert generation.

A unified framework for classification of methods for benefit-risk assessment.

BACKGROUND: Patients, physicians, and other decision makers make implicit but inevitable trade-offs among risks and benefits of treatments. Many methods have been proposed to promote transparent and rigorous benefit-risk analysis (BRA). OBJECTIVE: To propose a framework for classifying BRA methods on the basis of key factors that matter most for patients by using a common mathematical notation and compare their results using a hypothetical example. METHODS: We classified the available BRA methods into three categories: 1) unweighted metrics, which use only probabilities of benefits and risks; 2) metrics that incorporate preference weights and that account for the impact and duration of benefits and risks; and 3) metrics that incorporate weights based on decision makers' opinions. We used two hypothetical antiplatelet drugs (a and b) to compare the BRA methods within our proposed framework. RESULTS: Unweighted metrics include the number needed to treat and the number needed to harm. Metrics that incorporate preference weights include those that use maximum acceptable risk, those that use relative-value-adjusted life-years, and those that use quality-adjusted life-years. Metrics that use decision makers' weights include the multicriteria decision analysis, the benefit-less-risk analysis, Boers' 3 by 3 table, the Gail/NCI method, and the transparent uniform risk benefit overview. Most BRA methods can be derived as a special case of a generalized formula in which some are mathematically identical. Numerical comparison of methods highlights potential differences in BRA results and their interpretation. CONCLUSIONS: The proposed framework provides a unified, patient-centered approach to BRA methods classification based on the types of weights that are used across existing methods, a key differentiating feature.

Comparison of survival outcomes among cancer patients treated in and out of clinical trials.

BACKGROUND: Clinical trials test the efficacy of a treatment in a select patient population. We examined whether cancer clinical trial patients were similar to nontrial, "real-world" patients with respect to presenting characteristics and survival. METHODS: We reviewed the SWOG national clinical trials consortium database to identify candidate trials. Demographic factors, stage, and overall survival for patients in the standard arms were compared with nontrial control subjects selected from the Surveillance, Epidemiology, and End Results program. Multivariable survival analyses using Cox regression were conducted. The survival functions from aggregate data across all studies were compared separately by prognosis (≥50% vs <50% average 2-year survival). All statistical tests were two-sided. RESULTS: We analyzed 21 SWOG studies (11 good prognosis and 10 poor prognosis) comprising 5190 patients enrolled from 1987 to 2007. Trial patients were younger than nontrial patients (P < .001). In multivariable analysis, trial participation was not associated with improved overall survival for all 11 good-prognosis studies but was associated with better survival for nine of 10 poor-prognosis studies (P < .001). The impact of trial participation on overall survival endured for only 1 year. CONCLUSIONS: Trial participation was associated with better survival in the first year after diagnosis, likely because of eligibility criteria that excluded higher comorbidity patients from trials. Similar survival patterns between trial and nontrial patients after the first year suggest that trial standard arm outcomes are generalizable over the long term and may improve confidence that trial treatment effects will translate to the real-world setting. Reducing eligibility criteria would improve access to clinical trials.

Nativity and occupational class disparities in uninsurance and routine preventive care use among Asian Americans.

Using data from 1,530 Asian respondents of the 2002-2003 National Latino and Asian American Study, we examined how nativity and occupational class are associated with uninsurance, no routine physical check-up in the past year and no dental/eye exam use in the past year using weighted multivariate logistic regression models. Recent immigrants had increased odds of uninsurance and no dental/eye exam use than US-born Asians which became nonsignificant after controlling for occupational class and covariates. Unemployed and service workers had increased odds of uninsurance than white-collar workers even after controlling for income and limited English proficiency (LEP). Approximately 35-40 % of blue-collar and service workers reported neither type of preventive care use. Even after controlling for LEP, income, uninsurance, having a regular doctor or place of care, service workers had significantly increased odds of no physical check-up and no dental/eye exam use and blue-collar workers had marginally significant increased odds of no dental/eye exam use. Significant occupational disparities exist in access and preventive care use with workers in service occupations being particularly underserved.

