Surrogate endpoint trials: Benefit and pitfalls for clinical decision making

Basel Institute for Clinical Epidemiology & Biostatistics, Universitätsspital Basel, 4031, Basel, Switzerland.
Der Internist (Impact Factor: 0.31). 07/2008; 49(6):681-7. DOI: 10.1007/s00108-008-2126-8
Source: PubMed


Ideally clinicians should base their treatment decisions on results from randomised controlled trials which include patient-important outcomes, such as quality of life, prevented disease events or death. Conducting such trials often involves large sample sizes and extended follow-up periods. Therefore, researchers have aimed to conduct trials with surrogate endpoints by substituting patient-important outcomes in order to reduce sample size and observation time. Surrogate endpoints are outcomes that substitute for direct measures of how a patient feels, functions, or survives. In many countries drugs are approved based on data from surrogate endpoint trials. Recently, a controversy evolved on the reliability of results generated from these trials driven by unanticipated side effects or severe toxicity leading to the withdrawal of drugs that were solely approved based on evidence from surrogate endpoint trials. We present some recent examples and criteria how clinicians can critically evaluate the validity of claims by experts or the pharmaceutical industry in regard to the expected patients' benefit from drugs approved by results from surrogate endpoint trials.

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    ABSTRACT: Physicians and patients consider the balance between benefits and risks of treatment when making decisions about the use of anticoagulants for the prevention of venous thromboembolism (VTE). The results of early trials demonstrating the efficacy of heparin compared with placebo or no thromboprophylaxis for the prevention of fatal pulmonary embolism (PE) led to adoption of routine anticoagulant prophylaxis in patients considered to be at increased risk of VTE. More recent trials comparing new anticoagulants with heparin have most commonly used the composite outcome, asymptomatic (or "silent") deep vein thrombosis (DVT), detected by screening venography, and symptomatic (or "patient-important") VTE, as the primary measure of efficacy [1-3]. © 2012 International Society on Thrombosis and Haemostasis.
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    ABSTRACT: Surrogate markers are only acceptable in single exceptional cases to demonstrate a patient related true outcome in medical care. This is especially true in drug therapy. Although many surrogate markers are correlated with an outcome, only a few have been shown to capture the effect of a treatment on the outcome. The examples for aberrations in medical care are numerous: They include menopausal hormone therapy, the prevention of cancer or cardiovascular diseases with vitamins, the therapy of cardiac arrhythmias using a special type of drugs as well as the treatment of osteoporosis with fluoride. All these treatments caused more harm than good to the patients; and very often mortality increased. In summary, most of the surrogate markers are not worth discussing, and they should not be utilised to demonstrate patient related outcome; they may only be acceptable in rare cases and would then have to be rigorously validated to protect patients from harm. (As supplied by publisher)
    No preview · Article · Dec 2012 · Zeitschrift für Evidenz Fortbildung und Qualität im Gesundheitswesen