Section outline

  • Clinical outcome research seeks to monitor, understand and improve the impact of medical treatment on a specific patient or population. It does this by focusing on the clinical endpoints (overall outcomes). Some of these endpoints are reported directly by the patients. They could be quality of life or pain level. The main focus of outcome research is clinically relevant endpoints which means that they are directly related to the treatment of interest.

    Consider a clinical study where the effect of penicillin treatment is measured by the decrease of the amount of a specific protein (called ‘C-reactive protein’), always present in the blood. In a healthy person, the amount of this protein in the blood is very small, but it increases dramatically upon acute infection. This is therefore an indirect method to measure infection in the body. In this case the protein measured would serve as a ‘biomarker’ for an infection. A biomarker is a measurable indicator of a disease state. More specifically, a biomarker indicates a change in the amount or state of a protein. This then correlates with the risk or progress of a disease, or with how the disease is likely to respond to a given treatment. In daily practice, a blood sample is taken from the patient and the amount of the specific plasma protein measured.

    For outcome research, the endpoint would not be the amount of the biomarker, but rather something felt or observed by the patient receiving the treatment. In the case of penicillin, the patient might be less concerned with the biomarker level, and instead be concerned with no longer having a fever and feeling better. This means that their symptoms and the way they feel would be considered a direct assessment of their health status. This is separate from the measure of a biomarker.

    Many researchers define Patient Reported Outcomes as ‘relevant or important to patients’ however this is not always true. Patients and doctors may not always agree on which measures are important. What is clinically manageable may not necessarily be important to patients just because they are able to report on the specific measure. Therefore it is important to validate and document ‘patient relevance’ equal to what is clinically relevant when choosing Patient Reported Outcome measures.

    Moreover, the patient is also likely to be interested in potential side effects associated with the penicillin as well as the cost of the treatment. Examples of endpoints are listed in Table 1.

    ENDPOINT EXAMPLE
    Physiological measure
    • Blood pressure
    Clinical
    • Heart failure
    Symptoms
    • Coughing
    Functional and care
    • Measurement of function (e.g. ability to perform tasks of everyday living; questionnaires about Quality of Life)

    Table 1: Examples of endpoints relevant to outcome research studies.

    For cancer, an important clinical outcome relevant for the patient is the risk of dying from cancer (for the researcher ‘survival rate’).  Where there is a long study duration, outcome research studies can include the use of ‘surrogate endpoints’.

    A surrogate endpoint is when a biomarker is used to measure an outcome – it acts as a substitute for a clinical efficacy endpoint.

    Surrogate endpoints are a subset of pharmacodynamic biomarkers. These biomarkers are expected to predict clinical benefit (or harm, or lack of benefit or harm) based on epidemiologic, therapeutic, pathophysiologic, or other scientific evidence. Surrogate endpoints do not directly measure any clinical benefit to the patient, but predict benefit, such as a reduction in morbidity (incidence of a disease) or mortality (death).

    Not all biomarkers are considered surrogate endpoints. For example, you might look at the presence of biomarkers related to cancer found in blood samples taken from the patient. If the level of the biomarker goes up, the cancer gets worse and if it goes down the cancer gets better. In the context of a clinical trial, surrogates are selected because they are more readily observed, are less invasive, and/or are apparent sooner or more frequently that the ultimate outcome measure. Biomarkers that relate to significant changes in disease state, as described above, do not meet these criteria.

    It has to be underlined that for a surrogate endpoint to be used for regulatory purposes, the marker should have previously been confirmed or validated. It must be shown that changes in the biomarker correlate (correspond) with the clinical outcome of a specific disease and the treatment effect.

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