Skip to main content Accessibility help
Hostname: page-component-5d6d958fb5-x8cck Total loading time: 0.302 Render date: 2022-11-26T17:02:45.150Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "displayNetworkTab": true, "displayNetworkMapGraph": false, "useSa": true } hasContentIssue true

Research Methods in Healthcare Epidemiology and Antimicrobial Stewardship: Randomized Controlled Trials

Published online by Cambridge University Press:  25 April 2016

Deverick J. Anderson*
Duke University Medical Center, Division of Infectious Diseases, Durham, North Carolina
Manisha Juthani-Mehta
Yale University School of Medicine, Department of Internal Medicine, Section of Infectious Diseases, New Haven, Connecticut
Daniel J. Morgan
VA Maryland Healthcare System and University of Maryland School of Medicine, Baltimore, Maryland
Address correspondence to Deverick J. Anderson, MD, MPH, Associate Professor of Medicine, Division of Infectious Diseases, Box 102359, Duke University Medical Center, Durham, NC 27710 (


Randomized controlled trials (RCT) produce the strongest level of clinical evidence when comparing interventions. RCTs are technically difficult, costly, and require specific considerations including the use of patient- and cluster-level randomization and outcome selection. In this methods paper, we focus on key considerations for RCT methods in healthcare epidemiology and antimicrobial stewardship (HE&AS) research, including the need for cluster randomization, conduct at multiple sites, behavior modification interventions, and difficulty with identifying appropriate outcomes. We review key RCTs in HE&AS with a focus on advantages and disadvantages of methods used. A checklist is provided to aid in the development of RCTs in HE&AS.

Infect Control Hosp Epidemiol 2016;37:629–634

SHEA White Paper
© 2016 by The Society for Healthcare Epidemiology of America. All rights reserved 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)



