Knowledge Synthesis

The Knowledge Synthesis Program in the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery helps Mayo's clinical practice identify and examine existing knowledge to ensure the best available evidence is applied to patient care. The program's work also helps identify gaps in knowledge or implementation that Mayo Clinic can fill and supports Mayo's ability to provide the best possible care for every patient.

Knowledge synthesis is a research methodology within health care delivery science and a critical initial step in knowledge translation. Knowledge synthesis consists of evidence identification, appraisal and synthesis to produce a succinct summarization that informs best practice. The process includes performing systematic reviews and meta-analyses, developing clinical practice guidelines, and conducting methodology research.

The Knowledge Synthesis Program supports governmental entities and professional societies in developing national and international clinical practice guidelines spanning various conditions, diseases and methods of health care delivery.

Focus areas

• Providing stakeholders with the least biased and most precise and applicable results by conducting systematic reviews and meta-analyses
• Assisting professional organizations and medical societies in developing clinical practice guidelines that incorporate patients' values and preferences
• Conducting methodology research to advance the methods of translational research
• Creating future research agendas by identifying gaps in knowledge
• Ensuring that resources aren't wasted pursuing research questions that have already been answered
• Advising researchers who are conducting original studies about design features and analytical approaches to meet the needs of the end users of the resulting evidence

Projects

Examples of the work and major initiatives undertaken by the Knowledge Synthesis Program include the following projects.

Providing the best available evidence in a rapidly evolving pandemic

Early in 2020, the Knowledge Synthesis Program team developed and operationalized a framework for evidence synthesis programs to respond to a pandemic. One project conducted within this framework included the rapid systematic review and development of a practice guidance regarding anticoagulation in COVID-19. The project team answered the following questions:

• What abnormalities of coagulation occur with COVID-19?
• What is the role of anticoagulation for patients with COVID-19?
• What should be done in patients already in anticoagulation?

Other reviews investigated the effectiveness of mesenchymal stromal cells as a treatment for pneumonia induced by COVID-19 or other acute respiratory distress syndromes as well as the effects of COVID-19 on pregnant women and their newborns. The team also interrogated the idea that chloroquine or hydroxychloroquine may prevent hospitalization or death in people with COVID-19, whether given with or without the antibiotic azithromycin.

In later stages of the pandemic, the team is investigating pharmacological treatments via dynamic, or "living," systematic reviews that are refreshed regularly to ensure that Mayo Clinic health care providers have the best available evidence.

The Knowledge Synthesis Program's work also informs the AskMayoExpert COVID-19 Navigator, which provides Mayo Clinic's consensus-based expert clinical recommendations, protocols and best practices for COVID-19 — and which Mayo Clinic has made available for clinicians everywhere.

Related publications:

• Kashour Z, Riaz M, Garbati MA, AlDosary O, Tlayjeh H, Gerberi D, Murad MH, Sohail MR, Kashour T, Tleyjeh IM. Efficacy of chloroquine or hydroxychloroquine in COVID-19 patients: A systematic review and meta-analysis. Journal of Antimicrobial Chemotherapy. 2021; doi:10.1093/jac/dkaa403.
• Matar R, Alrahmani L, Monzer N, Debiane LG, Berbari E, Fares J, Fitzpatrick F, Murad MH. Clinical presentation and outcomes of pregnant women with coronavirus disease 2019: A systematic review and meta-analysis. Clinical Infectious Diseases. 2021; doi:10.1093/cid/ciaa828.
• McBane RD 2nd, Torres Roldan VD, Niven AS, Pruthi RK, Franco PM, Linderbaum JA, Casanegra AI, Oyen LJ, Houghton DE, Marshall AL, Ou NN, Siegel JL, Wysokinski WE, Padrnos LJ, Rivera CE, Flo GL, Shamoun FE, Silvers SM, Nayfeh T, Urtecho M, Shah S, Benkhadra R, Saadi SM, Firwana M, Jawaid T, Amin M, Prokop LJ, Murad MH. Anticoagulation in COVID-19: A systematic review, meta-analysis, and rapid guidance from Mayo Clinic. Mayo Clinic Proceedings. 2020; doi:10.1016/j.mayocp.2020.08.030.
• Murad MH, Nayfeh T, Urtecho Suarez M, Seisa MO, Abd-Rabu R, Farah MHE, Firwana M, Hasan B, Jawaid T, Shah S, Torres Roldan V, Prokop L, Wang Z, Saadi SM. A framework for evidence synthesis programs to respond to a pandemic. Mayo Clinic Proceedings. 2020; doi:10.1016/j.mayocp.2020.05.009.
• Qu W, Wang Z, Hare JM, Bu G, Mallea JM, Pascual JM, Caplan AI, Kurtzberg J, Zubair AC, Kubrova E, Engelberg-Cook E, Nayfeh T, Shah VP, Hill JC, Wolf ME, Prokop LJ, Murad MH, Sanfilippo FP. Cell-based therapy to reduce mortality from COVID-19: Systematic review and meta-analysis of human studies on acute respiratory distress syndrome. Stem Cells Translational Medicine. 2020; doi:10.1002/sctm.20-0146.

