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What Are Endpoints in Clinical Trials? A Comprehensive Guide

Shauni Fitzgerald 
Published : March 12, 2025

Clinical trials are vital in evaluating the safety, efficacy, and impact of interventions across multiple industries, from nutraceuticals to medical device development. Across these sectors, trials provide the essential data needed to support health claims, obtain regulatory approval, and guide product development. 

In this guide, we'll look at what are clinical trial endpoints, the importance of endpoints in clinical research, the various types of endpoints in clinical trials, examples of clinical trial endpoints, guidelines for endpoint selection in clinical trials, and factors related to the regulatory approval of clinical trial endpoints. 

Table of Contents


Understanding the Importance of Endpoints in Clinical Research

The importance of endpoints in clinical research cannot be underestimated, since these quantitative parameters determine whether an intervention has the intended effect. Endpoints also ensure that findings are scientifically valid and not caused by random variability or spurious correlation. In addition, they guide regulatory decision-making by providing evidence-based justification for product claims.

 

Defining Endpoints in Clinical Trials

What are Clinical Trial Endpoints?

A clinical trial’s endpoints are used to measure the outcomes in the trial. An endpoint is a predefined outcome in a clinical trial, used to determine the intervention’s effect by providing measurable indicators of success or failure.

 

Difference Between Primary & Secondary Clinical Trial Endpoints

Primary and secondary endpoints have distinct roles in clinical trials. Primary endpoints are the main outcomes that determine the study’s success. They are predefined, statistically measurable, and directly linked to the trial’s primary objective. Secondary endpoints provide supplementary information, like additional effects of a product or treatment.

 

Understanding the difference between primary and secondary endpoints is crucial because regulatory bodies primarily assess primary endpoints for efficacy claims, which is not the case of secondary endpoints.

 

The Relationship Between Endpoints & Study Objectives

Endpoints must be chosen for their relevance to a trial’s objectives. If endpoints are not aligned with the study’s objective, the findings may be deemed invalid, as the resulting data will fail to unequivocally support the study’s hypothesis.

 

Types of Endpoints in Clinical Trials

i. Primary Endpoints

These are measurable and intended outcomes or metrics, directly linked to the trial’s objective. 

 

ii. Secondary Endpoints

Demonstrate additional effects that provide supplementary information beyond the trial’s main scope or research question.

 

iii. Exploratory Endpoints

These are outcomes which, due to being too infrequent or less likely to have an effect, cannot be used to support the primary endpoint, but can be used to generate hypotheses for future research.

 

iv. Composite Endpoints

A combination of multiple individual endpoints into a single measure. By increasing incidence rates, composite endpoints can help reduce sample size requirements, trial costs, and duration.

 

v. Surrogate Endpoints in Clinical Trials

According to the FDA, a surrogate endpoint is “a clinical trial endpoint used as a substitute for a direct measure of how a patient feels, functions, or survives”.  

Surrogate endpoints in clinical trials replace a clinical outcome, when other types of endpoints in clinical trials would be unethical or impractical. As such, they can only predict (but not measure) clinical outcomes.

 

Endpoint Categories by Measurement Type

i. Clinical Trial Endpoints

These directly measure health outcomes, such as overall survival, disease progression, response duration, etc.

 

ii. Biomarker Endpoints in Clinical Trials

Biomarker endpoints in clinical trials play a crucial role in precision medicine, as they measure disease presence or progression or the effect of an intervention earlier than through clinical endpoints alone.

 

iii. Patient-Reported Outcomes (PROs)

Unlike primary and secondary endpoints or other predefined types of endpoints in clinical trials, PROs are self-reported by participants, which provides more comprehensive insights into the intervention's impact, beyond what clinical trial outcomes and endpoints measure.

 

iv. Economic Endpoints

These assess the cost-effectiveness, resource utilization, and economic impact of interventions.

 

v. Statistical Endpoints

Statistical significance (endpoints linked to a p-value) shouldn’t be confused with clinical significance, which is a measure of improvement in the function or quality of life of participants. An endpoint can be statistically significant, but not necessarily clinically relevant.

 

How to Choose the Right Endpoint in a Clinical Trial?

The Research Question and Objectives

Endpoints should be chosen based on their relevance to the study’s primary objective and their ability to confirm or disprove the research question. For example, if a trial aims to assess the effect of a supplement on metabolic health, endpoints might include blood glucose levels or insulin sensitivity.

