ReviewPatients included in randomised controlled trials do not represent those seen in clinical practice: focus on antimicrobial agents
Introduction
Clinicians are confronted with a wide variety of clinical questions and make decisions that affect individual patients. In this clinical decision-making process, evidence-based medicine may play a significant role by collecting and evaluating the best available evidence. Randomised controlled trials (RCTs), and meta-analyses of RCTs, are considered to provide evidence of the highest grade [1], [2]; thus, their findings, which are often easily accessed [3], [4], are implemented to answer clinically relevant questions [5].
The study populations of RCTs consist of individuals who must meet specific criteria, predefined by the researchers. In an attempt to increase homogeneity of the study population, researchers tend to use strict inclusion criteria. Thus, a proportion of screened patients do not fulfil the criteria for entry into RCTs; often this proportion of excluded patients seems not to be negligible. For instance, in a recent RCT evaluating the usefulness of silver-coated endotracheal tubes in preventing ventilator-associated pneumonia, 84% of the initially screened patients were excluded from the primary efficacy analysis [6]. In addition, the use of strict inclusion criteria may also contribute to the explanation of several paradoxical findings of RCTs. For example, in a meta-analysis conducted by our research team [7], all included RCTs evaluating the short versus long antimicrobial treatment of children with acute bacterial meningitis reported no death due to this well-known fatal infection (namely bacterial meningitis), a fact that presumably raises concerns regarding the external validity of the above RCTs [7].
Taking all the above into consideration, this study was performed to examine, by reviewing the exclusion criteria of RCTs, whether the patients included in RCTs are representative of those seeking medical care in real-life clinical situations.
Section snippets
Data sources
Potentially eligible articles were identified through search of the PubMed database. An article was considered eligible for inclusion in this study if it was a RCT that enrolled individuals with infections. Inclusion and exclusion criteria used in each RCT should have been clearly stated in the text. The first 30 articles that met all the above criteria and for which a full-text was obtained were included in this study. No lower time limit was applied to the search.
Data extraction and evaluation
The following information was extracted from each of the included RCTs: first author and year of publication; type of infection; characteristics of the groups to which the included patients were assigned; and inclusion and exclusion criteria as presented in the text by the authors of each study. Based on our clinical experience, the patient population that would be regarded as eligible for inclusion in each RCT was compared, in a qualitative manner, with the patient population with the same
Discussion
The main finding of this study is that the incorporation of extensive and stringent exclusion criteria of RCTs may lead to the enrolment of patients who are considerably different from those encountered in clinical practice. Thus, the conclusions generated from RCTs may not apply to a considerable proportion of patients viewed in real-life clinical situations.
Although RCTs and meta-analyses are considered to represent the top in the hierarchy of evidence-based medicine [38], the applicability
Conclusions
Patients included in RCTs appear to differ substantially from those seen in clinical practice. This fact may limit the applicability of the evidence derived from RCTs to real life. Thus, given that evidence-based medicine remains a useful tool in the decision process, clinicians should consider the limitations of the patient population involved in each clinical trial they are referring to in order to make treatment decisions as applied to individual patients encountered in every-day clinical
What is already known on this topic?
- 1.
Clinicians rely on the findings of RCTs to formulate clinical decisions regarding individual patients.
- 2.
In an attempt to increase homogeneity of study populations, researchers tend to use strict inclusion criteria.
What this study adds?
Incorporation of extensive and strict exclusion criteria of RCTs may lead to enrolment of patients that are considerably different from those seen in clinical practice.
Funding: No funding sources.
Competing interest: None declared.
Ethical approval: Not required.
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