Glycemic control associated with secure patient-provider messaging within a shared electronic medical record: a longitudinal analysis.

OBJECTIVE: To study differences in glycemic control and HbA1c testing associated with use of secure electronic patient-provider messaging. We hypothesized that messaging use would be associated with better glycemic control and a higher rate of adherence to HbA1c testing recommendations. RESEARCH DESIGN AND METHODS: Retrospective observational study of secure messaging at Group Health, a large nonprofit health care system. Our analysis included adults with diabetes who had registered for access to a shared electronic medical record (SMR) between 2003 and 2006. We fit log-linear regression models, using generalized estimating equations, to estimate the adjusted rate ratio of meeting three indicators of glycemic control (HbA1c <7%, HbA1c <8%, and HbA1c >9%) and HbA1c testing adherence by level of previous messaging use. Multiple imputation and inverse probability weights were used to account for missing data. RESULTS: During the study period, 6,301 adults with diabetes registered for access to the SMR. Of these individuals, 74% used messaging at least once during that time. Frequent use of messaging during the previous calendar quarter was associated with a higher rate of good glycemic control (HbA1c <7%: rate ratio, 1.26 [95% CI, 1.15-1.37]) and a higher rate testing adherence (1.20 [1.15-1.25]). CONCLUSIONS: Among SMR users, recent and frequent messaging use was associated with better glycemic control and a higher rate of HbA1c testing adherence. These results suggest that secure messaging may facilitate important processes of care and help some patients to achieve or maintain adequate glycemic control.

Improving low-wage, midsized employers' health promotion practices: a randomized controlled trial.

BACKGROUND: The Guide to Community Preventive Services (Community Guide) offers evidence-based intervention strategies to prevent chronic disease. The American Cancer Society (ACS) and the University of Washington Health Promotion Research Center co-developed ACS Workplace Solutions (WPS) to improve workplaces' implementation of Community Guide strategies. PURPOSE: To test the effectiveness of WPS for midsized employers in low-wage industries. DESIGN: Two-arm RCT; workplaces were randomized to receive WPS during the study (intervention group) or at the end of the study (delayed control group). SETTING/PARTICIPANTS: Forty-eight midsized employers (100-999 workers) in King County WA. INTERVENTION: WPS provides employers one-on-one consulting with an ACS interventionist via three meetings at the workplace. The interventionist recommends best practices to adopt based on the workplace's current practices, provides implementation toolkits for the best practices the employer chooses to adopt, conducts a follow-up visit at 6 months, and provides technical assistance. MAIN OUTCOME MEASURES: Employers' implementation of 16 best practices (in the categories of insurance benefits, health-related policies, programs, tracking, and health communications) at baseline (June 2007-June 2008) and 15-month follow-up (October 2008-December 2009). Data were analyzed in 2010-2011. RESULTS: Intervention employers demonstrated greater improvement from baseline than control employers in two of the five best-practice categories; implementing policies (baseline scores: 39% program, 43% control; follow-up scores: 49% program, 45% control; p=0.013) and communications (baseline scores: 42% program, 44% control; follow-up scores: 76% program, 55% control; p=0.007). Total best-practice implementation improvement did not differ between study groups (baseline scores: 32% intervention, 37% control; follow-up scores: 39% intervention, 42% control; p=0.328). CONCLUSIONS: WPS improved employers' health-related policies and communications but did not improve insurance benefits design, programs, or tracking. Many employers were unable to modify insurance benefits and reported that the time and costs of implementing best practices were major barriers. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov NCT00452816.

Disclosure of genital human papillomavirus infection to female sex partners by young men.

