Clinical trial designs can be classified into several categories, each with their own unique characteristics and objectives. This guide provides a broad look at the many different types of clinical trial designs available, suggesting which designs are most suitable for specific research objectives and highlighting their key features, benefits, and considerations.
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An observational study is one in which there is no treatment or intervention under the control of the investigators or study sponsors; instead, researchers simply observe and collect data on the participants. There may be active observation (e.g. taking laboratory samples) but no influence of treatments or interventions by those involved with the study. These designs can either be prospective, following a group of people forward in time, or retrospective, looking back in time at a group of people’s past data.
An observational study design is used to observe and measure the outcomes of a group of individuals without modifying the factors that may influence the outcome. This type of study design is used to identify associations between exposures and outcomes. They are often used to identify risk factors for a particular disease or condition and to generate hypotheses for future studies. Observational designs also may be used in situations where it may be unethical to actively influence participants into an intervention (e.g. a study of tobacco smoking could not make randomly-chosen participants to smoke tobacco given the known health risks). The two main types of observational study designs are cohort studies and case-control studies.
Cohort studies are a type of observational study which involve choosing participants based on their exposure to one or more risk factors of interest. Cohorts of participants are enrolled that have been and have not been exposed to the risk factors of interest. In a prospective cohort design, then researchers monitor any changes in the participants’ health or behaviour while collecting data at regular intervals. In a retrospective design, these cohorts’ medical histories and current conditions/illnesses are examined to determine are patterns between exposure and illness. These designs are useful for identifying risk factors for a certain illness or condition as well as for gauging the success of therapies.
Case-control studies are a kind of retrospective observational study that, are used to explore the relationship between risk factors of interest for a particular disease or condition. Researchers select individuals who have a condition of interest and also select a control group of individuals that do not have that condition but are otherwise fairly similar. These two groups are then compared to identify which participants were exposed to the risk factors in question to determine whether there appears to be an association between the risk factors and diseases/conditions.
Cross-sectional studies are a type of observational research design used to investigate a particular population or a group of people at a specific point in time. These studies aim to gather information about a population or a subgroup within it without following individuals over a long period.
Unlike cohort and case-control studies, a cross-sectional study only enrolls participants based on the specified inclusion/exclusion criteria, rather than specifically targeting participants based on risk exposure (cohort) or illness/condition (case-control). Enrolled participants have all their data collected through surveys, interviews, and observations at one time, including any exposures and conditions/outcomes of interest. This type of design is useful exploring the prevalence of diseases, health behaviors, attitudes and characteristics within a population, as ideally a cross-sectional design provides a representative group of participants who reflect the overall population. By examining the relationship between different variables at a specific point in time, researchers can identify correlations, assess risk factors and generate hypotheses for further investigation.
However, it is important to note that cross-sectional studies cannot establish causality or determine the temporal sequence of events. They provide a snapshot of the population at one moment and cannot assess the cause-effect relationship or the development of outcomes over time. For that reason, cross-sectional studies are often followed by longitudinal studies to investigate causal relationships and changes in variables over an extended period.
Interventional studies are used to test the efficacy and safety of new treatments, interventions or procedures. In this type of prospective study, the treatment or intervention is under the control of the investigators or study sponsors, who use manipulation of one or more factors (usually by randomization) to determine cause-and-effect relationships. There are many forms of interventional studies, with randomized controlled trials as one of the most popular.
A form of interventional study, Randomized Controlled Trials (RCTs) are often considered the gold standard in clinical research as they provide the strongest evidence for causality while reducing bias. In an RCT, participants are randomly assigned to a treatment, at least one of which is an active treatment and at least one of which is a control. Active groups receive the intervention(s) being tested, while control groups receive a placebo or standard of care. The outcomes of the active and control groups are then compared. RCTs are designed to minimize bias and are particularly useful for providing compelling evidence for evaluating the efficacy and safety of new interventions. They can, however, be expensive and time consuming to conduct and may not be appropriate for all types of research questions.
A block design study is a type of randomized trial in which participants are randomized within groups into blocks based on certain pre-specified characteristics such as age or disease stage. Within each block, participants are randomly assigned to a treatment group, independent of the treatment assignments in other blocks. The goal of this design is to reduce the potential for bias by ensuring that there are similar numbers of participants on each treatment for key characteristics that are suspected to affect the outcome.
Example: A study is being done both within the U.S. and in Europe with a blocked design that treats “region” as a block. Thus, this study randomizes participants separately within the U.S. and within Europe to balance of treatments/interventions is approximately the same within each region. If a blocked design weren’t used, then it could be possible for all participants in Europe to receive an experimental treatment while all participants in the U.S. receive a control, which may make inference more difficult.
In the world of clinical research, different types of clinical trial designs can be used to generate reliable evidence about the safety and efficacy of new treatments.
The selection of a trial design should be based on the specific research objectives, the nature of the intervention being tested, the target population, available resources, and ethical considerations. Since each design has its own unique features, benefits, and considerations, study design decisions should be made collaboratively using input from trial stakeholders, subject matter experts, and statistical experts to not only understand the strengths and limitations of each, but to also ensure that the chosen design is the best fit for the goals of the study.
As medical knowledge advances, it is important for researchers to continue exploring innovative trial designs that adapt to emerging evidence, maximize efficiency and ultimately lead to improvements in overall patient care.
This was Part 1 of our 4 part series on different types of Clinical Trial Designs.