 

Relevance to the Disease and Target Population

Endpoints must be clinically significant to the population and condition being studied. For example, in a gut health trial, microbiota composition or inflammatory markers would be more relevant than general wellbeing scores.

 

Regulatory Requirements & Disease-Specific Guidelines

Selection should be based on the guidelines for regulatory approval of clinical trial endpoints. Choosing endpoints aligned with these standards increases the chances of obtaining regulatory approval and streamlines the process.

 

Measurability and Reproducibility

Endpoints should be quantifiable and consistently measurable, so the study results can be reproduced by other researchers. Choosing analytically and clinically validated biomarkers can help ensure clinical trial endpoint measurement is reliable.

 

Importance of Aligning Endpoints with the Study Hypothesis

Endpoints should support the hypothesis being tested. For example, if a trial hypothesizes that a supplement reduces inflammation, endpoints could include CRP levels or cytokine measurements rather than unrelated or vaguely related endpoints like hospitalization or heart rate.

 

Our Chief Commercial Officer at Atlantia Clinical Trials, Barry Skillington states that - “At Atlantia, our science, medical and regulatory teams spend a lot of time deliberating and deciding on the most suitable endpoints to be used in our research. We feel this upfront investment of time is well spent on these decisions as endpoints have such a huge bearing on clinical success. This work also allows us to distinguish between active and placebo more than other CRO’s, which benefits our clients. Our job is to deliver the best possible science at the best possible budget for each and every client we work with.”

 

Regulatory Requirements on Endpoints

How Regulatory Bodies (FDA, EMA, EFSA) Evaluate Endpoints?

Regulatory bodies evaluate clinical trial outcomes and endpoints to guarantee they can reliably support the study's claims. They can do so by providing guidance documents that outline preferred and accepted primary and secondary endpoints, or by offering endpoint qualification pathways, like the Biomarker Qualification Program.

 

Pre-IND meetings in the pharmaceutical world are another option to explore the potential for regulatory approval of clinical trial endpoints.

 

In the nutraceuticals sector EFSA require that a trial be registered but do not engage in pre submission meetings so endpoint selection and suitability can only be assessed by historical applications or post EFSA panel review. 

 

Role of Endpoints in Gaining Drug Approval

When submitting a study for FDA approval, the agency reviews clinical trial endpoint measurement data and decides whether the chosen endpoints support efficacy and safety conclusions. Therefore, endpoints play a crucial role in the outcomes of regulatory submissions for claim petitions, NDAs, and BLAs.

 

Challenges in Endpoint Selection and Measurement

Ensuring endpoints are meaningful & reproducible

Endpoints must be clinically relevant (meaning they directly and unequivocally impact health outcomes), and scientifically reproducible, ensuring clinical trial endpoint measurement remains consistent across different studies and populations.

 

However, variations in data collection methods, study populations, protocols, equipment discrepancies in multi-center trials, or inter-observer and intra-observer variability can introduce inconsistencies, making it harder to compare results across trials.

 

Addressing variability in measurement tools

To minimize variability, researchers can standardize measurements by:

 

  • Implementing harmonized protocols (ICH-GCP)
  • Using validated measurement tools
  • Ensuring that personnel involved in endpoint assessment is fully trained
  • Employing centralized data monitoring and independent endpoint adjudication committees

 

Balancing Scientific Rigor with Practical Feasibility

Valid and scientifically rigorous endpoints don’t need to be complex. Selecting overly complex endpoints can slow down trials, increase costs, and discourage participants. To ensure endpoints meet rigorous standards and remain feasible, it can be useful to: 

 

  • Use real-world data and digital endpoints to minimize the participant burden
  • Prioritize non-invasive biomarker endpoints in clinical trials
  • Consider composite endpoints, which can reduce trial duration without compromising statistical power

 

Examples of Clinical Trials Endpoints

i. Inflammatory Markers in Blood & Stool

Erythrocyte sedimentation rate (ESR), plasma viscosity, and calprotectin are examples of clinical trials endpoints in studies targeting inflammatory conditions.

 

ii. Fatty Acid Profile in Blood & Stool

Endpoints like lauric acid or other biomarkers of lipid metabolism are useful in studies on metabolic health.

 

iii. Biochemical Pathway Markers

Indicators of specific biochemical processes, such as glucose transporter 1 in the glycolysis pathway, help understand biological mechanisms and their responses to interventions.