1. Ioannidis, JP, Haidich, AB, Pappa, M, et al. Comparison of evidence of treatment effects in randomized and nonrandomized studies. JAMA 2001;286:821830.CrossRefGoogle ScholarPubMed
2. Friedman, LM, Furberg, CD, DeMets, DL. Fundamentals of Clinical Trials, 3rd ed. New York, NY, USA: Springer, 1998.CrossRefGoogle Scholar
3. Eldridge, S, Kerry, S. A Practical Guide to Cluster Randomised Trials in Health Services Research. Wiley; 2012.CrossRefGoogle Scholar
4. Meurer, WJ, Lewis, RJ. Cluster randomized trials: evaluating treatments applied to groups. JAMA 2015;313:20682069.CrossRefGoogle ScholarPubMed
5. Campbell, MK, Elbourne, DR, Altman, DG. CONSORT statement: extension to cluster randomised trials. BMJ 2004;328:702708.CrossRefGoogle ScholarPubMed
6. Dans, AL, Dans, LF, Guyatt, GH, Richardson, S. Users’ guides to the medical literature: XIV. How to decide on the applicability of clinical trial results to your patient. Evidence-Based Medicine Working Group. JAMA 1998;279:545549.CrossRefGoogle ScholarPubMed
7. Baily, MA. Harming through protection? New Engl J Med 2008;358:768769.CrossRefGoogle ScholarPubMed
8. Pronovost, P, Needham, D, Berenholtz, S, et al. An intervention to decrease catheter-related bloodstream infections in the ICU. New Engl J Med 2006;355:27252732.CrossRefGoogle ScholarPubMed
9. Evans, SR, Rubin, D, Follmann, D, et al. Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR). Clin Infect Dis 2015;61:800806.CrossRefGoogle Scholar
10. Van Ness, PH, Peduzzi, PN, Quagliarello, VJ. Efficacy and effectiveness as aspects of cluster randomized trials with nursing home residents: methodological insights from a pneumonia prevention trial. Contemp Clin Trials 2012;33:11241131.CrossRefGoogle ScholarPubMed
11. Loeb, M, Dafoe, N, Mahony, J, et al. Surgical mask vs N95 respirator for preventing influenza among health care workers: a randomized trial. JAMA 2009;302:18651871.CrossRefGoogle ScholarPubMed
12. Darouiche, RO, Wall, MJ Jr, Itani, KM, et al. Chlorhexidine-alcohol versus povidone-iodine for surgical-site antisepsis. New Engl J Med 2010;362:1826.CrossRefGoogle ScholarPubMed
13. Timsit, JF, Schwebel, C, Bouadma, L, et al. Chlorhexidine-impregnated sponges and less frequent dressing changes for prevention of catheter-related infections in critically ill adults: a randomized controlled trial. JAMA 2009;301:12311241.CrossRefGoogle ScholarPubMed
14. Pickard, R, Lam, T, MacLennan, G, et al. Antimicrobial catheters for reduction of symptomatic urinary tract infection in adults requiring short-term catheterisation in hospital: a multicentre randomised controlled trial. Lancet 2012;380:19271935.CrossRefGoogle ScholarPubMed
15. Mody, L, Krein, SL, Saint, S, et al. A targeted infection prevention intervention in nursing home residents with indwelling devices: a randomized clinical trial. JAMA Intern Med 2015;175:714723.CrossRefGoogle ScholarPubMed
16. Salgado, CD, Sepkowitz, KA, John, JF, et al. Copper surfaces reduce the rate of healthcare-acquired infections in the intensive care unit. Infect Control Hosp Epidemiol 2013;34:479486.CrossRefGoogle ScholarPubMed
17. Climo, MW, Yokoe, DS, Warren, DK, et al. Effect of daily chlorhexidine bathing on hospital-acquired infection. New Engl J Med 2013;368:533542.CrossRefGoogle ScholarPubMed
18. Huang, SS, Septimus, E, Kleinman, K, et al. Targeted versus universal decolonization to prevent ICU infection. New Engl J Med 2013;368:22552265.CrossRefGoogle ScholarPubMed
19. Milstone, AM, Elward, A, Song, X, et al. Daily chlorhexidine bathing to reduce bacteraemia in critically ill children: a multicentre, cluster-randomised, crossover trial. Lancet 2013;381:10991106.CrossRefGoogle ScholarPubMed
20. Noto, MJ, Domenico, HJ, Byrne, DW, et al. Chlorhexidine bathing and health care-associated infections: a randomized clinical trial. JAMA 2015;313:369378.CrossRefGoogle ScholarPubMed
21. Derde, LP, Cooper, BS, Goossens, H, et al. Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial. Lancet Infect Dis 2014;14:3139.CrossRefGoogle ScholarPubMed
22. Huskins, WC, Huckabee, CM, O’Grady, NP, et al. Intervention to reduce transmission of resistant bacteria in intensive care. New Engl J Med 2011;364:14071418.CrossRefGoogle ScholarPubMed
23. Harris, AD, Pineles, L, Belton, B, et al. Universal glove and gown use and acquisition of antibiotic-resistant bacteria in the ICU: a randomized trial. JAMA 2013;310:15711580.Google ScholarPubMed
24. Bellini, C, Petignat, C, Masserey, E, et al. Universal screening and decolonization for control of MRSA in nursing homes: a cluster randomized controlled study. Infect Control Hosp Epidemiol 2015;36:401408.CrossRefGoogle ScholarPubMed
25. Juthani-Mehta, M, Van Ness, PH, McGloin, J, et al. A cluster-randomized controlled trial of a multicomponent intervention protocol for pneumonia prevention among nursing home elders. Clin Infect Dis 2015;60:849857.CrossRefGoogle ScholarPubMed
26. Gerber, JS, Prasad, PA, Fiks, AG, et al. Effect of an outpatient antimicrobial stewardship intervention on broad-spectrum antibiotic prescribing by primary care pediatricians: a randomized trial. JAMA 2013;309:23452352.CrossRefGoogle ScholarPubMed
27. Meeker, D, Knight, TK, Friedberg, MW, et al. Nudging guideline-concordant antibiotic prescribing: a randomized clinical trial. JAMA Intern Med 2014;174:425431.CrossRefGoogle ScholarPubMed
28. Fuller, C, Michie, S, Savage, J, et al. The Feedback Intervention Trial (FIT)—improving hand-hygiene compliance in UK healthcare workers: a stepped wedge cluster randomised controlled trial. PloS One 2012;7:e41617.CrossRefGoogle ScholarPubMed
29. Passaretti, CL, Otter, JA, Reich, NG, et al. An evaluation of environmental decontamination with hydrogen peroxide vapor for reducing the risk of patient acquisition of multidrug-resistant organisms. Clin Infect Dis 2013;56:2735.CrossRefGoogle ScholarPubMed
30. Stevenson, KB, Searle, K, Curry, G, et al. Infection control interventions in small rural hospitals with limited resources: results of a cluster-randomized feasibility trial. Antimicrob Resist Infect Control 2014;3:10.CrossRefGoogle ScholarPubMed
31. Haut, ER, Pronovost, PJ. Surveillance bias in outcomes reporting. JAMA 2011;305:24622463.CrossRefGoogle ScholarPubMed
32. Young, H, Knepper, B, Moore, EE, Johnson, JL, Mehler, P, Price, CS. Surgical site infection after colon surgery: National Healthcare Safety Network risk factors and modeled rates compared with published risk factors and rates. J Amer Coll Surg 2012;214:852859.CrossRefGoogle ScholarPubMed
33. Bode, LG, Kluytmans, JA, Wertheim, HF, et al. Preventing surgical-site infections in nasal carriers of Staphylococcus aureus . New Engl J Med 2010;362:917.CrossRefGoogle ScholarPubMed
34. Moher, D, Schulz, KF, Altman, DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials. Lancet 2001;357:11911194.CrossRefGoogle Scholar
Cited by

Save article to Kindle

To save this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the or variations. ‘’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Research Methods in Healthcare Epidemiology and Antimicrobial Stewardship: Randomized Controlled Trials
Available formats

Save article to Dropbox

To save this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

Research Methods in Healthcare Epidemiology and Antimicrobial Stewardship: Randomized Controlled Trials
Available formats

Save article to Google Drive

To save this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

Research Methods in Healthcare Epidemiology and Antimicrobial Stewardship: Randomized Controlled Trials
Available formats

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *