Mixed effects approach to the analysis of the stepped wedge cluster randomised trial—Investigating the confounding effect of time through simulation

<div><p>Background</p><p>A stepped wedge cluster randomised trial (SWCRT) is a multicentred study which allows an intervention to be rolled out at sites in a random order. Once the intervention is initiated at a site, all participants within that site remain exposed to the intervention for the remainder of the study.</p><p>The time since the start of the study (“calendar time”) may affect outcome measures through underlying time trends or periodicity. The time since the intervention was introduced to a site (“exposure time”) may also affect outcomes cumulatively for successful interventions, possibly in addition to a step change when the intervention began.</p><p>Methods</p><p>Motivated by a SWCRT of self-monitoring for bipolar disorder, we conducted a simulation study to compare model formulations to analyse data from a SWCRT under 36 different scenarios in which time was related to the outcome (improvement in mood score). The aim was to find a model specification that would produce reliable estimates of intervention effects under different scenarios. Nine different formulations of a linear mixed effects model were fitted to these datasets. These models varied in the specification of calendar and exposure times.</p><p>Results</p><p>Modelling the effects of the intervention was best accomplished by including terms for both calendar time and exposure time. Treating time as categorical (a separate parameter for each measurement time-step) achieved the best coverage probabilities and low bias, but at a cost of wider confidence intervals compared to simpler models for those scenarios which were sufficiently modelled by fewer parameters. Treating time as continuous and including a quadratic time term performed similarly well, with slightly larger variations in coverage probability, but narrower confidence intervals and in some cases lower bias. The impact of misspecifying the covariance structure was comparatively small.</p><p>Conclusions</p><p>We recommend that unless there is a priori information to indicate the form of the relationship between time and outcomes, data from SWCRTs should be analysed with a linear mixed effects model that includes separate categorical terms for calendar time and exposure time. Prespecified sensitivity analyses should consider the different formulations of these time effects in the model, to assess their impact on estimates of intervention effects.</p></div

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments

Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Impact on patients of expanded, general practice based, student teaching:observational and qualitative study

Objectives To compare patients' enablement and satisfaction after teaching and non-teaching consultations. To explore patients' views about the possible impact that increased community based teaching of student doctors in their practice may have on the delivery of service and their attitudes towards direct involvement with students. Design Observational study using validated survey instruments (patient enablement index—PEI, and consultation satisfaction questionnaire—CSQ) administered after teaching consultations and non-teaching consultations. Ten focus groups (two from each practice), comprising five with patients participating in prearranged teaching sessions and five with patients not participating in these. Setting Five general practices in west Suffolk and southern Norfolk, England, that teach student doctors on the Cambridge graduate medical course. Participants 240 patients attending teaching consultations (response rate 82%, 196 patients) and 409 patients attending non-teaching consultations (response rate 72%, 294 patients) received survey instruments. Ten focus groups with a total of 34 patients participating in prearranged teaching sessions and 20 patients not participating in these. Main outcome measures Scores on the patient enablement index and consultation satisfaction questionnaire, analysed at the level of all patients, allowing for age, sex, general practitioner, and practice, and at the level of the individual general practitioner teacher. Qualitative analysis of focus group data. Results Patients' enablement or satisfaction was not reduced after teaching consultations compared with non-teaching consultations (mean difference in scores on the patient enablement index and consultation satisfaction questionnaire with adjustment for confounders 2.24% and 1.70%, respectively). This held true for analysis by all patients and by general practitioner teacher. Qualitative data showed that patients generally supported the teaching of student doctors in their practice. However, this support was conditional on receiving sufficient information about reasons for doctors' absence, the characteristics of students, and the nature of teaching planned. Many patients viewed their general practice as different from hospital and expected greater control over students' presence during their consultations. Conclusions Patients' enablement and satisfaction are not impaired by students' participation in consultations. Patients generally support the teaching of student doctors in their general practice but expect to be provided with sufficient information and to have a choice about participation, so they can give informed consent. Recognising this when organising general practice based teaching is important

Adolescent problems and coping strategies : an investigation of stress, problems, coping, and self-esteem among Queensland secondary students preceding and following implementation of a new tertiary entrance system

