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What Is Clinical Research?

March 17, 2020 | in What is clinical research?, Tau Protein, Aducanumab (Biogen Trial), Women and Alzheimer's, Early Onset Alzheimer's, Alzheimer's Diagnosis

Author Spencer Hey, PhD
Harvard Center for Bioethics
Editorial Review Phoebe Stoye, A.B. in Neurobiology, Harvard College

Clinical research refers to scientific experiments that are intended to improve the quality of clinical care, either in the form of new treatments or optimizing the use of existing treatments.

However, clinical research is really just one component in a long process called translational medicine. Translational medicine refers to a series of scientific experiments whose goal is to take insights from the biology lab and leverage those insights into new drugs, devices, or procedures that improve outcomes for patients.

Preclinical Phase

The whole translational process typically begins with a preclinical phase, where compounds are screened for possible effects on human diseases. Compounds that look promising will then usually be tested in animals. If the animal studies show that the compound is safe and effective, then it may advance to the clinical research phase of testing—where this new, experimental treatment will be tested on human research subjects.

Phases of Clinical Research

Phase 1

The first phase of clinical research (called "phase 1" or "first-in-human" trials) usually only involves a few dozen or so healthy volunteers. The goal of these experiments is to determine the optimal dose or implementation of a new treatment, as well as to look for any serious side effects.

Phase 2

If the treatment appears safe in phase 1, then it moves on to phase 2 trials, where it will be tested in patients for the first time to see if it is actually effective against the target condition. Phase 2 trials typically involve less than 100 patients and are single-arm experiments—which means that everyone who is enrolled will receive the experimental intervention (i.e., the drug). Because the efficacy of the drug is not known at this point, patients in phase 2 are taking on considerable risks. Thus, patients who participate in phase 2 are often in advanced stages of their diseases, and have exhausted all the currently available treatment options.

Phase 3

Interventions that look promising after phase 2 may then advance into phase 3 trials—these are comparative trials that look to see if the new treatment is better than a control treatment (i.e., a treatment that is already used in practice or an inert placebo). Phase 3 trials often enroll hundreds, thousands, or sometimes even tens of thousands of patients. These trials are usually randomized and blinded trials, which means that once a patient enrolls in the trial, they will be randomly assigned to receive either the experimental treatment or the control–and they will not know which one. This is done to prevent any conscious or unconscious bias in the trial's result.

Phase 3 trials are usually the decisive test of whether the experimental treatment works. If the new treatment is shown to be effective in phase 3 trials, this is often sufficient for it to receive regulatory approval, after which point it becomes available in clinical practice.

Phase 4

But this is still not the end of the clinical research process! There is also phase 4, which includes post-marketing trials that are conducted after a treatment has entered the market. These trials are usually designed to measure long-term safety and effectiveness outcomes. Most pre-marketing trials (i.e., phases 1-3) only last between a few months or maybe a few years. Yet, patients may be taking medications for much longer than this. Phase 4 trials track how patients do on the new treatment over much longer time periods.

(Editor's note: Curious about the breakdown of phases for trials in your condition? Check out these pie charts showing the number of trials in each phase for Alzheimer's trials and Type 2 Diabetes trials.)

After The Four Phases Of Clinical Research: Implementation Research

After these pre-clinical and clinical phases of testing, there is also sometimes an implementation phase. If a treatment makes it all the way through clinical trials, this shows us that it can be beneficial. However, this is not necessarily the same as showing us how best to use that treatment. Indeed, the conditions in clinical practice–in reality–tend to vary much more widely than the conditions in clinical trials. Therefore, some treatments will undergo additional testing in implementation or pragmatic trials, which are designed to evaluate how a treatment performs once it is finally rolled out in the clinical setting.

What Clinical Research Is: The Big Picture

If that sounds like a long, complex, and arduous process—it is! Most experimental treatments that enter clinical research fail before they ever get to phase 3. And only about half of the treatments that make it to phase 3 succeed and earn a regulatory approval. That means that there are a lot of negative trials and failed treatment candidates—and the majority of these failures are an inevitable part of the scientific process. In science, sometimes a hypothesis has to fail in order for us to learn.

If you want to contribute towards research in your condition, search for Alzheimer's trials near you or Type 2 Diabetes trials near you.