The Four Phases of Clinical Trials and Why Transparency Matters Throughout

Major medical achievements or breakthroughs of modern medicine can be largely attributed to patient-based clinical trials, which are procedures where medical professionals and researchers test and evaluate novel medications or therapies to determine their efficacy and safety.¹ Before any experimental medicine is administered to a research participant as part of a clinical trial, extensive preclinical work is conducted to assess safety and risks as part of preliminary research.

A well-designed clinical trial provides reliable data that drives medical progress. Without that evidence, science sits at a standstill, leaving researchers in limbo between discovery and validated outcomes. 

The clinical-trial process progresses through four distinct phases.² While these trials are intended to examine the medication’s effectiveness, safety is always a core focus. Information about the study, including any risks related to the particular trial, is provided in advance to those who are interested in participating. This procedure is part of a process known as informed consent where a participant understands and agrees to the trial’s conditions.

Phase I marks the beginning of the clinical trial, as this is the first time a potential medication is administered to humans. This study, which involves a small group of 20 to 80 volunteers, aims to accurately assess the safety of the potential medicine and any immediate side effects while also helping researchers determine the appropriate dosage ranges. 

To create an initial safety profile, researchers observe the compound's movement and its processing in the body. Phase I trials last over a course of several months, with only 70 percent of drugs moving on to the next phase.³ At this point, transparency builds the foundation for public trust; accurate reporting of safety data reassures both volunteers and the larger medical community that advancements are being made responsibly. Once a treatment exhibits a reasonable safety profile, Phase II begins, shifting the primary focus from safety to performance.

Researchers broaden their testing pool in Phase II to gain a better understanding of the actual efficacy of the potential medicine or treatment. In this case, efficacy means the ability (of the drug or treatment) to produce a desired or intended result. Between 100 and 300 people typically participate in this trial being frequently selected by the condition the medicine is intended to treat. During this phase researchers modify dosage levels, identify short-term side effects, and report on how results differ across groups. Phase II research can last anywhere from several months to two years, with only one-third of drugs advancing to the next stage. This is often a gray area for researchers performing the trial as many treatments seen as promising typically fall short of expectations.

Success in early testing is only the beginning. Phase III is where researchers seek to demonstrate full efficacy before the treatment can be approved. Phase III expands to 1,000 to 3,000 participants, ideally a diverse mix by age, sex, race, and geography to confirm effectiveness and compare new treatments to existing or standard treatments. During this phase, researchers collect data that regulators use to assess a medicine's suitability for public consumption.

Phase III trials can last between one and four years, with about 25 to 30 percent of drugs advancing to the final stage. Since approval is based on accurate reproducibility and objective evidence as opposed to selective data, complete reporting of both successes and limitations is vital as these results influence national treatment guidelines.

Beyond regulatory approval, a treatment enters Phase IV, the post-marketing phase of clinical research. Here, scientists and physicians observe how a medicine performs in a non-controlled environment, gathering real-world data that continues to inform researchers about how the medicine is prescribed and monitored in clinical practice. 

Phase IV often reveals side effects that are considered too rare or delayed to appear during earlier testing. As more data becomes available, researchers may also test new therapeutic uses and modify dosages accordingly. Phase IV is where medications can change with their patients through continuous research assessing the long term safety and efficacy across a larger population.

Even so, the precision of clinical research faces significant challenges. Only 6 percent of treatments that start clinical trials ever reach the market due to a combination of safety concerns, lack of efficacy, insufficient funding, and one of the most pressing obstacles, patient enrollment and sustained participation.⁵ Nearly 80 percent of clinical trials fail to meet enrollment deadlines, and approximately 30 percent of participants drop out before completion.⁶ These statistics show a deeper problem with clinical trials, a crisis of trust.

The trials themselves would not exist without their participants, just as medical advancements would not be possible without clinical trials. On one hand, potential participants are reluctant to participate in clinical trials due to ambiguity surrounding the use, storage, and protection of their data.⁷ On the other hand, many never learn about the trials that could benefit them in the first place.

The success of future research depends not only on medical innovation, but also on open data, accountability, and transparency – values that empower patients to confidently be a part of clinical trials for the greater purpose of helping themselves and others. Platforms like FindMyClinicalTrial are helping to close this gap by providing patients with clear information, control over their participation, and full transparency regarding the use of their data.

When patients understand how their contributions advance medicine and trust that their information will be protected and used ethically, they become partners in the advancement of clinical trials. Building this trust requires more than brilliant scientists and state-of-the-art laboratories—it requires a commitment to openness through every phase of research, including publishing unsuccessful attempts. Behind every medical advancement lies a foundation of trust and transparency, maintained through accountability and strengthened through open data.

Blog written by Dominick A. Barfield 

References 

Friedman LM, Furberg CD, DeMets DL, Reboussin DM, Granger CB. Fundamentals of Clinical Trials. 5th ed. Springer; 2015.

U.S. Food and Drug Administration. The Drug Development Process. FDA.gov. Updated 2018.

Wong CH, Siah KW, Lo AW. Estimation of clinical trial success rates and related parameters. Biostatistics. 2019;20(2):273-286.

Dwan K, Gamble C, Williamson PR, Kirkham JJ. Systematic review of the empirical evidence of study publication bias and outcome reporting bias — an updated review. PLoS One. 2013;8(7):e66844.

Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J. Clinical development success rates for investigational drugs. Nat Biotechnol. 2014;32(1):40-51.

Huang GD, Bull J, Johnston McKee K, et al. Clinical trials recruitment planning: A proposed framework from the Clinical Trials Transformation Initiative. Contemp Clin Trials. 2018;66:74-79.

Kraft SA, Cho MK, Gillespie K, et al. Beyond consent: building trusting relationships with diverse populations in precision medicine research. Am J Bioeth. 2018;18(4):3-20.