Tag Archives: Cluster randomized trial

NIH Collaboratory ABATE Infection Trial Highlighted in Wall Street Journal

Clinical outcomes, Clinical trials, Cluster Randomized Trials, Learning health systems, Pragmatic clinical trials, , , , ,
Susan Huang, MD, MPH
Dr. Susan Huang

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

Read The Ultimate Battle Against MRSA in the WSJ.

Read more about the ABATE Infection trial.

Watch the ABATE Infection training video.

Trauma Survivors Outcomes and Support (TSOS) trial publishes design paper

Clinical trials, Cluster Randomized Trials, Comparative Effectiveness Research, Pragmatic clinical trials, Stepped-wedge, , , , ,

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 open access article is available here: An effectiveness-implementation hybrid trial study protocol targeting posttraumatic stress disorder and comorbidity

ABATE Infection Study Team Releases Training Video

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The Actiabate_fa_tag copy 2ve 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 mupirocin was 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.

Watch the training video here.

STOP CRC Trial: Analytic Challenges and Pragmatic Solutions

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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.

New Biostatistical Guidance Document Available – “Frailty Models in Cluster-Randomized Trials”

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Tools for ResearchThe NIH Collaboratory Biostatistics/Study Design Core has released a new guidance document concerning the use of frailty models in the setting of cluster-randomized trials (CRTs). This guidance, the fifth in a series from the Core, outlines considerations affecting power calculations in frailty models, as well as issues raised by the use of logistic regression models for time-to-event versus dichotomous outcomes in CRTs .

The guidance document can be found under Biostatistical Guidance Documents on the Tools for Research page on the Living Textbook, or accessed directly here (PDF).

Report from NIH Collaboratory Workshop Examines Ethical and Regulatory Challenges for Pragmatic Cluster Randomized Trials

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A new article by researchers from the NIH Collaboratory, published online this week in the journal Clinical Trials, explores some of the challenges facing physicians, scientists, and patient groups who are working to develop innovative methods for performing clinical trials. In the article, authors Monique Anderson, MD, Robert Califf, MD, and Jeremy Sugarman, MD, MPH, MA, describe and summarize discussions from a Collaboratory workshop on ethical and regulatory issues relating to pragmatic cluster-randomized trials.

Pragmatic Cluster-Randomized Trials

Many of the clinical trials that evaluate the safety and effectiveness of new therapies do so by assigning individual volunteers to receive either an experimental treatment or a comparator, such as an existing alternative treatment, or a placebo. However, this process can be complex, expensive, and slow to yield results. Further, because these studies often take place in specialized research settings and involve patients who have been carefully screened, there are  concerns that the results gathered from such trials may not be fully applicable to “real-world” patient populations.

For these reasons, some researchers, patients, and patient advocacy groups are interested in exploring different methods for conducting clinical trials, including designs known as pragmatic cluster-randomized trials, or CRTs. In a pragmatic CRT, groups of individuals (such as a clinic, hospital, or even an entire health system) are randomly assigned to receive one of two or more interventions being compared, with a focus on answering questions about therapies in the setting of actual clinical practice—the “pragmatic” part of “pragmatic CRT.”

Pragmatic CRTs have the potential to answer important questions quickly and less expensively, especially in an era in which patient data can be accessed directly from electronic health records. Just as importantly, that knowledge can then be fed back to support a “learning healthcare system” that is constantly improving in its approach to patient care.  However, while cluster-randomized trials are not themselves new, their widespread use in patient-care settings raises a number of potential challenges.

For example: in a typical individually randomized clinical trial, patients are enrolled in a study only after first providing written informed consent. However, in a CRT, the entire hospital may be assigned to provide a given therapy. In such a situation, how should informed consent be handled? How should patients be notified that research is taking place, and that they may be part of it? Will they be able to “opt out” of the research? What will happen to the data collected during their treatment? And what do federal regulations governing clinical trials have to say about this? These are just a few of the questions raised by the use of pragmatic CRTs in patient-care settings.

The NIH Collaboratory Workshop on Pragmatic Cluster-Randomized Trials

The NIH Collaboratory Workshop of Pragmatic CRTs, held in Bethesda, Maryland in July of 2103, convened a panel of experts in clinical trials, research ethics, and regulatory issues to outline the challenges associated with conducting  pragmatic CRTs and to explore ways for better understanding and overcoming them. Over the course of the intensive 1-day workshop, conference participants identified key areas for focused attention. These included issues relating to informed consent, patient privacy, oversight of research activities, insuring the integrity of data gathered during pragmatic CRTs, and special protections for vulnerable patient populations. The article by Anderson and colleagues provides a distillation of discussions that took place at the workshop, as well as noting possible directions for further work.

In the coming months and years, the NIH Collaboratory and its partners, including the National Patient-Centered Clinical Research Network (PCORnet), plan to build on this workshop experience. Together, they hope to explore these issues in greater detail and propose practical steps for moving forward with innovative clinical research methods, while at the same time maintaining robust protections for patients’ rights and well-being.

Jonathan McCall, MS, and Karen Staman, MS, contributed to this post.

Read the full text of the article here:

Anderson ML, Califf RM, Sugarman J. Ethical and regulatory issues of pragmatic cluster randomized trials in contemporary health systems. Clin Trials 2015 [e-Pub ahead of press].
doi:10.1177/1740774515571140 
For further reading:

Tunis SR, Stryer DB, Clancy CM. Practical clinical trials: Increasing the value of clinical research decision making in clinical and health policy. JAMA 2003;290(12):1624-32. PMID:14506122; doi:10.1001/jama.290.12.1624.

The Ottawa Hospital Research Institute Ethical Issues in Cluster Randomized Trials Wiki.

Special Report: Ethical Oversight of Learning Health Systems. Hastings Center Report 2013;43(s1):S2–S44, Si–Sii.

Sugarman J, Califf RM. Ethics and regulatory complexities for pragmatic clinical trials. JAMA 2014;311(23):2381-2. PMID: 24810723; doi: 10.1001/jama.2014.4164.

Collaboratory Investigators Publish Article on Ethical and Regulatory Complexities for Pragmatic Clinical Trials in JAMA

Cluster Randomized Trials, Informed Consent, Patient-Centered Outcomes Research, Pragmatic clinical trials, Regulatory issues, , , , , ,

“Ethics and Regulatory Complexities for Pragmatic Clinical Trials,” a Viewpoint article by Jeremy Sugarman, MD, MPH, MA, and Robert Califf, MD, was published online in JAMA today. In the article, the authors draw on early experiences from two large networks conducting pragmatic clinical trials, the NIH Collaboratory and the National Patient-Centered Clinical Research Network (PCORnet), to describe 10 ethical and regulatory complexities facing this new field of research. Topics covered include informed consent, risk determination, the role of gatekeepers, and institutional review board review and oversight, among others, as well as the ongoing need for further discussion and research as a key part of efforts aimed at creating a learning healthcare system.

Dr. Sugarman is chair of the Regulatory/Ethics Core of the NIH Collaboratory and deputy director for medicine of the Johns Hopkins Berman Institute of Bioethics. Dr. Califf is the principal investigator of the NIH Collaboratory Coordinating Center and director of the Duke Translational Medicine Institute.