Everyday, the news and other media share new information related to our health. This information is often backed up by a research study. Healthcare practices are thus always evolving due to new research evidence. But how are these scientific studies conducted, and how do we know they are credible? It is a common saying in research that not all scientific studies are created equally. Making sense of this new information requires us to understand the different kinds of research.
There are three main kinds of health research studies. These are preclinical, experimental, and epidemiologic research. Epidemiologic and preclinical studies often come first, followed by clinical trials involving human participants. In this guide, we’ll describe the types of studies, including what kind of information they can give us and how you can take part. We’ll also discuss how research studies are used in healthcare and medication development.
The writer, Dr. Merin Kuruvilla, is a board-certified academic allergist/immunologist with an interest in clinical research. She has authored several peer-reviewed clinical research publications in leading medical journals.
New research often starts with studies involving animals or individual cells. These studies are considered preclinical. They are important in paving the way for clinical studies that involve human participants. We cannot assume that the results from preclinical studies can be directly applied to human beings. The only way to know how research will affect humans is by studying them.
Experimental studies are also called intervention studies, or clinical trials. Researchers introduce a treatment or other intervention and study its effects.
Clinical trials can be randomized or nonrandomized. These trials are often “placebo controlled.” This means they compare the effect of the intervention with people who do not receive the intervention. This group that does not receive the intervention is called the placebo, or control group.
The term “randomized” means that people are assigned by chance to intervention or control groups. In a nonrandomized clinical trial, participants are not assigned randomly to different groups. The researchers may assign participants to different groups, or the participants may choose their group themselves.
A randomized controlled trial (RCT) is the best way to see if there is a cause-and-effect relationship between an intervention and a study outcome. The main aim of randomization in an RCT is to reduce “bias.” Bias occurs when a researcher unintentionally influences the research process. This can affect the study findings and outcome. Bias can occur if researchers were to choose who receives the intervention. This is because they may select those participants who would benefit the most.
For example, a researcher wants to see if a Mediterranean diet can prevent heart disease. In this case, the intervention group would eat a Mediterranean diet, and the control group would follow a low-fat diet. Without randomization, the researcher may assign participants with lower risk for heart disease to the intervention group. If this group had lower rates of heart disease at the end of the study, we would not know the cause. It could be due to the diet or due to underlying differences in risk.
“Blinding” is another technique used to reduce bias in RCTs. A blinded study means that the participants, researchers, or both, do not know who is in the intervention group. This would reduce bias in perceived improvement related to the intervention. It would also reduce bias in reporting side effects. For example, if a participant knows that they are receiving study medication, they are more likely to report side effects.
Randomized controlled trials can answer the following questions:
Is a new medication safer or more effective than standard treatment for a disease?
Is a diagnostic test better for earlier detection of a disease?
Does a specific intervention help to prevent a medical problem?
How can we improve the quality of life in people with chronic health problems?
The following are examples of each of these RCTs:
Observational studies observe groups of people in their normal environment. These studies do not involve any treatment or intervention. Rather, observational studies only observe how their participants' actions affect their health. In contrast to RCTs, these study designs cannot establish cause-and-effect relationships. Observational studies can only establish correlations. Their results can find ways to prevent or reduce disease.
Observational studies are used when an experimental design is inappropriate or not workable. For example, a researcher wants to study whether high doses of caffeine cause insomnia. It would not be right to give participants something that could cause sleep problems. Instead, he would find people who already drink large amounts of coffee in their usual lives. He would then compare their sleep habits with a group of people who do not consume high doses of caffeine.
Cohort, case control, and cross-sectional studies are different types of observational studies.
Cohort studies investigate a group, or “cohort,” of people over a period of time. Researchers study the effect of various exposures on health outcomes. For example, a recent cohort study investigated the risk of cancer with asbestos exposure at home. People exposed to this hazardous substance were compared with a group that was not. The researchers then evaluated how many people in each group developed cancer over several years.
Cohort studies can help to answer the following questions:
How common is a specific medical condition?
How often does a certain disease occur?
What factors can increase your risk of developing a medical condition?
