Clinical studies are medical research done on human volunteers. Data are collected from these studies and used to provide new medical knowledge, typically in the form of a published article.
Researchers do different types of clinical studies because they each have different research questions. Read on to learn about different clinical studies, which will help you better understand the articles you read and the studies you’re considering.
What you’ll learn in this post
• What clinical studies and clinical trials are (and how they’re different).
• The most common types of clinical studies.
• Many examples of different types of clinical studies to illustrate the differences and what these different studies find.
• Where you can get expert help with your clinical study.
What is a clinical study?
“Clinical study” is a general term for scientific research studies with human volunteers. Clinical studies can include both interventional (doing or giving something to the volunteers) and non-interventional (nothing is done to the volunteers) studies.
The terms “clinical trial” and “clinical study” are commonly confused or used as synonyms, but they are different in some fundamental ways. Understanding the difference is important because the official rules that govern them are different.
According to the National Institutes of Health, a clinical trial (explained below) involves giving something to volunteers (an intervention). Then, the volunteers are watched over time. Clinical studies, however, don’t automatically involve interventions. Therefore, while clinical trials are clinical studies, not all clinical studies are clinical trials.
Before a local regulatory authority (such as the U.S. Food and Drug Administration) can approve the start of any clinical study, researchers must show that their research protocols meet the regulations. This is to ensure volunteers’ well-being. The study can start once these regulations have been formally met.
There are many types (and subtypes) of clinical studies. The following are those you’re most likely to come across.
The two major categories of clinical studies
Study design is vital in the quality, execution, and interpretation of clinical studies. Different research questions require different methods to answer them. Interventional and observational studies are the two primary umbrellas for these different methods.
Interventional studies, which are, in fact, clinical trials, are designed in a way that requires investigators to give or do something as part of the study design. In this study, the researchers gave male dialysis patients testosterone to see if it improved their quality of life.
In observational studies, the investigator doesn’t give volunteers anything as part of the study design. However, volunteers may receive interventions as part of their routine medical care. Investigators collect data to assess health outcomes in volunteers as part of a protocol. Therefore, observational studies still require ethical clearance from the relevant local ethics board.
In this study among people with diabetes, researchers wanted to see if sex hormones and vascular complication are related. Nothing was given to the volunteers before the researchers measured the sex hormone levels.
What types of clinical trials are there?
Clinical trials have different complexity and design depending on the researchers’ specific aim.
Randomized controlled trials
In a randomized controlled trial (RCT), volunteers are randomly assigned either into a control group or an intervention group. The control group receives no intervention or a similar intervention that doesn’t actually do anything (e.g., placebo or sham procedure). An RCT can also compare at least two treatments.
RCTs are the gold standard for determining if cause-effect relationships exist between the intervention and the outcome of interest. This is because randomization ensures the only difference between the groups is the intervention received. The difference in outcomes is, therefore, the intervention’s effect. This puts them high up on the evidence pyramid.
In a trial involving 50 postmenopausal women with metabolic syndrome, investigators wanted to see how changes in insulin resistance, lipid profiles, and inflammation differed between women taking either oral or transdermal estradiol. The women were randomized into the oral or transdermal estradiol group. Oral estradiol worsened insulin resistance and inflammation. Meanwhile, transdermal estradiol had little effect on insulin resistance and reduced inflammation.
Multi-arm multi-stage (MAMS) trials
MAMS trials were created to accelerate the drug development process. MAMS trials typically have several groups:
• A fixed-control group (this group doesn’t change throughout the trial)
• Several treatment groups (this group can change throughout the trial)
As a MAMS trial goes on, researchers may find that some treatments are not as effective as they thought. These groups can be changed or even closed to more recruitment to focus the patients on more-effective drugs. New treatment groups or subgroups (called “arms”) can also be added.
MAMS trials aim to answer multiple questions simultaneously without planning another clinical trial to assess new treatments, thereby saving time and accelerating the drug development process.
The rEECur trial for a rare pediatric cancer is an example of a MAMS trial. This trial aims to find the optimal treatment for returning/non-responsive Ewing sarcoma by comparing four commonly used chemotherapy regimens. During each of the two pre-planned interim analyses (data analyses that happen before data collection is completed), the two least-promising regimens will be dropped. Then, the two most promising regimens will progress further along drug development stages (called “phases”).
Pilot studies and feasibility studies
Pilot and feasibility studies are smaller studies conducted before a larger clinical trial takes place. These studies are similar, but they serve different purposes.
Pilot studies are small, early-stage studies that help in the planning and adjusting of a larger clinical trial.
These studies are conducted before the main study to analyze the study design’s validity and help answer some research questions. Results from pilot studies are sometimes reported in the results of the larger clinical trial.
