Measuring clinical trial timelines: How long do clinical trial phases I-IV take?

As we all know too well, drug development is a lengthy process. The entire drug development timeline–from initial discovery through to FDA marketing approval–can easily span 15 years or more.

This long, complex, and arduous journey is not for the faint of heart. Failure rates are so high because of the stringency of the tests novel drugs are subjected to before being approved for use in humans. This allows for extensive precautions to be taken to ensure the protection of patients’ health and safety. Nonetheless, there are strong arguments for accelerating approval timelines in certain cases. Accelerated approval is already in practice in special cases, such as in rare and terminal diseases that are lacking in treatment options (More information: FDA Accelerated Approval).

In this article, we narrow-in on one part of the drug development pipeline and focus on clinical trials. During the clinical research phase, an investigational new drug or device is put through subsequent clinical trial phases aimed at progressively assessing its safety and effectiveness in humans. The length of each of these trial phases–aptly named phase I trials, phase II trials, phase III trials, and phase IV trials–can vary widely, but there are rough generalizations we can make.

Due to this wide variability in the timelines of clinical trials, particularly between different trial phases, the simple answer to the question is:

Q: How long do clinical trials take?

A: It depends

The overall timeline of a clinical trial depends on multiple factors, such as:

• The nature/type of drug/device being studied
• The condition it’s been developed to treat
• The clinical trial design
• The clinical trial phase
• The length of time and/or extent of data required to answer the research hypothesis
• Site identification and activation
• Patient recruitment; a step that is famously prone to delays
• Regulatory (FDA, IRB) submissions–and delays, re-submissions, etc.

Recent industry trends indicate that clinical trials are actually increasing in duration across all trial phases. This is partly due to the expanded possibilities and increasing complexity of trials, with most modern trials adopting highly customizable, trial-specific workflows powered by eClinical tools and software solutions.[1] While these technological advances have opened up new opportunities and certainly have the potential to enhance efficiency across many operations, they also represent an added degree of complexity in trial design and start-up, and potential fragmentation across multiple providers adds to the intricacy.

Overview of the drug development timeline

Development of most new drugs, from discovery to marketing approval, usually takes between 10 and 15 years, although this figure can vary widely.

In general, the drug development pipeline–including preclinical development, clinical research, and major regulatory approvals(*)–can be summarized as follows:

1. Drug discovery

2. Pre-clinical research / Preclinical development (laboratory studies)

3. *Investigational New Drug (IND) application

4. Clinical trials

• Phase 0 (optional)
• Phase I trial
• Phase II trial
• Phase III trial

5. *New Drug Application (NDA)

6. Phase IV (post-marketing surveillance studies)

In this article, we’re focusing on the clinical research phase. When a drug looks promising based on preclinical laboratory studies and possibly animal studies, the time comes to progressively test its safety and efficacy in humans. The clinical research phase involves phase I through III clinical trials, and potentially initial phase 0 trials and post-marketing surveillance studies, also known as phase IV trials.

How long do clinical trials take? Factors that impact a clinical study timeline

The variability in protocol design, sample size, treatment, study endpoints, patient availability, and the other factors we listed in the introduction means that we can’t give a simple answer to the question of how long clinical trials take. However, we can get a rough idea of ‘typical’ clinical trial timelines by looking at 3 main influencing factors: the trial phase, patient recruitment rate (accrual rate), and trial design.

Factor 1: Clinical trial phase

In general, phase I clinical trials are shorter than phase II clinical trials, and phase III trials are the longest. Phase IV trials can last for years, but are more passive in nature, with monitoring of the treatment under routine care practices. As a drug makes its way through preliminary safety trials, greater amounts of data are then collected from a larger pool of patients over a longer period of time to obtain higher-resolution insights into its effectiveness and longer-term safety. The timelines of each clinical trial phase given below are approximate and only generalizations.

1. Phase I trials

Phase I clinical trials usually last from one to four months. Researchers introduce the drug to humans (usually healthy volunteers) for the first time, and study how it’s processed in the body and how well it’s tolerated.