A survey was administered to male university students who tested positive for high-risk human papillomavirus. Disclosure was more likely in men with fewer partners, in main partnerships, and in longer partnerships. Disclosure was associated with discussing the Pap test/human papillomavirus vaccine with female partners and not associated with a worsening relationship.

Does a large-scale organizational transformation toward patient-centered access change the utilization and costs of care for patients with diabetes?

The authors examined whether Group Health's Access Initiative changed the utilization and costs of care among enrollees with diabetes. Using a single (one-group) interrupted time series design, repeated-measures generalized estimating equation models were used to estimate changes in utilization and costs during the Initiative rollout (2002-2003) and to compare the slopes (annual rates of change) for utilization and costs during the Pre-Initiative period (1998-2002) to the slopes during Full-Implementation (2003-2006) among 9,871 members continuously enrolled from 1997 to 2006 with type 1 or 2 diabetes. Total costs increased in Full-Implementation, but the annual change in total costs did not change. Primary care visits declined, but primary care contacts grew, largely from the Initiative's introduction of secure messaging. Specialty visits did not change; however, the Initiative may have increased emergency visits. To reduce emergency visits, future access initiatives should include proactive and comprehensive outpatient care for patients with diabetes.

Does an immigrant health paradox exist among Asian Americans? Associations of nativity and occupational class with self-rated health and mental disorders.

A robust socioeconomic gradient in health is well-documented, with higher socioeconomic status (SES) associated with better health across the SES spectrum. However, recent studies of U.S. racial/ethnic minorities and immigrants show complex SES-health patterns (e.g., flat gradients), with individuals of low SES having similar or better health than their richer, U.S.-born and more acculturated counterparts, a so-called "epidemiological paradox" or "immigrant health paradox". To examine whether this exists among Asian Americans, we investigate how nativity and occupational class (white-collar, blue-collar, service, unemployed) are associated with subjective health (self-rated physical health, self-rated mental health) and 12-month DSM-IV mental disorders (any mental disorder, anxiety, depression). We analyzed data from 1530 Asian respondents to the 2002-2003 National Latino and Asian American Study in the labor force using hierarchical multivariate logistic regression models controlling for confounders, subjective social status (SSS), material and psychosocial factors theorized to explain health inequalities. Compared to U.S.-born Asians, immigrants had worse socioeconomic profiles, and controlling for age and gender, increased odds for reporting fair/poor mental health and decreased odds for any DSM-IV mental disorder and anxiety. No strong occupational class-health gradients were found. The foreign-born health-protective effect persisted after controlling for SSS but became nonsignificant after controlling for material and psychosocial factors. Speaking fair/poor English was strongly associated with all outcomes. Material and psychosocial factors were associated with some outcomes--perceived financial need with subjective health, uninsurance with self-rated mental health and depression, social support, discrimination and acculturative stress with all or most DSM-IV outcomes. Our findings caution against using terms like "immigrant health paradox" which oversimplify complex patterns and mask negative outcomes among underserved sub-groups (e.g., speaking fair/poor English, experiencing acculturative stress). We discuss implications for better measurement of SES and health given the absence of a gradient and seemingly contradictory finding of nativity-related differences in self-rated health and DSM-IV mental disorders.

The reliability of medical group performance measurement in a single insurer's pay for performance program.

BACKGROUND: Most public reporting and pay for performance (P4P) programs in the United States continue to be organized and implemented by single insurers. Adequate medical group-level reliability on clinical care process measures is possible in multistakeholder initiatives because patient samples can be pooled across payers. However, the extent to which reliable measurement is achievable in single insurer P4P initiatives remains unclear. METHODS: This study uses 7 years (2001 to 2007) of patient-level clinical care process data from an insurer in Washington State involving 20 medical groups. Eight clinical care process measures were analyzed. We compared the medical group-level reliability and resulting sample size requirements for each of the 8 measures using unadjusted and adjusted binary mixed models. The relation of baseline intraclass correlation coefficients (ICCs) and medical group performance change over time was examined for each clinical care process measure. RESULTS: Only 45% of all medical group measurements (group-years for all observations) had sufficient sample sizes to achieve reliable estimates of group performance. Measures with the largest deficiencies in patient samples per group included appropriate asthma treatment and low-density lipoprotein screening for patients with coronary artery disease. There was an inconsistent relationship between the size of baseline ICCs and medical group performance improvement over time. CONCLUSIONS: Unreliable performance measurement is an important consequence of the prevailing organization and implementation of public reporting and P4P programs in the US. Multi-payer collaborations may be an important vehicle for ensuring reliable medical group performance measurement and comparisons on clinical care process measures.

