Metaanalyse zur Schätzung der in klinischen Studien zur Kataraktchirurgie zu erwartenden drop out-Rate

Zusammenfassung

Zielsetzung: Eine realistische Fallzahlplanung ist die Grundlage für signifikante Ergebnisse in klinischen Studien und beinhaltet den Einbezug der zu erwartenden drop out-Rate. Diese muss in Anlehnung an bereits durchgeführte Studien geschätzt werden, wodurch über- oder unterschätzte Fallzahlen entstehen können. In dieser Metaanalyse wurden drop out-Raten aus Studienberichten zur Kataraktchirurgie geschätzt, um diese als Grundlage für zukünftige Studienplanungen zur Verfügung zu stellen.

Methode: Die Datensammlung erfolgte als Vollerhebung aller prospektiven und auch retrospektiven Studienberichte aus 5 Fachzeitschriften der Jahrgänge 2002–2012. Hierbei wurde die Anzahl der Studienteilnehmer bei Nachuntersuchungen 3, 6, 12 und 24 Monate nach Rekrutierung dokumentiert. Als primärer Endpunkt der Metaanalyse wurde die berichtete drop out-Rate nach 6 Monaten festgelegt und mittels Studien-weiser 95 %-Konfidenzintervalle zur jeweils berichteten Rate sowie über alle Studien hinweg mittels eines 95 %-Konfidenzintervalls zur medianen Rate geschätzt. Die Schätzung der drop out-Raten erfolgte ferner stratifiziert nach Designspezifika der berichteten Studien.

Ergebnisse: Es zeigte sich ein Anstieg der medianen drop out-Rate innerhalb von 24 Monaten in prospektiven randomisierten Studien zur Kataraktchirurgie von im Median 4 % nach 3 Monaten auf 17 % nach 24 Monaten; für die 6-monatige drop out-Rate ergab sich eine mediane berichtete Rate von 3 % (95 %-Konfidenzintervall 0 %; 14 %).

Schlussfolgerung: Die Ergebnisse dieser Arbeit zeigen, dass in randomisierten klinischen Studien zur Kataraktchirurgie die angenommene drop out-Rate im Rahmen der Fallzahlplanung nicht selten als zu hoch erwartet wird, die resultierenden Studien also nicht selten zu groß dimensioniert werden mit entsprechenden ethischen und ökonomischen Konsequenzen. Die drop out-Rate ist bei einer halbjährigen Nachbeobachtungsdauer in randomisierten Studien zur Kataraktchirurgie im Median mit 5 % und entlang des hier sondierten Publikationsspektrums geringer als 15 % zu erwarten.

Abstract

Background: A realistic sample size calculation is crucial to achieve significant results in clinical trials. As an expected drop out-rate has to be included in the sample size calculation, current practice consists in the presumption of drop out-rates published in previous similar investigations. This approach may, however, result in severely over- or under-estimated sample sizes. Therefore this meta-analysis sought to aggregate the drop out-rates from published clinical trial reports on cataract surgery to derive a quantitative suggestion for the planning of future clinical trials.

Methods: The data collection was a complete review of all prospective and retrospective studies in five journals of the years 2002–2012; trial-wise recall rates of subjects at follow-up 3, 6, 12, and 24 months after recruitment were documented. The primary endpoint of the meta-analysis was the reported drop out-rates after 6 months. 95 % confidence intervals were calculated for each trial, respectively; a median drop out-rate was estimated including its 95 % confidence interval. The drop-out-rate estimates were furthermore stratified by design characteristics of the reported studies.

Results: For randomised clinical trials on cataract surgery, the median drop out-rate increased during the follow-up period of 24 months from 4 % at three months to 17 % at 24 months after recruitment; for the six-month drop out-rate a median drop-out rate of 3 % (95 % CI 0 %; 14 %) was estimated.

Conclusion: Drop out-rates in sample size calculations for clinical trials on cataract surgery were found to be over-estimated in general, ending up in the calculation of overly large patient numbers and thereby in both ethical and economic consequences. For randomised clinical trials on cataract surgery the median drop out-rate can be expected to be 5 % during a six-month follow-up and may rise up to 15 % during a 12-month trial period.

Schlüsselwörter

drop out - Fallzahlplanung - Kataraktchirurgie

Key words

drop out - sample size calculation - cataract surgery

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