By Kelly M. Pyrek
Editor's note: This is the first in a series of articles exploring imperatives relating to the research, behavioral and implementation sciences of infection prevention.
Members of the infection prevention and healthcare epidemiology community face hundreds of recommendations contained in guidelines designed to improve patient outcomes and protect healthcare personnel from infectious threats; however, lower-quality studies and unresolved issues still plague much of the body of scientific evidence clinicians consult daily. As Ganz (2015) acknowledges, "even when there is evidence that a particular healthcare screening tool or treatment can be beneficial, healthcare providers are not always sure whether it is good for their patients, or whether it will work in their environment."
Jeff Brady, MD, MPH, director of the Center for Quality Improvement and Patient Safety at Agency for Healthcare Research and Quality (AHRQ) and James Cleeman, MD, director of the Division of Healthcare-Associated Infections at the Center for Quality Improvement and Patient Safety, say that AHRQ seeks to help clinicians use available evidence, which may be scattered and incomplete, by synthesizing that knowledge into evidence reviews which are more applicable to everyday practice. Through the agency's various practice centers and programs, researchers "review the available evidence on the effectiveness of treatments, while also identifying potential harms," they say. "These evidence reviews play a role when it comes to evaluating the quality of evidence, providing clinicians with evidence-based information on common, costly medical conditions, treatments, and new healthcare technologies and strategies."
Patricia W. Stone PhD, RN, FAAN, director of the Center for Health Policy at the Columbia University School of Nursing, advises, "Evidence certainly has a hierarchy. When there is no research, the best evidence may be expert opinion."
Nasia Safdar, MD, PhD, associate professor in the Division of Infectious Disease at the University of Wisconsin School of Medicine and Public Health, served as lead author on a paper that outlined research imperatives for healthcare epidemiology. She suggests, "Use more than one study to guide decision-making; if the bulk of the evidence points toward a particular path, then use that as the basis. Study whatever practice is put in place and evaluate it as part of implementation research."
Four years ago, the Society for Healthcare Epidemiology of America (SHEA)'s Research Committee released its Road Map for Research (Safdar, et al. 2014), outlining additional research needed to address remaining knowledge gaps. Broadly, these research topics include:
• How to use relatively objective criteria to improve the reliability of HAI surveillance definitions while retaining clinical relevance and credibility
• Best ways to improve the efficiency of HAI surveillance methods and how to better utilize existing health information technology (HIT) and provide guidance for future HIT developments
• How to improve performance of HAI surveillance across the continuum of healthcare, including ambulatory sites, long-term care facilities, and tracking of patients who seek care across multiple healthcare facilities
• How to improve performance of HAI surveillance for special populations, including pediatric patients
• How to improve methods to provide HAI surveillance data to healthcare colleagues, hospital administrators, payors, and patients to drive improvements in HAI prevention practices and how to effectively account for nonmodifiable risk factors and place emphasis on facilities that continue to need improvement
In the years since this research agenda was put forth, Safdar says the SHEA Research Committee re-evaluates them periodically but there has been no formal update. In terms of evolution, she says that "Antibiotic stewardship has evolved as a top priority."
Quality research is more important than ever before, in the face of mounting infectious threats.
"Emerging pathogens, constrained resources and fewer treatments for resistant infections means that we must use evidence to guide our actions and that evidence is generated from research," Safdar says.
Stone concurs, noting, " Infection prevention is a global issue with emerging infectious diseases continuing and spread of multiple drug resistance organisms growing. We need to make sure the population as well as our own patients and healthcare workers are protected as best as possible from contagious diseases."