Validating the use of ICD-9-CM codes to evaluate gestational age and birth weight.

BACKGROUND: Efforts to reduce preterm and low-weight births are among the leading public health objectives in the United States and the world. A necessary component of any public health endeavor is surveillance. The Department of Defense (DoD) Birth and Infant Health Registry (Registry) uses electronic healthcare utilization data to assess reproductive health outcomes among military families. Infant health outcomes are coded using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). The objective of this study was to determine the accuracy of using electronically derived ICD-9-CM codes for assessing gestational age and birth weight among Registry infants compared to medical records. METHODS: The authors assessed birth outcome agreement by comparing electronic Registry data for infants born at military treatment facilities (MTFs) from 1999-2002 and 1,858 randomly selected birth medical records from 17 MTFs, with descriptive statistics and measures of agreement, including the kappa statistic. RESULTS: Of the 1,858 reviewed infant records, 1,669 were successfully matched to the Registry analytic dataset for analyses. Despite small differences in parental demographics, this investigation established "near perfect" agreement for the primary outcomes: kappa of 0.83 for preterm and 0.87 for low birth weight. Subgroup analyses revealed no significant differences in gestational age and birth-weight agreement based on the presence of a birth defect, military parent rank, branch of military service, or specific hospital characteristics. CONCLUSIONS: Electronically derived ICD-9-CM codes provide an accurate assessment of the gestational age and low birth weight reflected in the birth medical records of infants in a large birth and infant health registry. These findings support the integrity of Registry data for investigations assessing preterm and low-weight births among U.S. service member families.

Factors associated with early magnetic resonance imaging utilization for acute occupational low back pain: a population-based study from Washington State workers' compensation.

STUDY DESIGN: A population-based, prospective cohort study. OBJECTIVE: To identify demographic, job-related, psychosocial, and clinical factors associated with the use of magnetic resonance imaging (MRI) within 6 weeks from injury (early MRI) among workers' compensation claimants with acute occupational low back pain (LBP). SUMMARY OF BACKGROUND DATA: Early MRI may be associated with increased use of services for treatment and costs. To understand utilization and most appropriately apply guidelines, it is important to identify factors associated with early imaging use for occupational LBP. METHODS: Workers (N = 1830) were interviewed 3 weeks (median) after submitting a workers' compensation claim for a back injury. Demographic, work, health, clinical, and injury characteristics were ascertained from interviews, medical records, and administrative data. Modified Poisson regression analyses identified factors associated with early MRI use. RESULTS: Among respondents, 362 (19.8%) received an early MRI. Multivariable regression showed that male workers were 43% more likely to receive an early MRI than female workers (incident rate ratio [IRR]: 1.43, 95% confidence interval [CI]: 1.12-1.82). Initial visit type with a surgeon was associated with 78% greater likelihood of receiving an early MRI than that with a primary care physician (IRR: 1.78, 95% CI: 1.08-2.92). Having a chiropractor as the initial provider was associated with a reduced likelihood of early MRI (IRR: 0.53, 95% CI: 0.42-0.66). Workers with elevated work fear-avoidance, higher Roland scores, or increased injury severity were more likely to receive early MRI than counterparts with lower levels or scores. CONCLUSION: Nearly 20% of the injured workers with LBP receive early MRI, a rate similar to that reported elsewhere. Early MRI may lead to greater subsequent interventions, potentially poorer outcomes, and increased health care expenditures. On the basis of the characteristics of patients with uncomplicated occupational LBP, providers may be able to provide tailored care, and providers and policy makers may better understand the utilization of imaging and adherence to clinical guidelines.

