Framing the conversation: use of PRECIS-2 ratings to advance understanding of pragmatic trial design domains

Background  There continues to be debate about what constitutes a pragmatic trial and how it is distinguished from more traditional explanatory trials. The NIH Pragmatic Trials Collaborative Project, which includes five trials and a coordinating unit, has adopted the Pragmatic-Explanatory Continuum Indicator Summary (PRECIS-2) instrument. The purpose of the study was to collect PRECIS-2 ratings at two points in time to assess whether the tool was sensitive to change in trial design, and to explore with investigators the rationale for rating shifts.  Methods  A mixed-methods design included sequential collection and analysis of quantitative data (PRECIS-2 ratings) and qualitative data. Ratings were collected at two annual, in-person project meetings, and subsequent interviews conducted with investigators were recorded, transcribed, and coded using NVivo 11 Pro for Windows. Rating shifts were coded as either (1) actual change (reflects a change in procedure or protocol), (2) primarily a rating shift reflecting rater variability, or (3) themes that reflect important concepts about the tool and/or pragmatic trial design.  Results  Based on PRECIS-2 ratings, each trial was highly pragmatic at the planning phase and remained so 1year later in the early phases of trial implementation. Over half of the 45 paired ratings for the nine PRECIS-2 domains indicated a rating change from Time 1 to Time 2 (N = 24, 53%). Of the 24 rating changes, only three represented a true change in the design of the trial. Analysis of rationales for rating shifts identified critical themes associated with the tool or pragmatic trial design more generally. Each trial contributed one or more relevant comments, with Eligibility, Flexibility of Adherence, and Follow-up each accounting for more than one.  Conclusions  PRECIS-2 has proved useful for “framing the conversation” about trial design among members of the Pragmatic Trials Collaborative Project. Our findings suggest that design elements assessed by the PRECIS-2 tool may represent mostly stable decisions. Overall, there has been a positive response to using PRECIS-2 to guide conversations around trial design, and the project’s focus on the use of the tool by this group of early adopters has provided valuable feedback to inform future trainings on the tool

Reducing cardiovascular risk through treatment of obstructive sleep apnea: 2 methodological approaches

Obstructive sleep apnea (OSA) significantly impacts cardiovascular health, demonstrated by observational investigations showing an independently increased risk of ischemic heart disease, diabetes, hypertension, congestive heart failure, acute coronary syndrome, stroke, cardiovascular mortality, and all-cause mortality. Positive airway pressure (PAP), a medical therapy for sleep apnea, reverses airway obstruction and may help reduce cardiovascular risk. Prior to planning large phase III randomized controlled trials to test the impact of PAP on cardiovascular outcomes, several gaps in knowledge need to be addressed. This article describes 2 independent studies that worked collaboratively to fill these gaps. The populations, design features, and relative benefits/challenges of the 2 studies (SleepTight and BestAIR) are described. Both studies were encouraged to have multidisciplinary teams with expertise in behavioral interventions to improve PAP compliance. Both studies provide key information that will be useful to the research community in future large-scale, event-driven, randomized trials to evaluate the efficacy and/or effectiveness of strategies to identify and treat significant OSA for decreasing risk of major adverse cardiovascular events in high-risk patients

Assessing Psychological Well-Being: Self-Report Instruments for the NIH Toolbox

Objective— Psychological well-being (PWB) has a significant relationship with physical and mental health. As part of the NIH Toolbox for the Assessment of Neurological and Behavioral Function, we developed self-report item banks and short forms to assess PWB. Study Design and Setting— Expert feedback and literature review informed the selection of PWB concepts and the development of item pools for Positive Affect, Life Satisfaction, and Meaning and Purpose. Items were tested with a community-dwelling U.S. internet panel sample of adults aged 18 and above (N=552). Classical and item response theory (IRT) approaches were used to evaluate unidimensionality, fit of items to the overall measure, and calibrations of those items, including differential item function (DIF). Results— IRT-calibrated item banks were produced for Positive Affect (34 items), Life Satisfaction (16 items), and Meaning and Purpose (18 items). Their psychometric properties were supported based on results of factor analysis, fit statistics, and DIF evaluation. All banks measured the concepts precisely (reliability ≥0.90) for more than 98% of participants. Conclusion— These adult scales and item banks for PWB provide the flexibility, efficiency, and precision necessary to promote future epidemiological, observational, and intervention research on the relationship of PWB with physical and mental health

