Clinical Trial Basics: Clinical Outcomes in Research

What is a clinical outcome in clinical trials?

Many different metrics can be used to study and evaluate patient responses to medical treatments, therapies, and overall healthcare in clinical settings. Such a metric is known as a clinical outcome. A clinical outcome is defined as a measurable change in overall health, function, or quality of life, and describes how a patient feels and functions after receiving a given treatment.[¹]

Clinical outcomes are assessed and used in multiple settings, such as hospitals, clinics, and clinical trials, and also represent important data for medical research and policy. Clinical outcomes are used as endpoints during clinical trials to help researchers determine whether the new drug or therapy is safe and effective, either in general or in comparison to a placebo or an existing treatment for a given condition.[²]

Examples of clinical outcomes

In clinical trials, clinical outcomes are divided into primary and secondary outcomes. Primary clinical outcomes are those that are most directly relevant to the research question, and should typically also be of importance to the patient (patient-centric outcomes).[3] Secondary clinical outcomes are used to further assist with the interpretation of the study results and to supplement the primary outcome. There may be multiple secondary outcomes measured alongside the primary outcome.

In statistical terms, a clinical outcome is a dependent variable in a clinical study. The following list gives some examples of clinical outcomes that may be monitored in a clinical trial:

• Quality of life
• Survival rate or mortality
• Discomfort or pain
• Disease progression or recurrence
• Symptom relief
• Changes in specific biomarkers
• Safety (side effects/adverse events, or lack thereof)
• Patient-reported outcomes (PRO)

Importance of measuring clinical outcomes to determine the effectiveness of treatments

Clinical outcomes are fundamental to study design because they form the basis for drawing conclusions from the study data. They define the endpoint(s) that researchers will use to answer the research question, and thereby guide the design of the study such that it creates the experimental conditions necessary for measuring and interpreting those endpoints in a controlled manner. It is important to identify and select the primary outcome before the study begins in order to ensure that study results are statistically valid, as using too many primary outcomes can increase the risk of false-positive results (type I error).[⁴]

Clinical outcomes allow investigators to assess a patient’s health over the complete care cycle (from the onset of the treatment plan to follow-up care) and provide information about the benefits and adverse effects of the new drug or treatment.[⁵] In clinical trials, improving patient outcomes is the primary goal, and thus outcomes should ideally be patient-centered, meaning that the outcome is also of importance to the patient him/herself, beyond being clinically useful for researchers. In this way, a clinical trial will be able to provide conclusions about the effectiveness and/or safety of a new treatment which reflects the viewpoints of both the researchers and the patients themselves. For example, if endpoints were chosen without patient experience in mind, a study may deem a treatment to be effective despite it being perceived by patients as unjustifiably burdensome, painful, or expensive - in other words, patients would be unlikely to adhere to the treatment regardless of how promising the trial’s results were on paper.

How are clinical outcomes measured?

Clinical outcomes could either be measured/determined by the study physician or reported by the patient him/herself, and could be based on an established assessment scale (for example the visual analog scale [VAS] for pain), physiological measurements, surveys, or other methods. Here we will take a closer look at four different types of clinical outcome assessments (COAs) that can be used to assess health endpoints/outcomes in a clinical trial.

Patient-reported outcome (PRO) measures

Patient-reported outcomes (PRO) are based on data and responses inputted directly by the patient, without relying on any interpretation by a clinician.[¹] PRO measures have two distinct characteristics. First, they are clinically meaningful, having practical implications for disease recognition and management. Secondly, they include the unique patient perspective.[⁵] Data and results may be collected through surveys, interviews, or a patient reports containing open-ended questions, ratings, or numerical scores for various metrics, such as pain, symptom severity, etc. Such outcome measures bridge the gap between clinical practice and each patient’s subjective reality.

Observer-reported outcome (ObsRO) measures

In observer-reported outcomes (ObsRO), a patient’s physical or mental health status, symptom severity, or other observable symptoms or states are reported by a caregiver, parent, or anyone other than the patient or his/her doctor. Such outcome measures do not involve medical judgment or interpretation and are useful for patients who cannot report such measures themselves, such as in the case of disabilities.[¹],[⁶]

Clinician-reported outcome (ClinRO) measures

Clinician-reported outcomes (ClinRO) are assessments conducted by a trained healthcare professional who observes and/or measures aspects of the patient’s clinical status through a professional medical interpretation. They may involve rating scales like the Psoriasis Area and Severity Index (PASI) for measuring the severity and extent of a patient’s psoriasis or the Hamilton Depression Rating Scale (HAM-D) for depression assessment. They can also include clinical measures, such as levels of biomarkers or other physiological measurements.[¹]

Performance outcome (PerfO) measures

Performance outcome (PerfO) outcomes are used to assess a patient’s cognitive and physical abilities through tasks specified by healthcare professionals. They can either be administered by a professional or conducted independently, and may involve the use of different tools or devices. Examples include word recall tests for memory assessment or gait speed measurements.[¹],[⁶]