 

iv. Microbiological (Microbiome) Markers

Markers like Bacteroides or Prevotella are often used in studies on gut health. Full DNA sequencing (Shotgun, Shallow shotgun, qPCR) is often used to determine changes in the various microbiomes (Gut, Oral, Vaginal and Skin) and be a powerful endpoint in biotic trials. Short Chain Fatty acid profiles, metabolomics and proteomics are also frequently used as clinical markers of trial success.

 

The Evolving Landscape of Endpoints

Technological advances are reshaping endpoint selection and improving clinical trial endpoint measurement. Digital endpoints, which are collected outside clinical settings via sensors and wearables, are becoming more common in clinical trials. These deliver rich high-quality data, as well as an improved participant experience and serve research well in the areas of Real-World Evidence (RWE) which is fast becoming a standard with the research realm.

 

Innovations in Digital Endpoints

Technological innovations are improving the accuracy, scalability, and applicability of trials. For example, electrodermal activity (EDA) sensors are now incorporated into wearables to measure autonomic nervous system activity.

 

Similarly, smartphone-based applications can monitor gait, cognitive function, and even mental health parameters, whereas the development of ingestible sensors can measure medication adherence.

 

Regarding the security of data generated by clinical trial endpoints, blockchain technology has the potential to bulletproof data integrity, traceability, and auditability in endpoint collection. This may prove helpful in digital endpoint management during decentralized trials or in studies where there are multiple stakeholders involved in data handling.

 

Real-World Evidence (RWE) and its Role Shaping Endpoints

RWE is health data linked to the safety, effectiveness, and benefits of a product, collected outside traditional trial settings. This can include health records, medical claims data, and patient-generated data.

 

RWE can help identify novel clinical trial endpoints. When collected into large-scale datasets, it can also help validate clinical trial outcomes and endpoints in more diverse settings and broader populations, as well as improve post-market monitoring.

 

As a result, regulatory agencies are incorporating RWE into their decision-making processes. Currently, the FDA can process a submission exclusively supported by RWE.

 

Emerging trends like patient-centric endpoints

Researchers are increasingly assessing effectiveness by looking beyond predefined clinical trial outcomes and endpoints. The use of patient-centric endpoints is useful in determining how an intervention improves the well-being of participants.

 

Thanks to advanced technological tools, patient-centric endpoints can now measure PROs like symptom severity and relief (e.g. reductions in pain, discomfort, or fatigue), and quality of life metrics (e.g. mobility, sleep quality, social interactions), or parameters related to treatment satisfaction.

 

Trials that incorporate patient-centric endpoints can produce more meaningful findings and can benefit from higher enrollment and completion rates.

 

Conclusion 

Endpoints are vital when it comes to assessing an intervention’s effectiveness, so endpoint selection in clinical trials must be carefully done to ensure the results are scientifically valid, so that any subsequent claims can be accepted by regulatory bodies.

 

Clinical trial endpoints also matter when improving patient outcomes and the overall participant experience. This is evidenced by the insights offered by RWE, the appearance of digital endpoints, and patient-centric approaches, which can broaden our understanding of healthcare interventions, and support innovation in the design of relevant and high-impact research.

 

Frequently Asked Questions on Clinical Trial Endpoints

1. Why are endpoints important in clinical trials?

Endpoints are used to assess an intervention’s effectiveness, ensuring a trial’s results are scientifically valid and any claims made can be accepted by regulatory bodies.

 

2. What is the difference between primary and secondary endpoints?

The difference between primary and secondary endpoints is that the former address the study’s question or objective directly, whereas the latter offer additional insights that are not the study’s primary focus.

 

3. What are exploratory endpoints in clinical trials?

These outcomes cannot directly support the trial’s objective but can offer insights into emerging biomarkers or new mechanisms, so they can guide the objectives of future studies. 

 

4. How are patient-reported outcomes (PROs) used as endpoints?

PROs describe a participant’s subjective experience (e.g., pain levels or digestive discomfort). When used as endpoints, these outcomes can offer insights that couldn’t be captured by biological or clinical endpoints alone.

 

5. What challenges are associated with endpoint selection in clinical trials?

Challenges include ensuring endpoints are clinically meaningful and reproducible, addressing variability, and balancing scientific rigor with practical feasibility.

 

6. Can endpoints change during a clinical trial?

They can if new and significant insights appear, or due to feasibility issues or regulatory feedback. However, any changes to endpoints must be justified and declared in full disclosure.

 

7. How do researchers choose the most appropriate endpoint for a study?

When confronted with how to choose the right endpoint in a clinical trial, researchers focus on their alignment with study objectives, target population relevance, regulatory standards, reproducibility, and measurability.