Local versus Central Assessment of Venographies in a Multicenter Trial on the Prevention of Deep Vein Thrombosis in Neurosurgery

Abstract

SummaryVenography is the diagnostic method of choice for end-point measurement in multicenter trials on the prevention of postoperative deep vein thrombosis (DVT). The aim of the study was to determine the inter-observer agreement between the local and central assessment of venographies in a multicenter trial comparing enoxaparin and placebo in the prevention of DVT after elective neurosurgery.The study was run in seven centers experienced in venography trials on DVT prevention. The central and local adjudication panels were both blind with respect to the assigned treatment. The central panel was unaware of the local adjudication. Venographies were adjudicated as positive, negative or inadequate for adjudication and positive venographies as proximal or distal DVT. Inter-observer agreement was assessed according to the Cohen’s inter-observer variability index (K index).All 266 venographies (8 monolateral) were considered adequate for adjudication by both the central and local panels. A disagreement was found in 25 cases; K index = 0.75. Fourteen venographies adjudicated as negative centrally were considered positive locally (3 were proximal DVT). Eleven venographies adjudicated as positive centrally (1 was a proximal DVT) were considered negative locally. Enoxaparin was found to be more effective than placebo according to both the central and local adjudication: 16.9% versus 32.6% (Relative risk, RR = 0.52; CI95% 0.33-0.82) according to central adjudication; 18.5% versus 33.3% (RR = 0.56; CI95% 0.36-0.87) according to local adjudication.We conclude that a good inter-observer agreement in the assessment of venography was observed between the central and local adjudication in a study on DVT prevention run in a restricted experienced study framework. The cost and work overloading of central assessment of venographies in this study framework seems not to be justified.

Ultrasound screening for asymptomatic deep vein thrombosis after major orthopaedic surgery: the VENUS study

“…Despite this methodological rigor, which established that venous ultrasound can be optimized from a logistical point of view to match venography, we failed to demonstrate that it can be used as an alternative for the screening of asymptomatic DVT in this setting. In this trial, inter-observer agreement for centrally adjudicated venography, a measure of internal validity, was excellent, corroborating findings from a previous trial using the same standardized venography technique and the same venography adjudicators [20], and by far exceeded the figures reported in earlier studies [6][7][8][9]; however, it was poor for ultrasound. Agreement between readers for centrally adjudicated CCUS was in the lower range of what would be accepted for a diagnostic test.…”

“…In this trial, inter‐observer agreement for centrally adjudicated venography, a measure of internal validity, was excellent, corroborating findings from a previous trial using the same standardized venography technique and the same venography adjudicators [20], and by far exceeded the figures reported in earlier studies [6–9]; however, it was poor for ultrasound. Agreement between readers for centrally adjudicated CCUS was in the lower range of what would be accepted for a diagnostic test.…”

“…Moreover, venograms can be shipped easily, allowing central adjudication, an essential requirement for phase II and phase III trials. However, inter‐observer agreement in interpreting venograms is variable [6–10], and radiation burden and exposure to contrast agents pose risks to the patient, in addition to the cumbersome and occasionally painful nature of the procedure itself. Thus, non‐invasive alternatives to venography would be welcomed by patients and investigators.…”

Prophylaxis for deep venous thrombosis in patients with craniotomies: a review

“…It is extremely sensitive in identifying the location, extent, and degree of attachment of a clot. Rossi, et al, 53 state that venography remains the only reliable diagnostic method for DVT detection in patients who are asymptomatic postoperatively, but that it is not a practical screening test. Venography exposes the patient to radiation, it is painful, and it takes approximately 30 to 45 minutes to perform.…”

End Points in Studies on the Prevention of Deep Vein Thrombosis

“…More recently, Rossi et al 8,9 compared the local versus central assessment of venography in a study of the prevention of DVT in elective neurosurgery patients. In this study, 307 patients, all wearing compression stockings, were randomized to receive placebo or enoxaparin (40 mg) once daily.…”