An investigational compound is a substance that is still being studied and has not been approved for the use being tested, and clinical trial phases are the stepwise stages (Phase 1 to Phase 4) through which it is tested in people. Each phase answers different questions, from early safety to large-scale proof of benefit. Knowing where a compound sits in this process tells you a lot about how much, or how little, is really known about it.
Key Takeaways
- Investigational products have not been approved for the use being studied, and regulators have not found them safe and effective for that use [1].
- Phase 1 focuses on safety and dosing, Phase 2 on early effectiveness and side effects, Phase 3 on confirming benefit in larger groups, and Phase 4 on monitoring after approval [2][3].
- Many compounds do not make it from one phase to the next [2][4].
- Trials need regulatory and ethics approval before starting, and the process differs by jurisdiction [2][5][6].
- Trial registries let anyone look up what is being tested, where, and at what stage [6][7].
What Is an Investigational Compound?
"Investigational" is a regulatory status, not a description of a chemical. A compound is investigational for a particular use while it is being studied for that use. In the United States, the FDA describes investigational drugs, biologics and devices as products that have not yet been approved or cleared, and that the FDA has not found to be safe and effective for their specific use. The FDA adds that an investigational product may or may not be effective and may cause unexpected serious side effects [1].
In the European Union and the UK, the term investigational medicinal product (IMP) is used. UK guidance, for example, expects trial applications to include a dossier for each IMP, including placebos and reference products [6].
Being investigational does not mean a compound is dangerous, and it does not mean it is promising. It means the evidence needed to judge its benefits and risks for that use is still being gathered. For what approval does mean, see what "approved" actually means.
Before Human Trials: Preclinical Research
Before testing in people, compounds go through laboratory and animal research. The FDA notes that while preclinical research answers basic questions about safety, it is not a substitute for studying how a drug interacts with the human body [2]. The NIH describes the same sequence: new treatments are tested in the lab and in animals, and the most promising move into clinical trials [3].
This step is a major filter, and animal results do not always predict human outcomes. Our guide on how to judge peptide research explains why.
The Four Clinical Trial Phases
Phase definitions are broadly similar across regulators, though exact numbers vary by study and disease.
| Phase | Typical participants | Main purpose | Share moving to next phase (FDA estimate) |
|---|---|---|---|
| Phase 1 | 20–100 healthy volunteers or people with the condition | Safety and dosage | About 70% |
| Phase 2 | Up to several hundred people with the condition | Efficacy and side effects | About 33% |
| Phase 3 | 300–3,000 people with the condition | Efficacy and monitoring of adverse reactions | About 25–30% |
| Phase 4 | Several thousand people, after approval | Ongoing safety and effectiveness | — |
Source: FDA [2]. The NIH gives similar ranges, noting Phase 3 trials may involve 1,000–3,000 people [3].
Phase 1: Is it safe, and how does the body handle it?
Phase 1 trials are usually the first time a compound is given to people. According to the FDA, they gather information about how a drug interacts with the human body, how much can be tolerated, and what its short-term side effects are, and they inform the design of Phase 2 [2]. For some drugs, such as cancer treatments, Phase 1 is conducted in patients rather than healthy volunteers [2]. Phase 1 often studies pharmacokinetics, including concepts such as peptide half-life.
Phase 2: Does it seem to work?
Phase 2 trials give the compound to people with the target condition. The FDA explains that these studies provide additional safety data and help refine research questions, but they typically aren't large enough to show whether the drug will be beneficial [2]. The EMA describes Phase 2 as giving more information about the best doses and confirming that the medicine works [8].
Phase 3: Does it work better than the alternatives?
Phase 3 trials are larger and longer, and are sometimes called pivotal studies. They aim to demonstrate whether a product offers a treatment benefit to a specific population, and they provide most of the safety data, including less common side effects [2]. Phase 3 trials often compare the new medicine with a placebo or with existing treatments [3][8]. For rare diseases, the EMA notes that Phase 3 trials may be very small or not carried out at all [8].
Phase 4: What happens after approval?
Phase 4 studies take place after a medicine is approved, tracking its safety and use in the wider population [2][3].
Key Trial Design Terms
- Protocol: the detailed study plan, including who can take part, what is measured and how data are analysed [2][3].
- Placebo: an inactive product that looks like the test product [3].
- Randomisation: assigning participants to groups by chance, to avoid bias [3].
- Blinding (masking): keeping participants and/or researchers unaware of who receives which treatment [3].
- Informed consent: the process of giving participants key information before and during the study so they can decide whether to take part [3].
Internationally, trials supporting medicine applications are expected to follow Good Clinical Practice (GCP). The current ICH guideline, E6(R3), sets an international standard for the design, conduct, recording and reporting of trials, including protecting participants and the reliability of data [9].