Stone says she believes SHEA's research roadmap continues to be relevant in 2018. "The 2014 research priorities are categorized in terms of: 1) knowledge gaps related to a) surveillance, b) improving risk adjustment for HAIs, c) burden of HAIs in settings across the spectrum of healthcare; and 2) research gaps in the prevention of HAIs a) technology and detection of HAIs, b) pediatric specific issues, c) practices in infection prevention," she says. "This is a substantive and comprehensive list that still is pertinent today. However, I do think there are some areas that are not well covered. For example, while the burden of HAIs across the spectrum of healthcare is mentioned, I think there needs to be an increased emphasis, focus and support of non-acute care settings."
Stone continues, "In my own research, we are looking at best practices of infection prevention in both the home healthcare setting as well as nursing homes. It is a little bit like the 'wild, wild, west' in the non-acute care settings, without a lot of standardization to date. In 2012, the CDC’s National Healthcare Safety Network (NHSN) implemented the long-term care module. However, uptake had been relatively slow until CMS supported a national learning collaborative. It is not known if support for the nursing homes is going to continue. More recently CMS regulated that each nursing home in the nation have at least one IP whose primary responsibility is the infection and control program and that the IP serves as a member of the facility’s quality assessment and assurance committee. CMS also requires nursing homes to now have antimicrobial stewardship programs. In the home healthcare setting, which is growing faster than any other health industry, there has been even less attention to infection prevention."
The SHEA Research Network is a consortium of more than 100 hospitals collaborating on multi-center research projects to identify important gaps in the healthcare epidemiology science base and address them by contributing data and expertise. SHEA says that "Substantial knowledge gaps exist in our grasp of the pathogenesis and epidemiology of HAIs, including MDRO transmission and the understanding of the effectiveness of specific infection prevention practices." Examples of high-priority topics include:
- Evaluate HAI prevention across the spectrum of healthcare especially non-acute care settings
- Evaluate approaches for dissemination and implementation of HAI prevention methods
- Evaluate role of electronic monitoring tools in managing hand hygiene compliance
- Device-associated infections (DAI, including CLABSI, CAUTI, VAE)
- Examine the epidemiology of DAI in non-ICU settings
- Test novel technology and strategies for DAI prevention such as impregnated devices and maintenance bundles
- Examine the reliability and validity of surveillance definitions in different patient populations and their impact on outcomes and practices
- Compare various postoperative wound care strategies for reducing SSIs
- Assess the impact of an operating room checklist on SSI rates
- Evaluate patient-specific risk factor modification (such as smoking cessation) strategies for reducing SSIs
• MDROs and Clostridium difficile
- Assess transmission dynamics and novel interventions to prevent transmission in acute and non-acute care settings
- Evaluate the role of the environment and the impact of environmental disinfection on transmission
- Examine the role of laboratory technology to identify MDROs and guide infection prevention measures
• Employee health
- Identify approaches to improve influenza and other vaccinations in healthcare personnel (HCP) in settings where mandatory vaccination is not feasible
- Evaluate practices to prevent needlestick injuries and other bloodborne pathogen exposures in HCP and explore methods for post-exposure prophylaxis for prevention of HIV, HCV and HBV
- Assess the role of HCP in transmitting organisms including MDROs to patients
• Respiratory viruses
- Evaluate the effects of barrier precautions on respiratory virus transmission
- Assess the acceptability of N-95 masks for prevention of respiratory virus transmission
- Evaluate the role of novel diagnostics in preventing nosocomial respiratory viruses and identifying emerging respiratory viruses
• Antimicrobial stewardship
- Evaluate the impact of antimicrobial stewardship programs on emergence of resistance, patient outcomes, and cost
- Explore the benefits of alternative methods for antimicrobial stewardship such as post-prescription review
- Assess the use of performance metrics for antimicrobial stewardship
- Compare available touchless cleaning technologies for efficacy and acceptability
- Assess favored methods for surveillance of environmental cleaning
- Assess the role of hospital epidemiologists and infection preventionists in changing policy related to environmental cleaning
As Safdar, et al. (2014) notes, "The pressing issues in HAI prevention revolve around (1) improving our understanding of pathogenesis and epidemiology of HAIs, including the role of MDROs, risk factors, and HAI burden across different healthcare settings; (2) devising appropriate and widely generalizable strategies to prevent HAIs using knowledge generated through research on pathogenesis and epidemiology; (3) rigorously testing those strategies for efficacy, effectiveness, and cost-effectiveness; and (4) effectively and promptly meeting the challenge of containing new and emerging HAIs and MDROs. This agenda is ambitious but important. A well-planned and coordinated research infrastructure capable of addressing a variety of research needs and questions is essential to tackle these questions adequately in a multi-faceted manner."
