Clinical research is a branch of healthcare science that investigates the effectiveness or safety of a medical treatment in humans. It is conducted by pharmaceutical companies, universities, government agencies, and medical institutions.
Clinical trials are studies done in clinical research. The participants can be healthy individuals or patients with a certain disease. Clinical trials help to determine if the new drug or therapy helps to cure or prevent diseases. Research using human subjects falls into two broad categories: observational studies and interventional studies.
Observational studies observe what happens to a particular group of people. On the other hand, interventional studies involve giving people specific treatments, including new drugs or medical devices.
Observational studies are typically cross-sectional in design and assess associations between exposures/risk factors and health outcomes without assigning participants to specific interventions. In observational studies, investigators measure exposure(s) that are suspected to influence the risk of disease, or related outcomes/health endpoints. Observational studies generally collect data on participant characteristics and health status without directly manipulating variables in participants’ natural environment. While observational designs provide less evidence for causal inference relative to experimental designs, they often have the benefit of being less costly and more feasible to conduct, as they do not require the introduction of an intervention. Observational designs may be used to:
- investigate pathogenesis and processes underlying diseases or health endpoints;
- assess associations between exposures/risk factors and health outcomes without assigning participants to specific interventions;
- determine whether a hypothesized factor (e.g., exposure, risk factor) is valid or whether a novel factor is associated with an outcome of interest;
- test a treatment or preventive strategy for a disease or health endpoint that has already been demonstrated as efficacious in clinical trials.
Observational study designs can provide some insight into associations between exposures and health outcomes but can be confounded by factors that may influence the outcomes of interest and exposure (confounding variables), and in some cases, provide no information on causality or risk. Thus, when possible it is preferable to study exposures and health outcomes in an experimental, non-randomized setting (i.e., a clinical trial) in order to obtain more precise estimates of effect. For example, clinical trials are conducted to obtain evidence for health care decisions by disentangling the effects of treatment from the underlying disease or other factors that may influence outcomes (e.g., age) that cannot be randomly assigned.
In contrast to observational studies, clinical trials are interventional in design. In other words, they test the effect of a specific exposure or intervention on outcomes rather than simply observing associations between exposures and health outcomes.
For example, treatment trials seek to determine whether a new treatment is superior in effectiveness or toxicity compared to an existing therapy. They may either use a placebo control group (e.g., a sugar pill), which is considered the best method for determining if a treatment works, or compare two different treatments being used currently against one another. Randomized controlled trials are commonly known as the “gold standard” of clinical research because they possess certain attributes that increase confidence in research findings obtained from non-randomized, uncontrolled studies.
Diagnostic and predictive tests measure the ability of a test or device to correctly classify healthy people into groups that differ in their likelihood of developing a disease, such as between those with and without the presence of a particular microorganism. They are used as an initial screen to narrow the list of possible conditions, and as such, they provide very high specificity (a low rate of false-positive results) but low sensitivity (a high rate of false-negative results).
Preventive clinical trials aim to determine if new interventions will reduce morbidity and mortality from diseases and conditions before they occur. Prevention trials may focus on either primary prevention (to prevent the initial development of disease in healthy individuals) or secondary prevention (to prevent the occurrence of disease in individuals who already have symptoms).
Lastly, therapeutic trials may focus on either curative therapy (aimed at curing existing disease or alleviating symptoms) or palliative therapy (aimed at alleviating symptoms that are not capable of being cured).
Phases I, II, III, and IV
When designing clinical trials for new drugs or treatments it is necessary to carefully select the objectives of the trial. This is done by clearly defining what information needs to be obtained from the research. The most appropriate design can then be selected based on feasibility and acceptability within ethical, legal, and medical frameworks.
Phase I focuses on safety issues in small patient groups after a new drug has been given to healthy volunteers under strict supervision. In Phase II, the drug is tested in a larger patient population and those with the condition for which it is intended. Phase III involves multi-center studies designed to establish efficacy as well as additional safety issues and provide evidence of both overall benefit and risk/toxicity profiles. Phases I – III usually involve randomized controlled trial designs where one group of patients receive the treatment being studied while another—sometimes referred to as a control—receives either no treatment or an established treatment regimen.
Phase IV trials aim to monitor the long-term effectiveness, benefits, and risks associated with approved treatments, particularly after extended commercial use. This area evolved as industry sponsors often become involved in observational studies early on in the development process.
Clinical research is an enormous field with many different categories of study design. It provides importance to large-scale studies that can be replicated and validated, but small-scale investigations are also important in gaining a greater understanding of the biological mechanisms at work. The history of cancer research has seen tremendous successes as well as failures. Only through continued investigation, refinement of protocols, and collaboration between scientists will we further develop effective strategies for curing diseases.
About the Author
Deepak Behera, MD
Deepak Behera is a physician-scientist turned executive, with expertise in clinical development and medical affairs across clinical, academic, and pharmaceutical/biotechnology sectors. He has over 12 years of experience in clinical research and related regulatory policies and submissions. Deepak’s goal is to push healthcare towards better patient outcomes, while at the same time generating value for all stakeholders. Democratizing clinical trials for patients and physicians aligns perfectly with this goal, and is why he founded Adaptive Research. In addition, Deepak provides strategic and operational advice to multiple pharmaceutical and biotechnology companies in the areas of clinical development, medical affairs, and technology assessment. He received his MD from MKCG Medical College at Berhampur University in India, and earned his board certification in nuclear medicine from India’s National Board of Examinations. He serves on committees and boards of various professional societies, including the Society of Nuclear Medicine and Molecular Imaging and the Indo-American Society of Nuclear Medicine. In his free time, Deepak likes to mentor young professionals, play volleyball, go for long drives and have fun with his two kids.