2. Phase II trials

Phase II clinical trials might last anywhere from several months to two years. In phase II trials, researchers determine the optimal dosage, begin to assess the effects of the treatment on the condition it’s designed to treat, and collect further information about tolerability and side effects.

3. Phase III trials (Pivotal trials)

Phase III clinical trials can last for several years as researchers gather data about how well the novel drug works compared to standard therapies, in a larger number of participants and over a longer period of time. These studies are the last clinical trial phase conducted before submitting a request for FDA approval via a new drug application (NDA)–that is, if the results are promising.

4. Phase IV trials (Post-marketing surveillance studies)

After a drug gets approved for use in humans, some are subjected to so-called “post-marketing surveillance studies,” also known as phase IV studies. These are long-term studies of the effectiveness and safety of the drug in regular clinical practice (i.e., under real-world conditions, representing a type of real-world evidence [RWE] study). Phase IV trials can last for many years, and are usually designed to assess side effects of long-term use, economic costs of the treatment, quality of life for those taking the drug, and other similar broad questions about health outcomes that serve to improve public health decision-making.

For a more thorough overview of the stages of clinical research, including a closer look at the specific aims of each trial phase and details about the main regulatory approval steps, check out our article dedicated to clinical trial phases.

Factor 2: Patient recruitment and accrual rate

Patient recruitment is famously prone to delays. It was reported that 90% of clinical trials worldwide fail to meet enrollment timelines and are required to extend the recruitment timeframe to avoid having to cancel the study.[2] Traditional approaches to patient recruitment are based on stale patient databases and simply do not represent an effective use of resources. One key factor is patient accessibility, which is a double-edged problem; patients may not know about clinical trials or may have trouble finding clear information, and researchers often lack methods to directly access eligible patients. Power's modern patient recruitment marketplace is a revolution in this regard, empowering both sponsors and patients with a highly user-friendly interface, advanced search features, and a strong database of high-intent patients. Patient recruitment is a different beast and requires a unique set of skills; partnering with a dedicated recruitment specialist is one of the best ways to avoid common and costly delays or shortfalls in patient recruitment.

Factor 3: Clinical trial design – study endpoints, treatment type, etc.

The specific design of the clinical trial impacts the overall trial timeline in various ways:

Regulatory (IRB) approvals: All study materials, including the protocol, recruitment and promotional material, and the informed consent form must be approved by an IRB prior to them being used and before the study can commence. Amendments–whether due to rejections, changes that need to be made due to unforeseen circumstances or delays, or a number of other reasons–can be costly, with each required resubmissions easily adding a month or more to study start-up timelines.

Treatment type and study endpoints: Each drug and treatment has its own dosing schedule and duration due to the enormous variability in pharmacodynamics. Depending on how often and for how long a patient will need to take the study drug, collecting sufficient data to answer the research hypothesis may take as little as a few weeks or as long as multiple years. Further, different clinical endpoints–the metrics measured to assess the drug’s effects in the body–may require shorter or longer study timelines to capture the right data.

Protocol complexity and study design: Clinical trial design involves many variables, as we discuss in greater depth here: clinical trial study design. There is so much variability possible here that it’s difficult even to make a generalization. With the availability of data and the new opportunities opened up by eClinical tools, remote study endpoints, wearables, etc., sponsors must find a balance. The aim should be to collect sufficient data to make the necessary conclusions without overburdening patients, overextending timelines, or complicating data analysis by collecting exaggerated amounts of data just because it’s possible.

Conclusion

In summary, clinical trial timelines vary significantly from study to study. The question “how long does a trial last” does not have a straight answer.

If you’re considering participating in a clinical trial, it’s important to understand all the details of the trial, including its expected duration and the number of study visits required. Travel time and time off work are other factors that will play into your ability to make an informed decision about whether you can commit to the entirety of the trial. With the rise in decentralized clinical trials and the emphasis on patient centricity, many protocols are being designed with the aim of reducing patient burden, making it increasingly feasible to participate from home or for data to be collected remotely and even passively. In such cases, longer trial timelines are less of a concern.