In this pilot study, researchers wanted to find relevant kidney biomarkers to diagnose chronic kidney disease (CKD) of unknown cause. They grouped volunteers into five groups, each with different CKD causes. From eight kidney biomarkers, a three-marker panel of kidney biomarkers was the best-performing combination for differentiating between CKD causes. This three-marker panel could then potentially be tested later in a larger study.
Feasibility studies are conducted when researchers ask, “Is our main clinical trial possible?” Researchers then perform feasibility studies, which are smaller studies that assess the usefulness of doing the main clinical trial. A feasibility study can assess timelines, targets, and costs of the proposed (main) clinical trial, or identify potential intervention adjustments.
Danish researcher Engelbrecht Buur and colleagues wanted to design a shared decision-making intervention. They also want to see whether patients with kidney failure, their relatives, and health professionals could accept it. So, they did a feasibility study to look for evidence to answer their questions. The answer would be to initiate patient involvement in palliative care planning with nephrologists.
Prevention trials help find out whether an intervention would be able to prevent an outcome of interest from happening among volunteers without the outcome of interest. Prevention trials recruit many healthy volunteers, offer them therapy, then follow them for some time to see whether the outcome of interest happens.
There are two types of prevention trials: action studies and agent studies.
These studies ask whether actions people take (e.g., exercise or dietary changes) can prevent an outcome of interest from happening. This clinical trial showed that lifestyle changes are more effective than metformin in preventing diabetes.
These studies ask whether taking something (e.g., a drug or vitamin) may lower the risk of an outcome of interest. Aspirin has been extensively studied in randomized primary prevention trials, such as this one in NEJM. Low-dose aspirin lowered the risk of stroke but not the risk of heart attacks or death due to cardiovascular reasons.
Screening trials test new ways of detecting health conditions in asymptomatic people. Screening tests can include:
- Imaging tests that create pictures of inside the body
- Laboratory tests that check body fluids and tissues
- Genetic tests that look for disease-associated genetic markers
An example of screening tests that have become standard medical practice is pap-smears for cervical cancer.
Treatment trials occur in phases. Early phases check the safety and tolerability of new treatments. Later phases aim to see if a new treatment works better than the current treatment or a placebo.
In a large clinical trial among people with early-stage HER-negative breast cancer with an inherited BRCA mutation and those with recurrence risk, adding olaparib after surgery and chemotherapy were linked with significantly longer cancer-free survival.
What types of observational studies are there?
A cohort is a group of people who share common characteristics (e.g., people with diabetes, community-dwelling people, people of a specific age range, smokers). Researchers use various methods to recruit volunteers. For instance, they could contact people from a particular region or birth register.
There are two kinds of cohort studies: prospective and retrospective.
Prospective cohort studies
Prospective cohort studies follow volunteers over time to assess the development of the research outcome of interest among volunteers who have the exposure.
For example, in this study using data from 623 men undergoing hemodialysis, researchers wanted to determine whether associations exist between low testosterone, death, and quality of life (outcomes). They assessed testosterone levels at the start of the study. Then, using clinically relevant cutoffs, they defined low testosterone to find volunteers who had the exposure. As the volunteers were followed for 20 months, they had information on death and quality of life.
Retrospective cohort studies
Retrospective cohort studies look back in time for exposure information among volunteers after an outcome has occurred. Baseline exposure information has been assessed in the past and can be retrieved from health records.
In a study using data from 117 COVID-19 patients with severe and critical outcomes (SCO), the researchers wanted to determine the role of diabetes in COVID-19 patient outcomes. They reviewed electronic medical records to obtain information on diabetes status and clinical features. Patients with diabetes were more likely to progress to SCO. Also, older patients were more likely to have SCO. While medication usage was not linked with SCO, renin-angiotensin inhibitor usage was linked with a significantly lower risk of acute cardiac injury.
Case-control studies determine the association between an exposure and an outcome (e.g., an outcome of interest or a disease).
Case-control studies are usually retrospective, not because the researchers use previously collected data. Instead, the researchers first identify volunteers who have the outcome of interest (cases) and those who don’t (controls). Then, they look back in time to see who had the exposure in each group and compare the exposure frequency in each group (cases vs. controls).
Among the advantages of case-control studies:
- Rare diseases and outcomes can be studied
One case-control study found factors related to COVID-19 infections among healthcare workers in Colombia. The researchers randomly phone-interviewed healthcare workers. They found 110 workers with COVID-19 (cases) and 113 without COVID-19 (control). They saw that being a man, a nurse, and not using protective equipment were risk factors. Meanwhile, being a student, feeling scared, and using suitable protective equipment were protective.
Sometimes you need a bit of help with your study
That’s why Edanz offers a range of expert-led author-guidance services, from finding research ideas, to study design and preparation, to writing your manuscript, to editing your manuscript for publication. We can also do an expert scientific review of your study. Get in touch to see how we can help you.