Merrick Zwarenstein

Improving the reporting of pragmatic trials: an extension of the CONSORT statement

Background The CONSORT statement is intended to improve reporting of randomised controlled trials and focuses on minimising the risk of bias (internal validity). The applicability of a trial’s results (generalisability or external validity) is also important, particularly for pragmatic trials. A pragmatic trial (a term first used in 1967 by Schwartz and Lellouch) can be broadly defined as a randomised controlled trial whose purpose is to inform decisions about practice. This extension of the CONSORT statement is intended to improve the reporting of such trials and focuses on applicability. Methods At two, two-day meetings held in Toronto in 2005 and 2008, we reviewed the CONSORT statement and its extensions, the literature on pragmatic trials and applicability, and our experiences in conducting pragmatic trials. Recommendations We recommend extending eight CONSORT checklist items for reporting of pragmatic trials: the background, participants, interventions, outcomes, sample size, blinding, participant flow, and generalisability of the findings. These extensions are presented, along with illustrative examples of reporting, and an explanation of each extension. Adherence to these reporting criteria will make it easier for decision makers to judge how applicable the results of randomised controlled trials are to their own conditions. Empirical studies are needed to ascertain the usefulness and comprehensiveness of these CONSORT checklist item extensions. In the meantime we recommend that those who support, conduct, and report pragmatic trials should use this extension of the CONSORT statement to facilitate the use of trial results in decisions about health care. Pragmatic trials are designed to inform decisions about practice, but poor reporting can reduce their usefulness. The CONSORT and Practihc groups describe modifications to the CONSORT guidelines to help readers assess the applicability of the results

Randomised controlled trial of self-supervised and directly observed treatment of tuberculosis

BACKGROUND Tuberculosis is a major public-health problem in South Africa, made worse by poor adherence to and frequent interruption of treatment. Direct observation (DO) of tuberculosis patients taking their drugs is supposed to improve treatment completion and outcome. We compared DO with self-supervision, in which patients on the same drug regimen are not observed taking their pills, to assess the effect of each on the success of tuberculosis treatment. METHODS We undertook an unblinded randomised controlled trial in two communities with large tuberculosis caseloads. The trial included 216 adults who started pulmonary tuberculosis treatment for the first time, or who had a second course of treatment (retreatment patients). No changes to existing treatment delivery were made other than randomisation. Analysis was by intention to treat. Individual patient data from the two communities were combined. FINDINGS Treatment for tuberculosis was more successful among self-supervised patients (60% of patients) than among those on DO (54% of patients, difference between groups 6% [90% CI -5.1 to 17.0]). Retreatment patients had significantly more successful treatment outcomes if self-supervised (74% of patients) than on DO (42% of patients, difference between groups 32% [11%-52%]). INTERPRETATION At high rates of treatment interruption, self-supervision achieved equivalent outcomes to clinic DO at lower cost. Self-supervision achieved better outcomes for retreatment patients. Supportive patient-carer relations, rather than the authoritarian surveillance implicit in DO, may improve treatment outcomes and help to control tuberculosis.

Systematic reviews of the effectiveness of quality improvement strategies and programmes

Systematic reviews provide the best evidence on the effectiveness of healthcare interventions including quality improvement strategies. The methods of systematic review of individual patient randomised trials of healthcare interventions are well developed. We discuss methodological and practice issues that need to be considered when undertaking systematic reviews of quality improvement strategies including developing a review protocol, identifying and screening evidence sources, quality assessment and data abstraction, analytical methods, reporting systematic reviews, and appraising systematic reviews. This paper builds on our experiences within the Cochrane Effective Practice and Organisation of Care (EPOC) review group.

The effectiveness of interprofessional education: key findings from a new systematic review.

Over the past decade systematic reviews of interprofessional education (IPE) have provided a more informed understanding of the effects of this type of education. This paper contributes to this literature by reporting an update of a Cochrane systematic review published in this journal ten years ago (Zwarenstein et al., ). In updating this initial review, our current work involved searches of a number of electronic databases from 1999–2006, as well as reference lists, books, conference proceedings and websites. Like the previous review, only studies which employed randomized controlled trials, controlled-before and-after-studies and interrupted time series studies of IPE, and that reported validated professional practice and health care outcomes, were included. While the first review found no studies which met its inclusion criteria, the updated review located six IPE studies. This paper aims to add to the ongoing development of evidence for IPE. Despite some useful progress being made in relation to strengthening the evidence base for IPE, the paper concludes by stressing that further rigorous mixed method studies of IPE are needed to provide a greater clarity of IPE and its effects on professional practice and patient/client care.