Measuring family satisfaction with care and quality of dying in the intensive care unit: does patient age matter?

RATIONALE: Few studies have examined the role of patient age on family experiences of end-of-life care. OBJECTIVES: To assess measurement characteristics of two family-assessed questionnaires across three patient age groups. METHODS: Four hundred and ninety-six patients who died in an intensive care unit (ICU) at a single hospital were identified and one family member per patient was sent two questionnaires: 1) Family Satisfaction in the ICU (FS-ICU); and 2) Quality of Dying and Death (QODD). Two hundred and seventy-five surveys were returned (55.4%). We analyzed three age groups: <35, 35-64, and ≥65 years. Differences were evaluated using χ(2) tests to evaluate ceiling, floor, and missing responses; Kruskal-Wallis tests to compare median scores on items and total scores; and linear regression controlling for patient sex, race, diagnosis, and family-member sex, race, education, and relationship to provide adjusted comparisons of total and subscale scores. RESULTS: Measurement characteristics varied by age groups for both questionnaires. Missing values and floor endorsements were more common for the younger age groups for six items and one overall rating score. Ceiling endorsements were more common for the older group for 11 items. Fifteen items and four total scores were significantly higher in the older group. CONCLUSIONS: The FS-ICU and QODD questionnaires performed differently across patient age groups. Assessments of family satisfaction and quality of dying and death were higher in the oldest group, particularly in the area of clinician-family communication. Studies of the dying experience of older adults may not generalize to patients of other ages, and study instruments should be validated among different age groups.

Development of a survey to identify vaccine-hesitant parents: the parent attitudes about childhood vaccines survey.

OBJECTIVE: To develop a survey to accurately assess parental vaccine hesitancy. RESULTS: The initial survey contained 17 items in four content domains: (1) immunization behavior; (2) beliefs about vaccine safety and efficacy; (3) attitudes about vaccine mandates and exemptions; and (4) trust. Focus group data yielded an additional 10 survey items. Expert review of the survey resulted in the deletion of nine of 27 items and revisions to 11 of the remaining 18 survey items. Parent pretesting resulted in the deletion of one item, the addition of one item, the revision of four items, and formatting changes to enhance usability. The final survey contains 18 items in the original four content domains. METHODS: An iterative process was used to develop the survey. First, we reviewed previous studies and surveys on parental health beliefs regarding vaccination to develop content domains and draft initial survey items. Focus groups of parents and pediatricians generated additional themes and survey items. Six immunization experts reviewed the items in the resulting draft survey and ranked them on a 1-5 scale for significance in identifying vaccine-hesitant parents (5 indicative of a highly significant item). The lowest third of ranked items were dropped. The revised survey was pretested with 25 parents to assess face validity, usability and item understandability. CONCLUSIONS: The Parent Attitudes about Childhood Vaccines survey was constructed using qualitative methodology to identify vaccine-hesitant parents and has content and face validity. Further psychometric testing is needed.

Social marketing, stages of change, and public health smoking interventions.

As a "thought experiment," the authors used a modified stages of change model for smoking to define homogeneous segments within various hypothetical populations. The authors then estimated the population effect of public health interventions that targeted the different segments. Under most assumptions, interventions that emphasized primary and secondary prevention, by targeting the Never Smoker, Maintenance, or Action segments, resulted in the highest nonsmoking life expectancy. This result is consistent with both social marketing and public health principles. Although the best thing for an individual smoker is to stop smoking, the greatest public health benefit is achieved by interventions that target nonsmokers.

Associations between minimum wage policy and access to health care: evidence from the Behavioral Risk Factor Surveillance System, 1996-2007.