Advances from the Evidence-Based Practice Research Program

A major activity of the Knowledge Synthesis Program is to oversee Mayo Clinic's Evidence-Based Practice Research Program.

A recent example of this work was a comprehensive systematic review evaluating a diagnostic test for asthma commissioned by the Agency for Healthcare Research and Quality and the National Heart, Lung, and Blood Institute. The review supported the development of national asthma management guidelines.

Related websites:

• Agency for Healthcare Research and Quality — Evidence-Based Reports From Mayo Clinic
• National Heart, Lung, and Blood Institute — 2020 Focused Updates to the Asthma Management Guidelines: A Report From the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group

Methodology research and study design consultation

The Knowledge Synthesis Program conducts meta-epidemiological research to investigate various methodological and analytical approaches and improve future study design. Examples of these methodological studies include a guide for analysis of continuous outcomes in meta-analysis, a tool to assess risk of bias in case studies and case reports, and an approach to synthesis of noninferiority trials.

Program experts constantly appraise research and conduct methodology research in order to provide consultative support and guidance to other health services researchers. Some examples of studies that receive guidance on study design and analysis from the Knowledge Synthesis Program include one evaluating cardiovascular risk screening in migrant agricultural workers in Southeast Minnesota, another examining gender disparities in hospitalized patients, and a third reviewing outcomes of patients with heart disease admitted after hours.

Related publications:

• Alsawas M, Wang Z, Murad MH, Yousufuddin M. Gender disparities among hospitalised patients with acute myocardial infarction, acute decompensated heart failure or pneumonia: Retrospective cohort study. BMJ Open. 2019; doi:10.1136/bmjopen-2018-022782.
• Murad MH, Sultan S, Haffar S, Bazerbachi F. Methodological quality and synthesis of case series and case reports. BMJ Evidence-Based Medicine. 2018; doi:10.1136/bmjebm-2017-110853.
• Murad MH, Wang Z, Chu H, Lin L. When continuous outcomes are measured using different scales: Guide for meta-analysis and interpretation. BMJ. 2019; doi:10.1136/bmj.k4817. 
• Sorita A, Lennon RJ, Haydour Q, Ahmed A, Bell MR, Rihal CS, Gersh BJ, Holmen JL, Shah ND, Murad MH, Ting HH. Off-hour admission and outcomes for patients with acute myocardial infarction undergoing percutaneous coronary interventions. American Heart Journal. 2015; doi:10.1016/j.ahj.2014.08.012.
• Rajjo T, Mohammed K, Rho J, Murad MH. On-the-farm cardiovascular risk screening among migrant agricultural workers in Southeast Minnesota: A pilot prospective study. BMJ Open. 2018; doi:10.1136/bmjopen-2017-019547.
• Wang Z, Nayfeh T, Sofiyeva N, Ponte OJ, Rajjoub R, Malandris K, Seisa M, Chu H, Murad MH. Including non-inferiority trials in contemporary meta-analyses of chronic medical conditions: A meta-epidemiological study. Journal of General Internal Medicine. 2020; doi:10.1007/s11606-020-05821-2.

Living systematic reviews platform

The Knowledge Synthesis Program supported the development of a dynamic tool to help health care providers and researchers stay on top of the rapidly evolving research findings. One example was regarding treatments for kidney cancer. The project team summarized the evidence and updated it constantly using a variety of automated functions and displays that cater to the needs of different decision-makers. The team continues to refine the tool.

Related publication:

• Riaz IB, He H, Ryu AJ, Siddiqi R, Naqvi SAA, Yao Y, Husnain M, Narasimhulu DM, Mathew J, Sipra QUAR, Vandvik PO, Joseph RW, Liu H, Wang Z, Herasevich V, Singh P, Hussain SA, Ho TH, Bryce AH, Pagliaro LC, Murad MH, Costello BA. A living, interactive systematic review and network meta-analysis of first-line treatment of metastatic renal cell carcinoma. European Urology. 2021; doi:10.1016/j.eururo.2021.03.016.

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