Making trials matter: pragmatic and explanatory trials and the problem of applicability

Randomised controlled trials are the best research design for decisions about the effect of different interventions but randomisation does not, of itself, promote the applicability of a trials results to situations other than the precise one in which the trial was done. While methodologists and trialists have rightly paid great attention to internal validity, much less has been given to applicability.This narrative review is aimed at those planning to conduct trials, and those aiming to use the information in them. It is intended to help the former group make their trials more widely useful and to help the latter group make more informed decisions about the wider use of existing trials. We review the differences between the design of most randomised trials (which have an explanatory attitude) and the design of trials more able to inform decision making (which have a pragmatic attitude) and discuss approaches used to assert applicability of trial results.If we want evidence from trials to be used in clinical practice and policy, trialists should make every effort to make their trial widely applicable, which means that more trials should be pragmatic in attitude.

The PRECIS-2 tool: designing trials that are fit for purpose

PRECIS is a tool to help trialists make design decisions consistent with the intended purpose of their trial. This paper gives guidance on how to use an improved, validated version, PRECIS-2, which has been developed with the help of over 80 international trialists, clinicians, and policymakers. Keeping the original simple wheel format, PRECIS-2 has nine domains—eligibility criteria, recruitment, setting, organisation, flexibility (delivery), flexibility (adherence), follow-up, primary outcome, and primary analysis—scored from 1 (very explanatory) to 5 (very pragmatic) to facilitate domain discussion and consensus. It is hoped PRECIS-2 will be valuable in supporting the explicit matching of design decisions to how the trial results are intended to be used

A scoping review to improve conceptual clarity of interprofessional interventions

Interprofessional education (IPE) and interprofessional collaboration (IPC) have been identified in health education and health care as playing an important role in improving health care services and patient outcomes. Despite a growth in the amount of research in these areas, poor conceptualizations of these interprofessional activities have persisted. Given the conceptual challenges, a scoping review of the interprofessional field was undertaken to map the literature available in order to identify key concepts, theories and sources of evidence. The objective of this review was to develop a theoretically based and empirically tested understanding of IPE and IPC. A total of 104 studies met the criteria and were included for analysis. Studies were examined for their approach to conceptualization, implementation, and assessment of their interprofessional interventions. Half of the studies were used for interprofessional framework development and half for framework testing and refinement. The final framework contains three main types of interprofessional interventions: IPE; interprofessional practice; and interprofessional organization; and describes the nature of each type of intervention by stage, participants, intervention type, interprofessional objectives, and outcomes. The outcomes are delineated as intermediate, patient, and system outcomes. There was very limited use of theory in the studies, and thus theoretical aspects could not be incorporated into the framework. This study offers an initial step in mapping out the interprofessional field and outlines possible ways forward for future research and practice.

Association of ICU or Hospital Admission With Unintentional Discontinuation of Medications for Chronic Diseases