OBJECTIVES: We examined whether minimum wage policy is associated with access to medical care among low-skilled workers in the United States. METHODS: We used multilevel logistic regression to analyze a data set consisting of individual-level indicators of uninsurance and unmet medical need from the Behavioral Risk Factor Surveillance System and state-level ecological controls from the US Census, Bureau of Labor Statistics, and several other sources in all 50 states and the District of Columbia between 1996 and 2007. RESULTS: Higher state-level minimum wage rates were associated with significantly reduced odds of reporting unmet medical need after control for the ecological covariates, substate region fixed effects, and individual demographic and health characteristics (odds ratio = 0.853; 95% confidence interval = 0.750, 0.971). Minimum wage rates were not significantly associated with being uninsured. CONCLUSIONS: Higher minimum wages may be associated with a reduced likelihood of experiencing unmet medical need among low-skilled workers, and do not appear to be associated with uninsurance. These findings appear to refute the suggestion that minimum wage laws have detrimental effects on access to health care, as opponents of the policies have suggested.

Prescriber and staff perceptions of an electronic prescribing system in primary care: a qualitative assessment.

BACKGROUND: The United States (US) Health Information Technology for Economic and Clinical Health Act of 2009 has spurred adoption of electronic health records. The corresponding meaningful use criteria proposed by the Centers for Medicare and Medicaid Services mandates use of computerized provider order entry (CPOE) systems. Yet, adoption in the US and other Western countries is low and descriptions of successful implementations are primarily from the inpatient setting; less frequently the ambulatory setting. We describe prescriber and staff perceptions of implementation of a CPOE system for medications (electronic- or e-prescribing system) in the ambulatory setting. METHODS: Using a cross-sectional study design, we conducted eight focus groups at three primary care sites in an independent medical group. Each site represented a unique stage of e-prescribing implementation - pre/transition/post. We used a theoretically based, semi-structured questionnaire to elicit physician (n = 17) and staff (n = 53) perceptions of implementation of the e-prescribing system. We conducted a thematic analysis of focus group discussions using formal qualitative analytic techniques (i.e. deductive framework and grounded theory). Two coders independently coded to theoretical saturation and resolved discrepancies through discussions. RESULTS: Ten themes emerged that describe perceptions of e-prescribing implementation: 1) improved availability of clinical information resulted in prescribing efficiencies and more coordinated care; 2) improved documentation resulted in safer care; 3) efficiencies were gained by using fewer paper charts; 4) organizational support facilitated adoption; 5) transition required time; resulted in workload shift to staff; 6) hardware configurations and network stability were important in facilitating workflow; 7) e-prescribing was time-neutral or time-saving; 8) changes in patient interactions enhanced patient care but required education; 9) pharmacy communications were enhanced but required education; 10) positive attitudes facilitated adoption. CONCLUSIONS: Prescribers and staff worked through the transition to successfully adopt e-prescribing, and noted the benefits. Overall impressions were favorable. No one wished to return to paper-based prescribing.

Associations between state minimum wage policy and health care access: a multi-level analysis of the 2004 Behavioral Risk Factor survey.

Minimum wage policies have been advanced as mechanisms to improve the economic conditions of the working poor. Both positive and negative effects of such policies on health care access have been hypothesized, but associations have yet to be thoroughly tested. To examine whether the presence of minimum wage policies in excess of the federal standard of $5.15 per hour was associated with health care access indicators among low-skilled adults of working age, a cross-sectional analysis of 2004 Behavioral Risk Factor Surveillance System data was conducted. Self-reported health insurance status and experience with cost-related barriers to needed medical care were adjusted in multi-level logistic regression models to control for potential confounding at the state, county, and individual levels. State-level wage policy was not found to be associated with insurance status or unmet medical need in the models, providing early evidence that increased minimum wage rates may neither strengthen nor weaken access to care as previously predicted.