The lifecycle of a new treatment begins in the lab.

First, researchers identify a new substance (often a chemical compound) that seems likely to act on living bodies in a way that might prevent or improve an undesirable condition. That’s called drug discovery. Next, they investigate that substance’s likelihood to consistently create that desired effect with minimal negative consequences, and explore the feasibility of making, storing, distributing, and administering the substance in a viable and repeatable manner. This process is called preclinical research.

Once discovery and preclinical research are complete, often after years and significant investment of capital and effort, the researchers are ready to find out how the new substance behaves in humans. This is where clinical research begins: the human study portion of the process of bringing a new drug to market, during which the researchers seek marketing approval from regulators by demonstrating that the drug can safely and effectively treat or prevent a target condition in living patients.

In the United States, the body that determines which drugs can be marketed and sold is the Food & Drug Administration (FDA), and more specifically the Center for Drug Evaluation and Research (CDER, pronounced “see-der”), one of eight constituent Centers of FDA. To secure approval, the researchers and their backer submit an Investigational New Drug application (IND), which contains a description of the process that they’ll undergo to prove safety and effectiveness. That process covers four phases, which themselves contain units of investigation called studies.

Another major group concerned with drug research in the United States is the National Institutes of Health (NIH), which is the federal government’s body for overseeing medical research. NIH conducts and funds studies in addition to operating clinicaltrials.gov, which hosts information about every study conducted in the United States. And lastly, some drug research is conducted under the oversight of the Center for Biologic Evaluation and Research (CBER, “see-ber”) rather than under CDER.

From here on out, this guide will focus on the process for seeking marketing approval for a new drug from CDER and FDA in the United States.

Here are the four phases of human trials, and the questions about the investigational drug each phase answers:

Phase 1: is it safe?

Phase one involves a small group (10–50) of usually healthy volunteers. The goal is to establish the levels of drug that can be delivered without negative effects, and how the drug moves throughout a patient’s body. Typically, in this phase, researchers step up the dosage they administer to patients across cohorts, and participants are generally compensated for their involvement.

Phase 2: does it work?

Phase two trials usually include somewhere around 100 volunteers who have the indication the drug is intended to treat. The goal is to determine the extent to which the drug affects the condition in question, and often also to determine the parameters (like dosage and frequency) under which the drug works most optimally.

Phase 3: does it work reliably?

Phase three trials are large and usually distributed across sites, geographies, and populations, in part because they require administering the investigational drug to hundreds or thousands of patients. Studies in this phase are usually randomized, meaning that patients are sorted randomly into a control group (given a placebo) or a study group (given the drug under study), and they can be either double- or single-blind. In single-blind trials, the patients do not know which group they are in, but clinicians and researchers do. In double-blind trials, nobody knows until the trial is over.

Phase 4: what are the side effects and broader implications?

Phase four trials are larger, ongoing studies that generally take place after FDA approval has been secured. The purpose of these studies is to continue to learn about the investigational drug’s behavior in larger populations, more diverse conditions, and over time.

In addition to regulations from the FDA, trials take place in the context of rules, regulations, and practices established both locally and internationally. Worldwide, clinical research generally conforms to good clinical practice (GCP), which is an international standard created by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). GCP is a continuation of the principles outlined in the Declaration of Helsinki from 1964. The ICH GCP standards are continually updated, with the most recent update (ICH E6(R3)) having been released in January 2025.

GCP covers a range of topics from ethical considerations to data collection standards. FDA does not exactly follow the standards recommended by ICH and does not explicitly require that personnel on drug trials receive GCP training (although NIH-funded studies do require it), but their guidance very closely follows the standards released by ICH and they do require staff to observe most of the same principles.

Despite FDA’s slightly softened formal requirements, GCP practices remain a baseline expectation from contributors to clinical research in the United States. That means that your staff should take training to understand and conduct themselves according to GCP. A great resource for learning about clinical research is the CITI Program, which offers courses on many related topics, and their course on GCP is a great place to start.

In addition to their guidance about GCP adherence, FDA enforces standards for clinical research that are derived from the much broader federal-level “Common Rule” (technically called the Federal Policy for the Protection of Human Subjects), which also covers the rules applying to IRBs, informed consent, and other relevant topics for researchers.

Finally, there are sometimes state- and city-level regulations and laws that cover research with human subjects, which this guide can’t usefully cover.

While much clinical research takes place in academic research facilities, increasingly, the work of testing and evaluating drug behavior in human subjects is being distributed across networks of independent medical providers. Beginning in the 1980s and 90s, research has grown in footprint to incorporate dozens of sites, sometimes through integrated site networks run by site management organizations (SMOs), but often including independent sites as well.

For research beyond phase one trials, this distribution helps researchers achieve their goals because few or no individual sites will have access to hundreds or thousands of patients who meet the study’s patient inclusion/exclusion criteria in their immediate geographic area at any given time. Distributing the research gives the study a much larger surface area across disparate patient populations. Because participant recruitment, enrollment, and retention are major hurdles for researchers, site networks and distributed research offer a solution to the problem of finding eligible participants.

In exchange for offering access to their patient populations, care sites, and clinical and research staff, independent sites receive a number of benefits.

First: revenue. Study conduct comes with a budget, and savvy sites can negotiate clinical trial agreements and arrangements for subcontracted services that maximize their margin. Operational efficiency and effective practices for recruitment, screening, and retention can further enhance revenue capture through conducting research.

Second: facility utilization and efficiency. Few AICs are packed 24/7—most have vacant chairs and difficulty booking patients to consistently maximize the capacity of their scheduled clinical staff at any given time. Clinical trials offer patient visits at more or less predictable volume over time (for example, you’ll enroll 5 patients for 10 appointments each over 104 weeks) and can therefore be reliably fit into existing schedules, offering a demand constant.

Beyond revenue, for AICs especially, there are a few benefits downstream of the relationship AICs form with study sponsors (i.e. drug manufacturers) by participating in research. One is earlier access to drug development pipelines and timelines. Another is the relationship with the manufacturer, which is obviously valuable in itself and offers more touchpoints and better lines of communication. Perhaps more importantly, the AIC enjoys early experience with new drugs: if an AIC expects to offer a treatment should it be approved for marketability, trials offer an opportunity for staff to get valuable hands-on experience working with that treatment before competitors can. 

Trial research can enhance relationships with the rest of the medical provider community as well. On one hand, it confers status as a contributor to medical science, which can help AICs position themselves as experts and leaders in the space. On the other, it gives the participating AIC’s referring providers an opportunity to give better care for their patients—many trial volunteers are referred to the study by their care team, and physicians who are made able to flag attractive local studies to their patients will likely appreciate the possibility of sending them to their city’s infusion center versus a research institution four hours away in a major urban center.