This study investigated adolescent stress, problems, and coping strategies, preceding and following the implementation of a new tertiary entrance system in Queensland, Australia. Data were collected in 1988 from 1664 students (Ss) attending seven secondary schools (three state high schools, two Catholic schools, and two independent schools) in South-East Queensland, and in 1993 from an additional 1620 Ss from six of these same schools. (One of the state high schools did not participate on the second occasion.) In 1993, the views of 178 secondary teachers (Ts) on adolescent stress were also obtained, with Ts from the same six schools as the 1993 Ss agreeing to participate, and a further 59 secondary Ts who were part-time students at Queensland University of Technology also participating. A further extension in the 1993 part of the study was an investigation of the relationships between self-esteem and adolescent stress, problems, and coping strategies. The theoretical underpinnings of the study were provided through the development of an eclectic perspective on stress in which common links were established among such apparently divergent orientations as Selye's (1956) physiologically-based theory, the attributional theories of Bandura (1977), Rotter (1966), and de Charms (1968), and the transactional theories of Holmes and Rahe (1967), Lazarus (1966), Friedman and Rosenman (1974), and Kobasa (1979). The study also sought to respond to the expanding overseas and Australian literature which seemed to be pointing to increasing stress levels among many adolescents, particularly in the context of the school. Instruments used during data collection included the 68-item Australian Adolescent Problems Inventory (AAPI), the 54-item Adolescent Coping Inventory (ACI), the 12-item Self-Esteem Scale (SES), the 8-item Tertiary Entrance Questionnaire (TEQ), and Goldberg's (1972) 12-item General Health Questionnaire (GHQ-12). The AAPI, SES, and TEQ were especially developed for the study, while the ACI was adapted from Patterson and McCubbin's (1987) Adolescent Coping Orientation for Problem Experiences (A-COPE). Following data collection, the AAP1 and the ACI were refined using Confirmatory Factor Analysis (CFA). The revised problems instrument (the AAPl-R) contained 35 items and 9 subscales, while the revised coping instrument (the ACl-R) contained 26 items and 10 subscales. In addition to the CFAs, the data were analysed using simple descriptive statistics, MANOVAs, ANOVAs, t-tests, and correlational analyses. Major findings included: close similarities between 1993 and 1988 in Ss' stress levels, identification of their biggest and smallest problems, and identification of their most used and least used coping strategies; a substantial inverse relationship between self-esteem and stress; and a considerable amount of incongruence between the responses of Ss and Ts, with the Ts attributing to their students greater stress, greater intensity in their problems, and lower self-esteem than the Ss attributed to themselves, and the Ts also projecting a less positive view of adolescent coping strategies than did the Ss. In both 1988 and 1993, female Ss had significantly higher GHQ scores than male Ss, GHQ means generally increased as year levels increased, there was generally an inverse relationship between ability levels and GHQ scores, and Ss at private schools had significantly higher GHQ scores than Ss at state schools. Self esteem scores, measured only in 1993, were significantly higher among male Ss than among female Ss, among younger Ss than among older Ss, and among more able Ss than among less able Ss. In response to the literature suggesting increasing levels in adolescent stress, the present study provided little evidence for such increases, but it did support the view that stress among Queensland secondary students continues to be an important area of concern, with Ss' problems and stress levels in 1993 being comparable to what they had been prior to the implementation of the new tertiary entrance system. In addressing the educational implications of the above results, attention was given to ways of making schooling less stressful for adolescents, changes in teachers' behaviour which might help to reduce student stress, and ways of enhancing students' coping abilities. Suggestions included the pursuit of viable alternatives to the competitive academic curriculum that continues to dominate Queensland secondary education under the new tertiary entrance system, the encouragement of teachers to practice good interpersonal skills, and the suggestion that an appropriate stress management program for students could be based on the eclectic conceptualization of stress developed in Chapter 2. It was argued that self-esteem building, and the development of such positive coping orientations as hardiness, self-efficacy, internal locus of control, seeking social support, and developing good interpersonal skills would help to alleviate student stress

Students' and Teachers' Perceptions of Adolescents' Problems and Coping Strategies

In an investigation of the problems and coping strategies of Australian high school students, comparisons were made between the responses of 1664 students enrolled in years 8 to 12 in 1988, 1620 students enrolled in the same year levels in 1993, and 178 high school teachers in 1993. The subjects completed the High School Stressors Scale and the Adolescent Coping Strategies Scale. Data analyses using MANOVAs, ANOVAs, and t- tests revealed close similarities between the responses of the 1993 students and those of the 1988 students, but a considerable amount of incongruence between the responses of the students and those of the teachers. In particular, the teachers generally seemed to regard their students' problems as being more serious than was acknowledged by the students, and the teachers generally seemed to project a less positive view of adolescents' coping strategies than did the students. These discrepancies are discussed in terms of the different orientations that students and teachers bring to the student- teacher relationship. It is suggested that teachers and counsellors need to take cognisance of the differences between adolescents' perspectives and their own if they are going to be effective in assisting students to develop positive coping strategies and in creating more positive learning environments