INTRODUCTION

Whenever we think about starting a research project, we face the situation of how to outline the best possible study. And the most important thing of all: which should the optimal study be for the question that we, as researchers, have just posed?

This question that the researcher asks should ideally orbit around 4 elements: patient, intervention, comparison, and outcome.

This question is typically framed within what is referred to as “PICO.” Although the components “intervention” and “comparison” suggest the experimental nature of clinical trials and may seem to restrict the system to issues regarding treatment, it can also be used for questions on etiology, diagnosis, or prognosis, as shown in table I.

Table I. PICO method to formulate questions in epidemiology. 

This question formulation technique reveals the need researchers have of a structured approach regarding the initiation of such questions and the appropriate studies, on a routine basis, to provide answers to these questions (Table II).

Table II. Trial recommended to address the epidemiological question (PICO). 

How many times have we heard that a clinical trial is “the best”? Well, it depends. We can hardly conduct a clinical trial to study the association between smoking and AAAs. That would involve an absurdity: randomly force the study participants to smoke and others not to, to see if one group develops more AAAs than the other. Ethical considerations logically prevent these absurdities from happening, which underscores the importance of having a clear understanding of what we want to study to choose the most suitable trial to do so.

The objective I propose is to analyze together the most widely used studies, their characteristics, strengths, and weaknesses. But before doing so, I first suggest to understand the overall characteristics that will allow us to do better individual interpretations of each study.

OBSERVATIONAL VS EXPERIMENTAL TRIALS

An observational design is a study in which the researcher merely “observes.” The study participants decide what they are exposed to, but the researcher only chooses the association he/she wants to analyze without introducing the study factor to the participants or deciding who will receive such factor.

Unlike observational trials, experimental trials are characterized by the researcher's active involvement. On the one hand, the researcher introduces the study factor. On the other hand, he/she decides what participants will receive, or not, the study factor.

Let's consider an example of both situations. Imagine we want to conduct a study to see if atorvastatin reduces cholesterol more than simvastatin does. Firstly, the researcher has introduced the treatments that the subjects will receive. Secondly, the researcher will play a decisive role in determining who will receive either one of the two treatments.

Regarding how the study factor is assigned, it can be randomized, meaning determined by chance, which minimizes the likelihood of biases, or non-randomized (here chance doesn't play a role).

ANALYTICAL VS DESCRIPTIVE TRIALS

A descriptive trial is one that is limited to defining or describing an event seen in a group of participants. There is no option for comparison because there's only one group or cohort under study. For instance, the frequency of smoking in our patients with AAA.

In contrast, analytical trials allow us to “analyze” relationships between risk factors and diseases because there are 2 groups or cohorts. For example, when we're comparing if smoking is more common in patients with AAA than in healthy individuals, what we're actually doing is analyzing the smoking-AAA association, which can be quantified using measures of association such as relative risk or odds ratios.

Based on the parameters discussed above, we can create the following outline of the most common type of clinical trials conducted, as shown in figure 1.

Figure 1. Types of trials. C&C: cases and controls; RCT: randomized clinical trial; Semi-Exp.: semi-experimental. 

Regarding the outline shown in figure 1, and although it holds more didactic than theoretical importance, 3 points should be summarized here:

In this article, we will be analyzing some of the most widely used observational designs to date, sparing experimental trials—basically randomized clinical trials—for a different occasion.

OBSERVATIONAL TRIALS

CASE REPORT SERIES

Case reports and case series are a significant portion of the scientific output in conferences organized by multiple scientific societies.

They are defined as a type of publication that reports on a series of cases that share common characteristics that makes them groupable such as being syndromic, etiological, anatomical, histological, physiological, genetic, molecular, treatment-related, sharing treatment-related adverse events, or characteristics from a supplementary trial.

An example of this kind of study is the one published by Díaz Cruz et al. (³) on their experience with IMA embolization during EVAR.

Although these designs are very useful to formulate hypotheses, they are not good to assess or test the presence of a statistical association. The presence of an association can be a random finding. The most important limitation of these studies is, ultimately, lacking a control group.

ECOLOGICAL TRIALS

This type of descriptive, observational trial is unique in that the unit of measurement is not the individual, but the collective. As we will discuss below, these trials have some issues but also many advantages, as they allow the study of variables hard to analyze individually. For example, are low atmospheric pressures associated with a higher incidence of AAA tear? Is environmental pollution associated with a higher risk of cardiovascular diseases?

These are trials in which the unit of analysis is groups of individuals, not individuals themselves (such as school classes, cities, regions, etc.). The main characteristic of this type of trial is that information on exposure or the event itself is available for the entire cluster. However, individual information for each member of the group is unknown.

Ecological trials have a wide range of advantages and limitations. These are some of the former:

However, these advantages are no stranger to limitations:

In upcoming installments, we will explore different types of analytical trials, both observational and experimental.