How Trials Are Authorised: It Depends on Jurisdiction
| Jurisdiction | Before a trial can start | Notes |
|---|---|---|
| United States | Sponsor submits an Investigational New Drug (IND) application to the FDA, including animal and toxicity data, manufacturing information and protocols [2] | The FDA has 30 days to review an initial IND and may allow the trial or place it on clinical hold [2] |
| European Union | Authorisation from the national competent authorities of each country involved, via a single submission in the Clinical Trials Information System (CTIS) under Regulation (EU) No 536/2014 [5][8] | The EMA itself does not authorise clinical trials [8] |
| United Kingdom | A joint clinical trial approval: an MHRA authorisation plus a favourable opinion from an ethics committee [6] | Amended UK clinical trial regulations took full effect on 28 April 2026 [6] |
Other regulators, including the TGA in Australia and Health Canada, operate their own clinical trial schemes. In the US, most trials are also reviewed and monitored by an Institutional Review Board (IRB) [3].
How Often Do Compounds Succeed?
Most compounds that enter human trials never reach approval. The FDA's phase-by-phase estimates above show how many drop out at each stage [2]. A large MIT analysis of over 400,000 clinical trial entries covering more than 21,000 compounds between 2000 and 2015 found success rates varied widely by disease area; for example, it estimated an overall success rate of 3.4% for oncology drugs in its sample [4].
The takeaway: early-phase or animal results, however exciting, are not a reliable predictor of eventual approval.
Access Outside Trials
In the United States, expanded access (sometimes called "compassionate use") is a potential pathway for patients with serious or immediately life-threatening conditions to access an investigational product outside a clinical trial, when there are no comparable or satisfactory alternatives and certain other conditions are met [1]. Other jurisdictions have their own mechanisms. These pathways operate under regulatory and medical oversight; they are not a route to obtaining unregulated products.
How to Look Up a Trial
Trial registries are public databases of clinical studies. Useful starting points include:
- ClinicalTrials.gov, a widely used registry based in the United States.
- The EU Clinical Trials Information System (CTIS), which makes most trial information public [5].
- The WHO International Clinical Trials Registry Platform (ICTRP) search portal, which brings together records from registries around the world [7].
In the UK, trials must be registered in a public registry, generally before the first participant consents or within 90 days of approval, whichever is earlier [6]. Registration helps reveal studies whose results might otherwise never be published.
Regulatory Status
Clinical trial rules, and the status of any given investigational compound, differ between jurisdictions and change over time. Regulatory status varies by jurisdiction and may change over time. Consult the relevant regulatory authority for current information. For manufacturing standards that apply to trial materials, see research-grade vs. pharmaceutical-grade.
Frequently Asked Questions
What does "investigational" mean?
It means a product is still being studied for a particular use and has not been approved for that use. Regulators have not found it safe and effective for that purpose [1].
What is the difference between Phase 1, 2 and 3 trials?
Phase 1 tests safety and dosing in a small group, Phase 2 looks for early signs of effectiveness and more safety data, and Phase 3 confirms benefit and monitors side effects in larger groups [2][3].
Does a successful Phase 2 trial mean a drug will be approved?
No. Phase 2 trials are usually too small to show whether a drug is beneficial, and many drugs that reach Phase 3 do not succeed [2].
What is an IND?
An Investigational New Drug application is what a sponsor submits to the FDA before starting clinical research in the United States [2].
How can I find out if a compound is in clinical trials?
Search public registries such as ClinicalTrials.gov, the EU CTIS, or the WHO ICTRP search portal [5][7].
References
- U.S. Food and Drug Administration. Expanded Access. https://www.fda.gov/news-events/public-health-focus/expanded-access ↗
- U.S. Food and Drug Administration. Step 3: Clinical Research. https://www.fda.gov/patients/drug-development-process/step-3-clinical-research ↗
- National Institutes of Health. NIH Clinical Research Trials and You: The Basics. https://www.nih.gov/health-information/nih-clinical-research-trials-you/basics ↗
- Wong CH, Siah KW, Lo AW. Estimation of clinical trial success rates and related parameters. Biostatistics. 2019;20(2):273-286. https://doi.org/10.1093/biostatistics/kxx069 ↗
- European Commission. Clinical trials - Regulation EU No 536/2014. https://health.ec.europa.eu/medicinal-products/clinical-trials/clinical-trials-regulation-eu-no-5362014_en ↗
- Medicines and Healthcare products Regulatory Agency (GOV.UK). Clinical trials for medicines: apply for approval in the UK. https://www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-approval-in-the-uk ↗
- World Health Organization. International Clinical Trials Registry Platform (ICTRP). https://www.who.int/tools/clinical-trials-registry-platform ↗
- European Medicines Agency. Authorisation of medicines. https://www.ema.europa.eu/en/about-us/what-we-do/authorisation-medicines ↗
- European Medicines Agency. ICH E6 Good clinical practice - Scientific guideline. https://www.ema.europa.eu/en/ich-e6-good-clinical-practice-scientific-guideline ↗
This article is for educational purposes only and is not medical or legal advice. It does not recommend participating in, or avoiding, any trial. For health decisions, consult a qualified healthcare professional, and for regulatory questions, consult the medicines regulator in your jurisdiction.