CONTEXT Patients discharged from acute care hospitals may be at risk for unintentional discontinuation of medications prescribed for chronic diseases. The intensive care unit (ICU) may pose an even greater risk because of the focus on acute events and the presence of multiple transitions in care. OBJECTIVE To evaluate rates of potentially unintentional discontinuation of medications following hospital or ICU admission. DESIGN, SETTING, AND PATIENTS A population-based cohort study using administrative records from 1997 to 2009 of all hospitalizations and outpatient prescriptions in Ontario, Canada; it included 396,380 patients aged 66 years or older with continuous use of at least 1 of 5 evidence-based medication groups prescribed for long-term use: (1) statins, (2) antiplatelet/anticoagulant agents, (3) levothyroxine, (4) respiratory inhalers, and (5) gastric acid-suppressing drugs. Rates of medication discontinuation were compared across 3 groups: patients admitted to the ICU, patients hospitalized without ICU admission, and nonhospitalized patients (controls). Odds ratios (ORs) were calculated and adjusted for patient demographics, clinical factors, and health services use. MAIN OUTCOME MEASURES The primary outcome was failure to renew the prescription within 90 days after hospital discharge. RESULTS Patients admitted to the hospital (n = 187,912) were more likely to experience potentially unintentional discontinuation of medications than controls (n = 208,468) across all medication groups examined. The adjusted ORs (AORs) ranged from 1.18 (95% CI, 1.14-1.23) for discontinuing levothyroxine in 12.3% of hospitalized patients (n = 6831) vs 11.0% of controls (n = 7114) to an AOR of 1.86 (95% CI, 1.77-1.97) for discontinuing antiplatelet/anticoagulant agents in 19.4% of hospitalized patients (n = 5564) vs 11.8% of controls (n = 2535). With ICU exposure, the AORs ranged from 1.48 (95% CI, 1.39-1.57) for discontinuing statins in 14.6% of ICU patients (n = 1484) to an AOR of 2.31 (95% CI, 2.07-2.57) for discontinuing antiplatelet/anticoagulant agents in 22.8% of ICU patients (n = 522) vs the control group. Admission to an ICU was associated with an additional risk of medication discontinuation in 4 of 5 medication groups vs hospitalizations without an ICU admission. One-year follow-up of patients who discontinued medications showed an elevated AOR for the secondary composite outcome of death, emergency department visit, or emergent hospitalization of 1.07 (95% CI, 1.03-1.11) in the statins group and of 1.10 (95% CI, 1.03-1.16) in the antiplatelet/anticoagulant agents group. CONCLUSIONS Patients prescribed medications for chronic diseases were at risk for potentially unintentional discontinuation after hospital admission. Admission to the ICU was generally associated with an even higher risk of medication discontinuation.

A multifaceted intervention for quality improvement in a network of intensive care units: a cluster randomized trial.

CONTEXT Evidence-based practices improve intensive care unit (ICU) outcomes, but eligible patients may not receive them. Community hospitals treat most critically ill patients but may have few resources dedicated to quality improvement. OBJECTIVE To determine the effectiveness of a multicenter quality improvement program to increase delivery of 6 evidence-based ICU practices. DESIGN, SETTING, AND PARTICIPANTS Pragmatic cluster-randomized trial among 15 community hospital ICUs in Ontario, Canada. A total of 9269 admissions occurred during the trial (November 2005 to October 2006) and 7141 admissions during a decay-monitoring period (December 2006 to August 2007). INTERVENTION We implemented a videoconference-based forum including audit and feedback, expert-led educational sessions, and dissemination of algorithms to sequentially improve delivery of 6 practices. We randomized ICUs into 2 groups. Each group received this intervention, targeting a new practice every 4 months, while acting as control for the other group, in which a different practice was targeted in the same period. MAIN MEASURE OUTCOMES: The primary outcome was the summary ratio of odds ratios (ORs) for improvement in adoption (determined by daily data collection) of all 6 practices during the trial in intervention vs control ICUs. RESULTS Overall, adoption of the targeted practices was greater in intervention ICUs than in controls (summary ratio of ORs, 2.79; 95% confidence interval [CI], 1.00-7.74). Improved delivery in intervention ICUs was greatest for semirecumbent positioning to prevent ventilator-associated pneumonia (90.0% of patient-days in last month vs 50.0% in first month; OR, 6.35; 95% CI, 1.85-21.79) and precautions to prevent catheter-related bloodstream infection (70.0% of patients receiving central lines vs 10.6%; OR, 30.06; 95% CI, 11.00-82.17). Adoption of other practices, many with high baseline adherence, changed little. CONCLUSION In a collaborative network of community ICUs, a multifaceted quality improvement intervention improved adoption of care practices. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00332982.

Effectiveness of pre-licensure interprofessional education and post-licensure collaborative interventions

In this paper we scanned and summarized the empirical research evidence and found that the effects of pre-licensure interprofessional education on patient/client care are unknown. In contrast, for post-licensure collaboration interventions, there is a growing body of evidence suggesting positive effects on the delivery of care. The coverage of this latter evidence, however, is patchy, being especially weak in primary care. In interprofessional education, where policy level interventions have been value driven for the last half century, we have identified a base of evidence for the effectiveness of certain post-licensure collaboration interventions; this evidence is lacking for pre-licensure interprofessional education. If interventions and policies for both pre-licensure interprofessional education and post-licensure collaboration are implemented without accompanying rigorous evaluation research, we will remain mired in this same uncertainty into the future.