Safety Assessment and Power Analyses in Published Anti-Vascular Endothelial Growth Factor Randomized Controlled Trials.
OBJECTIVE
To investigate a certain set of methodological limitations in published anti-vascular endothelial growth factor (VEGF) randomized controlled trials (RCTs).


METHODS
Descriptive methodological study.


METHODS
We did a PubMed search with the terms "bevacizumab OR ranibizumab OR pegaptanib OR aflibercept" and the limitations "humans" and "randomized controlled trials" in 15 of the highest-impact-factor general medicine and ophthalmology journals. We included only RCTs published as original articles, where an anti-VEGF agent was used to treat eye disease. Two independent observers (O.A., P.K.) read through each article and classified the articles according to a predefined set of criteria.


RESULTS
The PubMed search yielded 209 articles, and 93 were classified as eligible. In most of the studies, the study drug was bevacizumab (52.6%, n = 49), followed by ranibizumab (44.1%, n = 41), pegaptanib (7.5%, n = 7), and aflibercept (5.4%, n = 5). Basic epidemiologic data, including sex distribution (2.2%, n = 2) and mean age (3.2%, n = 3), were missing in 3.2% of the published RCTs. The power calculation for efficacy was mentioned in 48% (n = 45) of the published work, and a power calculation for safety was considered in only 1 study (1.1%). Only 6 RCTs (6.5%) reported negative results.


CONCLUSIONS
Power calculations for efficacy, an important component of an RCT, were missing in 51% of the RCTs we surveyed, while a power calculation for safety was only present in 1.1%. Around 60% of the published RCTs were labeled as an "efficacy and safety trial," and none of those studies had a power calculation for safety.
Devrek State Hospital, Ophthalmology Clinic, Zonguldak, Turkey. Electronic address: fehimesen@yahoo.com.
Fehim
F
Esen
Marmara University School of Medicine, Istanbul, Turkey.
Ozlem
O
Alhan
Department of Physiology, Marmara University School of Medicine, Istanbul, Turkey.
Pinar
P
Kuru
Department of Ophthalmology, Marmara University School of Medicine, Istanbul, Turkey.
Ozlem
O
Sahin
D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D052157:Aptamers, Nucleotide / Q000009:adverse effects / Q000627:therapeutic use; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use; D016208:Databases, Factual; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D016032:Randomized Controlled Trials as Topic; D000069579:Ranibizumab / Q000009:adverse effects / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
D020533:Angiogenesis Inhibitors; D052157:Aptamers, Nucleotide; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; C495058:pegaptanib; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab