The National Institutes of Health’s Office of Disease Prevention (ODP) has just released a free, self-paced online course on designing and analyzing pragmatic and group-randomized trials. The course, which is presented by ODP Director Dr. David Murray, includes a series of seven video presentations plus slide sets, reference materials, and guided activities.
Course segments typically last 25 to 35 minutes. Presentations can be accessed individually and include the following topics:
Course presenter Dr. David Murray, Director, Office of Disease Prevention, NIH (image courtesy NIH)
A new funding opportunity announcement from the NIH solicits applications to support Demonstration Projects that include an efficient, large-scale pragmatic clinical trial. Trials must be conducted across two or more health care systems (HCS) and must be conducted as part of the NIH HCS Research Collaboratory supported through the NIH Common Fund. Awards made through this FOA will initially support a one-year milestone-driven planning phase (UG3), with possible rapid transition to the second implementation phase (UH3) for a pragmatic trial Demonstration Project.
Important Due Dates Earliest submission date: May 2, 2017 Letter of intent date: 30 days prior to application due date Application due date: June 2, 2017
Jerry Jarvik, MD, MPH, Principal Investigator, LIRE Trial
The NIH Collaboratory Demonstration Project, Lumbar Imaging with Reporting of Epidemiology (LIRE), has completed enrollment as of September 30, 2016. LIRE is a pragmatic, cluster-randomized trial testing the effectiveness of inserting epidemiologic benchmarks into lumbar spine imaging reports for reducing subsequent tests and treatments for back pain. Given the rate of age-related, incidental imaging findings in individuals without back pain, many follow-up interventions for back pain based on imaging results are unnecessary. With back pain as one of the most common reasons for doctor visits, this inexpensive intervention has the potential for a large public health impact. The trial will continue to follow subjects for up to 2 years after enrollment using data from the electronic health record, but no new subjects will be enrolled.
Congratulations to the LIRE study team on this important milestone!
The ABATE Infection trial, an NIH Collaboratory project led by Dr. Susan Huang, is featured in the September 12 Health section of the Wall Street Journal. The article describes several studies aimed at preventing the hospital-associated infection MRSA (methicillin-resistant Staphylococcus aureus).
In the Reduce MRSA trial, published in 2013, Dr. Huang’s team demonstrated that treating ICU patients with a germ-fighting soap plus a nasal antibiotic ointment, an approach called “universal decolonization,” was superior to standard approaches in preventing MRSA infections. The ABATE Infection trial examines similar approaches to decolonization for all patients in non–critical care medical and surgical units, comparing the use of an antiseptic bath and nasal ointment to standard bathing and showering. More than 1 million showers and baths were taken over the course of the study, which has now completed enrollment. Data from ABATE are currently being analyzed, with the results expected to inform whether this strategy is effective in reducing hospital-associated infections.
“These are preventable infections and we should be able to drive them down to zero.” Susan Huang, MD
The NIH Collaboratory has developed a tool to assist authors in the complete and transparent reporting of their pragmatic clinical trials (PCTs). In the PCT Reporting Template, users will find descriptions of reporting elements based on CONSORT guidance as well as on expertise from the NIH Collaboratory Demonstration Projects and Core working groups.
Particularly relevant to PCTs are recommendations on how to report the use of data from electronic health records. Other elements of importance to PCTs include reporting wider stakeholder engagement, monitoring for unanticipated changes in study arms, and specific approaches to human subjects protection. The template contains numerous links to online material in the Living Textbook, CONSORT, and the Pragmatic–Explanatory Continuum Indicator Summary tool known as PRECIS-2.
This resource is intended to assist authors in developing primary journal publications. It will be updated over time as new best practices emerge for the transparent reporting of PCTs.
Please note: this document opens as an Adobe PDF. If you do not have software that can open a PDF, click here to download a free version of Adobe Acrobat Reader.
This work was supported by a cooperative agreement (U54 AT007748) from the NIH Common Fund for the NIH Health Care Systems Research Collaboratory. The views presented in this document are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
Originally published on September 1, 2016.
Questions or comments can be submitted via email. Please add “Living Textbook” to the Subject line of the email.
In the systematic review, the researchers found that imaging findings of spine degeneration are present in high proportions of asymptomatic individuals, and these findings increase with age. Thus, many degenerative features found on spine imaging are likely part of normal aging. Given that advanced imaging is increasingly used in the evaluation of patients with lower back pain, knowing the prevalence of degenerative findings in asymptomatic individuals can help clinicians and patients when interpreting imaging findings.
The LIRE pragmatic trial is testing the insertion of these epidemiologic benchmarks into lumbar spine imaging reports with the goal of reducing subsequent tests and treatments, including MRI and CT, opioid prescriptions, spinal injections, or surgery.
The study team for the Trauma Survivors Outcomes and Support (TSOS) trial recently published their study protocol in Implementation Science. TSOS, an NIH Health Care Systems Research Collaboratory Demonstration Project, is an effectiveness-implementation hybrid trial designed to test the delivery of screening and intervention for PTSD and comorbidities across 24 U.S. level I trauma center sites. The study employs a stepped-wedge, cluster-randomized design in which sites are randomized sequentially to initiate the intervention. The study aims to determine if injured patients receiving a collaborative care intervention demonstrate significant reductions in PTSD symptoms when compared with control patients receiving usual care. The study will also evaluate whether intervention patients demonstrate significant reductions in depressive symptoms and associated suicidal ideation, alcohol use problems, and improvements in physical function.
The Active Bathing to Eliminate (ABATE) Infection trial was conducted in nearly 200 non-critical care hospital units across the United States. The ABATE study team developed a training video to teach nurses and nursing assistants how to approach patients to administer a bath with a topical antiseptic agent containing chlorhexidine (CHG), or help patients take a shower using the liquid CHG soap. If the results of the trial demonstrate a reduction in unit-attributable infections or multi-drug resistant organism (MDRO) burden for the intervention units, this video could be used to train nurses and staff to implement CHG bathing in healthcare systems around the nation.
The ABATE trial (ClinicalTrials.gov #NCT02063867) is a large-scale, cluster-randomized pragmatic clinical trial (PCT) designed to assess a bathing approach for reducing multidrug-resistant organisms and hospital-associated infections (HAIs) in patients hospitalized in non-critical care units. Patients were bathed either according to the hospital unit’s usual care procedures (the control group) or bathed with a topical antiseptic agent containing chlorhexidine (CHG; the intervention group). Patients in the intervention group could shower using liquid CHG soap and a mesh sponge, or have a self-assisted or nurse-assisted bed bath using the CHG cloths. If a patient in the intervention group was colonized with, infected with, or had a recent history of methicillin-resistant Staphylococcus aureus (MRSA), the antibiotic mupirocinwas additionally administered nasally for 5 days.
The investigators hypothesize that this regimen will reduce the burden of vancomycin-resistant enterococci (VRE) and Staphylococcus aureus (MRSA) in these units and translate to a reduction in overall bloodstream and urinary tract infections. They will also evaluate its ability to reduce antibiotic-resistant gram-negative bacteria and Clostridium difficile.
The ABATE Infection Trial has been conducted in hospitals in the Hospital Corporation of America (HCA) health system and is an NIH Health Care Systems Research Collaboratory UH3 Demonstration Project supported by the National Institutes of Allergy and Infectious Diseases (NIAID) and the Common Fund at the National Institutes of Health. This video was created and scripted for the trial by study investigators and filmed by Sage Products, LLC.
The Active Bathing to Eliminate (ABATE) Infection trial (ClinicalTrials.gov #NCT02063867) has completed its intervention phase—the first NIH Health Care Systems Research Collaboratory UH3 Demonstration Project to reach this major milestone. The large-scale, cluster-randomized pragmatic clinical trial (PCT) was designed to assess an approach for reducing multidrug-resistant organisms and hospital-associated infections (HAIs) in nearly 200 non-critical care hospital units affiliated with Hospital Corporation of America (HCA) across the United States.
ABATE study PI Dr. Susan Huang
The ABATE study is led by principal investigator Dr. Susan Huang of the University of California, Irvine, who stated “We are elated to reach the successful completion of the trial thanks to an incredible investigative team at HCA, Harvard Pilgrim Health Care, Rush University, the University of Massachusetts Amherst, and UC Irvine. We look forward to what the trial data will tell us and hope that we can continue to find effective ways to protect patients from infection.”
