Randomized controlled trials and real life studies. Approaches and methodologies: a clinical point of view.

Abstract

a b s t r a c tRandomized Controlled Trials (RCTs) are the "gold standard" for evaluating treatment outcomes providing information on treatments "efficacy". They are designed to test a therapeutic hypothesis under optimal setting in the absence of confounding factors. For this reason they have high internal validity. The strict and controlled conditions in which they are conducted, leads to low generalizability because they are performed in conditions very different from real life usual care. Conversely, real life studies inform on the "effectiveness" of a treatment, that is, the measure of the extent to which an intervention does what is intended to do in routine circumstances. At variance to RCTs, real life trials have high generalizability, but low internal validity. Recently the number of real life studies has been rapidly growing in different areas of respiratory medicine, particularly in asthma and COPD. The role of such studies is becoming a hot topic in respiratory medicine, attracting research interest and debate.In the first part of this review we discuss some of the advantages and disadvantages of different types of RCTs and analyze the strengths and weaknesses of real life trials, considering the recent examples of some studies conducted in COPD. We then discuss methodological approaches and options to overcome some of the limitations of real life studies.Comparing the conclusions of effectiveness and efficacy trials can provide important pieces of information. Indeed, these approaches can result complementary, and they can guide the interpretation of each other results.

Self-Management Program for People with Chronic Kidney Disease in Vietnam: A Pragmatic Randomised Controlled Trial

“…for evaluating an intervention program on measured outcomes (Relton, Torgerson, O'Cathain, & Nicholl, 2010;Saturni et al, 2014). However, using the "gold standard" has limitations in everyday clinical practice (Concato, Shah, & Horwitz, 2000;Herland, Akselsen, Skjønsberg, & Bjermer, 2005;Saturni et al, 2014;Ware & Hamel, 2011).…”

“…However, using the "gold standard" has limitations in everyday clinical practice (Concato, Shah, & Horwitz, 2000;Herland, Akselsen, Skjønsberg, & Bjermer, 2005;Saturni et al, 2014;Ware & Hamel, 2011). For example, the use of rigorous patient selection based on inclusion and exclusion criteria could result in a study population that differs from the actual patient population (Ware & Hamel, 2011).…”

“…For example, the use of rigorous patient selection based on inclusion and exclusion criteria could result in a study population that differs from the actual patient population (Ware & Hamel, 2011). A pragmatic RCT (pRCT) design is useful to evaluate interventions in routine clinical care (Saturni et al, 2014). In CKD, using a pRCT enables a broader range of patients to be included to test an intervention applicable to patient care and to measure relevant patient-centred outcomes, thus enhancing external validity and the translation of …”

Randomized Controlled Trial versus Real-World Study in Postherpetic Neuralgia

“…However, as potential flaws resulting from the strict design and implementation of RCTs are being increasingly discussed, it is apparent that better understanding of factors that may improve the design of neuropathic pain trials is needed [9,10]. It has also become clear that since RCTs are designed to test a therapeutic hypothesis under an optimal setting, several factors may comprise their strict and controlled conditions and thus restrict their application to real-world clinical practice [11]. For example, certain study characteristics (such as larger sample size or parallel-study groups) may be important for decreasing placebo response rates in RCTs and thus increasing the likelihood of positive outcomes [12].…”

“…In contrast to RCTs, real-world studies measure the effectiveness and safety of an intervention in clinical practice [11]. They are not as strictly designed, are open-label, and patient exclusion criteria are limited to those in the product label.…”