Faculty Bibliography

OBJECTIVE: To describe the challenges to blinding in behavioral interventions, specifically those for asymptomatic medical conditions, where the intervention is through counseling, and to provide recommendations for achieving blinding in behavioral randomized controlled trials (RCTs). METHODS: This paper reviews the challenges of preserving blinding in behavioral RCTs with a focus on interventions for asymptomatic medical conditions. This is illustrated using a case study of an ongoing behavioral intervention to improve hypertension control. RESULTS: In contrast to easily keeping study investigators and participants masked to treatment assignment through the use of identical pills or sham treatments, the need to have differing levels of blinding among study personnel and participants in randomized behavioral intervention trials is presented. Recommendations for achieving this are provided. CONCLUSIONS: Despite the challenges inherent in behavioral interventions, it is possible to achieve differing levels of blinding across study personnel and participants to minimize bias and generate valid data in RCTs that test interventions for asymptomatic medical conditions such as hypertension. Modifications may be needed for RCTs in symptomatic medical conditions. PRACTICE IMPLICATIONS: Researchers designing behavioral RCTs should be aware of the challenges to blinding all staff and study participants, and plan to have procedures in place to standardize outcome data collection and intervention delivery without compromising the varying levels of blinding. The challenges and recommendations described may need modifications in behavioral intervention studies for symptomatic conditions

Weighted survey data with missing data for some covariates presents a substantial challenge for analysis. We addressed this problem by using a reweighting technique in a logistic regression model to estimate parameters. Each survey weight was adjusted by the inverse of the probability that the possibly missing covariate was observed. The reweighted estimating equations procedure was compared with a complete case analysis (after discarding any subjects with missing data) in a simulation study to assess bias reduction. The method was also applied to data obtained from a national health survey (National Health and Nutritional Examination Survey or NHANES). Adjusting the sampling weights by the inverse probability of being completely observed appears to be effective in accounting for missing data and reducing the bias of the complete case estimate of the regression coefficients

BackgroundAlthough the Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure (BP) in hypertensive adults, its effect on mortality is unclear.MethodsThis prospective cohort study evaluated the association between diet and mortality in 5,532 hypertensive adults in the Third National Health and Nutrition Examination Survey. Hypertension was determined by self-report, medication use, or BP measurement. Diet was ascertained by 24-h dietary recall using nine nutrient targets. The primary outcome was all-cause mortality. Secondary outcomes included specific causes of mortality (cardiovascular disease (CVD), ischemic heart disease (IHD), stroke, and cancer).ResultsOf the 5,532 participants, 391 (7.1%) consumed a DASH-like diet. During an average of 8.2 person-years of follow-up, there were 1,537 all-cause deaths; this included 312 cancer deaths and 788 cardiovascular deaths, of which 447 were due to IHD and 142 were due to stroke. After adjusting for multiple confounders while accounting for the complex survey design by utilizing survey weights, strata, and clusters in Cox proportional hazards models, a DASH-like diet was associated with lower mortality from all causes (hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.52-0.92, P = 0.01) and stroke (HR 0.11, 95% CI 0.03-0.47, P = 0.003). Mortality risk from CVD (HR 0.92, 95% CI 0.63-1.35, P = 0.67), IHD (HR 0.77, 95% CI 0.47-1.24, P = 0.28), and cancer (HR 0.51, 95% CI 0.23-1.10, P = 0.09) did not reach statistical significance.ConclusionsThough findings for specific causes of mortality are mixed, consumption of a DASH-like diet is associated with lower all-cause mortality in adults with hypertension.American Journal of Hypertension 2009; doi:10.1038/ajh.2009.10American Journal of Hypertension 2009; doi:10.1038/ajh.2009.10

We evaluated whether hypertension control differs by ethnicity after accounting for patient characteristics, treatment, and adherence to treatment using the third National Health and Nutrition Examination Survey (US population estimate, 42,511,379). Outcome measures were prescribed treatment, treatment adherence, hypertension control (blood pressure [BP]<140/90 mm Hg). Multivariate logistic regression was performed with non-Hispanic whites (NHW) as the comparison group. Non-Hispanic blacks (NHB) were more likely to report medication prescription (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.1-2.5) and being advised to restrict salt (OR 1.5, CI: 1.2-2.0). Among those advised, NHB were more likely to report salt restriction (OR 1.5, CI: 1.1-2.1) and weight-loss attempts (OR 1.7, CI: 1.3-2.3). Among persons advised to follow exercise, alcohol restriction, smoking cessation, tension reduction, or diet modification, NHB (OR 2.2, CI: 1.6-3.0) and Mexican Americans (OR 2.0, CI: 1.1-3.9) were more likely to report adherence. The likelihood of uncontrolled hypertension was higher in NHB (OR 1.4, CI: 1.1-1.7) and Mexican Americans (OR 1.5, CI 1.1-2.0) despite medication adherence. Even after adjustment for treatment and adherence, substantial ethnic differences in hypertension control were found. Initiating treatment, while crucial, is not sufficient and future guidelines should emphasize aggressive treatment escalation to achieve hypertension control

Complex survey sampling is often used to sample a fraction of a large finite population. In general, the survey is conducted so that each unit (e.g. subject) in the sample has a different probability of being selected into the sample. For generalizability of the sample to the population, both the design and the probability of being selected into the sample must be incorporated in the analysis. In this paper we focus on non-standard regression models for complex survey data. In our motivating example, which is based on data from the Medical Expenditure Panel Survey, the outcome variable is the subject's 'total health care expenditures in the year 2002'. Previous analyses of medical cost data suggest that the variance is approximately equal to the mean raised to the power of 1.5, which is a non-standard variance function. Currently, the regression parameters for this model cannot be easily estimated in standard statistical software packages. We propose a simple two-step method to obtain consistent regression parameter and variance estimates; the method proposed can be implemented within any standard sample survey package. The approach is applicable to complex sample surveys with any number of stages

OBJECTIVES: We evaluated the usefulness of a simple run-in period to reduce drop-outs in a behavioral intervention to improve blood pressure (BP). In a pilot study where a run-in period was not used, we had a 25% drop-out rate. METHODS: A prospective evaluation was performed in the context of a blinded 3-arm randomized trial. Participants are eligible if they have uncontrolled BP on 2 consecutive visits. Potential participants are approached during a routine visit, informed, consented and enrolled. After a 1-month run-in period during which all participants receive a phone call to: i) verify phone availability, ii) get basic information on treatment, and iii) confirm the baseline visit, participants return for a baseline visit. They are then randomized to one of the three treatment arms: usual care, non-tailored counseling, or tailored counseling. Participants make return visits at 3, 6 and 12 months. RESULTS: Of the 1275 potential participants who received detailed study information, 301 consented to participate, of whom 226 were enrolled. During the run-in period, 73 withdrew consent and 153 participants were randomized; 7 subsequently dropped out. There were no differences (p>.1) between the 73 cancelled and the 153 randomized patients. There were fewer drop-outs than in the pilot study (5% vs. 25%, p<.0001). CONCLUSIONS: The run-in period reduces the number of drop-outs after randomization and improves statistical power. In order to retain external validity, it is important to compare participants who remain in the study and those that cancel, and incorporate that in generalizing from the study

PURPOSE: Statins are potent drugs for reducing cholesterol and cardiovascular disease; however, their effectiveness is significantly compromised by poor adherence. This prospective study was designed to identify potentially modifiable patient factors including medication, disease, and diet beliefs related to statin adherence. METHODS: Veterans (n = 71) given their first prescription of a statin for primary prevention were interviewed at baseline, 3 months, and 6 months regarding medication, disease, and diet beliefs along with self-reported statin adherence. RESULTS: At 6-month follow-up, 55% of the cohort was non-adherent with 10% reporting never having started their statin, 50% reporting misconceptions about the duration of treatment and a median use of <2 months among those who discontinued their statin. Multivariate predictors of non-adherence were expected short treatment duration (OR = 3.6, 1.4-9.4), low perceived risk of myocardial infarction (OR = 3.1, 1.1-8.7), concern about potential harm from statins (OR = 2.5, 1.0-6.3), being Hispanic (OR = 3.9, 1.0-15.2), and younger age (OR = 4.2, 1.1-15.8). CONCLUSIONS: Poor adherence to statins was common in this primary prevention population with frequent early discontinuation despite access to low-cost medicines. Patient factors regarding the perception of risk, toxic effects of medication, expected treatment duration, as well as socio-demographic factors, were significant predictors of poor adherence and warrant further exploration