Versorgungsforschung der Anti-VEGF-Therapie: Selektion und methodische Besonderheiten

 

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Zusammenfassung

Die anwendungsnahe Versorgungsforschung hat zum Ziel, die Wirksamkeit und Qualität einer Behandlung wie der Anti-VEGF-Therapie im Alltag zu verbessern. Sie eröffnet darüber hinaus die Möglichkeit, über eine kritische Analyse der Kosten die Wirtschaftlichkeit darzustellen und Entscheidungen von Gesundheitspolitikern und Kostenträgern zu unterstützen. Prospektiv kontrollierte Studien (Randomized controlled Trials; RCTs) haben zwar ohne Frage ihre Berechtigung, die Wirksamkeit einer Therapie unter kontrollierten Einflussfaktoren zu erfassen. Trotz niedriger Verzerrungspotenziale bilden sie aber nur eine kleine Stichprobe großer, heterogener Patientengruppen z. B. mit neovaskulärer Makuladegeneration und diabetischem Makulaödem ab. RCTs beantworten somit oft auch nicht relevante Fragen, z. B. wie eine Behandlung konkret umgesetzt werden sollte oder wie sich Einflussfaktoren (Behandlungsverzögerung, Adhärenz, seltene Nebenwirkungen, Pharmakovigilanz) auf den Einsatz in der klinischen Routine auswirken.

Wenn aufgrund von Komorbiditäten, Drop-out-Raten oder seltener Phänotypen der Einschluss in RCTs nicht sinnvoll oder möglich ist, stellen Beobachtungsstudien ohne Randomisierung oder Behandlungsvorgaben gute Alternativen dar, ergänzende Aspekte zu evaluieren. Nichtsdestotrotz ist es gerade für die Erhebung weicherer Zielparameter wie Visus und patientenbezogener Parameter (Patient related Outcome; PRO) von Bedeutung, die Limitationen und Stärken eines nicht interventionellen Designs zu kennen. Eine genaue Kenntnis statistischer Phänomene (Floor/Ceiling Effect) oder Vorgaben/Einschränkungen kann verhindern, dass Selektionsphänomene übersehen oder fehlinterpretiert werden. Zu viele Studien verzichten jedoch leider auf die Angabe zeitabhängiger Parameter und liefern über das Ausblenden von Patienten mit schlechterem Ansprechen ein positives Zerrbild der Wirklichkeit.

Abstract

Health care research has emerged as an approach to assess and improve quality of care and patient outcomes in the real world. It also has the potential to reduce healthcare costs by providing evidence to guide healthcare decisions.

Randomised controlled trials (RCTs) theoretically offer the ideal study design to support treatment decisions. In RCTs, randomisation (formal chance) determines treatment allocation, which prevents selection bias from distorting the parameters of anti-VEGF treatment effects. Despite this advantage, only a minority of patients qualify for inclusion in neovascular age-related macular degeneration or diabetic macular oedema trials, which limits the validity of the results to the whole patient population seen in clinical practice. The evidence base for anti-VEGF is deficient in terms of matching the characteristics of patients encountered in clinical practice, and a more representative sample of older people and those with significant disability must be included in future trials. RCTs often do not address other knowledge gaps, including treatment delay, comparisons for less frequent types of CNV, monitoring of rare or late toxicity events or systemic safety.

Observational studies, or studies in which treatment allocation occurs independently of investigatorsʼ choice or randomisation, can complement RCTs by providing data that is more relevant to the circumstances under which intravitreal therapy is routinely practiced. However, it is important to be aware of the strengths and limitations of such observational study designs, in order to optimise the design as well as the analytic techniques. Selection bias and loss-to-follow-up cause make comprehensive interpretation and careful analysis necessary. Future reports should focus on time-to-event analysis, as this is much less prone to loss-to-follow-up and improves adherence of (functionally) one-eyed or good responders. Observational studies and pragmatic trials can test new hypotheses and possible license extensions. The bearing of RCT findings on day-to-day practice can then be assessed. The data can be interpreted in a more meaningful manner by practicing clinicians if evidence is integrated from a variety of different study designs and methodologies.

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