In the ABATE study, patients hospitalized in non-critical care units were bathed either according to the hospital unit’s usual care procedures (the control group) or bathed with the topical antibacterial agent chlorhexidine (plus nasal administration of the antibiotic mupirocin for those patients who were colonized or infected with, or had a history of methicillin-resistant Staphylococcus aureus [MRSA] [the intervention group]). The study investigators will compare the number of unit-attributable, multidrug-resistant organisms in clinical cultures between the study arms; these organisms include vancomycin-resistant enterococci (VRE), MRSA, and gram-negative bacteria. In addition, the investigators will compare the number of unit-attributable infections in the bloodstream and urinary tract (all pathogens) and Clostridium difficile infections. Cultures were collected at baseline and post intervention and will be assessed to determine whether resistance emerged to decolonization products.
“We are elated to reach the successful completion of the trial thanks to an incredible investigative team at HCA, Harvard Pilgrim Health Care, Rush University, the University of Massachusetts Amherst, and UC Irvine.We look forward to what the trial data will tell us and hope that we can continue to find effective ways to protect patients from infection.”
Healthcare-associated infections caused by common bacteria, including MRSA and VRE, are a leading cause of preventable illness and death in the United States and are associated with upward of $6.5 billion in annual healthcare costs. Although these bacteria normally live on the skin or in the nose, under certain circumstances they can cause serious or even life-threatening infections. Hospitalized patients who are ill or who have weakened immune systems are especially at risk for such infections. Because these pathogens are resistant to many antibiotics, they can be difficult to treat.
In intensive care units (ICUs), reducing the amount of such bacteria (a process referred to as decolonization) by treating patients’ skin with chlorhexidine and their noses with mupirocin ointment has been shown to reduce MRSA infections and all-cause bacteremias. However, relatively little is known about the effects of decolonization in hospital settings outside of critical care units, although this is where the majority of such infections occur. The ABATE trial, in contrast, is testing its bathing and decolonization strategy in adult medical, surgical, oncology, and step-down units (pediatric, psychology, peri-partum, and bone marrow transplantation units were excluded).
Over the course of the study, more than a million showers and baths were taken, and all sites have completed the intervention. The next steps for the ABATE investigators are to finish strain collection over the coming weeks, and then clean, validate, and analyze the data over the coming months.
Resources: NIH Health Care Systems Collaboratory Demonstration Project. Active Bathing to Eliminate (ABATE) Infection trial. 2014. Available at: https://www.nihcollaboratory.org/demonstration-projects/Pages/ABATE.aspx. Accessed February 2, 2015.
Huang SS, Septimus E, Moody J, et al. Randomized Evaluation of Decolonization vs. Universal Clearance to Eliminate Methicillin-Resistant Staphylococcus aureus in ICUs (REDUCE MRSA Trial). 2012. Available at: https://idsa.confex.com/idsa/2012/webprogram/Paper36049.html. Accessed December 15, 1024.
Huang SS, Septimus E, Kleinman K, et al. Targeted versus universal decolonization to prevent ICU infection. N Engl J Med 2013;368:2255–2265. PMID: 23718152. doi: 10.1056/NEJMoa1207290.
Investigators from the STOP CRC pragmatic trial, an NIH Collaboratory Demonstration Project, have recently published an article in the journal eGEMs describing solutions to issues that arose in the trial’s implementation phase. STOP CRC tests a program to improve colorectal cancer screening rates in a collaborative network of Federally Qualified Health Centers by mailing fecal immunochemical testing (FIT) kits to screen-eligible patients at clinics in the intervention arm. Clinics in the control arm provided opportunistic colorectal-cancer screening to patients at clinic visits in Year 1 and implemented the intervention in Year 2. In this cluster-randomized trial, clinics are the unit of analysis, rather than individual patients, with the primary outcome being the proportion of screen-eligible patients at each clinic who complete a FIT.
The team dealt with various challenges that threatened the validity of their primary analysis, one of which related to potential contamination of the primary outcome due to the timing of the intervention rollout: for control participants, the Year 2 intervention actively overlapped with the Year 1 control measurements. The other challenge was due to a lack of synchronization between the measurement and accrual windows. To deal with these issues, the team had to slightly modify the study design in addition to developing a few sensitivity analyses to better estimate the true impact of the intervention.
“While the nature of the challenges we encountered are not unique to pragmatic trials, we believe they are likely to be more common in such trials due to both the types of designs commonly used in such studies and the challenges of implementing system-based interventions within freestanding health clinics.” (Vollmer et al. eGEMs 2015)
The Publish EDM Forum Community publishes eGEMs (generating evidence & methods to improve patient outcomes) and provides free and open access to this methods case study. Readers can access the article here.