Case-control studies compare a group who has a certain disease (cases) with a group that does not (controls). The two groups are analyzed for any exposures or other factors that may explain their differences. This study design is useful to investigate rare diseases or outcomes.
For example, one case-control study investigated whether aspirin use causes chronic kidney disease. The cases were people with chronic kidney disease. The controls were people from the general population without chronic kidney disease. The study found that the cases used aspirin more frequently than controls. The researchers thus found a correlation between aspirin use and kidney disease.
Case-control studies help to answer questions such as:
What factors increase the risk of a specific disease?
What factors are associated with developing rare diseases?
What are the odds of developing a disease with a particular exposure?
Cross-sectional studies investigate participants at a single timepoint. An example of this study design is a questionnaire survey. For instance, a large questionnaire study looked at how often children with allergies have itchy, watery eyes. The study was able to find a frequent association of eye symptoms in more than a third of children with allergies.
Cross-sectional studies can answer the following questions:
How commonly does a specific condition occur?
What are the characteristics of a population?
Systematic reviews and meta-analyses combine findings from many studies. They help researchers to sum up all the data on a subject. A systematic review summarizes all the research on a specific research question. A meta-analysis is a specialized type of systematic review. It uses statistics to pool data from several previous studies. This helps to arrive at new conclusions that are stronger than the results of any one study. Both of these studies are generally considered to be high-quality scientific evidence.
Several different types of research are used in healthcare settings. Healthcare research often starts with observational studies. This is because observational studies help to understand the prevalence and trends of a medical condition. Observational studies are followed by preclinical studies in the laboratory on tissues or animals.
Observational and preclinical studies are often the precursor to clinical research involving human participation. Clinical trials are critical for the development of new treatments. Every new treatment starts with the participation of volunteers in clinical trials. This is the only way to know if a treatment is safe and effective.
RCTs are the “gold standard” to assess the effectiveness of a new medication. Clinical trials that test medication safety and efficacy are usually referred to by the phase of testing.
Phase 1: In the first phase, a new medication is tested on a small number of people (20-100) to make sure that it is safe.
Phase 2: The medication is tested on a larger group of people (100-300) with the disease or condition. This is to make sure that it works.
Phase 3: The medication is tested in large studies (hundreds to thousands of people). The third phase seeks to assess whether it is superior to the current standard of care.
Phase 4: The medication is tested in the real world after FDA approval.
There are many reasons to participate in clinical research. If you wish to take part in a clinical trial, here are a few ways to help you find the right one:
Clinicaltrials.gov is a database of ongoing research studies in the U.S. You can search for a study being conducted in your location.
Websites for organizations related to your health condition may also have information on research studies.
You may also see advertisements for research studies on social media.
Your healthcare provider or nearest large health center may be able to direct you to studies in your area.
It is important to make your healthcare provider aware about participation in any research study.
There are many other factors to consider when reading a research report. It is important to know who paid for the study. For instance, a pharmaceutical company will have vested interests in setting up their products for success in a clinical trial. Another factor to consider is the reputation of the scientific journal that has published the research. One way to rank a journal is by its impact factor. The higher the impact factor, the greater its reputation.
Another point to keep in mind is whether the participants studied in a trial are similar to the population its findings will be applied to. For instance, Black and Hispanic children are at higher risk for severe food allergic reactions than white children. However, minority children are also severely underrepresented in clinical trials for food allergy. So, results from these clinical trials cannot necessarily be applied to populations that are underrepresented in these studies.
Ahn EJ, et al. (2018). Introduction to systematic review and meta-analysis. Korean J Anesthesiol.
Bhide A, et al. (2018). A simplified guide to randomized controlled trials. Acta Obstet Gynecol Scand.
Concato J, et al. (2000). Randomized, Controlled Trials, Observational Studies, and the Hierarchy of Research Designs. N Engl J Med.
Concato J. (2013). Study design and "evidence" in patient-oriented research. Am J Respir Crit Care Med.
Gilmartin-Thomas J, et al. (2018). Observational studies and their utility for practice. Aust Prescr.
Wang X, et al. (2020). Cross-Sectional Studies. Chest.