The selection of comparators for randomized controlled trials of health-related behavioral interventions : recommendations of an NIH expert panel

Funding and logistical support for the expert panel was provided by the National Institutes of Health Office of Behavioral and Social Sciences Research.Peer reviewedPostprin

Assessment of stress and self-efficacy for the NIH Toolbox for Neurological and Behavioral Function

Background and objectivesThe NIH Toolbox for Neurological and Behavioral Function assessment battery contains measures in the domains of cognitive function, motor function, sensory function, and emotional health. It was designed for use in epidemiological and clinical trials health-related research.DesignThis paper describes the first phase of instrument development for the stress and self-efficacy subdomain of emotional health. Based on an extensive literature review and expert consultation, 127 measures were initially considered for inclusion in this subdomain, including measures of stress, self-efficacy, emotion regulation, and coping.ResultsSeveral measures, including emotion regulation and measures of coping strategies, did not meet criteria that were a priori established for inclusion. Psychometric properties of the remaining candidate measures were evaluated using data from five independent samples (combined N = 3175). Confirmatory and exploratory factor analyses indicated the Perceived Stress Scale and the General Self-Efficacy Scale each assessed single dimensions.ConclusionsBased on their psychometric performance, these two instruments were selected for inclusion and subsequent national norming for the NIH Toolbox

Hostility and the metabolic syndrome in older males: The Normative Aging Study

Objective: Several studies have shown that hostility, as measured by the Minnesota Multiphasic Personality Inventory-derived Cook-Medley Hostility Scale (Ho), is positively associated with several cardiovascular risk factors, possibly accounting for the relationship between Ho scores and cardiovascular mortality. This study was undertaken to examine associations between hostility and cardiovascular risk factors representing the metabolic syndrome in 1081 older men who participated in the Normative Aging Study. Methods: Subjects included men who completed the Minnesota Multiphasic Personality Inventory in 1986 and who participated in a subsequent laboratory examination within 1 to 4 years. Total and subscale Ho scores were computed, and associations with anthropometric data, cigarette smoking, dietary information, serum lipids, blood pressure, and fasting glucose and insulin levels were examined. Results: The total Ho score was positively associated with waist/hip ratio, body mass index, total caloric intake, fasting insulin level, and serum triglycerides. The Ho score was inversely related to education and high-density lipoprotein cholesterol concentration. Path analysis also suggested that the effects of hostility on insulin, triglycerides, and high-density lipoprotein cholesterol were mediated by its effects on body mass index and waist/hip ratio, which, in turn, exerted their effects on lipids and blood pressure through insulin. Conclusions: The results are consistent with those of prior research and also suggest that, in older men, hostility may be associated with a pattern of obesity, central adiposity, and insulin resistance, which can exert effects on blood pressure and serum lipids. Furthermore, effects of hostility on the metabolic syndrome appear to be mediated by body mass index and waist/hip ratio

Influence of Age, Sex, and Family on Type A and Hostile Attitudes and Behaviors

We describe the influence of age, sex, and family on Type A and hostility indices that have been related to rates of coronary heart disease (CHD). The sample consisted of 120 girls and 95 boys (ages 6 to 18 years) and 141 women and 120 men (ages 31 to 62 years) from 142 families residing in an upper middle class community. Results showed little familial aggregation of Type A and hostility. Adults had higher Structured Interview (SI) Potential for Hostility ratings than did children, whereas children had higher Minnesota Multiphasic Personality Inventory (MMPI)-derived Hostility scores and SI Anger-In ratings than did adults. Male adults and male children had higher SI Potential for Hostility ratings and MMPI-derived Hostility scores than did their female counterparts. The heightened hostility of males may account, in part, for their heightened risk of CHD relative to females'. Key words: age, sex, familial aggregation, hostility, Type