Randomized controlled trials in CMI
Authors: L. Leibovici, M. Paul
Journal: Clinical Microbiology and Infection (2018)

Randomized controlled trials (RCTs) are probably the best design to remove bias in clinical research. Their results have better chances of influencing practice than the results of studies of other designs. This is why we welcome submissions of articles describing results of RCTs. We have requirements for the submission and reporting of RCTs. The trial should be registered in a clinical trial registry. We will consider a trial that was registered after inception, but would much prefer one that was registered before recruiting the first participant. This plays a role in our editorial decisions. We request the article to be written according to the CONSORT guideline, and we ask the authors to upload a (filled-in) CONSORT checklist. We are asking for a detailed description of the methodology, and a careful interpretation of the results. We require a description of how the recruitment sequence was generated, ensuring that it was random, and if and how the persons recruiting the patient were blinded to the patient's allocation before enrolling the patient. Blinding after randomization is not a requirement and its importance is dependent on the context of the trial and the outcomes measured. We expect the conclusions of the study to be based on the main outcome defined in the protocol, and on results that have both clinical and statistical significance. It goes without saying that the RCTs should be approved by the relevant Research Ethics Committee, and that informed consent was obtained from the participants. In addition, we assess ourselves whether the study complies with the ethical requirements of the Helsinki Declaration (https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/). Having said that, we are eager to follow the discussion on modes of patients' consent that will allow RCTs in patients with a severe infection [[1]Huttner A. Leibovici L. Theuretzbacher U. Huttner B. Paul M. Closing the evidence gap in infectious disease: point-of-care randomization and informed consent.Clin Microbiol Infect. 2017; 23: 73-77Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar]. In the transparency declaration, we want to make sure that all the support that went into the trial and any conflict of interest are acknowledged, and that a person is identified who is the guarantor for the data and the analysis, and will continue to have full access to the data in the following years. We will be especially happy to publish researcher-initiated trials, assessing questions that matter to patients, and using patient-oriented main outcomes (for examples please see references [2Figueiredo-Mello C. Naucler P. Negra M.D. Levin A.S. Ceftriaxone versus ceftriaxone plus a macrolide for community-acquired pneumonia in hospitalized patients with HIV/AIDS: a randomized controlled trial.Clin Microbiol Infect. 2018; 24: 146-151Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar, 3van Daalen F.V. Prins J.M. Opmeer B.C. Boermeester M.A. Visser C.E. van Hest R.M. et al.Effect of an antibiotic checklist on length of hospital stay and appropriate antibiotic use in adult patients treated with intravenous antibiotics: a stepped wedge cluster randomized trial.Clin Microbiol Infect. 2017; 23 (485.e1-e8)Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar, 4Davis J.S. Mackrow C. Binks P. Fletcher W. Dettwiller P. Marshall C. et al.A double-blind randomized controlled trial of ibuprofen compared to placebo for uncomplicated cellulitis of the upper or lower limb.Clin Microbiol Infect. 2017; 23: 242-246Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar, 5Santolaya M.E. Alvarez A.M. Acuña M. Avilés C.L. Salgado C. Tordecilla J. et al.Efficacy and safety of withholding antimicrobial treatment in children with cancer, fever and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial.Clin Microbiol Infect. 2017; 23: 173-178Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar, 6Torfoss D. Fladhagen T. Holte H. Brinch L. Schjesvold F.H. Fløisand Y. et al.Benzylpenicillin plus an aminoglycoside versus meropenem in neutropenic lymphoma and leukaemia patients with a suspected bacterial infection: a randomized, controlled trial.Clin Microbiol Infect. 2017; 23: 179-187Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar]). There are many clinical decisions we make with no evidence-base, and trials are needed to support them. Examples are duration of antibiotic treatment (unsettled for many infections); combination vs. single antibiotic treatment in enterococcal endocarditis or for pseudomonal infections; and many others. All trials led by the industry should be published and we encourage the industry partners leading the trial to author their papers; only researchers who have participated in the trial design, analysis, interpretation, and write-up should author the article [[7]Paul M. On transparency, responsibility, and accountability.Clin Microbiol Infect. 2009; 15: 1100-1102Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar]. The affiliation of the lead author has no significance in the decision for publication. We will also be happy to publish trials in which a diagnostic test or pathway was tested to see whether it improved patients' outcomes. The use of a new test that enhances identification of a pathogen probably does not need proof in a RCT. However the use of a diagnostic pathway does, while addressing the problems of internal and external validity that might be unique to this kind of questions. We encounter now and then trials with less than perfect methodology, the most common fault being recruitment of fewer participants than planned, or no a priori calculation of sample size at all. We are not sure whether to publish them. An incorrect interpretation of such studies can lead to bias and mismanagement of patients. On the other hand, we feel a duty to the participants in the trial: for their pains they have been promised that the results of the trial will be made public and used for the benefit of future patients. If interpreted with care, even results of imperfect RCTs can be informative. If you have completed such a trial and are not sure of acceptance, please contact us with a pre-submission enquiry, detailing in short the design, results, and problems and we will continue the dialogue from there. To sum up, we welcome submissions of RCT results to CMI, especially when they have addressed a question that matters to patients, and examined outcomes that are relevant to patients. Publication is also an acknowledgement of the efforts and goodwill of the participants in the trial and of the researchers who performed it.