The researchers addressed the need to construct the infrastructure to advance these research agenda, including improving study design itself as a building block. As Safdar, et al. (2014) explain, "Infection prevention research has undergone considerable evolution over the last decade, with a better application of quasi-experimental design. As a result, methods have improved from the original core literature, which was focused largely on interventions in response to outbreaks. Although many study designs are applicable to infection control research, the most robust method for testing infection control and prevention interventions is the randomized controlled trial (RCT). Generally, multi-site studies are needed to achieve sufficient statistical power. Cluster RCTs that randomize healthcare units or entire facilities provide an ideal and much needed method for comparing the effectiveness of quality improvement strategies that cannot be allocated at an individual level. In the last few years, an increase in cluster RCTs for testing of infection prevention interventions has occurred. Cluster RCTs are advantageous, because they allow comparisons of infection prevention strategies under conditions of actual use and account for confounding factors. When large cluster RCTs are performed across a variety of healthcare facilities, these trials can achieve broad generalizability and sufficient power to answer important questions that are unable to be answered by single center or small multicenter studies. They can also be considerably more cost-effective than RCTs, because they may be able to leverage existing quality improvement infrastructure. The ability to harness administrative capacities of healthcare systems to make data collection less cumbersome is needed as an important enhancement to the practicality of RCTs."
Granted that RCTs are the most robust form of inquiry, but they are expensive and time-consuming and may be out of reach of the average team of researchers, and the merit of other types of studies are debated.
"Many other study designs have merit," says Safdar, "especially if well conducted but when possible, an RCT answers a question in a way that few other study designs can."
Stone comments, "RCTs are definitely are a very important and can be very effective in decreasing bias. However, comparative effectiveness research, that focuses on using real world data (i.e., not controlled in a laboratory) are also very effective," she says. "In comparative effectiveness research multiple methods may used. Sometime pragmatic trials are called for other times using existing data sources (e.g., NHSN, survey or administrative data) may be more appropriate. It depends on the question at hand."
As Safdar, et al. (2014) explain, "A number of issues must be overcome before cluster RCTs become commonly used. First, institutions must reach agreement on the concept of group randomization, which may involve waiver of individual informed consent. Currently, institutions vary in their approach to and acceptance of trials that randomize entire units of individuals. Second, infrastructure must be developed to allow involvement of multiple facilities in the most streamlined way possible. Third, regulatory requirements, such as institutional review board (IRB) approval, must be streamlined, ideally by creating or using an existing central IRB to which participating institutions can defer. Fourth, study designs within cluster RCTs should be explored to better achieve balance of baseline covariates, such as use of stratified randomization or a cross-over design."
In terms of coordination of research from discovery to dissemination, the researchers observe, "Research in HAI prevention is needed on all fronts and across the entire spectrum of basic and translational research. Transmission of MDROs serves as an example. Basic research elucidates the molecular basis of resistance and transmission, which leads to clinical and translational research to identify risk factors and mechanisms of transmission. Researchers should employ clinical trials (phases 1 to 3) to test interventions to reduce transmission in a variety of settings. Implementation and dissemination research would be used to examine effectiveness, feasibility, and fidelity of large-scale implementation across the entire spectrum of healthcare. Health services research would assess the outcomes of MDRO transmission and prevention of transmission as well as the institutional and societal economic cost of these infections. Finally, health policy research would examine the public health impact of governance strategies on HAI prevention."
Research requires resources and funding, and research must function in real-world conditions. Columbia University's Stone has built a career upon studying the complications and rigor of conducting real-world comparative and economic evaluations in the context of improving the quality of care and specifically preventing healthcare-associated infections. She underscores the importance of securing the resources necessary to ensure continued study of imperatives facing infection prevention and control.
"The funding for research has become increasingly complex as well as competitive," Stone says. "Therefore, researchers need to make sure their ideas are well articulated. It usually takes an interdisciplinary team to have enough expertise at the table to understand all the issues." Stone continues, "Infection prevention and control research is imperative. Funding from federal agencies is needed."
Safdar, et al. (2014) acknowledged the need to secure resourcing: "To close the gaps … the ability to conduct well-designed, large-scale studies is essential. To undertake this work, funding organizations must make HAI prevention research a priority. Historically, funding for HAI research has been very limited compared with that for many other disciplines of comparable magnitude and importance. The previous SHEA white paper highlighted this major obstacle to progress. With increasing visibility and calls to action for HAI research, federal organizations have begun to release funding opportunities for HAI research.
For example, the Agency for Healthcare Research and Quality (AHRQ) and the CDC have released recent funding opportunities focused on HAI prevention. Although this is a welcome step, additional support in this area is needed urgently. In this regard, funding by industry offers potential opportunities but also necessitates careful, considered navigation of interactions and collaboration between industry and academia to ensure that research is free of bias and conflict of interest."
Safdar says barriers to research be broken, but it requires "sustained, high priority of funding agencies, creation of networks with infrastructure to allow efficient, well conducted large scale studies, commitment by healthcare organizations to facilitate research."
Implementing research will be addressed in the next installment of this series, but Ganz (2015) acknowledges that "although we don't have a universal recipe for successfully implementing guidelines," there are some key questions to consider during the guideline and/or research implementation process. They are as follows:
- What are the motivations for implementation?
- What is the political climate surrounding implementation?
- What is the culture of your workplace?
- Do you have the resources to move forward?
- Assuming that your answers to the first four questions above support moving forward with guideline implementation, have you considered how you will introduce practice changes based on the guideline into your organization?
- What are your aims with respect to guideline implementation?
- How will you measure your guideline implementation progress?
- Does the guideline tell you anything about how it should be implemented?
- Does a small test of guideline implementation work?
- If answers to the first 9 questions are supportive of guideline implementation, how will you roll out that initiative more broadly in your organization?
The interpretation of research and recommendations contained in guidelines is the first step, but it requires critical thinking skills on the part of the clinician for proper and effective implementation. To be discerning when wading through an ocean of research, both Safdar and Stone offer their advice.
"Understanding study design, and does it apply to their patient population, is important," Safdar says. "What are the weaknesses of the study?"
"Clinicians need to know how to understand the quality of the evidence," Stone suggests. "There are many evidence-based practice resources available to clinicians. They should make sure they use these resources so they will know how to critically assess the evidence available and make sound decisions based on the best evidence available."
Ganz DA. Implementing Guidelines in Your Organization: What Questions Should You Be Asking? AHRQ. July 13, 2015. Accessible at: https://www.guideline.gov/expert/expert-commentary/49423/implementing-guidelines-in-your-organization-what-questions-should-you-be-asking
Safdar N, Anderson DJ, Braun BI, Carling P, Cohen S, Donskey C, Drees M, Harris A, Henderson DK, Huang SS, Juthani-Mehta M, Lautenbach E, Linkin DR, Meddings J, Miller LG, Milstone A, Morgan D, Sengupta S, Varman M, Yokoe D and Zerr DM. The Evolving Landscape of Healthcare-Associated Infections: Recent Advances in Prevention and a Road Map for Research. Infection Control and Hospital Epidemiology. Vol. 35, No. 5. Pp. 480-493. May 2014.